Clinical risk factors for early mortality in patients with community-acquired septic shock. The importance of adequate source control.

OBJECTIVE: To evaluate the incidence and risk factors for early mortality (EM) in the ICU in patients with community-acquired septic shock (CASS). DESIGN: A retrospective cohort study of patients with CASS admitted to the ICU (2003-2016). SETTING: ICU at a University Hospital in Spain. PATIENTS: All consecutive patients admitted to the ICU with CASS. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: CASS was defined according to the Sepsis-3 definitions. EM were defined as occurring within of 72h following ICU admission. A multinomial logistic regression analysis was performed to identify the risk factors associated with early deaths. RESULTS: During the study period, 625 patients met the Sepsis-3 criteria and admitted with CASS. 14.4% of all patients died within the first 72h. Of 161 patients who died in the ICU, 90 (55.9%) died within the first 72h. The percentage of early and late mortality did not vary significantly during the study period. The need and adequacy of source control were significantly lower in patients with EM. In the multivariate analysis, ARDS, non-respiratory infections, bacteremia and severity at admission were variables independently associated with EM. The only factor that decreased EM was adequate source control in patients with infections amenable to source control. CONCLUSIONS: The incidence of EM has remained stable over time, which means that more than half of the patients who die from CASS do so within the first 72h. Infections where adequate source control can be performed have lower EM.

Clinical risk factors for early mortality in patients with community-acquired septic shock. The importance of adequate source control.

OBJECTIVE: To evaluate the incidence and risk factors for early mortality (EM) in the ICU in patients with community-acquired septic shock (CASS). DESIGN: A retrospective cohort study of patients with CASS admitted to the ICU (2003-2016). SETTING: ICU at a University Hospital in Spain. PATIENTS: All consecutive patients admitted to the ICU with CASS. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: CASS was defined according to the Sepsis-3 definitions. EM were defined as occurring within of 72h following ICU admission. A multinomial logistic regression analysis was performed to identify the risk factors associated with early deaths. RESULTS: During the study period, 625 patients met the Sepsis-3 criteria and admitted with CASS. 14.4% of all patients died within the first 72h. Of 161 patients who died in the ICU, 90 (55.9%) died within the first 72h. The percentage of early and late mortality did not vary significantly during the study period. The need and adequacy of source control were significantly lower in patients with EM. In the multivariate analysis, ARDS, non-respiratory infections, bacteremia and severity at admission were variables independently associated with EM. The only factor that decreased EM was adequate source control in patients with infections amenable to source control. CONCLUSIONS: The incidence of EM has remained stable over time, which means that more than half of the patients who die from CASS do so within the first 72h. Infections where adequate source control can be performed have lower EM.

Comparison of the defined daily dose and days of treatment methods for evaluating the consumption of antibiotics and antifungals in the intensive care unit / Comparación de la dosis diaria definida y los días de tratamiento para evaluar el consumo de antibióticos y antifúngicos en la unidad de cuidados intensivos

OBJECTIVE: To compare the measurement of antimicrobial consumption by defined daily dose (DDD) versus by days of therapy (DOT). DESIGN: Retrospective analysis of clinical and administrative data from patients admitted to a polyvalent ICU. SETTING: ICU at a University Hospital in Spain. PATIENTS: All patients admitted to the ICU. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: For the DDD method, the World Health Organization (WHO)-assigned DDD was determined for the all the prescribed antimicrobials. For the DOT method, one DOT represented the administration of a single agent on a given day regardless of the number of doses administered. To express aggregate use, total DDDs and total DOTs were normalized to 100 patient-days. RESULTS: During the study period, 2393 adult patients were admitted to the ICU. Total median antimicrobial drugs measured by DDDs was 535.3 (IQR 319.8-845.5) vs. 344.0 (IQR 117.2-544.5) when measured by DOTs, p < 0.001. When antimicrobial consumption was normalized to 100 patient-days, median antimicrobial consumption was also higher when measured by DDDs [2.98/100 patient-days (IQR 1.76-5.25) vs. 1.89/100 patient-days (IQR 0.64-3.0) when measured by DOTs, p < 0.001]. CONCLUSIONS: For most antibacterial and antifungal drugs used in critically ill patients, estimates of aggregate antibiotic use by DDDs per 100 patient-days and DOTs per 100 patient-days are discordant because the administered dose is dissimilar from the WHO-assigned DDD. DOT methods should be recommended to avoid the overestimation that occurs with DDDs in adult critically ill patients

OBJETIVO: Comparar la medición del consumo de antimicrobianos por dosis diarias definidas (DDD) y por días de tratamiento (DOT). DISEÑO: Análisis retrospectivo de datos clínicos y administrativos de los pacientes ingresados en una unidad de cuidados intensivos (UCI) polivalente. Ámbito: La UCI de un hospital universitario de España. PACIENTES: Todos los pacientes ingresados en la UCI.: INTERVENCIONES: Ninguna. PRINCIPALES VARIABLES DE INTERÉS: Se determinó la DDD asignada por la Organización Mundial de la Salud (OMS) para todos los antimicrobianos prescritos. La DOT representó los días de utilización de cada antimicrobiano independientemente del número de dosis administradas cada día. Las DDD totales y los DOT totales se normalizaron por cada 100 estancias. RESULTADOS: Durante el período de estudio, 2.393 pacientes adultos ingresaron en la UCI. La mediana de los antimicrobianos medidos por DDD fue de 535,3 (RIQ: 319,8-845,5) frente a 344,0 (RIQ: 117,2-544,5) cuando se midió mediante DOT; p < 0,001. Cuando el consumo de antimicrobianos se normalizó por 100 estancias, el consumo de antimicrobianos también fue mayor cuando se midió con DDD (2,98/100 estancias [RIQ: 1,76-5,25] vs. 1,89/100 estancias [RIQ: 0,64-3,0] cuando se midió por DOT; p < 0,001). CONCLUSIONES: Para la mayoría de los antimicrobianos utilizados en la UCI, el consumo global y medido por DDD/100 estancias y DOT/100 estancias son discordantes porque la dosis administrada es diferente de la DDD asignada por la OMS. Se debe recomendar la utilización de las DOT para evitar la sobreestimación que se produce con las DDD en pacientes adultos críticamente enfermos

Comparison of the defined daily dose and days of treatment methods for evaluating the consumption of antibiotics and antifungals in the intensive care unit.

OBJECTIVE: To compare the measurement of antimicrobial consumption by defined daily dose (DDD) versus by days of therapy (DOT). DESIGN: Retrospective analysis of clinical and administrative data from patients admitted to a polyvalent ICU. SETTING: ICU at a University Hospital in Spain. PATIENTS: All patients admitted to the ICU. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: For the DDD method, the World Health Organization (WHO)-assigned DDD was determined for the all the prescribed antimicrobials. For the DOT method, one DOT represented the administration of a single agent on a given day regardless of the number of doses administered. To express aggregate use, total DDDs and total DOTs were normalized to 100 patient-days. RESULTS: During the study period, 2393 adult patients were admitted to the ICU. Total median antimicrobial drugs measured by DDDs was 535.3 (IQR 319.8-845.5) vs. 344.0 (IQR 117.2-544.5) when measured by DOTs, p<0.001. When antimicrobial consumption was normalized to 100 patient-days, median antimicrobial consumption was also higher when measured by DDDs [2.98/100 patient-days (IQR 1.76-5.25) vs. 1.89/100 patient-days (IQR 0.64-3.0) when measured by DOTs, p<0.001]. CONCLUSIONS: For most antibacterial and antifungal drugs used in critically ill patients, estimates of aggregate antibiotic use by DDDs per 100 patient-days and DOTs per 100 patient-days are discordant because the administered dose is dissimilar from the WHO-assigned DDD. DOT methods should be recommended to avoid the overestimation that occurs with DDDs in adult critically ill patients.

Change in nuclear DNA content and pollen size with polyploidisation in the sweet potato (Ipomoea batatas, Convolvulaceae) complex.

Genome size evolution and its relationship with pollen grain size has been investigated in sweet potato (Ipomoea batatas), an economically important crop which is closely related to diploid and tetraploid species, assessing the nuclear DNA content of 22 accessions from five Ipomoea species, ten sweet potato varieties and two outgroup taxa. Nuclear DNA amounts were determined using flow cytometry. Pollen grains were studied using scanning and transmission electron microscopy. 2C DNA content of hexaploid I. batatas ranged between 3.12-3.29 pg; the mean monoploid genome size being 0.539 pg (527 Mbp), similar to the related diploid accessions. In tetraploid species I. trifida and I. tabascana, 2C DNA content was, respectively, 2.07 and 2.03 pg. In the diploid species closely related to sweet potato e.g. I. ×leucantha, I. tiliacea, I. trifida and I. triloba, 2C DNA content was 1.01-1.12 pg. However, two diploid outgroup species, I. setosa and I. purpurea, were clearly different from the other diploid species, with 2C of 1.47-1.49 pg; they also have larger chromosomes. The I. batatas genome presents 60.0% AT bases. DNA content and ploidy level were positively correlated within this complex. In I. batatas and the more closely related species I. trifida, the genome size and ploidy levels were correlated with pollen size. Our results allow us to propose alternative or complementary hypotheses to that currently proposed for the formation of hexaploid Ipomoea batatas.

In silico dynamic characterization of the femur: Physiological versus mechanical boundary conditions.

It is established that bone tissue adapts and responds to mechanical loading. Several studies have suggested an existence of positive influence of vibration on the bone mass maintenance. Thus, some bone regeneration therapies are based on vibration of bone tissue under circumstances of disease to stimulate its formation. Frequency of loading should be properly selected and therefore a correct characterization of the dynamic properties of this tissue may be critical for the success of such orthopedic techniques. On the other hand, many studies implement vibration techniques with in silico models. Numerical results are exclusively dependent on properties of bone tissue, i.e. geometry, density distribution and stiffness, as well as boundary conditions. In the present study, the influence of boundary conditions and material properties on the dynamic characteristics of bone tissue was explored in a human femur. Bone shape and density were directly reconstructed from computer tomographies, whereas natural frequencies and modes of vibration were obtained for different boundary conditions including physiological and mechanical ones. Results of this study show the moderate effect of material properties compared to the much substantial effect of boundary conditions. A factor of 2 in the natural frequency was obtained depending on imposed boundary conditions, highlighting the importance in the selection of appropriate conditions in the analysis of the bone organ.

Diagnosis and treatment of catheter-related bloodstream infection: Clinical guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology and (SEIMC) and the Spanish Society of Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC).

Catheter-related bloodstream infections (CRBSI) constitute an important cause of hospital-acquired infection associated with morbidity, mortality, and cost. The aim of these guidelines is to provide updated recommendations for the diagnosis and management of CRBSI in adults. Prevention of CRBSI is excluded. Experts in the field were designated by the two participating Societies (the Spanish Society of Infectious Diseases and Clinical Microbiology and [SEIMC] and the Spanish Society of Spanish Society of Intensive and Critical Care Medicine and Coronary Units [SEMICYUC]). Short-term peripheral venous catheters, non-tunneled and long-term central venous catheters, tunneled catheters and hemodialysis catheters are covered by these guidelines. The panel identified 39 key topics that were formulated in accordance with the PICO format. The strength of the recommendations and quality of the evidence were graded in accordance with ESCMID guidelines. Recommendations are made for the diagnosis of CRBSI with and without catheter removal and of tunnel infection. The document establishes the clinical situations in which a conservative diagnosis of CRBSI (diagnosis without catheter removal) is feasible. Recommendations are also made regarding empirical therapy, pathogen-specific treatment (coagulase-negative staphylococci, Staphylococcus aureus, Enterococcus spp., Gram-negative bacilli, and Candida spp.), antibiotic lock therapy, diagnosis and management of suppurative thrombophlebitis and local complications.

Diagnosis and treatment of catheter-related bloodstream infection: Clinical guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology and (SEIMC) and the Spanish Society of Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) / Diagnóstico y tratamiento de la bacteriemia relacionada con catéter: guía de práctica clínica de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) y de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC)

Catheter-related bloodstream infections (CRBSI) constitute an important cause of hospital-acquired infection associated with morbidity, mortality, and cost. The aim of these guidelines is to provide updated recommendations for the diagnosis and management of CRBSI in adults. Prevention of CRBSI is excluded. Experts in the field were designated by the two participating Societies (the Spanish Society of Infectious Diseases and Clinical Microbiology and [SEIMC] and the Spanish Society of Spanish Society of Intensive and Critical Care Medicine and Coronary Units [SEMICYUC]). Short-term peripheral venous catheters, non-tunneled and long-term central venous catheters, tunneled catheters and hemodialysis catheters are covered by these guidelines. The panel identified 39 key topics that were formulated in accordance with the PICO format. The strength of the recommendations and quality of the evidence were graded in accordance with ESCMID guidelines. Recommendations are made for the diagnosis of CRBSI with and without catheter removal and of tunnel infection. The document establishes the clinical situations in which a conservative diagnosis of CRBSI (diagnosis without catheter removal) is feasible. Recommendations are also made regarding empirical therapy, pathogen-specific treatment (coagulase-negative staphylococci, Staphylococcus aureus, Enterococcus spp., Gram-negative bacilli, and Candida spp.), antibiotic lock therapy, diagnosis and management of suppurative thrombophlebitis and local complications (AU)

La bacteriemia relacionada con catéteres (BRC) es una causa importante de infección hospitalaria y se asocia con elevados morbilidad, mortalidad y costes. El objetivo de esta guía de práctica clínica es proporcionar recomendaciones actualizadas para el diagnóstico y tratamiento de la BRC en pacientes adultos. De este documento se excluye la prevención de la BRC. Expertos en la materia fueron designados por las dos Sociedades participantes (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica y Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias). Los catéteres venosos periféricos a corto plazo, los catéteres venosos centrales no tunelizados y de largo plazo, los catéteres tunelizados y los catéteres de hemodiálisis están incluidos en estas guías. El panel identificó 39 temas clave que fueron formulados de acuerdo con el formato PICO. La fuerza de las recomendaciones y la calidad de la evidencia se clasificaron de acuerdo con las directrices de la ESCMID. Se dan recomendaciones para el diagnóstico de BRC con extracción de catéter y sin él, y de la infección en túnel. El documento establece las situaciones clínicas en que es factible un diagnóstico conservador de CRBSI (diagnóstico sin retirada de catéter). También se dan recomendaciones respecto a la terapia empírica, el tratamiento específico según el patógeno identificado (estafilococos coagulasa-negativos, Staphylococcus aureus, Enterococcus spp., bacilos gramnegativos y Candida spp.), la terapia con sellado del catéter y el diagnóstico, así como tratamiento de la tromboflebitis supurativa y las complicaciones locales (AU)

Success factors for implementing and sustaining a mature electronic medical record in a low-resource setting: a case study of iSanté in Haiti.

Electronic health information systems, including electronic medical records (EMRs), have the potential to improve access to information and quality of care, among other things. Success factors and challenges for novel EMR implementations in low-resource settings have increasingly been studied, although less is known about maturing systems and sustainability. One systematic review identified seven categories of implementation success factors: ethical, financial, functionality, organizational, political, technical and training. This case study applies this framework to iSanté, Haiti's national EMR in use in more than 100 sites and housing records for more than 750 000 patients. The author group, consisting of representatives of different agencies within the Haitian Ministry of Health (MSPP), funding partner the Centers for Disease Control and Prevention (CDC) Haiti, and implementing partner the International Training and Education Center for Health (I-TECH), identify successes and lessons learned according to the seven identified categories, and propose an additional cross-cutting category, sustainability. Factors important for long-term implementation success of complex information systems are balancing investments in hardware and software infrastructure upkeep, user capacity and data quality control; designing and building a system within the context of the greater eHealth ecosystem with a plan for interoperability and data exchange; establishing system governance and strong leadership to support local system ownership and planning for system financing to ensure sustainability. Lessons learned from 10 years of implementation of the iSanté EMR system are relevant to sustainability of a full range of increasingly interrelated information systems (e.g. for laboratory, supply chain, pharmacy and human resources) in the health sector in low-resource settings.

Carga de trabajo y cumplimiento por parte de las enfermeras de las medidas no farmacológicas para la prevención de la neumonía asociada a la ventilación mecánica. Estudio piloto / Nursing workload and adherence to non-pharmacological measures in the prevention of ventilator-associated pneumonia. A pilot study

Objetivo: Analizar si el cumplimiento de las medidas no farmacológicas para la prevención de la neumonía asociada a la ventilación mecánica (NAV) se asocia a la carga de trabajo de las enfermeras. Método: Estudio observacional prospectivo llevado a cabo en una UCI médico-quirúrgica. Se evaluó a las enfermeras a cargo de pacientes con soporte ventilatorio. Variables: cuestionario de conocimiento, aplicación de las medidas no farmacológicas de prevención de la NAV, carga de trabajo medida mediante el Nine Equivalents of Nursing Manpower Use Score. Fases: 1) las enfermeras realizaron un programa educativo, basado en conferencias de 60 min sobre medidas no farmacológicas para la prevención de NAV, completando al finalizar un cuestionario de conocimiento; 2) periodo de observaciones; 3) cuestionario de conocimiento. Resultados: De un total de 67 enfermeras de UCI, 54 completaron el programa formativo y fueron incluidos en el estudio. Se llevaron a cabo un total de 160 observaciones de 49 enfermeros/as. El correcto conocimiento de las medidas de prevención se confirmó tanto en el cuestionario inicial como final. La aplicación de las medidas de prevención varió desde el 11% para el lavado de manos preaspiración hasta el 97% para el uso de sonda de aspiración estéril. La puntuación del Nine Equivalents of Nursing Manpower Use Score fue de 50±13. No se observaron asociaciones significativas entre el grado de conocimiento y la aplicación de medidas de prevención, ni entre la carga de trabajo y la aplicación de dichas medidas. Conclusiones: El conocimiento de las enfermeras de las medidas de prevención de la NAV no se traslada necesariamente a la práctica diaria. En la población estudiada, la falta de aplicación de estas medidas no está sujeta a la falta de conocimiento ni a la carga de trabajo, sino probablemente a los factores contextuales (AU)

Objective: To analyse whether adherence to non-pharmacological measures in the prevention of ventilator-associated pneumonia (VAP) is associated with nursing workload. Methods: A prospective observational study performed in a single medical-surgical ICU. Nurses in charge of patients under ventilator support were assessed. Variables: knowledge questionnaire, application of non-pharmacological VAP prevention measures, and workload (Nine Equivalents of Nursing Manpower Use Score). Phases: 1) the nurses carried out a educational programme, consisting of 60-minute lectures on non-pharmacological measures for VAP prevention, and at the end completed a questionnaire knowledge; 2) observation period; 3) knowledge questionnaire. Results: Among 67 ICU-staff nurses, 54 completed the educational programme and were observed. A total of 160 observations of 49 nurses were made. Adequate knowledge was confirmed in both the initial and final questionnaires. Application of preventive measures ranged from 11% for hand washing pre-aspiration to 97% for the use of a sterile aspiration probe. The Nine Equivalents of Nursing Manpower Use Score was 50±13. No significant differences were observed between the association of the nurses' knowledge and the application of preventive measures or between workload and the application of preventive measures. Conclusions: Nurses' knowledge of VAP prevention measures is not necessarily applied in daily practice. Failure to follow these measures is not subject to lack of knowledge or to increased workload, but presumably to contextual factors (AU)

Nursing workload and adherence to non-pharmacological measures in the prevention of ventilator-associated pneumonia. A pilot study. / Carga de trabajo y cumplimiento por parte de las enfermeras de las medidas no farmacológicas para la prevención de la neumonía asociada a la ventilación mecánica. Estudio piloto.

OBJECTIVE: To analyse whether adherence to non-pharmacological measures in the prevention of ventilator-associated pneumonia (VAP) is associated with nursing workload. METHODS: A prospective observational study performed in a single medical-surgical ICU. Nurses in charge of patients under ventilator support were assessed. VARIABLES: knowledge questionnaire, application of non-pharmacological VAP prevention measures, and workload (Nine Equivalents of Nursing Manpower Use Score). Phases: 1) the nurses carried out a educational programme, consisting of 60-minute lectures on non-pharmacological measures for VAP prevention, and at the end completed a questionnaire knowledge; 2) observation period; 3) knowledge questionnaire. RESULTS: Among 67 ICU-staff nurses, 54 completed the educational programme and were observed. A total of 160 observations of 49 nurses were made. Adequate knowledge was confirmed in both the initial and final questionnaires. Application of preventive measures ranged from 11% for hand washing pre-aspiration to 97% for the use of a sterile aspiration probe. The Nine Equivalents of Nursing Manpower Use Score was 50±13. No significant differences were observed between the association of the nurses' knowledge and the application of preventive measures or between workload and the application of preventive measures. CONCLUSIONS: Nurses' knowledge of VAP prevention measures is not necessarily applied in daily practice. Failure to follow these measures is not subject to lack of knowledge or to increased workload, but presumably to contextual factors.

Improved survival among ICU-hospitalized patients with community-acquired pneumonia by unidentified organisms: a multicenter case-control study.

A retrospective analysis from prospectively collected data was conducted in intensive care units (ICUs) at 33 hospitals in Europe comparing the trend in ICU survival among adults with severe community-acquired pneumonia (CAP) due to unknown organisms from 2000 to 2015. The secondary objective was to establish whether changes in antibiotic policies were associated with different outcomes. ICU mortality decreased (p = 0.02) from 26.9 % in the first study period (2000-2002) to 15.7 % in the second period (2008-2015). Demographic data and clinical severity at admission were comparable between groups, except for age over 65 years and incidence of cardiomyopathy. Over time, patients received higher rates of combination therapy (94.3 vs. 77.2 %; p < 0.01) and early (<3 h) antibiotic delivery (72.9 vs. 50.3 %; p < 0.01); likewise, the 2008-2015 group was more likely to receive adequate antibiotic prescription [as defined by the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines] than the 2000-2002 group (70.7 vs. 48.2 %; p < 0.01). Multivariate analysis showed an independent association between decreased ICU mortality and early (<3 h) antibiotic administration [odds ratio (OR) 3.48 [1.70-7.15], p < 0.01] or adequate antibiotic prescription according to guidelines (OR 2.22 [1.11-4.43], p = 0.02). In conclusion, our findings suggest that ICU mortality in severe CAP due to unidentified organisms has decreased in the last 15 years. Several changes in management and better compliance with guidelines over time were associated with increased survival.

Driving a Superconductor to Insulator Transition with Random Gauge Fields.

Typically the disorder that alters the interference of particle waves to produce Anderson localization is potential scattering from randomly placed impurities. Here we show that disorder in the form of random gauge fields that act directly on particle phases can also drive localization. We present evidence of a superfluid bose glass to insulator transition at a critical level of this gauge field disorder in a nano-patterned array of amorphous Bi islands. This transition shows signs of metallic transport near the critical point characterized by a resistance , indicative of a quantum phase transition. The critical disorder depends on interisland coupling in agreement with recent Quantum Monte Carlo simulations. We discuss how this disorder tuned SIT differs from the common frustration tuned SIT that also occurs in magnetic fields. Its discovery enables new high fidelity comparisons between theoretical and experimental studies of disorder effects on quantum critical systems.

Evolution over a 15-year period of the clinical characteristics and outcomes of critically ill patients with severe community-acquired pneumonia / Evolución durante un período de 15 años de las características clínicas y resultados de los pacientes críticamente enfermos con neumonía comunitaria grave

OBJECTIVES: To study the characteristics and outcomes of patients in the ICU with severe community-acquired pneumonia (SCAP) over a 15-year surveillance period. METHODS: We conducted a retrospective cohort study of episodes of SCAP, and assessed the epidemiology, etiology, treatment and outcomes of patients admitted to the ICU, comparing three periods (1999-2003, 2004-2008 and 2009-2013). RESULTS: A total of 458 patients were diagnosed with SCAP. The overall cumulative incidence was 37.4 episodes/1000 admissions, with a progressive increase over the three periods (P < 0.001). Patients fulfilling the two major IDSA/ATS criteria at admission increased from 64.2% in the first period to 82.5% in the last period (P = 0.005). Streptococcus pneumoniae was the prevalent pathogen. The incidence of bacteremia was 23.1%, and a progressive significant reduction in overall incidence was observed over the three periods (P = 0.02). Globally, 91% of the patients received appropriate empiric antibiotic treatment, increasing from 78.3% in the first period to 97.7% in the last period (P < 0.001). Combination antibiotic therapy (betalactam+macrolide or fluoroquinolone) increased significantly from the first period (61%) to the last period (81.3%) (P < 0.001). Global ICU mortality was 25.1%, and decreased over the three periods (P = 0.001). CONCLUSIONS: Despite a progressively higher incidence and severity of SCAP in our ICU, crude ICU mortality decreased by 18%. The increased use of combined antibiotic therapy and the decreasing rates of bacteremia were associated to improved patient prognosis

OBJETIVOS: Estudiar las características y el pronóstico de los pacientes con neumonía grave adquirida en la comunidad ingresados en una unidad de cuidados intensivos (UCI) durante un período de 15 años. MATERIAL Y MÉTODOS: Estudio retrospectivo de una cohorte de pacientes con neumonía grave comunitaria en los que se analizó la evolución en la epidemiología, etiología, tratamiento y pronóstico durante un período de 15 años, comparando 3 períodos (1999-2003, 2004-2008 y 2009-2013). RESULTADOS: Un total de 458 pacientes fueron diagnosticados de neumonía. La incidencia media global durante el período estudiado fue de 37,4 episodios/1.000 ingresos, encontrándose un incremento progresivo durante los 3 períodos estudiados (p < 0,001). Los pacientes que cumplían con los 2 criterios mayores de neumonía grave de la ATS/IDSA aumentaron de un 64,2% en el primer período a un 82,5% en el último período (p = 0,005). Streptococcus pneumoniae fue el microorganismo más frecuente aislado. La incidencia de bacteriemia fue del 23,1%, encontrándose una reducción significativa y progresiva en la incidencia a lo largo de los 3 períodos (p = 0,02). El 91% de los pacientes recibió tratamiento antibiótico empírico apropiado, encontrándose un incremento entre el primer y el último período del 78,3% al 97,7% (p < 0,001). El tratamiento combinado (betalactámico+macrólido o quinolona) aumentó de un 61% en el primer período a un 81,3% en el último (p < 0,001). La mortalidad en la unidad de cuidados intensivos durante todo el período fue del 25,1%, encontrándose una disminución progresiva durante los 3 períodos (p=0,001). CONCLUSIONES: A pesar de un incremento progresivo en la incidencia y gravedad de las neumonías ingresadas en unidad de cuidados intensivos, la mortalidad se redujo en un 18%. El incremento en la utilización de tratamiento combinado y la disminución en la incidencia de bacteriemia se asociaron a una mejoría en el pronóstico

Evolution over a 15-year period of the clinical characteristics and outcomes of critically ill patients with severe community-acquired pneumonia.

OBJECTIVES: To study the characteristics and outcomes of patients in the ICU with severe community-acquired pneumonia (SCAP) over a 15-year surveillance period. METHODS: We conducted a retrospective cohort study of episodes of SCAP, and assessed the epidemiology, etiology, treatment and outcomes of patients admitted to the ICU, comparing three periods (1999-2003, 2004-2008 and 2009-2013). RESULTS: A total of 458 patients were diagnosed with SCAP. The overall cumulative incidence was 37.4 episodes/1000 admissions, with a progressive increase over the three periods (P<0.001). Patients fulfilling the two major IDSA/ATS criteria at admission increased from 64.2% in the first period to 82.5% in the last period (P=0.005). Streptococcus pneumoniae was the prevalent pathogen. The incidence of bacteremia was 23.1%, and a progressive significant reduction in overall incidence was observed over the three periods (P=0.02). Globally, 91% of the patients received appropriate empiric antibiotic treatment, increasing from 78.3% in the first period to 97.7% in the last period (P<0.001). Combination antibiotic therapy (betalactam+macrolide or fluoroquinolone) increased significantly from the first period (61%) to the last period (81.3%) (P<0.001). Global ICU mortality was 25.1%, and decreased over the three periods (P=0.001). CONCLUSIONS: Despite a progressively higher incidence and severity of SCAP in our ICU, crude ICU mortality decreased by 18%. The increased use of combined antibiotic therapy and the decreasing rates of bacteremia were associated to improved patient prognosis.

An assessment of data quality in a multi-site electronic medical record system in Haiti.

OBJECTIVES: Strong data quality (DQ) is a precursor to strong data use. In resource limited settings, routine DQ assessment (DQA) within electronic medical record (EMR) systems can be resource-intensive using manual methods such as audit and chart review; automated queries offer an efficient alternative. This DQA focused on Haiti's national EMR - iSanté - and included longitudinal data for over 100,000 persons living with HIV (PLHIV) enrolled in HIV care and treatment services at 95 health care facilities (HCF). METHODS: This mixed-methods evaluation used a qualitative Delphi process to identify DQ priorities among local stakeholders, followed by a quantitative DQA on these priority areas. The quantitative DQA examined 13 indicators of completeness, accuracy, and timeliness of retrospective data collected from 2005 to 2013. We described levels of DQ for each indicator over time, and examined the consistency of within-HCF performance and associations between DQ and HCF and EMR system characteristics. RESULTS: Over all iSanté data, age was incomplete in <1% of cases, while height, pregnancy status, TB status, and ART eligibility were more incomplete (approximately 20-40%). Suspicious data flags were present for <3% of cases of male sex, ART dispenses, CD4 values, and visit dates, but for 26% of cases of age. Discontinuation forms were available for about half of all patients without visits for 180 or more days, and >60% of encounter forms were entered late. For most indicators, DQ tended to improve over time. DQ was highly variable across HCF, and within HCFs DQ was variable across indicators. In adjusted analyses, HCF and system factors with generally favorable and statistically significant associations with DQ were University hospital category, private sector governance, presence of local iSante server, greater HCF experience with the EMR, greater maturity of the EMR itself, and having more system users but fewer new users. In qualitative feedback, local stakeholders emphasized lack of stable power supply as a key challenge to data quality and use of the iSanté EMR. CONCLUSIONS: Variable performance on key DQ indicators across HCF suggests that excellent DQ is achievable in Haiti, but further effort is needed to systematize and routinize DQ approaches within HCFs. A dynamic, interactive "DQ dashboard" within iSanté could bring transparency and motivate improvement. While the results of the study are specific to Haiti's iSanté data system, the study's methods and thematic lessons learned holdgeneralized relevance for other large-scale EMR systems in resource-limited countries.

The histone deacetylase sirtuin 2 is a new player in the regulation of platelet function.

BACKGROUND: Histone deacetylases (HDACs) play a key role in signaling in many cell types. However, little is known about the participation of HDACs, particularly sirtuins (SIRTs), in platelet reactivity. OBJECTIVE: To investigate the role of HDACs in platelets, we examined the effects of SIRT inhibition on platelet function and protein acetylation in human platelets. METHODS: We used washed platelets obtained from healthy subjects. Cambinol (SIRT1 and SIRT2 inhibitor), AGK2 (specific SIRT2 inhibitor) and EX527 (specific SIRT1 inhibitor) were used as SIRT inhibitors. Platelets were stimulated with collagen, thrombin, or U46619, and platelet responses were determined according to optical aggregometry findings, dense granule release, and cytosolic calcium levels (Fura-2AM fluorescence). Protein acetylation and phosphorylation were assessed by immunoblotting. RESULTS: SIRT inhibition remarkably reduced platelet responses (aggregation, granule release, and cytosolic calcium level; P < 0.05). SIRT2 was present in platelets at the level of mRNA and protein, and its specific inhibition reduced platelet responses. The acetylated protein pattern observed in resting platelets changed during platelet aggregation. Inhibition of SIRT2 increased the acetylation of Akt kinase, which in turn blocked agonist-induced Akt phosphorylation and glycogen synthase kinase-3ß phosphorylation, which are markers of Akt activity. Finally, collagen-induced aggregation provoked Akt acetylation. CONCLUSIONS: Regulation of protein acetylation by SIRT2 plays a central role in platelet function. The effects of SIRT2 are mediated in part by the acetylation and inhibition of Akt. These results open a new avenue for research into the control of platelet function, and may help to identify new therapeutic targets.

The association of thromboxane A2 receptor with lipid rafts is a determinant for platelet functional responses.

We have investigated the presence of thromboxane A2 (TXA2) receptor associated with lipid rafts in human platelets and the regulation of platelet function in response to TXA2 receptor agonists when lipid rafts are disrupted by cholesterol extraction. Platelet aggregation with TXA2 analogs U46619 and IBOP was almost blunted in cholesterol-depleted platelets, as well as αIIbß3 integrin activation and P-selectin exposure. Raft disruption also inhibited TXA2-induced cytosolic calcium increase and nucleotide release, ruling out an implication of P2Y12 receptor. An important proportion of TXA2 receptor (40%) was colocalized at lipid rafts. The presence of the TXA2 receptor associated with lipid rafts in platelets is important for functional platelet responses to TXA2.

HIV/AIDS stigma: measurement and relationships to psycho-behavioral factors in Latino gay/bisexual men and transgender women.

Despite the increased interest in HIV/AIDS stigma and its negative effects on the health and social support of people living with HIV/AIDS (PLWHA), little attention has been given to its assessment among Latino gay/ bisexual men and transgender women (GBT) living with HIV/AIDS. The purpose of this paper is twofold: to develop a multidimensional assessment of HIV/AIDS stigma for Latino GBT living with HIV/AIDS, and to test whether such stigma is related to self-esteem, safe sex self-efficacy, social support, and alcohol, and drug use. The sample included 170 HIV+ Latino GBT persons. The results revealed three dimensions of stigma: internalized, perceived, and enacted HIV/AIDS stigma. Enacted HIV/AIDS stigma comprised two domains: generalized and romantic and sexual. Generalized enacted HIV/AIDS stigma was related to most outcomes. Internalized HIV/AIDS stigma mediated the associations between generalized enacted HIV/AIDS stigma and self-esteem and safe sex self-efficacy. In addition, romantic and sexual enacted HIV/AIDS stigma significantly predicted drug use. Perceived HIV/AIDS stigma was not associated with any outcome. These findings expand the understanding of the multidimensionality of stigma and the manner in which various features impact marginalized PLWHA.

Macrolide-based regimens in absence of bacterial co-infection in critically ill H1N1 patients with primary viral pneumonia.

PURPOSE: To determine whether macrolide-based treatment is associated with mortality in critically ill H1N1 patients with primary viral pneumonia. METHODS: Secondary analysis of a prospective, observational, multicenter study conducted across 148 Intensive Care Units (ICU) in Spain. RESULTS: Primary viral pneumonia was present in 733 ICU patients with pandemic influenza A (H1N1) virus infection with severe respiratory failure. Macrolide-based treatment was administered to 190 (25.9 %) patients. Patients who received macrolides had chronic obstructive pulmonary disease more often, lower severity on admission (APACHE II score on ICU admission (13.1 ± 6.8 vs. 14.4 ± 7.4 points, p < 0.05), and multiple organ dysfunction syndrome less often (23.4 vs. 30.1 %, p < 0.05). Length of ICU stay in survivors was not significantly different in patients who received macrolides compared to patients who did not (10 (IQR 4-20) vs. 10 (IQR 5-20), p = 0.9). ICU mortality was 24.1 % (n = 177). Patients with macrolide-based treatment had lower ICU mortality in the univariate analysis (19.2 vs. 28.1 %, p = 0.02); however, a propensity score analysis showed no effect of macrolide-based treatment on ICU mortality (OR = 0.87; 95 % CI 0.55-1.37, p = 0.5). Moreover, the sensitivity analysis revealed very similar results (OR = 0.91; 95 % CI 0.58-1.44, p = 0.7). A separate analysis of patients under mechanical ventilation yielded similar results (OR = 0.77; 95 % CI 0.44-1.35, p = 0.4). CONCLUSION: Our results suggest that macrolide-based treatment was not associated with improved survival in critically ill H1N1 patients with primary viral pneumonia.