Desarrollo y escalamiento productivo de un nuevo surfactante pulmonar

Este trabajo es una guía referencial para el desarrollo de nuevos productos biofarmacéuticos y se basa en la experiencia obtenida del desarrollo de un nuevo Surfactante Pulmonar. Mediante las estadísticas de nacimientos prematuros, se estimó que la demanda del producto en los países del ALBA es de 45.000 viales de 120 mg/vial por año para el año 2007. Para la extracción y purificación del nuevo surfactante, a partir pulmones de porcinos, se desarrolló un protocolo novedoso que es aplicable a nivel industrial. El medicamento consiste en una sustancia biológica liofilizada, clasificada como polvo estéril para reconstituir, formulado para resuspenderse en 3ml. de agua para inyectables, para su aplicación por vía endotraqueal. Los proveedores de la materia prima son mataderos industriales, certificados por la autoridad sanitaria (MPPS), y por la autoridad ambiental (MINAMB). Para garantizar que el sistema productivo mantenga los atributos de calidad del medicamento, desde la producción, pasando por su distribución en el mercado, hasta la utilización del surfactante en neonatos, se diseñó una infraestructura apropiada y calificada para la producción masiva. El proceso para la industrialización del medicamento se basa en la normativa sanitaria vigente, que exige el control de todas sus fases: concepción, diseño, construcción, equipamiento, adecuaciones, puesta en marcha y funcionamiento de la planta. Este control implica el establecimiento de un Sistema de Aseguramiento de la Calidad, con alcance a todos los ámbitos de la empresa fabril y su cadena de distribución, que garantice la ejecución continua y consistente de todos los procesos.&nbsp

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Boundary shifts and vote alignment in Catalonia

This paper analyses the dynamics between ethnic boundaries and electoral alignment in the context of western minority nationalisms by focusing on the Catalan case. In particular, the research explores the changes in boundary shifts at the electoral level, whether they affect differently pro-sovereignty and pro-union parties, and to what extent changes have reinforced the ethnic alignment of vote. Methodologically, the analysis is based on observational data from the elections of 2010 and 2012, which allows control over some of the traditional limits of opinion studies. The results suggest that ethnicity is a dynamic factor that has gained relevance for both sub-state and state-wide parties, and that processes of boundary contraction are not necessarily associated with electoral failure.Este artículo analiza la dinámica entre las fronteras étnicas y la alineación electoral en el contexto de los nacionalismos de las minorías occidentales, centrándose en el caso catalán. En particular, la investigación explora los cambios en los desplazamientos de frontera a nivel electoral, si afectan de manera diferente a los partidos pro-soberanía y sindicalistas, y hasta qué punto los cambios han reforzado la alineación étnica del voto. Metodológicamente, el análisis se basa en datos observacionales de las elecciones de 2010 y 2012, lo que permite controlar algunos de los límites tradicionales de los estudios de opinión. Los resultados sugieren que la etnicidad es un factor dinámico que ha ganado relevancia para los partidos estatales y subnacionales, y que los procesos de contracción de frontera no están necesariamente asociados con el fracaso electoral.Aquest article analitza la dinàmica entre les fronteres ètniques i l'alineació electoral en el context dels nacionalismes de les minories occidentals, centrant-se en el cas català. En particular, la investigació explora els canvis en els desplaçaments de frontera a nivell electoral, si afecten de manera diferent als partits pro-sobirania i sindicalistes, i fins a quin punt els canvis han reforçat l'alineació ètnica del vot. Metodològicament, l'anàlisi es basa en dades observacionals de les eleccions de 2010 i 2012, el que permet controlar alguns dels límits tradicionals dels estudis d'opinió. Els resultats suggereixen que l'etnicitat és un factor dinàmic que ha guanyat rellevància per als partits estatals i subnacionals, i que els processos de contracció de frontera no estan necessàriament associats amb el fracàs electoral

Boundary shifts and vote alignment in Catalonia

This paper analyses the dynamics between ethnic boundaries and electoral alignment in the context of western minority nationalisms by focusing on the Catalan case. In particular, the research explores the changes in boundary shifts at the electoral level, whether they affect differently pro-sovereignty and pro-union parties, and to what extent changes have reinforced the ethnic alignment of vote. Methodologically, the analysis is based on observational data from the elections of 2010 and 2012, which allows control over some of the traditional limits of opinion studies. The results suggest that ethnicity is a dynamic factor that has gained relevance for both sub-state and state-wide parties, and that processes of boundary contraction are not necessarily associated with electoral failure.Este artículo analiza la dinámica entre las fronteras étnicas y la alineación electoral en el contexto de los nacionalismos de las minorías occidentales, centrándose en el caso catalán. En particular, la investigación explora los cambios en los desplazamientos de frontera a nivel electoral, si afectan de manera diferente a los partidos pro-soberanía y sindicalistas, y hasta qué punto los cambios han reforzado la alineación étnica del voto. Metodológicamente, el análisis se basa en datos observacionales de las elecciones de 2010 y 2012, lo que permite controlar algunos de los límites tradicionales de los estudios de opinión. Los resultados sugieren que la etnicidad es un factor dinámico que ha ganado relevancia para los partidos estatales y subnacionales, y que los procesos de contracción de frontera no están necesariamente asociados con el fracaso electoral.Aquest article analitza la dinàmica entre les fronteres ètniques i l'alineació electoral en el context dels nacionalismes de les minories occidentals, centrant-se en el cas català. En particular, la investigació explora els canvis en els desplaçaments de frontera a nivell electoral, si afecten de manera diferent als partits pro-sobirania i sindicalistes, i fins a quin punt els canvis han reforçat l'alineació ètnica del vot. Metodològicament, l'anàlisi es basa en dades observacionals de les eleccions de 2010 i 2012, el que permet controlar alguns dels límits tradicionals dels estudis d'opinió. Els resultats suggereixen que l'etnicitat és un factor dinàmic que ha guanyat rellevància per als partits estatals i subnacionals, i que els processos de contracció de frontera no estan necessàriament associats amb el fracàs electoral

Pré-condicionamento isquêmico e monitorização da função medular na abordagem da aorta torácica descendente Ischemic preconditioning and spinal cord function monitoring in the descending thoracic aorta approach

OBJETIVOS: Avaliar a eficácia do pré-condicionamento isquêmico (PI) agudo, guiado por potenciais evocados somatossensoriais (PESS), como método de proteção medular em cães e analisar o valor dos PESS na monitorização da função medular. MÉTODOS: Foram utilizados 28 cães submetidos à isquemia medular obtida pelo pinçamento da aorta torácica descendente. No grupo C45, o tempo de oclusão aórtica foi de 45 min (n = 7); no grupo PI45, os cães foram submetidos ao PI antes do pinçamento aórtico por 45 min (n = 7). No grupo C60, os cães foram submetidos a 60 min de oclusão aórtica (n = 7) e no grupo PI60, os cães foram submetidos ao PI, seguido pelo pinçamento aórtico por 60 min. Os ciclos de PI foram determinados pelas alterações dos PESS. RESULTADOS: Os índices de Tarlov dos grupos pré-condicionados foram significativamente melhores que os dos grupos de controle (p = 0,005). Observou-se paraplegia em três cães do C45 e em seis do C60, enquanto todos os cães do PI45 permaneceram neurologicamente normais, assim como quatro do grupo PI60. Houve correlação entre o tempo de recuperação dos PESS após a reperfusão aórtica e o estado neurológico pós-operatório (p = 0,011), com sensibilidade e especificidade de 0,75 e 0,83, respectivamente. CONCLUSÃO: O PI agudo repetitivo, baseado na monitorização do PESS, induziu proteção à isquemia medular causada pelo pinçamento aórtico prolongado. A monitorização do PESS parece ser um bom método de detecção precoce do comprometimento isquêmico medular.<br>OBJECTIVES: To evaluate the effectiveness of acute ischemic preconditioning (IP), based on somatosensory evoked potentials (SSEP) monitoring, as a method of spinal cord protection and to asses SSEP importance in spinal cord neuromonitoring. METHODS: Twenty-eight dogs were submitted to spinal cord ischemic injury attained by descending thoracic aorta cross-clamping. In the C45 group, the aortic cross-clamping time was 45 min (n=7); in the IP45 group, the dogs were submitted to IP before the aortic cross-clamping for 45 min (n=7). In the C60 group, the dogs were submitted to 60 min of aortic cross-clamping (n=7), as in the IP60 group that was previously submitted to IP. The IP cycles were determined based on SSEP changes. RESULTS: Tarlov scores of the IP groups were significantly better than those of the controls (p = 0.005). Paraplegia was observed in 3 dogs from C45 and in 6 from C60 group, although all dogs from IP45 group were neurologically normal, as 4 dogs from IP60. There was a significant correlation between SSEP recovery time until one hour of aortic reperfusion and the neurological status (p = 0.011), showing sensitivity of 75% and specificity of 83%. CONCLUSION: Repetitive acute IP based on SSEP is a protection factor during spinal cord ischemia, decreasing paraplegia incidence. SSEP monitoring seems to be a good neurological injury assessment method during surgical procedures that involve spinal cord ischemia

Endomyocardial fibrosis in infancy

The patient was a 4-month-old infant, who underwent persistent ductus arteriosus interruption with titanium clips at the age of 13 days and, since the age of 2 months, had crises of hypoxia and hypertonicity. After clinical investigation, the presence of pulmonary hypertension was confirmed and left ventricular inflow tract obstruction was suspected. The patient underwent surgical treatment at the age of 4 months, during which right and left ventricular endocardial fibrosis was identified. The fibrosis was resected, but the infant had an unfavorable clinical evolution with significant diastolic restriction and died on the sixth postoperative day. Anatomicopathological and surgical findings suggested endomyocardial fibrosis, although that pathology is very rare at the patient's age

Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Background: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.Methods: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method.Results: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.Conclusions: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids