Abstract In this work, an ELISA was optimized through the application of full factorial designs of experiments, to detect IgA anti-RBD antibodies to SARS-CoV-2 in breast milk of puerperal women who received, during pregnancy, three doses of the Abdala anti-COVID-19 vaccine, created on the protein subunit platform. Based on a preliminary non-optimized protocol, the interactions between the factors and levels, at the step of RBD antigen coating of the plate and in the reaction of the antigen with the breast milk antibodies, were evaluated; the dilution factor to apply the enzyme conjugate in the assay was also determined. The optimized ELISA protocol was established with the best combination of factors and levels, with which it was possible to increase the signal to noise ratio of the assay by 4.67 times compared to the non-optimized one. The new protocol will guarantee the detection of SARS-CoV-2 IgA anti-RBD antibodies in breast milk samples with a low content of these antibodies and that would probably have an absorbance signal close to the assay blank if the non-optimized ELISA were applied.

Resumen En este trabajo se optimizó un ELISA, mediante la aplicación de diseños factoriales completos de experimentos, para detectar anticuerpos IgA anti-RBD del SARS-CoV-2 en leche materna de puérperas que recibieron durante el embarazo tres dosis de la vacuna anti-COVID-19 Abdala, basada en la plataforma de subunidades proteicas. A partir de un protocolo preliminar no optimizado, se evaluaron las interacciones entre los factores y niveles en el paso de recubrimiento de la placa con el antígeno RBD y en el paso de reacción del antígeno con los anticuerpos de la leche; se determinó además el factor dilución para aplicar el conjugado enzimático en el ensayo. Se estableció la combinación óptima de factores y niveles para conformar el protocolo optimizado del ELISA, con el que se logró incrementar 4,67 veces la relación señal/ruido del ensayo respecto al no optimizado. El nuevo protocolo garantizará la detección de anticuerpos IgA anti-RBD del SARS-CoV-2 en las muestras de leche materna con bajo contenido de estos anticuerpos y que probablemente tuvieran una señal de absorbancia cercana al blanco del ensayo si se aplicara el ELISA no optimizado.

Objective: To evaluate the incidence and costs of adverse events registered in an administrative dataset in Spanish hospitals from 2008 to 2010. Methods: A retrospective study was carried out that estimated the incremental cost per episode, depending on the presence of adverse events. Costs were obtained from the database of the Spanish Network of Hospital Costs. This database contains data from 12 hospitals that have costs per patient records based on activities and clinical records. Adverse events were identified through the Patient Safety Indicators (validated in the Spanish Health System) created by the Agency for Healthcare Research and Quality together with indicators of the EuroDRG European project. Results: This study included 245,320 episodes with a total cost of 1,308,791,871€. Approximately 17,000 patients (6.8%) experienced an adverse event, representing 16.2% of the total cost. Adverse events, adjusted by diagnosis-related groups, added a mean incremental cost of between €5,260 and €11,905. Six of the 10 adverse events with the highest incremental cost were related to surgical interventions. The total incremental cost of adverse events was € 88,268,906, amounting to an additional 6.7% of total health expenditure. Conclusions: Assessment of the impact of adverse events revealed that these episodes represent significant costs that could be reduced by improving the quality and safety of the Spanish Health System.

Objetivo: Evaluar la incidencia y los costes de los eventos adversos presentes en el Conjunto Mínimo Básico de Datos (CMBD) en los hospitales españoles en el período 2008-2010. Método: Estudio retrospectivo que estima el coste incremental por episodio, según la presencia de eventos adversos. El coste se obtiene de la Red Española de Costes Hospitalarios (RECH), creada a partir de los registros de costes por paciente basados en actividades y CMBD. Los eventos adversos se han identificado mediante Indicadores de Seguridad del Paciente (validados en el Sistema Sanitario español) de la Agency of Healthcare Research and Quality, junto a indicadores del proyecto europeo EuroDRG. Resultados: Se incluyen 245.320 episodios, con un coste de 1.308.791.871 €. Aproximadamente 17.000 episodios (6,8%) sufrieron un evento adverso, lo que representa un 16,2% del coste total. Los eventos adversos, ajustados por el Grupo Relacionado por el Diagnóstico, añaden un coste incremental medio que oscila entre 5.260 € y 11.905 €. Seis de los diez eventos adversos con mayor coste incremental son posteriores a intervenciones quirúrgicas. El coste incremental total de los eventos adversos es de 88.268.906€, un 6,7% adicional del total del gasto sanitario. Conclusiones: Valorando su impacto, los eventos adversos representan relevantes costes que pueden revertirse en mejora de la calidad y la seguridad del sistema de salud.

Objective: To evaluate the incidence and costs of adverse events registered in an administrative dataset in Spanish hospitals from 2008 to 2010. Methods: A retrospective study was carried out that estimated the incremental cost per episode, depending on the presence of adverse events. Costs were obtained from the database of the Spanish Network of Hospital Costs. This database contains data from 12 hospitals that have costs per patient records based on activities and clinical records. Adverse events were identified through the Patient Safety Indicators (validated in the Spanish Health System) created by the Agency for Healthcare Research and Quality together with indicators of the EuroDRG European project. Results: This study included 245,320 episodes with a total cost of 1,308,791,871€. Approximately 17,000 patients (6.8%) experienced an adverse event, representing 16.2% of the total cost. Adverse events, adjusted by diagnosis-related groups, added a mean incremental cost of between €5,260 and €11,905. Six of the 10 adverse events with the highest incremental cost were related to surgical interventions. The total incremental cost of adverse events was € 88,268,906, amounting to an additional 6.7% of total health expenditure. Conclusions: Assessment of the impact of adverse events revealed that these episodes represent significant costs that could be reduced by improving the quality and safety of the Spanish Health System.

Objetivo: Evaluar la incidencia y los costes de los eventos adversos presentes en el Conjunto Mínimo Básico de Datos (CMBD) en los hospitales españoles en el período 2008-2010. Método: Estudio retrospectivo que estima el coste incremental por episodio, según la presencia de eventos adversos. El coste se obtiene de la Red Española de Costes Hospitalarios (RECH), creada a partir de los registros de costes por paciente basados en actividades y CMBD. Los eventos adversos se han identificado mediante Indicadores de Seguridad del Paciente (validados en el Sistema Sanitario español) de la Agency of Healthcare Research and Quality, junto a indicadores del proyecto europeo EuroDRG. Resultados: Se incluyen 245.320 episodios, con un coste de 1.308.791.871 €. Aproximadamente 17.000 episodios (6,8%) sufrieron un evento adverso, lo que representa un 16,2% del coste total. Los eventos adversos, ajustados por el Grupo Relacionado por el Diagnóstico, añaden un coste incremental medio que oscila entre 5.260 € y 11.905 €. Seis de los diez eventos adversos con mayor coste incremental son posteriores a intervenciones quirúrgicas. El coste incremental total de los eventos adversos es de 88.268.906€, un 6,7% adicional del total del gasto sanitario. Conclusiones: Valorando su impacto, los eventos adversos representan relevantes costes que pueden revertirse en mejora de la calidad y la seguridad del sistema de salud.