[Association between influenza vaccination and mortality due to COVID-19]. / Asociación entre la vacunación contra influenza y la mortalidad por COVID-19.

Background: It has recently been suggested that influenza vaccination may be a factor associated with decreased COVID-19 mortality. Methods: An age-matched case-control study based on hospital cases. We included subjects aged 18 years and older with a diagnosis of moderate to severe COVID-19. Infection was corroborated by RT-PCR test for SARS-COV-2. Deceased subjects were considered cases, controls were patients discharged due to improvement of acute symptoms. We used bivariate analysis to determine factors associated with death from COVID-19, and calculated odds ratios and 95% confidence intervals. Results: A total of 560 patients were included in the study, 214 (38.2%) were considered cases and 346 (61.7%) controls. A significant difference was observed with the presence of type 2 diabetes mellitus [54% vs. 39.3% between cases and controls, respectively (p=.04)] and having received influenza vaccination (p= .02). Type 2 diabetes mellitus was associated with higher COVID-19 mortality [OR 1.8 (95% CI 1.2-2.5) p=.01], whereas having been immunised against influenza in 2019 was associated with lower mortality in this group of patients [OR .6 (95% CI .4-.9) p=.02]. Conclusions: Influenza vaccination in the previous year appears to be associated with lower mortality from COVID-19; whereas type 2 diabetes mellitus is confirmed as a condition associated with higher mortality.

Molecular mechanisms of cell death induced in glioblastoma by experimental and antineoplastic drugs: New and old drugs induce apoptosis in glioblastoma.

Glioblastoma multiforme (GBM) is one of the most aggressive astrocytic tumors; it is resistant to most chemotherapeutic agents currently available and is associated with a poor patient survival. Thus, the development of new anticancer compounds is urgently required. Herein, we studied the molecular mechanisms of cell death induced by the experimental drugs resveratrol and MG132 or the antineoplastic drugs cisplatin and etoposide on a human GBM cell line (D54) and on primary cultured mouse astrocytes (PCMAs). Caspases, Bcl-2, inhibitors of apoptosis proteins (IAP) family members, and p53 were identified as potential molecular targets for these drugs. All drugs had a cytotoxic effect on D54 cells and PCMAs, with a similar inhibitory concentration (IC50) after 24 h. However, MG132 and cisplatin were more effective to induce apoptosis and autophagy than resveratrol and etoposide. Cell death by apoptosis involved the activation of caspases-3/7, -8, and -9, increased lysosomal permeability, LC3 lipidation, poly-(ADP-ribose) polymerase (PARP)-1 fragmentation, and a differential expression of genes related with apoptosis and autophagy like Mcl-1, Survivin, Noxa, LC3, and Beclin. In addition, apoptosis activation was partially dependent on p53 activation. Since experimental and antineoplastic drugs yielded similar results, further work is required to justify their use in clinical protocols.

Costo económico marginal del fracaso terapéutico con ampicilina más amikacina en el tratamiento de la sepsis neonatal temprana / Cost of therapeutic failure of ampicillin plus amikacin in the treatment of early neonatal sepsis

Objetivo: Evaluar el costo marginal de la falla terapéutica del esquema antimicrobiano ampicilina más amikacina en el tratamiento de sepsis neonatal temprana. Métodos: Un total de 86 de 121 recién nacidos menores de 72h de vida, estudiados entre 2001 y 2005 en la unidad de cuidados intensivos neonatales con sospecha de sepsis neonatal se consideraron con fracaso terapéutico cuando se administró tratamiento con ampicilina más amikacina como primera opción. En todos ellos se trató con vancomicina o cefotaxima como segundo esquema de tratamiento. Se utilizó el método contable o directo para abordar el análisis de costos, en particular el enfoque del gasto por actividades, y se identificaron los gastos ejercidos en el tratamiento de estos 86 pacientes. Resultados: Los costos por medicamentos, por hospitalización, por insumos y por honorarios del personal son mayores al utilizar vancomicina o cefotaxima (350,924 dólares o 275,116 euros) que los gastos que se realizan al utilizar ampicilina más amikacina (159,251 dólares o 124,878 euros). Sin embargo, este último gasto no representa beneficio alguno para el paciente ni para la institución. Resultados: Al compararlos como factores que favorecen la curación clínica se encuentra lo siguiente: ampicilina más amikacina (riesgo relativo [RR] de 1,09, intervalo de confianza [IC] del 95%: 0,39 a 2,1; p=0,8) frente a cefotaxima o vancomicina (RR de 0,02, IC del 95%: 0,04 a 0,32; p<0,05). Conclusiones: Aunque de inicio el costo es mayor con el uso de vancomicina o cefotaxima, el ahorro al dejar de utilizar un esquema poco eficaz, como ampicilina más amikacina, supera el gasto que se realiza al utilizar un esquema de rescate (AU)

Objective: To evaluate the marginal cost of therapeutic failure with Ampicillin/amikacin as the first-line antibiotic treatment of early-onset neonatal sepsis (ENS). Methods: Out of a total of 121 newborns, 86 failed to respond to Ampicillin/amikacin when it was used as first-line treatment within their first 72h of life. All of them were admitted to the NICU between 2001 and 2005 with suspicion of sepsis. After this failure to respond, vancomycin and/or cefotaxime were used as the second treatment option for these newborns. Using a full cost method we performed a cost analysis with an activity-based-costing (ABC) perspective, identifying the costs generated by these 86 patients. Results: The costs comprising medication, hospitalization, supplies and clinical staff salaries were higher when vancomycin and/or cefotaxime were used (350,924 dollars or 275,116 euros) compared to those generated with an Ampicillin/amikacin regimen (159,251 dollars or 124,878 euros).ResultsWhen compared as protective factors, the relative risk was 1.09 (95% CI; 0.39 2.1 P=0.8) for Ampicillin/amikacin vs. 0.02 (95% CI; 0.04 0.32 P<0.05) for vancomycin and/or cefotaxime. Conclusions: Even though vancomycin and/or cefotaxime are initially more costly, there is a cost saving derived from the use of this antibiotic treatment as the first-line therapeutic option instead of as a rescue therapy when a lower-efficacy regimen (Ampicillin/amikacin) has failed (AU)

[Cost of therapeutic failure of ampicillin plus amikacin in the treatment of early neonatal sepsis]. / Costo económico marginal del fracaso terapéutico con ampicilina más amikacina en el tratamiento de la sepsis neonatal temprana.

OBJECTIVE: To evaluate the marginal cost of therapeutic failure with Ampicillin/amikacin as the first-line antibiotic treatment of early-onset neonatal sepsis (ENS). METHODS: Out of a total of 121 newborns, 86 failed to respond to Ampicillin/amikacin when it was used as first-line treatment within their first 72h of life. All of them were admitted to the NICU between 2001 and 2005 with suspicion of sepsis. After this failure to respond, vancomycin and/or cefotaxime were used as the second treatment option for these newborns. Using a full cost method we performed a cost analysis with an activity-based-costing (ABC) perspective, identifying the costs generated by these 86 patients. RESULTS: The costs comprising medication, hospitalization, supplies and clinical staff salaries were higher when vancomycin and/or cefotaxime were used (350,924 dollars or 275,116 euros) compared to those generated with an Ampicillin/amikacin regimen (159,251 dollars or 124,878 euros). When compared as protective factors, the relative risk was 1.09 (95% CI; 0.39-2.1 P=0.8) for Ampicillin/amikacin vs. 0.02 (95% CI; 0.04-0.32 P<0.05) for vancomycin and/or cefotaxime. CONCLUSIONS: Even though vancomycin and/or cefotaxime are initially more costly, there is a cost saving derived from the use of this antibiotic treatment as the first-line therapeutic option instead of as a rescue therapy when a lower-efficacy regimen (Ampicillin/amikacin) has failed.

[Neonatal candidiasis: therapeutic options]. / Candidiasis neonatal: Opciones terapeuticas.

Diverse factors (such as preterm babies with low body weight staying for long-term periods at intensive care units, subjected to invasive procedures, receiving one or more antibiotic schemes, parenteral nutrition, etc.) are considered to pose a risk for the development of infections by opportunistic agents. Of the latter, Candida albicans is considered the main cause of neonatal candidiasis. The most frequently involved Candida species are C. albicans, C. parapsilosis and C. tropicalis. The advent of new antimycotic agents has increased the therapeutic possibilities for the treatment of candidiasis. Antimycotic agents used for the treatment of neonatal candidiasis include: amphotericin B deoxycolate, lipid-associated compounds of amphotericin B, fluconazole and itraconazol, and caspofungin.

[Disparity in the criteria for including patients with neonatal sepsis in scientific medical studies. Are we swimming in a sea without limits?]. / Disparidad en los criterios para incluir pacientes con sepsis neonatal en estudios médicos científicos. 'Nadamos en un mar sin límites?

OBJECTIVE: To characterize disparity in the criteria used for patient enrollment in clinical research on neonatal sepsis. MATERIAL AND METHODS: We used MEDLINE to identify clinical research in neonatal sepsis published in English from 1993 to 2005. We used the criteria of the International Consensus Conference Panel: International Pediatric Sepsis Consensus Conference: Definitions for Sepsis and Organ Dysfunction in Pediatrics (IPSCC) published in 2005 as an arbitrary standard in each of the articles. Articles were considered to define neonatal sepsis clearly if they mentioned the criteria and described the values used. Articles were considered not to define neonatal sepsis clearly if they used the phrase "septic patients were included" without describing the variables or values used for inclusion. RESULTS: We identified 150 articles, of which 26.6 % specified the criteria and values of the IPSCC. The remaining 110 articles did not mention the values or the variables used to define neonatal sepsis. CONCLUSION: There is a disparity in the criteria used to operatively define neonatal sepsis in clinical studies performed in distinct parts of the world.

Disparidad en los criterios para incluir pacientes con sepsis neonatal en estudios médicos científicos. ¿Nadamos en un mar sin límites? / Disparity in the criteria for including patients with neonatal sepsis in scientific medical studies. Are we swimming in a sea without limits?

Objetivo Observar la disparidad de los criterios utilizados para incluir pacientes considerados con sepsis neonatal en la literatura médica científica. Material y métodos Buscamos mediante la base de datos Medline, artículos que utilizaron poblaciones definidas como "sepsis neonatal", publicados en el idioma inglés de los años 1993 a 2005. Utilizamos como estándar arbitrario en cada uno de los artículos los criterios del Consenso Internacional de Sepsis Pediátrica (CISP) publicada en 2005. Consideramos como artículos que la definieron claramente, a los que mencionaron los criterios y describieron los valores utilizados. Se consideraron como artículos con definición poco clara de sepsis neonatal a los que utilizaron el párrafo "se incluyeron pacientes sépticos" sin describir variables ni valores utilizados para la inclusión. Resultados Fueron evaluados 150 artículos, el 26,6 % especificaban los criterios y valores del CISP. Los restantes 110 no mencionaron los valores y/o las variables que tomaban en cuenta. Conclusión Existe disparidad en los criterios utilizados para definir operativamente sepsis neonatal en los estudios clínicos realizados a nivel mundial

Objective To characterize disparity in the criteria used for patient enrollment in clinical research on neonatal sepsis. Material and methods We used MEDLINE to identify clinical research in neonatal sepsis published in English from 1993 to 2005. We used the criteria of the International Consensus Conference Panel: International Pediatric Sepsis Consensus Conference: Definitions for Sepsis and Organ Dysfunction in Pediatrics (IPSCC) published in 2005 as an arbitrary standard in each of the articles. Articles were considered to define neonatal sepsis clearly if they mentioned the criteria and described the values used. Articles were considered not to define neonatal sepsis clearly if they used the phrase "septic patients were included" without describing the variables or values used for inclusion. Results We identified 150 articles, of which 26.6 % specified the criteria and values of the IPSCC. The remaining 110 articles did not mention the values or the variables used to define neonatal sepsis. Conclusion There is a disparity in the criteria used to operatively define neonatal sepsis in clinical studies performed in distinct parts of the world