Opportunities for antibiotic optimisation and outcome improvement in patients with negative blood cultures: study protocol for a cluster-­randomised crossover trial, the NO-­BACT study.

Introduction Patients with negative blood cultures (BCx) represent 85%–90% of all patients with BCx taken during hospital admission. This population usually includes a heterogeneous group of patients admitted with infectious diseases or febrile syndromes that require a blood culture. There is very little evidence of the clinical characteristics and antibiotic treatment given to these patients. Methods and analysis In a preliminary exploratory prospective cohort study of patients with BCx taken, the clinical/therapeutic characteristics and outcomes/ antimicrobial stewardship opportunities of a population of patients with negative BCx will be analysed. In the second phase, using a cluster randomised crossover design, the implementation of an antimicrobial stewardship intervention targeting patients with negative BCx will be evaluated in terms of quality of antimicrobial use (duration and de-escalation), length of hospital stay and mortality. Ethics and dissemination This study has been and registered with clinicaltrials.gov. The findings of our study may support the implementation in clinical practice of an antimicrobial stewardship intervention to optimise the use of antibiotics in patients with negative BCx. The results of this study will be published in peer-reviewed journals and disseminated at national and international conferences. Trial registration number NCT03535324.Instituto de Salud Carlos III PI17 / 01809Plataforma Española de Investigación Clínica y Ensayos Clínicos, SCReN (Red Española de Investigación Clínica), financiada por la Subdirección General de Evaluación y Promoción de la Investigación ISCIII: PT17 / 0017/0012. Cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER)

Desarrollo de una presentación interactiva y multimedia orientada a la docencia del análisis cinemático del Movimiento Armónico Simple

Nowadays, computers suppose a great potential as complementary didactic tool to traditional means of education. For that reason, the advantage of this potential is considered by the work group, creating interactive and multimedia presentations oriented to facilitate teaching of different physics fields. In particular, the objective of this work is the design of a presentation oriented to teaching kinematical aspects of the simple harmonic movement. Given the dynamic nature of the subject, it is evident the adventages that suppose an animated presentation which it helps the student to understand the kinematical magnitudes. This tool will be very useful to the professor as complement of theoretical classes, and available to the students in the reinforcement of the knowledge.Es evidente el gran potencial que el ordenador supone como herramienta didáctica complementaria a los medios de enseñanza tradicionales. Es por ello que el grupo de trabajo se plantea el aprovechamiento de este potencial, creando presentaciones interactivas y multimedia orientadas a la docencia en los distintos campos de la física.En concreto, en este trabajo se plantea el diseño de una presentación orientada a la docencia de los aspectos cinemáticas del movimiento armónico simple. Dada la naturaleza dinámica del tema en cuestión, es evidente las ventajas que supone disponer de una presentación animada del mismo que ayude al alumno a entender la magnitudes cinemáticas implicadas, herramientas de gran utilidad para el profesor como complemento de sus clases teóricas, y disponible para alumnos de ayuda en el afianzamiento de los conocimientos

An International Prospective Cohort Study To Validate 2 Prediction Rules for Infections Caused by Third-generation Cephalosporin-resistant Enterobacterales

[Background] The possibility of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacterales (3GC-R-BSI) leads to a trade-off between empiric inappropriate treatment (IAT) and unnecessary carbapenem use (UCU). Accurately predicting 3GC-R-BSI could reduce IAT and UCU. We externally validate 2 previously derived prediction rules for community-onset (CO) and hospital-onset (HO) suspected bloodstream infections.[Methods] In 33 hospitals in 13 countries we prospectively enrolled 200 patients per hospital in whom blood cultures were obtained and intravenous antibiotics with coverage for Enterobacterales were empirically started. Cases were defined as 3GC-R-BSI or 3GC-R gram-negative infection (3GC-R-GNI) (analysis 2); all other outcomes served as a comparator. Model discrimination and calibration were assessed. Impact on carbapenem use was assessed at several cutoff points.[Results] 4650 CO infection episodes were included and the prevalence of 3GC-R-BSI was 2.1% (n = 97). IAT occurred in 69 of 97 (71.1%) 3GC-R-BSI and UCU in 398 of 4553 non–3GC-R-BSI patients (8.7%). Model calibration was good, and the AUC was .79 (95% CI, .75–.83) for 3GC-R-BSI. The prediction rule potentially reduced IAT to 62% (60/97) while keeping UCU comparable at 8.4% or could reduce UCU to 6.3% (287/4553) while keeping IAT equal. IAT and UCU in all 3GC-R-GNIs (analysis 2) improved at similar percentages. 1683 HO infection episodes were included and the prevalence of 3GC-R-BSI was 4.9% (n = 83). Here model calibration was insufficient.[Conclusions] A prediction rule for CO 3GC-R infection was validated in an international cohort and could improve empirical antibiotic use. Validation of the HO rule yielded suboptimal performance.J. R.-B. receives funds for research from Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001), co-financed by the European Development Regional Fund “A Way to Achieve Europe,” Operative Program Intelligent Growth 2014-2020.Peer reviewe

A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn

<p>Abstract</p> <p>Background</p> <p>Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn.</p> <p>Methods and design</p> <p>320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: <it>1. Control group: </it>usual prenatal care (PC) and placebo (maltodextrine). <it>2. Exercise group: </it>PC, placebo and aerobic physical exercise. <it>3. Micronutrients group: </it>PC and a micronutrients capsule consisting of zinc (30 mg), selenium (70 μg), vitamin A (400 μg), alphatocopherol (30 mg), vitamin C (200 mg), and niacin (100 mg)<it>. 4. Combined interventions Group: </it>PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions.</p> <p>Discussion</p> <p>Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00872365">NCT00872365</a>.</p

Oportunidades para la optimización del tratamiento antibiótico y pronóstico en pacientes con hemocultivo negativo (Proyecto NO-BACT)

Los pacientes con sospecha de infección y extracción de hemocultivo son un grupo clínicamente heterogéneo. Dentro de ellos, aquellos en los que los hemocultivos son negativos han sido muy poco estudiados, a pesar de suponer lo mayoría de pacientes dentro de este grupo. El estudio pronóstico y de la calidad del uso de antimicrobianos en este subgrupo podría permitir la elaboración de Programas de Optimización Antibiótica. HIPÓTESIS Y OBJETIVOS 1. Los pacientes con hemocultivo negativo presentan mejor pronóstico que los pacientes con hemocultivo positivo. El primer objetivo por tanto fue analizar los factores relacionados con el pronóstico en pacientes con sospecha de infección y extracción de hemocultivo, y en concreto, si la positividad de los hemocultivos tiene influencia pronóstica. 2. El tratamiento antibiótico inapropiado en pacientes con hemocultivo negativo puede tener influencia pronóstica. El objetivo fue analizar las variables predictoras de mortalidad en día 30 en pacientes con sospecha de infección y hemocultivo negativo, y específicamente, la influencia del tratamiento antimicrobiano inapropiado. 3. El tratamiento antibiótico en pacientes con hemocultivo negativo es frecuentemente inapropiado. Como objetivo, planteamos analizar los factores relacionados con el uso apropiado del tratamiento antibiótico en pacientes con hemocultivo negativo. MATERIAL Y MÉTODOS El proyecto NO-BACT es un estudio de cohortes prospectivo multicéntrico en pacientes adultos con sospecha de infección y extracción de hemocultivos desarrollado en tres hospitales españoles de tercer nivel, entre febrero de 2018 y junio de 2022. Se realizó una evaluación por pares de parámetros clínicos, analíticos y de la prescripción antibiótica en día 0, 2 y en día 5-7 tras extracción de hemocultivo. Se incluyeron variables demográficas, características clínicas y terapéuticas. Se ha realizado un estudio descriptivo, bivariante y multivariante para cada uno de los objetivos mencionados. RESULTADOS Se recogieron un total de 1011 pacientes con extracción de hemocultivos, de los que 803 (79%) resultaron negativos. Los pacientes con hemocultivo negativo presentaron un 9% de mortalidad a los 30 días de extracción del hemocultivo, frente a un 16% de los pacientes con hemocultivo positivo. OBJETIVO 1: Analizar los factores relacionados con el pronóstico en pacientes con sospecha de infección y extracción de hemocultivo Los pacientes con sospecha de infección y extracción de hemocultivo presentaron un 10% de mortalidad a 30 días. Las variables relacionadas de forma independiente con la mortalidad fueron la edad (OR 1.03; IC95% 1.02-1.05), la demencia (OR 1.93; IC 95% 1.00-3.72), la neoplasia activa (OR 2.75; IC 95% 1.69-4.45), la antibioterapia administrada en las 48 horas previas a la extracción de hemocultivo (OR 2.14; IC95% 1.35-3.40), sepsis grave o shock séptico el día de extracción de hemocultivo (OR 2.12; IC95% 1.26-3.56), el defecto de cobertura en base a guías locales en día 2 tras extracción de hemocultivo (OR 2.31; IC95% 1.34-3.99), y la presencia de hemocultivo positivo (OR 2.48; IC95% 1.47-4.20). El foco urinario/catéter/biliar se asoció con menos mortalidad (OR 0.38; IC95% 0.22-0.66). OBJETIVO 2: analizar las variables predictoras de mortalidad en día 30 en pacientes con sospecha de infección y hemocultivo negativo Los pacientes con hemocultivo negativo presentaron un 9% de mortalidad a los 30 días de extracción del hemocultivo Las variables relacionadas de forma independiente con mayor mortalidad fueron la edad (OR 1.05; IC 95% 1.03-1.07), neoplasia activa (OR 2.73; IC95% 1.64-4.56), sepsis grave/shock séptico en día de extracción de hemocultivo (OR1.70; IC95% 0.93-3.06), antibioterapia administrada en las 48 horas previas a la extracción de hemocultivo (OR 2.06; IC95%1.23-3.43), y el defecto de cobertura antibiótica en base a guías locales en día 2 (OR 2.35; IC95% 1.39-4.00). El foco urinario/catéter/biliar se asoció con menos mortalidad (OR 0.40; IC95% 0.20-0.81) OBJETIVO 3: analizar los factores relacionados con el uso apropiado del tratamiento antibiótico en pacientes con hemocultivo negativo En pacientes con hemocultivo negativo, hubo un 40% y un 46% de prescripciones inapropiadas en día 2 y en día 5 tras extracción de hemocultivo, respectivamente. Entre los motivos destacan un 18% de antibióticos no necesarios, 18% de exceso y otro 18% de defecto de cobertura en día 2. En día 5-7, destaca un 26% de antibióticos no necesarios, un 24% de excesos de cobertura y un 20% de vía inadecuada. Las variables asociadas con la terapia antimicrobiana apropiada (inapropiada en este caso) en día 2 fueron el uso de antibióticos en las 48 horas previas a la extracción de hemocultivo (OR 0.69; IC95% 0.51-0.94) y el foco neumonía (OR 0.70; IC95% 0.51-0.96). En día 5 lo fueron el foco neumonía (OR 0.46; IC95% 0.32-0.68), y el foco urinario (OR 0.40, IC95% 0.26-0.64). CONCLUSIONES 1. Las variables asociadas de forma independiente con mayor mortalidad en pacientes a los que se ha extraído hemocultivos fueron una mayor edad, determinadas comorbilidades (demencia, neoplasia activa), la administración de antibioterapia en las 48 horas previas a la extracción de hemocultivo, la gravedad de presentación (sepsis grave/shock séptico), el defecto de cobertura antibiótica en día 2, y los focos distintos del urinario, catéter y biliar. Asimismo, la positividad de los hemocultivos se asoció con mayor mortalidad. 2. En los pacientes con hemocultivo negativo, las variables asociadas a la mortalidad fueron similares (a excepción de la positividad del hemocultivo). 3. Un alto porcentaje de pacientes con hemocultivo negativo recibieron tratamientos antibióticos inapropiados, destacando entre los motivos el espectro de los antibióticos administrados y la vía de administración. Este hecho y la mayor mortalidad en pacientes con cobertura inapropiada en el día 2 sugieren que se trata de un grupo diana adecuado para intervenciones PROA. 4. La utilización de antibioterapia en las 48 horas previas a la extracción de hemocultivo y los focos neumonía y urinario se relacionaron de forma independiente con la indicación de tratamientos inapropiados en pacientes con hemocultivo negativo

Monocyte and Lymphocyte Activation and Regulation in Multiple Sclerosis Patients. Therapy Effects

Analysis of gut barrier status, monocyte and lymphocyte activation and T regulatory (Treg) cells at diagnosis before and after therapy, in patients with multiple sclerosis (MS). Analysis of differential effects of interferon beta (IFN-β), glatiramer acetate (GA) and natalizumab. Thirty-five patients with untreated MS were included. Gut barrier status (serum concentrations of intestinal fatty acid binding protein), monocyte (serum levels of soluble CD14, soluble CD163 and interleukin 6) and T lymphocyte activation (CD4 + DR+ and CD8 + DR+) and Treg (CD4 + CD25highFoxP3+) cells were analyzed. Patients with clinical isolated syndrome and relapsing-remitting forms were treated with IFN-β or GA, and immune characteristics were reevaluated following up after 6 months. A sample of 56 stable RR MS patients, in treatment with IFN-β, GA or natalizumab, and 50 healthy individuals were included as controls. Gut barrier status was similar in MS patients and healthy controls. Untreated patients with relapsing-remitting and primary progressive patterns of MS showed increased serum levels of soluble CD14. At baseline, significant increases in activated T lymphocytes and Treg were detected in patients. A significant decrease of CD4 + DR+, CD8 + DR+, and Treg percentages after 6 months of therapy was observed. In previously treated patients, IFN-β, GA, or natalizumab therapies were associated with a comparable cell proportion of activated lymphocytes and Treg. MS patients have a baseline state characterized by monocyte and lymphocyte activation, not related with gut barrier lesion. An increase in Treg number, correlated with activated T CD8+ lymphocytes, was detected. Treatment with IFN-β, GA or natalizumab was associated with a comparable decrease in activated lymphocytes and Treg.This work was supported by a Grant from Neurología, Fundación para la Investigación Biomédica de Cádiz. MCGO was the recipient of this Grant

Opportunities for antibiotic optimisation and outcome improvement in patients with negative blood cultures: study protocol for a cluster-randomised crossover trial, the NO-BACT study

[Introduction] Patients with negative blood cultures (BCx) represent 85%–90% of all patients with BCx taken during hospital admission. This population usually includes a heterogeneous group of patients admitted with infectious diseases or febrile syndromes that require a blood culture. There is very little evidence of the clinical characteristics and antibiotic treatment given to these patients.[Methods and analysis] In a preliminary exploratory prospective cohort study of patients with BCx taken, the clinical/therapeutic characteristics and outcomes/antimicrobial stewardship opportunities of a population of patients with negative BCx will be analysed. In the second phase, using a cluster randomised crossover design, the implementation of an antimicrobial stewardship intervention targeting patients with negative BCx will be evaluated in terms of quality of antimicrobial use (duration and de-escalation), length of hospital stay and mortality.[Ethics and dissemination] This study has been and registered with clinicaltrials.gov. The findings of our study may support the implementation in clinical practice of an antimicrobial stewardship intervention to optimise the use of antibiotics in patients with negative BCx. The results of this study will be published in peer-reviewed journals and disseminated at national and international conferences.Trial registration number NCT03535324.This work is being supported by the Spanish Clinical Research and Clinical Trials Platform, SCReN (Spanish Clinical Research Network), funded by the ISCIII-General Subdirectorate for Evaluation and Promotion of Research, through project PT17/0017/0012) integrated in the State R & D Plan 2013-2016 and co-financed by and the European Regional Development Fund (FEDER). In addition, is being supported by the Project “PI17/01809”, funded by Instituto de Salud Carlos III, integrated in the national I+D+i Plan 2017-2020 and co-funded by European Union (ERDF/ESF, “Investing in your future”).Peer reviewe