Índice neutrófilo-linfocito e índice plaquetas-linfocito: herramientas pronósticas del cáncer de pulmón

El cáncer de pulmón es la neoplasia maligna que causa mayor mortalidad en el mundo. Dentro de los factores pronósticos de esta entidad, se encuentran el índice neutrófilo-linfocito y el índice plaquetas-linfocito, parámetros hematológicos que se utilizan para evaluar la inflamación y la respuesta inmunitaria en el cuerpo humano. Se realizó una revisión bibliográfica con el objetivo de exponer el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón, teniendo en cuenta la evidencia científica publicada hasta el momento. Se estudiaron 46 artículos, 28 de los cuales resultaron seleccionados para la elaboración de la investigación. Se emplearon como criterios de selección la calidad de los estudios, el nivel de actualización sobre el tema en cuestión, así como la fiabilidad de la fuente. Se usaron los recursos disponibles en la red Infomed para la selección de la información, entre ellos: PubMed, SciELO, EBSCO, Cumed, LILACS y Scopus, además de Medline, Academic Search Premier y MedicLatina. Se expuso el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón de células no pequeñas, en todos los estadios y con modalidades terapéuticas diferentes.

Lung cancer is the malignant neoplasm that causes higher mortality in the world. Among the prognostic factors of this entity are the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, hematological parameters that are used to assess inflammation and the immune response in the human body. A bibliographic review was carried out with the objective of exposing the value of the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool for lung cancer, taking into account the scientific evidence published to date. A total of 46 articles were studied, of which 28 were selected for the development of the research. The quality of the studies, the level of updating on the subject in question, as well as the reliability of the source was used as selection criteria. The resources available in the Infomed network were used to select the information, including PubMed, SciELO and EBSCO, Cumed, LILACS and Scopus, as well as Medline, Academic Search Premier and MedicLatina databases. The value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool in non-small cell lung cancer at all stages and with different therapeutic modalities was exposed.

Farmacovigilancia intensiva de vacunas SOBERANA®02 y Soberana®Plus en población pediátrica en el Centro de Inmunología Molecular / Intensive pharmacovigilance of SOBERANA®02 and Soberana®Plus vaccines in pediatric population at the Center for Molecular Immunology

Las vacunas SOBERANA®02 y SOBERANA® Plus contra el coronavirus tipo 2 causante del síndrome respiratorio agudo severo, recibieron autorización de uso en emergencia por la autoridad reguladora de Cuba, y de inmediato aconteció una campaña de vacunación masiva en población pediátrica, lo que devino en una inminente movilización de centros de vacunación y vigilancia de sus eventos adversos. El Centro de Inmunología Molecular realizó un estudio de farmacovigilancia intensiva que evalúo el cumplimiento del esquema heterólogo con ambas vacunas, su seguridad y la incidencia de casos positivos a COVID-19 en niños y adolescentes después de completar el esquema de inmunización. Desde el 15 de septiembre al 31 de diciembre del 2021, participaron 529 sujetos entre 2 y 18 años de edad, de ambos sexos, sin antecedentes de infección por coronavirus tipo 2 del síndrome respiratorio agudo severo, procedentes de 35 municipios y 12 provincias cubanas, quienes recibieron vacuna SOBERANA®02 (dos dosis) y SOBERANA®Plus (una dosis). Se realizó vigilancia de eventos adversos hasta 30 días después de la última dosis recibida. Se consultó la plataforma informática nacional Higia Andariego para identificar los casos positivos al virus del síndrome respiratorio agudo severo coronavirus 2, hasta 3 meses de haber completado la vacunación. El 98,5 por ciento de los participantes completó el esquema de vacunación y en el 6,6 por ciento se notificó algún evento adverso con relación consistente a la vacunación. Predominaron las reacciones locales (dolor, eritema, inflamación), sobre las reacciones sistémicas (fatiga y febrícula), de intensidad ligera o moderada. Se logró un elevado cumplimiento del esquema de inmunización, con un perfil de seguridad favorable, los sujetos con esquema completo de inmunización no enfermaron de COVID-19(AU)

The severe acute respiratory syndrome coronavirus 2 vaccines, SOBERANA®02 and SOBERANA®Plus, received authorization for emergency use by the Cuban regulatory authority; a massive vaccination campaign was immediately launched in the pediatric population, which led to an imminent mobilization of vaccination centers and surveillance of adverse events. The Molecular Immunology Center conducted an intensive pharmacovigilance study to evaluate compliance of the heterologous scheme with both vaccines, their safety, and the incidence of COVID-19 positive cases in children and adolescents after completing the immunization schedule. From September 15 to December 31, 2021, a total of 529 subjects between 2 and 18 years of age, of both sexes, without a history of infection by severe acute respiratory syndrome coronavirus type 2, from 35 municipalities and 12 Cuban provinces, who received SOBERANA®02 (two doses) and SOBERANA®Plus (one dose) vaccines, were included in the study. Surveillance for adverse events was performed up to 30 days after the last dose received. The national computer platform Higia Andariego was consulted to identify positive cases for severe acute respiratory syndrome coronavirus 2 up to 3 months after completing vaccination. According to the report, 98.5percent of the participants completed the vaccination schedule and 6.6percent of them reported some adverse event consistently related to vaccination. Local reactions (pain, erythema, inflammation) prevailed over systemic reactions (fatigue and fever), of light or moderate intensity. High compliance with the immunization schedule was achieved, with a favorable safety profile; subjects with a complete immunization schedule did not become ill with COVID-19(AU)

Safety and effectiveness of CIMAvax-EGF administered in community polyclinics.

In spite of the advances in immunotherapy and targeted therapies, lung cancer continues to be the leading cause of cancer-related death. The epidermal growth factor receptor is an established target for non-small cell lung cancer (NSCLC), and its overactivation by the ligands can induce accelerated proliferation, angiogenesis, and metastasis as well as proinflammatory or immunosuppressive signals. CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy that is approved for the treatment of NSCLC patients in Cuba. The study was designed as a phase IV trial to characterize the safety and effectiveness of CIMAvax-EGF in advanced NSCLC patients treated in 119 community polyclinics and 24 hospitals. CIMAvax-EGF treatment consisted of four bi-weekly doses followed by monthly boosters. Overall, 741 NSCLC patients ineligible for further cancer-specific treatment were enrolled. CIMAvax-EGF was safe, and the most common adverse events consisted of mild-to-moderate injection site reactions, fever, chills, tremors, and headache. For patients completing the loading doses, the median survival was 9.9 months. For individuals achieving at least stable disease to the frontline and completing vaccination induction, the median survival was 12 months. Most of the functional activities and symptoms evaluated through the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire improved over time. In conclusion, this real-world trial demonstrated that CIMAvax-EGF was safe and effective in patients who were vaccinated in the maintenance scenario. A larger effect was seen in subjects with poor prognosis like those with squamous tumors and high EGF levels. Remarkably, this community-based intervention was very important because it demonstrated the feasibility of treating advanced lung cancer patients with active immunotherapy in primary care institutions. In addition to CIMAvax-EGF, patients received supportive care at the community clinic. Vaccine administration by the family doctors at the polyclinics reduced the patients' burden on the medical oncology services that continued providing chemotherapy and other complex therapies. We conclude that community polyclinics constitute the optimal scenario for administering those cancer vaccines that are safe and require prolonged maintenance in patients with advanced cancer, despite the continuous deterioration of their general condition. Clinical trial registration: https://rpcec.sld.cu/trials/RPCEC00000205-En, identifier RPCEC00000205.

Nimotuzumab in the Treatment of Inoperable Esophageal Tumors of Epithelial Origin.

Background: Nimotuzumab is a humanized monoclonal antibody that targets the epidermal growth factor receptor. It was approved in Cuba for the indication of inoperable malignant tumors of the esophagus of epithelial origin. The purpose of this study was to evaluate the safety, overall and progression-free survival, clinical response, and quality of life, in adult patients with inoperable esophageal tumors of epithelial origin treated with nimotuzumab in a practical context. Material and Methods. The number of patients who developed adverse events was determined, and the frequency, seriousness, causality, and severity of these adverse events were determined. It also determined the median of survival and progression-free survival and rates at 12 and 24 months and the quality of life. Results: A total of 111 patients were included. The proportion of serious and related AE with the use of nimotuzumab was 1.3%. Most of the related AEs were mild and moderate, and the most frequent AEs were diarrhea, chills, and tremors. New diagnosed patients who received nimotuzumab concurrent with chemotherapy and radiotherapy reached a median OS of 12.2 months (95% CI, 6.9-17.5) and 12- and 24-month survival rates of 51.0% and 17.0%, respectively. Median PFS was 7.8 months (95% CI, 6.2-9.5), and 12- and 24-month PFS rates were 39.3% and 11.2%, respectively. A favorable evolution of the general state of health (p=0.03) was obtained from the beginning of treatment until month 12, with a significant reduction in the appearance of nausea (p=0.009), insomnia (p=0.04), constipation (p=0.04), eating difficulties (p=0.0006), and choking when swallowing (p=0.0001), but increased in dysphagia (p=0.02). Conclusions: The administration of nimotuzumab was safe in the real-world setting. New diagnosed patients that received nimotuzumab concurrent with chemotherapy and radiotherapy reached a higher overall and progression-free survival and better quality of life than the rest of the patients. Trial registration is RPCEC00000215 (Cuban Registry of Clinical Trials; https://registroclinico.sld.cu/en/home). It is registered prospectively on June 30, 2016.

Erythropoietin in Spinocerebellar Ataxia Type 2: Feasibility and Proof-of-Principle Issues from a Randomized Controlled Study.

BACKGROUND: Several pieces of evidence have shown the neurotrophic effect of erythropoietin (EPO) and its introduction in the therapeutic practice of neurological diseases. However, its usefulness in the treatment of spinocerebellar ataxia type 2 (SCA2) has not been proven despite the fact that it is endogenously reduced in these patients. OBJECTIVE: The study aims to investigate the safety, tolerability, and clinical effects of a nasally administered recombinant EPO in SCA2 patients. METHODS: Thirty-four patients were enrolled in this double-blind, randomized, placebo-controlled, phase I-II clinical trial of the nasally administered human-recombinant EPO (NeuroEPO) for 6 months. The primary outcome was the change in the spinocerebellar ataxia functional index (SCAFI), while other motor, neuropsychological, and oculomotor measures were assessed. RESULTS: The 6-month changes in SCAFI score were slightly higher in the patients allocated to NeuroEPO treatment than placebo in spite of the important placebo effect observed for this parameter. However, saccade latency was significantly decreased in the NeuroEPO group but not in placebo. The frequency and severity of adverse events were similar between both groups, without evidences of hematopoietic activity of the drug. CONCLUSIONS: This study demonstrated the safety and tolerability of NeuroEPO in SCA2 patients after 6 months of treatments and suggested a small clinical effect of this drug on motor and cognitive abnormalities, but confirmatory studies are warranted. © 2022 International Parkinson and Movement Disorder Society.

Evaluación de la calidad de vida de pacientes con cáncer de pulmón de células no pequeñas tratados con la vacuna CIMAvaxEGF® / Evaluation of quality of life in patients with non-small cell lung cancer treated with CIMAvaxEGF® vaccine

Este reporte corresponde al análisis de la calidad de vida de los pacientes que se incluyeron en el ensayo clínico fase III de evaluación de la vacuna CIMAvaxEGF® en cáncer de pulmón de células no pequeñas. La calidad de vida se evaluó empleando los cuestionarios EORTC QLQ-C30 y QLQ-C13, al inicio y cada 3 meses hasta el fallecimiento del paciente a criterio del investigador. Para comparar las medianas entre los dos grupos se utilizó la prueba no paramétrica de Mann-Whitney. Las comparaciones entre el nivel basal y los diferentes tiempos de seguimiento se realizaron a través de la prueba no paramétrica de Wilcoxon. El cuestionario QLQ-C30 evidenció un beneficio en cuanto a calidad de vida para el grupo vacunado con la vacuna CIMAvaxEGF® en las escalas funcionales (global, rol y social), en las escalas de síntomas de la enfermedad y del tratamiento (dolor) se observó que mejora la calidad de los mismos a favor de los pacientes tratados con la vacuna CIMAvaxEGF®. El cuestionario QLQ-C13, también evidenció ventajas para el grupo vacunado desde el punto de vista de beneficio clínico en los síntomas (disnea, disfagia, alopecia y dolor en el pecho). Se señala como significativo que disminuye la hemoptisis y la tos en el grupo vacunado, observándose un empeoramiento en el grupo control(AU)

This report corresponds to quality of life analysis of patient with non-small cell lung cancer included in the phase III clinical trials Evaluation of CIMAvaxEGF® vaccine in lung cancer. The quality of life was evaluate using the EORTC questionnaires QLQ-C30 y QLQ-C13, at the beginning and every 3 months. To compare the median between two groups the Mann-Whitney non-parametric test was used. To compare the baseline and different follows times the Wilcoxon non-parametric test was used. The QLQ-C30 questionnaire showed a benefit in terms of the quality of life for the CIMAvaxEGF® vaccine group on the functional scores (global, role and social) and symptoms of the disease (pain). The QLQ-LC13 questionnaire showed a benefit in terms of the quality of life for the CIMAvaxEGF® vaccine group on the symptoms scores (dyspnea, dysphagia, alopecia and chest pain). It is noted as significant that the hemoptysis decreases in the group vaccinated as well as the dysphagia, the cough and the dyspnea observing a worsening in the control group(AU)

Reliability and Dimensionality of EPREVO ("Experiencias de Parto Relacionadas a Violencia Obstétrica"): Development of a New Instrument, Ecuador.

BACKGROUND: A new instrument called EPREVO has been developed to measure obstetric violence in Ecuador and the objective of this work is to validate its reliability and structural dimensionality. METHODS: Using confirmatory factor analysis (CFA) with a tetrachoric correlation approach. We examined the factor structure of EPREVO, a Spanish instrument to measure obstetric violence. Kuder Richardson values were used to assess the internal consistency of the scale and dimensionality was confirmed with confirmatory factor analysis. RESULTS: Confirmatory factor analysis supported a 3-factor solution. Most item-to-factor-correlations presented moderate to strong magnitude. Total Kuder Richardson was 0.87, while for the three factors were 0.23, 0.47 and 0.94, respectively. The model's goodness-of-fit indexes were satisfactory (χ2 = 1458.83; χ2/g.l = 2.60, p < 0.001; NNFI = 0.90; RMSEA = 0.09); most of the factor loads were greater than 0.30. A confirmatory factor analysis suggested a 3-dimensional structure of EPREVO. CONCLUSION: The scale's factor structure presented satisfactory validity and reliability results, except for one factor. The 30 items scale could potentially be used as an instrument for assessing obstetric violence in different healthcare settings.

Nimotuzumab (CIMAher®) en pacientes cubanos con cáncer de cabeza y cuello estadios III/IV: Análisis de impacto presupuestario / Nimotuzumab (CIMAher®) in Cuban patients with head and neck cancer stage III/IV: Budget impact analysis

En Cuba, el cáncer es la segunda causa de muerte con 24.902 defunciones en el 2018; de ellas, 795 fueron por tumores de laringe y 826 por tumores de labio, cavidad bucal y faringe. El anticuerpo monoclonal nimotuzumab (CIMAher®) está registrado como tratamiento combinado con radioterapia o quimioterapia para el cáncer de células escamosas de cabeza y cuello estadios avanzados. Del mismo se conoce su efectividad y perfil de seguridad, no así el impacto económico que acarrearía la incorporación del mismo al Sistema Nacional de Salud (SNS) cubano; de forma tal de asignar y reajustar presupuestos en la esfera de medicamentos. Por tanto, se hizo necesario realizar un análisis de impacto presupuestario, con el objetivo de estimar el impacto financiero de la incorporación del nimotuzumab (CIMAher®) al paquete de beneficios del SNS cubano. Se tomaron los datos de prevalencia e incidencia de la enfermedad en los estadios III/IV. Se estableció un escenario actual con la terapia radio/quimioterapia secuencial y una tasa de penetración de 100%. El escenario futuro fue radio/quimioterapia secuencial + nimotuzumab (CIMAher®) con tasa anual de penetración 20, 40, 60, 80 y 100 por ciento. La perspectiva fue desde el SNS y un horizonte temporal de 5 años (2019-2023). El análisis de impacto presupuestal mostró que, desde perspectiva, horizonte y tasa de penetración establecidos, el SNS debe invertir aproximadamente de 10 a 65 millones de pesos cubanos (CUP); cifras menores al presupuesto destinado a salud pública(AU)

In Cuba, cancer is the second cause of death with 24,902 deaths in 2018; 795 were due to laryngeal tumors and 826 due to tumors of the lip, oral cavity and pharynx. The monoclonal antibody nimotuzumab (CIMAher®) is registered as a combined treatment with radiotherapy or chemotherapy for advanced squamous cell carcinoma of the head and neck. Its effectiveness and safety profile are known, but not their economic impact into the Cuban National Health System (NHS); in order to allocate and readjust budgets in the field of medicines. Therefore, it was necessary to perform a budget impact analysis in order to estimate the financial impact of the incorporation of nimotuzumab (CIMAher®) into the benefits package of the Cuban NHS. Data on prevalence and incidence of the disease in stages III / IV were taken into account. The current scenario was with the therapy radio/sequential chemotherapy and penetration rate of 100 percent. The future scenario was radio/sequential chemotherapy + nimotuzumab (CIMAher®) and annual penetration rate of 20, 40, 60, 80 and 100 percent. The perspective was from the NHS and a time horizon of five years (2019-2023). The budget impact analysis showed that from an established perspective, horizon and penetration rate, the NHS must invest 10-65 million Cuban pesos (CUP) approximately; lower values than the budget allocated to Public Health(AU)

Calidad de vida relacionada con la salud en la morbilidad del paciente en hemodiálisis periódica / Quality of Life related to health in the morbidity of periodic hemodialysis patient

RESUMEN Fundamento: La insuficiencia renal crónica tiene un impacto negativo en la calidad de vida y esta constituye un predictor de morbilidad en los pacientes en hemodiálisis periódica. Objetivo: evaluar la influencia de la calidad de vida relacionada con la salud en la morbilidad de pacientes en hemodiálisis periódica intermitente. Métodos: se realizó un estudio descriptivo, en pacientes con tres meses y más de tratamiento con hemodiálisis periódica intermitente en el servicio de Nefrología, del Hospital Militar Dr. Carlos J. Finlay, de La Habana, en un período de seguimiento de 12 meses. Se analizaron las variables: edad, sexo, tiempo de tratamiento sustitutivo de la función renal, índice de morbilidad, tipo de morbilidad en hemodiálisis e índice de ingreso hospitalario. Se aplicó el Cuestionario para calidad de vida en pacientes con enfermedad renal (versión 1.3). Resultados: predominaron los pacientes menores de 60 años, masculinos, de nivel escolar alto, con hipertensión arterial como causa principal de la insuficiencia renal. Las morbilidades más frecuentes fueron: escalofríos, hipotensión arterial, hipertensión arterial y complicaciones asociadas al acceso vascular. El índice de hospitalización fue bajo. El sumario componente físico fue el de menor puntuación, seguido por el sumario componente mental. Entre estos y la edad se encontró correlación inversamente proporcional; así como entre índice de morbilidad y el sumario componente físico. Conclusión: los resultados obtenidos guardan relación con los de estudios precedentes. El sumario componente físico resulta el de mayor afectación, sobre todo, en el adulto mayor, teniendo una relación negativa con el índice de morbilidad y de hospitalización.

ABSTRACT Foundation: chronic renal failure has a negative impact in the quality of life and constitutes a morbidity predictor in patients with periodic hemodialysis. Objective: to evaluate the influence of quality of life related to health in the morbidity of patients in intermittent periodic hemodialysis. Methods: a descriptive study was done in patients with three or more time of intermittent periodic hemodialysis at the Nephrology service of the Military Hospital Dr. Carlos J. Finlay. Havana, in a 12 month follow up period. The variables analyzed were: age, sex, time with the substituting renal function treatment, morbidity rate, type of morbidity in hemodialysis and hospital admission rate. A questionnaire for quality of life in patients with renal disease (version 1.3) was applied. Results: patients under 60 years old predominated, of high schooling level, with blood hypertension mainly due to renal failure. The most frequent morbidities were: chills, arterial Hypotension, and complications related to vascular access. The admission rate was low. The summary physical component had the lower punctuation followed by the summary mental component. Among these and age there was found an inversely proportional correlation, so as the morbidity rate and the summary physical component. Conclusion: the results obtained are related to preceding studies. The physical component summary results with higher involvement, mainly in the older adult, considering the negative relation with the morbidity rate and hospital admission.

Metodología y sistemas para meta-análisis de ensayos clínicos / Methodology and systems for meta-analysis of clinical trials

Introducción: Frecuentemente la información médica sobre determinado aspecto clínico, es tan poco clara y contradictoria, que en ocasiones el profesional de la salud no tiene el tiempo o la orientación para poder analizarla en su totalidad, y poder así aprovecharla en su real magnitud. Objetivo: Revisar la metodología y los sistemas que existen para realizar meta-análisis de ensayos clínico. Métodos: Se ha revisado el proceso de análisis de esos conocimientos, llamado meta-análisis; éste es un estudio sistemático, cualitativo y cuantitativo de un grupo de informes o artículos de investigación, generalmente enfocado al análisis de un aspecto clínico. Resultados: En este artículo de revisión, se muestra cómo se diseña, se ejecuta y reporta el meta-análisis, así como los pasos para la realización del meta-análisis. Discusión: Se resumen y se comparan los sistemas que más se utilizan para realizar meta-análisis. Conclusiones: Con este trabajo se conocen que los análisis de sensibilidad, acumulado y de sesgo de publicación no pueden faltar para un meta-análisis, así los sistemas donde poder realizar cada uno de estos análisis(AU)

Introduction: Frequently the medical information on a certain clinical aspect is so unclear and contradictory, that health professional does not have the time or guidance to be able to analyze it in its entirety, and thus be able to take advantage of it in its real magnitude. Objective: To review the existing methodology and systems to perform meta-analysis of clinical trials. Methods: The process of analyzing this knowledge, called meta-analysis, has been reviewed; this is a systematic, qualitative and quantitative study of a group of reports or research articles, generally focused on the analysis of a clinical aspect. Results: In this review article, we show how the meta-analysis is designed, executed and reported, as well as the steps to carry out the meta-analysis. Discussion: The systems most used to perform meta-analysis are summarized and compared. Conclusions: With this work we know that the analysis of sensitivity, accumulated and publication bias cannot be missing for a meta-analysis, as well as the systems where each of these analyzes can be performed(AU)

Metodología y sistemas para meta-análisis de ensayos clínicos / Methodology and systems for meta-analysis of clinical trials

Introducción: Frecuentemente la información médica sobre determinado aspecto clínico, es tan poco clara y contradictoria, que en ocasiones el profesional de la salud no tiene el tiempo o la orientación para poder analizarla en su totalidad, y poder así aprovecharla en su real magnitud. Objetivo: Revisar la metodología y los sistemas que existen para realizar meta-análisis de ensayos clínico. Métodos: Se ha revisado el proceso de análisis de esos conocimientos, llamado meta-análisis; éste es un estudio sistemático, cualitativo y cuantitativo de un grupo de informes o artículos de investigación, generalmente enfocado al análisis de un aspecto clínico. Resultados: En este artículo de revisión, se muestra cómo se diseña, se ejecuta y reporta el meta-análisis, así como los pasos para la realización del meta-análisis. Discusión: Se resumen y se comparan los sistemas que más se utilizan para realizar meta-análisis. Conclusiones: Con este trabajo se conocen que los análisis de sensibilidad, acumulado y de sesgo de publicación no pueden faltar para un meta-análisis, así los sistemas donde poder realizar cada uno de estos análisis(AU)

Introduction: Frequently the medical information on a certain clinical aspect is so unclear and contradictory, that health professional does not have the time or guidance to be able to analyze it in its entirety, and thus be able to take advantage of it in its real magnitude. Objective: To review the existing methodology and systems to perform meta-analysis of clinical trials. Methods: The process of analyzing this knowledge, called meta-analysis, has been reviewed; this is a systematic, qualitative and quantitative study of a group of reports or research articles, generally focused on the analysis of a clinical aspect. Results: In this review article, we show how the meta-analysis is designed, executed and reported, as well as the steps to carry out the meta-analysis. Discussion: The systems most used to perform meta-analysis are summarized and compared. Conclusions: With this work we know that the analysis of sensitivity, accumulated and publication bias cannot be missing for a meta-analysis, as well as the systems where each of these analyzes can be performed(AU)

Seguridad y efecto del uso compasivo del anticuerpo monoclonal anti-CD20 CIMABior® / Safety and response to treatment of compassionate use of an anti-CD20 monoclonal antibody CIMABior®

Introducción: el uso de anticuerpos monoclonales transformó el tratamiento de los linfomas no hodgkinianos. El Centro de Inmunología Molecular generó un anticuerpo anti-CD20 (CIMABior®) biosimilar del rituximab, que se ha caracterizado desde el punto de vista biológico, pero la seguridad y eficacia aún están en estudio. Objetivo: evaluar la seguridad y la respuesta al tratamiento con CIMABior ®, en pacientes con síndromes linfoproliferativos de células B tratados con intención compasiva. Métodos: estudio multicéntrico, exploratorio, con dos grupos de tratamiento (monoterapia o combinado con quimioterapia) no controlado, ni aleatorizado. Se incluyeron adultos con linfomas no hodgkinianos y leucemia linfocítica crónica, no elegibles para el ensayo clínico en ejecución con este producto. Se determinó la frecuencia de eventos adversos y se caracterizaron. La respuesta al tratamiento se definió como: remisión completa, remisión parcial, enfermedad estable o en progresión. Se calculó la tasa de respuesta objetiva (remisión completa más remisión parcial) con el intervalo de confianza al 95 por ciento, se evaluó la relación de algunas variables con la respuesta y se estimó la razón de Odss. Como medida de balance beneficio-riesgo se estimó el factor de Bayes. Resultados: los eventos adversos más frecuentes fueron: temblor (12,8 por ciento) y fiebre (10,3 por ciento). Los relacionados con el producto (43,4 por ciento) fueron leves o moderados y evolucionaron hacia la recuperación. No se informó muerte asociada directamente al tratamiento. Se constató respuesta objetiva global de 71,2 por ciento (59,6 por ciento de remisiones completas y 11,5 por ciento, parciales). La respuesta objetiva en el grupo de monoterapia fue de 66,7 por ciento y de 73,0 por ciento en el grupo de CIMABior® más quimioterapia, con remisiones completas de 46,7 por ciento y 64,9 por ciento, respectivamente. Conclusiones: el AcM CIMABior® es seguro, bien tolerado y se demostraron evidencias de efecto. El tratamiento aportó un beneficio clínico superior al riesgo de desarrollar algún evento adverso grave(AU)

Introduction : The use of monoclonal antibodies transformed the treatment of non-Hodgkin lymphomas. The Center of Molecular Immunology created an anti-CD20 monoclonal antibody (CIMABior®), biosimilar of rituximab, which has been characterized from a biological point of view, but the safety and effectiveness are still being studied. Objective: Evaluate the safety and response to treatment, in patients with B-cell malignancies with compassionate use of CIMABior®. Methods : A multicenter, exploratory, non-controlled, non-randomized study was conducted with two variants of treatments (monotherapy or combined with chemotherapy). Adults with non-Hodgkin lymphomas and chronic lymphocytic leukemia not eligible for clinical trial with this product were included. Frequency of adverse events was calculated and those were characterized. The response to treatment was defined as: complete response, partial response, stable disease or progressive disease. Overall response rate (complete plus partial remission) was calculated with 95 percent confidence interval. The relation of some variables with response was estimated per Odss ratio. As a measure of the benefit-risk balance, the Bayes factor was estimated. Results : The more frequent adverse events were: tremors (12.8 percent) and fever (10.3 percent). Those related to the product (43.4 percent) were minor and evolved to recovery. There were no deaths in reference to the treatment. An overall response of 71.2 percent was confirmed (59.6 percent complete remissions and 11.5 percent partial remission). The monotherapy group objective response was 66.7 percent and 73.0 percent in the CIMABior® plus chemotherapy group, with complete remissions of 46.7 percent and 64.9 percent respectively. Conclusions: The monoclonal antibodies CIMABor® is safe, well tolerated and evidences of its effectiveness was demonstrated. The treatment provided a superior clinical benefit to the risk of developing a severe adverse event(AU)

Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety study.

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.

Desde la investigación biomédica a la clínica: avances del Centro Nacional Coordinador de Ensayos Clínicos

El Centro Nacional Coordinador de Ensayos Clínicos, encaminado a la eficacia en la evaluación clínica de los productos médico-farmacéuticos y biotecnológicos, así como de equipos cubanos, y atendiendo además a la importancia que tiene para todos los profesionales de la salud conocer los avances científicos-técnicos desarrollados desde su creación en 1991 hasta la actualidad, en busca de la eficacia y la seguridad de los productos que se evalúan bajo el cumplimiento estricto de las normas internacionales y las buenas prácticas clínicas, se realizó la presente revisión, donde se describe la incorporación de las tendencias mundiales más novedosas y su expansión a toda la red nacional. Se trabaja además en elevar el nivel científico-técnico de los profesionales, para lo cual se desarrollan diferentes modalidades de capacitación para todo la red nacional de los ensayos clínicos. Para la realización de este trabajo se consultaron fuentes relacionadas con el tema (AU)

The National Coordinating Center for Clinical Trials, aimed at the efficiency in the clinical evaluation of medical-pharmaceutical and biotechnology products, as well as Cuban equipments, and also taking into account the importance for all health professionals to know the scientific-technical advances developed since its creation in 1991 until today, in search of the efficiency and safety of the products that are evaluated under strict compliance with international standards and good clinical practice, the present review was conducted, in which it is described the incorporation of the latest global trends and their expansion into the national network. The center also works to raise the scientific and technical level of professionals, for which different training modalities are developed for all the national network of clinical trials. For the realization of this work sources related to the subject were consulted (AU)

Effect of blockade of the EGF system on wound healing in patients vaccinated with CIMAvax® EGF.

BACKGROUND: The epidermal growth factor receptor (EGFR) signaling system is frequently unbalanced in human malignancies due to increased ligand production, receptor overexpression, receptor mutations, and/or cross-talk with other receptor systems. For this reason, the EGFR is an attractive target for anticancer therapy. The epidermal growth factor also plays an important role in regulating multiple facets of cutaneous wound healing, including inflammation, wound contraction, proliferation, migration, and angiogenesis. In the Center of Molecular Immunology, a cancer vaccine is produced (CIMAvax® EGF) that blocks the binding of EGF to its receptor. This blockade causes a significant inverse association between the anti-EGF antibody titers and EGF concentration. Around 1,500 patients with non-small cell lung cancer have been treated, showing that this vaccine is safe, immunogenic, increases survival and improves quality of life. Taking into account the therapeutic benefits of CIMAvax® EGF vaccination and the role of EGF-EGFR system in the wound healing process, we decided to conduct a retrospective research with the aim of determining the effect to the CIMAvax® EGF vaccine on the wound healing process in patients undergoing surgical treatment. METHODS: Medical records of 452 vaccinated patients were reviewed and only six patients receiving surgical treatment were identified. Further information about these six patients was obtained from source documents, including medical records and operative reports using an observational list that included different variables. Post-surgical wound healing complications were identified using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTC) version 3.0. RESULTS: None of the six patients operated on presented adverse events related to the wound healing, that is to say, no wound dehiscence, wound infection, delayed wound healing, fistula formation, abscess formation or hemorrhage/bleeding associated with surgery during treatment with CIMAvax® EGF occurred. CONCLUSIONS: These results suggest that the use of CIMAvax® EGF does not produce a deleterious effect in the wound healing process.

Sistema para la inclusión de pacientes en ensayos clínicos en tiempo real / System for the real time inclusion of patients in clinical trials

El Centro de Inmunología Molecular ha venido desarrollando una serie de biomoléculas para el tratamiento del cáncer. El pronóstico anual de inclusión de pacientes al ensayo clínico es de 3000. El objetivo de este trabajo fue encontrar una forma de controlar este proceso. El grupo de manejo de datos, en conjunto con el Centro Nacional Coordinador de Ensayos Clínicos, comenzó la inclusión de pacientes en ensayos clínicos por vía telefónica y a través de correo electrónico. A partir del 2010 se creó el sitio de Inclusión de Ensayos Clínicos (http://cimensayossp/clinica/default.aspx), el cual es una potente herramienta que permite controlar la situación de la inclusión de los pacientes. El mismo permitió reportar el número de inclusión y conocer el ritmo de inclusión real en cada ensayo para poder tomar acciones y mejorar así la inclusión planificada. Además se garantiza que no existan retrasos en la entrega del producto de investigación(AU)

The Molecular Immunology Center has developed a series of biomolecules for cancer treatment. With a forecast for the inclusion of 3000 patients per year in clinical trials, the aim of this study was to find a way to control that process. The data management group, in conjunction with the National Coordinating Center for Clinical Trials, began enrolling patients in clinical trials by phone and through email. In 2010 the web site (http://cimensayossp/clinica/default.aspx) was created to Include Clinical Trials, which is a powerful tool to control the status of patient inclusion. It allowed reporting the number of inclusions and to know the actual inclusion rate in each trial to take action and improve the planned inclusion. In addition, it ensures no delays in the delivery of the investigational product(AU)

Aula virtual de Estadística en soporte multimedia / Statistics virtual clasroom in multimedia

El proceso de enseñanza-aprendizaje en el área de la Estadística experimenta una mejoría con las prácticas en los sistemas estadísticos. En algunas ocasiones las carreras universitarias que incluyen asignaturas relacionadas con la Estadística no tienen concebido en su Plan de Estudios prácticas con sistemas Estadísticos, y en otros, estas no son suficientes para desarrollar las habilidades prácticas que requiere esta disciplina. De modo general, las limitaciones materiales condicionan la ausencia total o parcial de actividades prácticas. El creciente desarrollo de las Tecnologías de la Información y la Comunicación (TIC) ha brindado la posibilidad de suplir estas carencias, con el desarrollo de Multimedias Interactivas y Aulas Virtuales. Este proyecto incluye un conjunto de Prácticas de Estadística en soporte Multimedia, que tienen como objetivo preparar al estudiante para obtener el máximo rendimiento en los sistemas estadísticos. Este producto puede ser utilizado como sustituto del Aula real en aquellos casos en que por razones de tiempo, espacio, la práctica real no sea posible(AU)

The process of teaching and learning quality in the area of statistics is determined largely by the good clinical practices. Sometimes university courses that include subjects related to Statistics are not viewed in its practical curriculum statistical system, and in others, these are not sufficient to develop the practical skills required for this discipline. In general, the material constraints condition the total or partial absence of practical activities. The increasing development of Information Technology and Communication (ICT) has provided the possibility of filling these gaps, with the development of Interactive Multimedia and Virtual Classrooms. This project includes a set of Practice of Statistics in multimedia, which aim to prepare the student to obtain maximum performance in statistical systems. This product can be used as a substitute for real classroom in those cases where for reasons of time, space, actual practice is not possible(AU)

Mejoras en el acceso a la información de los ensayos clínicos / Improved access to clinical assay information

El Centro de Inmunología Molecular ha venido desarrollando biomoléculas para el tratamiento del cáncer. En la medida que se avanza en el desarrollo de estos productos, se avanza en las fases I, II, III y IV de los ensayos clínicos, lo que trae aparejado un incremento en el número de pacientes a tratar y en el número de hospitales involucrados. Se cuenta con diez productos diferentes, implicados en más de 50 ensayos clínicos, nacionales y multinacionales, con un pronóstico de inclusión de 2 500 pacientes nuevos por año. En este proceso están incluidos alrededor de 30 hospitales en 13 provincias del país. Para mejorar el acceso a la información de ensayos clínicos por parte de los investigadores comprometidos, se creó un sitio Web formado por cuatro secciones fundamentales, relacionadas con los productos y sus indicaciones, buenas prácticas clínicas, la entrada remota de datos y la gerencia de los ensayos clínicos. Todo lo anterior mejora fundamentalmente la calidad de la información brindada a los investigadores clínicos involucrados y redunda en una mayor organización de la compleja actividad de los ensayos clínicos en Cuba

The Molecular Immunology Center has been developing biomolecules for cancer treatment. As the development of such products continues, phases I, II, III and IV of clinical assays also advance, which leads to an increase of the number of patients to be treated and the number of involved hospitals. There are ten different products involved in over 50 national and multinational clinical assays in which 2 500 patients are predicted to be included every year. Approximately 30 hospitals from 13 provinces are included in this process. For the purpose of improving the access of committed researchers to the clinical assay information, a new Website with four sections was devised. Those sections are related to products and their indications, good clinical practice, remote data entry and clinical assay management. All the above-mentioned improves the quality of the information given to involved clinical researchers and results in better organization of the complex activity of clinical assays in Cuba

Mejoras en el acceso a la información de los ensayos clínicos / Improved access to clinical assay information

El Centro de Inmunología Molecular ha venido desarrollando biomoléculas para el tratamiento del cáncer. En la medida que se avanza en el desarrollo de estos productos, se avanza en las fases I, II, III y IV de los ensayos clínicos, lo que trae aparejado un incremento en el número de pacientes a tratar y en el número de hospitales involucrados. Se cuenta con diez productos diferentes, implicados en más de 50 ensayos clínicos, nacionales y multinacionales, con un pronóstico de inclusión de 2 500 pacientes nuevos por año. En este proceso están incluidos alrededor de 30 hospitales en 13 provincias del país. Para mejorar el acceso a la información de ensayos clínicos por parte de los investigadores comprometidos, se creó un sitio Web formado por cuatro secciones fundamentales, relacionadas con los productos y sus indicaciones, buenas prácticas clínicas, la entrada remota de datos y la gerencia de los ensayos clínicos. Todo lo anterior mejora fundamentalmente la calidad de la información brindada a los investigadores clínicos involucrados y redunda en una mayor organización de la compleja actividad de los ensayos clínicos en Cuba(AU)

The Molecular Immunology Center has been developing biomolecules for cancer treatment. As the development of such products continues, phases I, II, III and IV of clinical assays also advance, which leads to an increase of the number of patients to be treated and the number of involved hospitals. There are ten different products involved in over 50 national and multinational clinical assays in which 2 500 patients are predicted to be included every year. Approximately 30 hospitals from 13 provinces are included in this process. For the purpose of improving the access of committed researchers to the clinical assay information, a new Website with four sections was devised. Those sections are related to products and their indications, good clinical practice, remote data entry and clinical assay management. All the above-mentioned improves the quality of the information given to involved clinical researchers and results in better organization of the complex activity of clinical assays in Cuba(AU)