Immune response and reactogenicity after immunization with two-doses of an experimental COVID-19 vaccine (CVnCOV) followed by a third-fourth shot with a standard mRNA vaccine (BNT162b2): RescueVacs multicenter cohort study.

Background: There is no evidence to date on immunogenic response among individuals who participated in clinical trials of COVID-19 experimental vaccines redirected to standard national vaccination regimens. Methods: This multicentre, prospective controlled cohort study included subjects who received a COVID-19 experimental vaccine (CVnCoV)(test group, TG) - and unvaccinated subjects (control group, CG), selected among individuals to be vaccinated according to the Spanish vaccination program. All study subjects received BNT162b2 as a standard national vaccination schedule, except 8 (from CG) who received mRNA-1273 and were excluded from immunogenicity analyses. Anti-RBD antibodies level and neutralising titres (NT50) against G614, Beta, Mu, Delta and Omicron variants were analysed. Reactogenicity was also assessed. Findings: 130 participants (TG:92; CG:38) completed standard vaccination. In TG, median (IQR) of anti-RBD antibodies after first BNT162b2 dose were 10740·0 BAU/mL (4466·0-12500) compared to 29·8 BAU/mL (14·5-47·8) in CG (p <0·0001). Median NT50 (IQR) of G614 was 2674·0 (1865·0-3997·0) in TG and 63·0 (16·0-123·1) in CG (p <0·0001). After second BNT162b2 dose, anti-RBD levels increased to ≥12500 BAU/mL (11625·0-12500) in TG compared to 1859·0 BAU/mL (915·4-3820·0) in CG (p <0·0001). NT50 was 2626·5 (1756·0-5472·0) and 850·4 (525·1-1608·0), respectively (p <0·0001). Variant-specific (Beta, Mu, Omicron) response was also assessed. Most frequent adverse reactions were headache, myalgia, and local pain. No severe AEs were reported. Interpretation: Heterologous BNT162b2 as third and fourth doses in previously suboptimal immunized individuals elicit stronger immune response than that obtained with two doses of BNT162b2. This apparent benefit was also observed in variant-specific response. No safety concerns arose. Funding: Partly funded by the Institute of Health Carlos-III and COVID-19 Fund, co-financed by the European Regional Development Fund (FEDER) "A way to make Europe".

[Seasonal flu vaccination for older people: Evaluation of the quadrivalent vaccine. Positioning report]. / Vacunación frente a la gripe estacional en las personas mayores. Evaluación de la vacuna tetravalente. Informe de posicionamiento.

Influenza is a significant health problem, particularly in those persons susceptible to having associated complications, older people, children less than 2 years, patients with chronic diseases, immunocompromised patients, and pregnant women. But influenza also has a large impact on the health system, with an increase in the healthcare demand and a spectacular increase in outpatient visits, overloading the emergency and hospital services. During epidemic outbreaks, the hospital admission rates of people over 65 years are at a maximum, and the mortality notified for the 2017/2018 influenza season was 960 deaths. The seasonal anti-influenza vaccine is the method with a better cost-effective ratio of primary prevention of influenza, reducing associated respiratory diseases, the number of hospital admissions, and deaths in high risk individuals, as well as work absenteeism in adults. In the last few years, influenza B has received little attention in the scientific literature, although in the periods between epidemics influenza B can be one of the main causes of seasonal epidemics, causing considerable morbidity and mortality and an increase in costs. The quadrivalent vaccine has a second-line immunological protection against influenza B, and according to a critical review of the scientific literature, it provides wider protection without affecting immunogenicity of the other three vaccine strains common to the trivalent and tetravalent vaccine. The quadrivalent vaccine is cost-effective in reducing the number of influenza cases, and is always a worthwhile intervention, with a significant cost saving for the health system and for society, by reducing the hospital admission rates and mortality associated with the complications of influenza. Supplement information: This article is part of a supplement entitled 'Seasonal flu vaccination for older people: Evaluation of the quadrivalent vaccine' which is sponsored by Sanofi-Aventis, S.A.

Vacunación frente a la gripe estacional en las personas mayores. Evaluación de la vacuna adyuvada. Informe de posicionamiento / Seasonal flu vaccination for older people: evaluation of the adjuvanted vaccine. Positioning report

La gripe es un importante problema de salud pública, particularmente en las personas mayores, con una significativa carga clínica y económica y con una alta mortalidad. En España, durante la temporada 2015- 2016, se han notificado 3.101 casos graves hospitalizados confirmados por gripe, de los que han fallecido el 11% (352 casos). Además, hay un gran aumento de costes económicos y sanitarios por sus complicaciones y los mayores de 65 años representan aproximadamente el 64% del total de costes de la gripe. La vacuna antigripal estacional es la estrategia fundamental, y los estudios de coste-beneficio y coste-efectividad así lo demuestran. Uno de los objetivos prioritarios es mejorar la respuesta inmune de las vacunas, y una línea importante de investigación es la búsqueda e inclusión en las vacunas de adyuvantes o inmunoestimuladores. En este informe de posicionamiento se evalúa la vacunación en las personas mayores y la importancia de la vacuna adyuvada en los mayores, que refuerza la inmunogenicidad mediante una revisión crítica de la bibliografía relacionada con la mayor evidencia disponible sobre su inmunogenicidad, efectividad y evaluación económica (AU)

Flu is a major public health problem, particularly for older people, and creates an important clinical and economic burden. A high mortality rate was reported in Spain during the period 2015 to 2016; 3,101 serious cases were hospitalised with a confirmed diagnosis of flu, of which 11% died (352 cases). Furthermore, financial and health costs are greatly increased by the complications of flu; people aged over 65 years represent approximately 64% of the total costs. Seasonal flu vaccination is the fundamental strategy, as demonstrated by cost-benefit and cost-effectiveness studies. A priority objective is to improve the vaccine’s immune response and the search for and inclusion of adjuvants and immunostimulants in vaccines is a major line of research. This positioning report evaluates vaccination for older people and the importance of the adjuvanted vaccine in the elderly in strengthening immunogenicity, by means of a critical review of the literature based on the best evidence available on its immunogenicity and effectiveness, and an economic assessment (AU)

[Seasonal flu vaccination for older people: Evaluation of the adjuvanted vaccine. Positioning report]. / Vacunación frente a la gripe estacional en las personas mayores. Evaluación de la vacuna adyuvada: Informe de posicionamiento.

Flu is a major public health problem, particularly for older people, and creates an important clinical and economic burden. A high mortality rate was reported in Spain during the period 2015 to 2016; 3,101 serious cases were hospitalised with a confirmed diagnosis of flu, of which 11% died (352 cases). Furthermore, financial and health costs are greatly increased by the complications of flu; people aged over 65 years represent approximately 64% of the total costs. Seasonal flu vaccination is the fundamental strategy, as demonstrated by cost-benefit and cost-effectiveness studies. A priority objective is to improve the vaccine's immune response and the search for and inclusion of adjuvants and immunostimulants in vaccines is a major line of research. This positioning report evaluates vaccination for older people and the importance of the adjuvanted vaccine in the elderly in strengthening immunogenicity, by means of a critical review of the literature based on the best evidence available on its immunogenicity and effectiveness, and an economic assessment.

Vacunación antigripal en personas mayores / Flu vaccination in the elderly

En las personas mayores, la gripe estacional es un importantísimo problema de salud pública por su morbimortalidad y los costes económicos y sociales que conlleva. El objetivo de esta revisión es describir la magnitud y la trascendencia de la gripe estacional en este grupo de población y su prevención mediante la vacunación. Para ello se realiza una exposición actualizada sobre la composición de la vacuna, su pauta y vía de administración, la seguridad vacunal y la evaluación de la inmunogenicidad y efectividad de la vacunación. Entre los diferentes países y organismos oficiales existe variabilidad en las recomendaciones sobre la edad a partir de la cual se debe establecer la vacunación antigripal en las personas mayores. Para mejorar la cobertura vacunal frente a la gripe en España es necesario implantar nuevas estrategias de vacunación antigripal(AU)

Seasonal flu is a very serious public health problem in the elderly due to its morbidity and mortality and financial and social costs arising from this. The aim of this review is to describe the magnitude and importance of seasonal flu in this population group, and its prevention by means of vaccination. For this reason, an updated account of the composition of the vaccine, its dosage and administration route, vaccine safety and the evaluation of the immunogenicity and effectiveness of vaccination. There is variation between different countries and official organisations on the age at which flu vaccination must be established in the elderly. New flu vaccination strategies need to be introduced, to further improve flu vaccination cover in Spain(AU)

[Flu vaccination in the elderly]. / Vacunación antigripal en personas mayores.

Seasonal flu is a very serious public health problem in the elderly due to its morbidity and mortality and financial and social costs arising from this. The aim of this review is to describe the magnitude and importance of seasonal flu in this population group, and its prevention by means of vaccination. For this reason, an updated account of the composition of the vaccine, its dosage and administration route, vaccine safety and the evaluation of the immunogenicity and effectiveness of vaccination. There is variation between different countries and official organisations on the age at which flu vaccination must be established in the elderly. New flu vaccination strategies need to be introduced, to further improve flu vaccination cover in Spain.

[Vaccination coverage against Streptococcus pneumoniae in splenectomized patients in a fourth-level hospital (1999-2004)]. / Evolución de la cobertura vacunal frente a Streptococcus pneumoniae en pacientes esplenectomizados en un hospital de cuarto nivel (1999-2004).

INTRODUCTION: Patients in whom the spleen has been removed have a higher risk of acquiring infection by capsulated microorganisms, particularly Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis. AIMS: Determine the vaccination coverage against S. pneumoniae of splenectomized patients in Hospital Clínico San Carlos (HCSC, Madrid) and to identify variables related to the level of vaccination coverage reached. METHODS: From January 1, 1999 to December 31, 2004, a retrospective cohort study of all splenectomized patients was carried out in HCSC. Patients were identified from the Medical Records Department and the vaccination registry of the Preventive Medicine Service. RESULTS: During the study period, 248 splenectomies were carried out. The median age was 61.0 years (interquartile range, 39.0-71.0). The most frequent reason for splenectomy was malignant gastrointestinal neoplasm (34.7%). Overall vaccination coverage against S. pneumoniae for the period studied was 48.4%. A significant increase in vaccination coverage per year was observed (P < .001). Multivariate analysis identified the following variables associated with a greater risk of not being vaccinated: male sex, patients proceeding from surgical services, and patients undergoing splenectomy during 1999 to 2001. CONCLUSIONS: Vaccination coverage has increased every year since implementation of the protocol. Nevertheless, it necessary to extend the vaccination program within daily clinical practice.

Evolución de la cobertura vacunal frente a Streptococcus pneumoniae en pacientes esplenectomizados en un hospital de cuarto nivel (1999-2004) / Vaccination coverage against Streptococcus pneumoniae in splenectomized patients in a fourth-level hospital (1999-2004)

Introducción. Los pacientes sin bazo presentan mayor riesgo de infección por bacterias encapsuladas, especialmente por Streptococcus pneumoniae, Haemophilus influenzae tipo b y Neisseria meningitidis. Objetivos. Conocer la cobertura vacunal frente a S. pneumoniae de los pacientes esplenectomizados en el Hospital Clínico San Carlos (HCSC) y la identificación de las variables relacionadas con los niveles de cobertura vacunal alcanzados. Métodos. Se realizó un estudio de cohorte retrospectivo de todos los pacientes esplenectomizados desde el 1 de enero de 1999 hasta el 31 de diciembre de 2004 en el HCSC. Los pacientes se identificaron mediante la base de datos del Servicio de Archivos y Documentación Clínica y los registros de vacunación del Servicio de Medicina Preventiva. Resultados. Durante el período de estudio se llevaron a cabo 248 esplenectomías. La mediana de edad fue de 61,0 años, rango intercuartílico (39,0-71,0). Las neoplasias del aparato digestivo (34,7%) fueron la causa más frecuente de esplenectomía. La cobertura vacunal frente S. pneumoniae alcanzada durante el período de estudio fue del 48,4%, detectándose una tendencia ascendente estadísticamente significativa (p < 0,001) al analizar las coberturas vacunales específicas por año. Las variables, identificadas mediante el análisis multivariado, relacionadas con un mayor riesgo de no vacunación, fueron el género masculino, los pacientes procedentes de servicios quirúrgicos y los esplenectomizados durante el período 1999-2001. Conclusiones. Las coberturas vacunales se han incrementado todos los años desde la implantación del protocolo. Sin embargo, sería necesario difundir y ampliar el programa de vacunación dentro de la práctica clínica diaria (AU)

Introduction. Patients in whom the spleen has been removed have a higher risk of acquiring infection by capsulated microorganisms, particularly Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis. Aims. Determine the vaccination coverage against S. pneumoniae of splenectomized patients in Hospital Clínico San Carlos (HCSC, Madrid) and to identify variables related to the level of vaccination coverage reached. Methods. From January 1, 1999 to December 31, 2004, a retrospective cohort study of all splenectomized patients was carried out in HCSC. Patients were identified from the Medical Records Department and the vaccination registry of the Preventive Medicine Service. Results. During the study period, 248 splenectomies were carried out. The median age was 61.0 years (interquartile range, 39.0-71.0). The most frequent reason for splenectomy was malignant gastrointestinal neoplasm (34.7%). Overall vaccination coverage against S. pneumoniae for the period studied was 48.4%. A significant increase in vaccination coverage per year was observed (P <.001). Multivariate analysis identified the following variables associated with a greater risk of not being vaccinated: male sex, patients proceeding from surgical services, and patients undergoing splenectomy during 1999 to 2001. Conclusions. Vaccination coverage has increased every year since implementation of the protocol. Nevertheless, it necessary to extend the vaccination program within daily clinical practice (AU)

[Choosing study design in urologic research]. / Elección del diseño de estudio en investigación urológica.

The design of an epidemiological study includes the procedures, methods and techniques by which the researcher tries to obtain valid (avoiding systematic errors or bias) and precise (avoiding random errors) answers to the research question posed. This principal question aimed to be answered is the specific objective of the study, which guides the election of an adequate type of design. The objective of this article is to describe the classification criteria (finality, temporal sequence, directionality, and control of the assignation of different study factors) of the different types of epidemiological studies (experimental, almost-experimental, and observational) and the main advantages, disadvantages, utilities and objectives of each investigation design.

[Writing an original research article]. / Elaboración de un artículo original de investigación.

Publication of a scientific work is the final and obligatory stage of any research. Among the various existing types of medical publications, the research original article is the prototype of scientific article. Its finality is to communicate the investigation undertaken to the reader in a coherent, clear and precise manner. With that purpose, the discoveries found by the authors as an answer to a hypothesis are presented and discussed. To send the original article to a biomedical journal, the manuscript should present some adequate formal characteristics, in addition to contain scientifically valid information. That can be achieved by complying with the rules past by the International Committee of Biomedical Journal Editors which have been adopted by a great number of scientific journals as publication requisites. The objective of this article is to describe the structure of the various parts (first page, abstract, introduction, material and methods, results, discussion, and bibliographic references) that constitute the format of the research original article, exposing the main adverse to be avoided during its preparation.

Elección del diseño de estudio en investigación urológica / Selection of study design in urological research

Se denomina diseño de un estudio epidemiológico a los procedimientos, métodos y técnicas mediante las cuales el investigador intenta obtener una respuesta válida (evitando errores sistemáticos o sesgos) y precisa (evitando errores aleatorios) a la pregunta de investigación planteada. Esta pregunta principal que se desea contestar es el objetivo específico del estudio, el cual guía la elección del tipo de diseño adecuado. El objetivo de este artículo es describir los criterios de clasificación (finalidad, secuencia temporal, direccionalidad y control de la asignación de los factores de estudio) de los diferentes tipos de estudios epidemiológicos (experimentales, cuasi experimentales y observacionales) y las principales ventajas, inconvenientes, utilidades y objetivos de cada diseño de investigación (AU)

Elaboración de un artículo original de investigación / Elaboration of a research original article

La publicación de un trabajo científico es la etapa final y obligada de cualquier investigación. Entre los distintos tipos de publicaciones médicas existentes, el artículo original de investigación es el prototipo de artículo científico. Su finalidad es comunicar al lector de forma coherente, clara y precisa la investigación llevada a cabo. Para ello se presentan y discuten los hallazgos encontrados por los autores en respuesta a una hipótesis.Para enviar el artículo original a una revista biomédica, el manuscrito, además de contener una información científicamente válida, debe presentar unas adecuadas características formales. Ello se consigue cumpliendo las normas aprobadas por el Comité Internacional de Editores de Revistas Biomédicas que han sido adoptadas por gran número de revistas científicas como requisitos de publicación.El objetivo de este artículo es describir la estructura de los diferentes apartados (primera página, resumen, introducción, material y métodos, resultados, discusión y referencias bibliográficas) que constituyen el formato del artículo original de investigación, exponiendo los principales errores a evitar en su elaboración (AU)