Performance of a Quantitative PCR-Based Assay and Beta-d-Glucan Detection for Diagnosis of Invasive Candidiasis in Very-Low-Birth-Weight Preterm Neonatal Patients (CANDINEO Study)

An epidemiological, multicenter, noninterventional, observational case-control study was conducted to describe the performance of serum beta-d-glucan (BDG) and Candida PCR in blood, serum, and sterile samples for the diagnosis of invasive candidiasis (IC) in very-low-birth-weight (VLBW) preterm neonates and to compare these techniques with culture of samples from blood and other sterile sites. Seventeen centers participated in the study, and the number of episodes analyzed was 159. A total of 9 episodes of IC from 9 patients (7 confirmed and 2 probable) and 150 episodes of suspected sepsis from 117 controls were identified. The prevalence of IC was 5.7% (95% confidence interval [95% CI], 2.1 to 9.3). The mortality was significantly higher in episodes of IC (44.4%) than in the non-IC episodes (11.1%, P < 0.01). The sensitivity and specificity of the PCR performed on blood/serum samples were 87.5% and 81.6%, respectively. The sensitivity and specificity of the BDG results were lower (75.0% and 64.6%). For cases with negative culture results, the PCR and the BDG results were positive in 27 (17.4%) and 52 (33.5%) episodes, respectively. The presence of multiorgan failure, improvement with empirical antifungal therapy, thrombocytopenia, and Candida colonization were significantly associated (P < 0.01) with PCR or BDG positivity regardless of the results of the cultures. Serum BDG analysis and Candida PCR could be used as complementary diagnostic techniques to detect IC in VLBW neonates.This study was initiated and financially supported by Astellas Pharma Inc. Manuel Cuenca-Estrella has received grant support from Astellas Pharma Inc., bioMérieux, Basilea, Gilead Sciences, Merck Sharp & Dohme, Pfizer, Schering Plough, Soria Melguizo SA, Ferrer International, the European Union, the ALBAN program, the Spanish Agency for International Cooperation, the Spanish Ministry of Culture and Education, the Spanish Health Research Fund, Instituto de Salud Carlos III (Spanish Ministry of Economy and Competitiveness), the Ramon Areces Foundation, and the Mutua Madrileña Foundation. Jose T. Ramos has received fees for conferences from Gilead Sciences, ViiV Healthcare, and Janssen-Cilag and grant support from the Gilead Fellowship Program. Elena Bergon-Sendin received grant support from Astellas Pharma Inc. during the conduct of the study. Paloma Anguita Alonso is an employee of Astellas Pharma Inc. The rest of us have no conflicts to report. Medical writing support was provided by Lucy Kanan on behalf of Bioscript Medical Ltd., funded by Astellas Pharma IncS

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Garenoxacin Treatment of Experimental Endocarditis Caused by Viridans Group Streptococci

The activity of garenoxacin was compared to that of levofloxacin or penicillin in a rabbit model of Streptococcus mitis group (penicillin MIC, 0.125 μg/ml) and Streptococcus sanguinis group (penicillin MIC, 0.25 μg/ml) endocarditis. Garenoxacin and levofloxacin had MICs of 0.125 and 0.5 μg/ml, respectively, for both study isolates. Rabbits with catheter-induced aortic valve endocarditis were given no treatment, penicillin at 1.2 × 10(6) IU/8 h intramuscularly, garenoxacin at 20 mg/kg of body weight/12 h intravenously, or levofloxacin at 40 mg/kg/12 h intravenously. For both isolates tested, garenoxacin area under the curve (AUC)/MIC and maximum concentration of drug in serum (C(max))/MIC ratios were 368 and 91, respectively. Rabbits were sacrificed after 3 days of treatment; cardiac valve vegetations were aseptically removed and quantitatively cultured. For S. mitis group experimental endocarditis, all studied antimicrobial agents were more active than no treatment (P < 0.001), whereas for S. sanguinis group endocarditis, no studied antimicrobial agents were more active than no treatment. We conclude that AUC/MIC and C(max)/MIC ratios may not predict activity of some quinolones in experimental viridans group endocarditis and that garenoxacin and levofloxacin may not be ideal choices for serious infections caused by some quinolone-susceptible viridans group streptococci

RNAIII-Inhibiting-Peptide-Loaded Polymethylmethacrylate Prevents In Vivo Staphylococcus aureus Biofilm Formation▿

Staphylococci, common orthopedic pathogens, form antibiotic-resistant biofilms. Polymethylmethacrylate (PMMA) beads loaded with the quorum-sensing inhibitor RNAIII-inhibiting peptide (RIP) were implanted in rats and shown to prevent methicillin-resistant Staphylococcus aureus infection. RIP release was bimodal, typical of previously-tested antibiotics. These results suggest that RIP-PMMA warrants further evaluation for management of orthopedic infections caused by staphylococci

Factores neuro-psicolinguísticos y estrategias cognitivas implicadas en el aprendizaje de la lectura y programa de entrenamiento

Hacer una revisión de investigaciones directamente relacionadas con el tema propuesto. Demostrar empíricamente el peso relativo que poseen en el aprendizaje inicial de la lectura unos factores de naturaleza neuro-psicolingüística, tradicionalmente considerados como madurativos, pero entendidos por los autores como competencias básicas para el aprendizaje. Demostrar experimentalmente la eficacia de un programa de entrenamiento, consistente en la aplicación de una serie de tareas psicomotrices, psicolingüísticas y cognitivas, tendentes a modificar el ritmo de adquisición de tales competencias básicas en un grupo de niños de bajo nivel y, en consecuencia, a mejorar su aprendizaje de la lectura, mediante la puesta en práctica de un modelo didáctico propio. El universo de la investigación hace referencia a niños entre 4 años y medio y 6 años, ubicados en último curso de la enseñanza infantil, sin evidencia empírica de problema cerebral ni de retraso mental. La muestra real del primer diseño la componen 348 niños de ambos sexos, de Zaragoza, Valladolid, Vigo y Baeza. La muestra del segundo diseño fue la siguiente: se seleccionaron los 15 niños de puntuaciones más bajas de los 130 que formaban parte de la muestra de Zaragoza, para formar el grupo experimental. Los 15 niños del grupo de control fueron seleccionados en 5 aulas de Valladolid y Vigo: los 3 de cada una de esas aulas con puntuaciones más bajas en la batería diagnóstica aplicada. Estructura dividida en 3 partes. El núcleo básico de las 2 primeras partes es una amplia revisión de investigaciones directamente relacionadas con la vasta y compleja problemática de los procesos de la pedagogía del lenguaje escrito. En la parte tercera se presentan las bases técnico-prácticas de un modelo didáctico propio, publicado hace unos cuantos años y actualizado para esta obra, como asimismo la validación empírica y experimental de dicho modelo. Para llevar a cabo esa validación el autor se ha valido predominantemente de una metodología cuantitativa pero también se ha apoyado en datos cualitativos obtenidos a través de un proceso de observación sistemática. Muchas de las experiencias pedagógicas que se autodenominan 'enseñanza temprana de la lectura' no son tales, pues dichos resultados demuestran que a los 4 años un niño normal está en condiciones de acceder al lenguaje escrito si se le facilitan los medios y se respetan los distintos momentos evolutivos. Es necesaria una investigación más abundante acerca de las características de los textos empleados en la enseñanza de la lectura, tomando como referencia las distintas gramáticas textuales, los modelos cognitivos del aprendizaje de la lectura y empleando pruebas de evaluación de la comprensión lectora con suficiente validez de constructo y empírica, como asímismo fórmulas de lecturabilidad textual más complejas.AragónBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; Fax +34917748026; [email protected]

Health-related quality of life in men with localized prostate cancer treated with radiotherapy: validation of an abbreviated version of the Expanded Prostate Cancer Index Composite for Clinical Practice in Spain.

Health-related quality of life (HRQoL) is greatly affected by prostate cancer (PCa) and associated treatments. This study aimed to measure the impact of radiotherapy on HRQoL and to further validate the Spanish version of the 16-item Expanded Prostate Cancer Index Composite (EPIC-16) in routine clinical practice. An observational, non-interventional, multicenter study was conducted in Spain with localized PCa patients initiating treatment with external beam radiotherapy (EBRT) or brachytherapy (BQT). Changes from baseline in EPIC-16, University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), and patient-perceived health status were longitudinally assessed at end of radiotherapy (V2) and 90 days thereafter (V3). Psychometric evaluations of the Spanish EPIC-16 were conducted. Of 516 patients enrolled, 495 were included in the analysis (EBRT, n = 361; BQT, n = 134). At baseline, mean (standard deviation [SD]) EPIC-16 global scores were 11.9 (7.5) and 10.3 (7.7) for EBRT and BQT patients, respectively; scores increased, i.e., HRQoL worsened, from baseline, by mean (SD) of 6.8 (7.6) at V2 and 2.4 (7.4) at V3 for EBRT and 4.2 (7.6) and 3.9 (8.2) for BQT patients. Changes in Spanish EPIC-16 domains correlated well with urinary, bowel, and sexual UCLA-PCI domains. EPIC-16 showed good internal consistency (Cronbach's alpha = .84), reliability, and construct validity. The Spanish EPIC-16 questionnaire demonstrated sensitivity, strong discriminative properties and reliability, and validity for use in clinical practice. EPIC-16 scores worsened after radiotherapy in different HRQoL domains; however, a strong tendency towards recovery was seen at the 3-month follow-up visit

Performance of a Quantitative PCR-Based Assay and Beta- d

An epidemiological, multicenter, noninterventional, observational case-control study was conducted to describe the performance of serum beta-d-glucan (BDG) and Candida PCR in blood, serum, and sterile samples for the diagnosis of invasive candidiasis (IC) in very-low-birth-weight (VLBW) preterm neonates and to compare these techniques with culture of samples from blood and other sterile sites. Seventeen centers participated in the study, and the number of episodes analyzed was 159. A total of 9 episodes of IC from 9 patients (7 confirmed and 2 probable) and 150 episodes of suspected sepsis from 117 controls were identified. The prevalence of IC was 5.7% (95% confidence interval [95% CI], 2.1 to 9.3). The mortality was significantly higher in episodes of IC (44.4%) than in the non-IC episodes (11.1%, P < 0.01). The sensitivity and specificity of the PCR performed on blood/serum samples were 87.5% and 81.6%, respectively. The sensitivity and specificity of the BDG results were lower (75.0% and 64.6%). For cases with negative culture results, the PCR and the BDG results were positive in 27 (17.4%) and 52 (33.5%) episodes, respectively. The presence of multiorgan failure, improvement with empirical antifungal therapy, thrombocytopenia, and Candida colonization were significantly associated (P < 0.01) with PCR or BDG positivity regardless of the results of the cultures. Serum BDG analysis and Candida PCR could be used as complementary diagnostic techniques to detect IC in VLBW neonates.This study was initiated and financially supported by Astellas Pharma Inc. Manuel Cuenca-Estrella has received grant support from Astellas Pharma Inc., bioMérieux, Basilea, Gilead Sciences, Merck Sharp & Dohme, Pfizer, Schering Plough, Soria Melguizo SA, Ferrer International, the European Union, the ALBAN program, the Spanish Agency for International Cooperation, the Spanish Ministry of Culture and Education, the Spanish Health Research Fund, Instituto de Salud Carlos III (Spanish Ministry of Economy and Competitiveness), the Ramon Areces Foundation, and the Mutua Madrileña Foundation. Jose T. Ramos has received fees for conferences from Gilead Sciences, ViiV Healthcare, and Janssen-Cilag and grant support from the Gilead Fellowship Program. Elena Bergon-Sendin received grant support from Astellas Pharma Inc. during the conduct of the study. Paloma Anguita Alonso is an employee of Astellas Pharma Inc. The rest of us have no conflicts to report. Medical writing support was provided by Lucy Kanan on behalf of Bioscript Medical Ltd., funded by Astellas Pharma IncS

Epidemiología y factores de riesgo para la infección por Clostridium difficile en pacientes críticos en España: Estudio PROCRID

[EN] Introduction: Our objectives were to describe the incidence, clinical characteristics, and risk factors for Clostridium difficile infection (CDI) in critically ill patients and to determine C. difficile PCR-ribotypes. Methods: Prospective, observational study in 26 Spanish ICUs. Patients with diarrhea meeting ESCMID criteria for CDI were included. Molecular characterization of isolates was performed using PCR ribotyping. Results: Of 4258 patients admitted to the ICUs, 190 (4.5%) developed diarrhea. Only 16 patients (8.4%) were diagnosed with CDI. Ribotype 078/126 (25.0%) was the most frequently identified. The mortality rate was similar in patients with ICD compared to patients with diarrhea not caused by C. difficile (p = 0.115). Chronic renal insufficiency was identified as the only factor independently associated with the development of CDI (OR 5.87, 95% CI 1.24–27.83; p = 0.026). Conclusions: The incidence of CDI in Spanish ICUs is low. Only chronic renal insufficiency was observed to be a risk factor for CDI development.[ES] Introducción: Pretendemos describir la incidencia, las características clínicas y los factores de riesgo de la infección por Clostridium difficile (ICD) en pacientes ingresados en unidades de cuidados intensivos, así como los ribotipos identificados. Métodos: Estudio observacional, prospectivo, realizado en 26 unidades de cuidados intensivos de España. Se incluyeron pacientes con diarrea y criterios clínicos de la ESCMID por sospecha de ICD. La caracterización molecular se realizó mediante PCR. Resultados: De 4.258 pacientes ingresados, 190 (4,5%) presentaron diarrea; en 16 causada por ICD. El ribotipo más frecuentemente aislado fue 078/126 (25%). La tasa de mortalidad cruda fue similar en pacientes con ICD y en pacientes con diarrea no causada por Clostridium difficile (p = 0,115). La insuficiencia renal crónica fue identificada como factor independientemente asociado a desarrollo de ICD (OR: 5,87; IC 95%: 1,24-27,83; p = 0,026). Conclusiones: La incidencia de ICD en las unidades de cuidados intensivos españolas es baja. La insuficiencia renal crónica es el único factor identificado para desarrollo de ICD.Peer reviewe