Evaluation of S201086/GLPG1972, an ADAMTS-5 inhibitor, for the treatment of knee osteoarthritis in ROCCELLA: a phase 2 randomized clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of the anti-catabolic ADAMTS-5 inhibitor S201086/GLPG1972 for the treatment of symptomatic knee osteoarthritis. DESIGN: ROCCELLA (NCT03595618) was a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 trial in adults (aged 40-75 years) with knee osteoarthritis. Participants had moderate-to-severe pain in the target knee, Kellgren-Lawrence grade 2 or 3 and Osteoarthritis Research Society International joint space narrowing (grade 1 or 2). Participants were randomized 1:1:1:1 to once-daily oral S201086/GLPG1972 75, 150 or 300 mg, or placebo for 52 weeks. The primary endpoint was change from baseline to week 52 in central medial femorotibial compartment (cMFTC) cartilage thickness assessed quantitatively by magnetic resonance imaging. Secondary endpoints included change from baseline to week 52 in radiographic joint space width, Western Ontario and McMaster Universities Osteoarthritis Index total and subscores, and pain (visual analogue scale). Treatment-emergent adverse events (TEAEs) were also recorded. RESULTS: Overall, 932 participants were enrolled. No significant differences in cMFTC cartilage loss were observed between placebo and S201086/GLPG1972 therapeutic groups: placebo vs 75 mg, P = 0.165; vs 150 mg, P = 0.939; vs 300 mg, P = 0.682. No significant differences in any of the secondary endpoints were observed between placebo and treatment groups. Similar proportions of participants across treatment groups experienced TEAEs. CONCLUSIONS: Despite enrolment of participants who experienced substantial cartilage loss over 52 weeks, during the same time period, S201086/GLPG1972 did not significantly reduce rates of cartilage loss or modify symptoms in adults with symptomatic knee osteoarthritis.

High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson's disease patients.

C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the Freezing of Gait Questionnaire (FOG-Q). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 ± 9.5 years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 ± 6.1 years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 ± 0.52 vs 0.16 ± 0.21 vs 0.21 ± 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105-17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113-7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005-1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.

The ROSAS Cohort: A Prospective, Longitudinal Study of Biomarkers for Alzheimer's Disease. Strategy, Methods and Initial Results.

OBJECTIVE: The aims of the Research Of biomarkers in Alzheimer's diseaSe (ROSAS) study were to determine the biofluid and imaging biomarkers permitting an early diagnosis of Alzheimer's disease and better characterisation of cognitive and behavioural course of the pathology. This paper outlines the overall strategy, methodology of the study, baseline characteristics of the population and first longitudinal results from the ROSAS cohort. METHODS: Longitudinal prospective monocentric observational study performed at the Alzheimer's disease Research centre in Toulouse. A total of 387 patients were studied and analyzed in 3 groups: 184 patients with dementia of Alzheimer's type, 96 patients with memory disorders without dementia (Mild Cognitive Impairment) and 107 patients without abnormal memory tests (control group), and were followed up during 4 years. Patient's sociodemographic characteristics, risk factors, medical conditions, previous and current medications, neuropsychological assessment and overall cognitive status were recorded. Blood and urine samples were collected at every year, Magnetic Resonance Imaging were performed at inclusion, after one year of follow-up and at the end of the study. RESULTS: At baseline, three different groups of the cohort differed interestingly in age, level of education, and in percentage of ApoEε4 carriers whereas the history of cardiovascular and endocrine pathologies were similar among the groups. During the follow-up period (3-4 years) 42 mild cognitive impairment patients (43.8%) progressed to dementia, 7 controls progressed into mild cognitive impairment and 1 patient in the control group converted from mild cognitive impairment group to dementia of Alzheimer's type group. During the first year of follow up, the incidence of progression from mild cognitive impairment to dementia of Alzheimer's type was 12.7 per 100, during the second year 33.9 per 100 and 46.7 per 100 for the third year. CONCLUSION: This paper presents the baseline characteristics of the unique French prospective monocenter study in which the natural course of dementia of Alzheimer's type was evaluated. Future analysis of blood and urine samples collection from the ROSAS study will permit to identify possible biofluid biomarkers predicting the early stages of the dementia of Alzheimer's type and risk of progression from Mild Cognitive Impairment to Alzheimer's disease.

Candidate-gene association study searching for genetic factors involved in migraine chronification.

INTRODUCTION: Chronic migraine (CM) is at the severe end of the clinical migraine spectrum, but its genetic background is unknown. Our study searched for evidence that genetic factors are involved in the chronification process. METHODS: We initially selected 144 single-nucleotide polymorphisms (SNPs) from 48 candidate genes, which we tested for association in two stages: The first stage encompassed 262 CM patients, the second investigated 226 patients with high-frequency migraine (HFM). Subsequently, SNPs with p values < 0.05 were forwarded to the replication stage containing 531 patients with CM or HFM. RESULTS: Eight SNPs were significantly associated with CM and HFM in the two-stage phase. None survived replication in the third stage. DISCUSSION: We present the first comprehensive genetic association study for migraine chronification. There were no significant findings. Future studies may benefit from larger, genome-wide data sets or should use other genetic approaches to identify genetic factors involved in migraine chronification.

Relationship between volume and survival in closed intensive care units is weak and apparent only in mechanically ventilated patients.

BACKGROUND: Recent studies have found an association between increased volume and increased intensive care unit (ICU) survival; however, this association might not hold true in ICUs with permanent intensivist coverage. Our objective was to determine whether ICU volume correlates with survival in the Spanish healthcare system. METHODS: Post hoc analysis of a prospective study of all patients admitted to 29 ICUs during 3 months. At ICU discharge, the authors recorded demographic variables, severity score, and specific ICU treatments. Follow-up variables included ICU readmission and hospital mortality. Statistics include logistic multivariate analyses for hospital mortality according to quartiles of volume of patients. RESULTS: The authors studied 4,001 patients with a mean predicted risk of death of 23% (range at hospital level: 14-46%). Observed hospital mortality was 19% (range at hospital level: 11-35%), resulting in a standardized mortality ratio of 0.81 (range: 0.5-1.3). Among the 1,923 patients needing mechanical ventilation, the predicted risk of death was 32% (14-60%) and observed hospital mortality was 30% (12-61%), resulting in a standardized mortality ratio of 0.96 (0.5-1.7). The authors found no correlation between standardized mortality ratio and ICU volume in the entire population or in mechanically ventilated patients. Only mechanically ventilated patients in very low-volume ICUs had slightly worse outcome. CONCLUSION: In the currently studied healthcare system characterized by 24/7 intensivist coverage, the authors found wide variability in outcome among ICUs even after adjusting for severity of illness but no relationship between ICU volume and outcome. Only mechanically ventilated patients in very low-volume centers had slightly worse outcomes.

Prevalencia y factores asociados al consumo de tabaco en alumnos de enseñanza secundaria de Cataluña / Cigarette smoking prevalence and associated factors in secondary school children in Catalunya

Objetivos: Analizar aquellos factores asociados al consumo de tabaco en adolescentes para plantear futuras intervenciones de promoción de la salud desarrolladas por las escuelas y centros de atención primaria. Diseño: Estudio transversal, muestreo por conglomerados bietápico. Emplazamiento: Se incluyeron 97 centros escolares de Cataluña, 2005-2006. Participantes: Se obtuvieron 9.340 cuestionarios completos de estudiantes entre 14-16 años. Mediciones principales: Encuesta autoadministrada que recogía variables sociodemográficas, académicas, estado de salud, familiares, relaciones sexuales, sustancias adictivas, estados de ánimo y variables de opinión sobre el consumo. Se analizó la asociación de estas variables con la variable dependiente fumador/no fumador y también fueron analizadas como factores que aumentaban la probabilidad de ser fumador mediante modelos multinivel. Resultados: Se incluyeron 4.653 chicos y 4.687 chicas, con una edad media de 15,2 años. El 71,1% de los estudiantes eran no fumadores, el 75% de los chicos y el 67,3% de las chicas. Aumentaban la probabilidad de ser fumador (OR e IC 95%): ser chica 0,60 (0,53-0,68), cursar 4.o ESO 1,27 (1,12-1,43), tener un rendimiento escolar bajo 3,38 (2,74-4,17), tener una autopercepción de salud regular/mala 2,81 (2,21-3,58), tener padres fumadores 1,68 (1,45-1,95), consumir alcohol 5,05 (4,35-5,86), tener 3 o más problemas de estado de ánimo 1,22 (1,05-1,41), vivir sin ningún progenitor 1,59 (1,07-2,38), estar de acuerdo en que exista publicidad sobre tabaco 1,64 (1,45-1,85), y opinar que el tabaco ayuda a relajarse 3,57 (3,23-4,17). Conclusiones: Aunque la mayoría de los estudiantes eran no fumadores, el consumo de tabaco era más prevalente en las chicas. Factores sociodemográficos, socioculturales, del entorno y opinión se asociaban con el consumo de tabaco entre los jóvenes (AU)

Objective: The aim of this study was to analyze those factors associated with cigarette smoking in adolescent school children, in order to plan future school interventions for promoting good health strategies developed by the schools and Primary Health Care professionals. Design: Cross-sectional study with a two-stage cluster sampling. Setting: The study included 97 schools, and was carried out in 2005-06 in Catalonia (Spain). Participants: 14-16 year-old secondary school children. Main measures: The survey was based on a self-administered paper-based questionnaire that collected sociodemographic variables, academic level, health status, family variables, sexual relations, addictive substances, mood state, and variables related to opinions on cigarette smoking The association between these variables and smoker/non-smoker variable was analyzed, as well as factors that could increase the probability of becoming a smoker using multilevel models. Results: A total of 9340 completed questionnaires, including 4653 from males, were received from the pupils, with a mean age of 15.2 years. The results showed that 71.1% of pupils were non-smokers, 75% of whom were males and 67.3% of females. The following factors increased the probability of becoming a smoker (OR and 95%CI): being a female 0.60 (0.53-0.68), being in the 4th year 1.27 (1.12-1.43), low academic performance 3.38 (2.74-4.17), self-reported regular/poor health status 2.81 (2.21-3.58), smoking parents 1.68 (1.45-1.95), alcohol consumption 5.05 (4.35-5.86), having 3 or more problems of mood state 1.22 (1.05-1.41), living without parents 1.59 (1.07-2.38), agreeing with tobacco industry advertising 1.64 (1.45-1.85) and believing that tobacco acts as a relaxant 3.57 (3.23-4.17) (AU)

Conclusions: Although the majority of pupils were non-smokers, smoking was more prevalent among females. The factors associated with cigarette smoking in the adolescents included sociodemographic, sociocultural, and personal environmental factors, as well as their opinions on the habit (AU)

Quality control of the surveillance programme of ICU-acquired infection (ENVIN-HELICS registry) in Spain.

BACKGROUND: Data validation is an essential aspect for the accuracy of a nosocomial infection surveillance registry. AIM: To report the results of the first quality control programme in the national surveillance programme of intensive care unit (ICU)-acquired infection in Spain (ENVIN-HELICS registry). METHOD: During 2008, of 13,824 records included in the database, 1500 (10.8%) registries from 20 ICUs were reviewed. These ICUs were selected at random and stratified according to the number of cases included in the registry. The proportion of infected patients, which was 9.6% [95% confidence interval (CI) 8.09-11.16], was maintained during the selection of cases for review. Two physicians were trained for the purpose of the study and undertook the review. RESULTS: Overall sensitivity, specificity and positive and negative predictive values of the ENVIN-HELICS registry for the identification of patients with any device-related infection acquired during their ICU stay were 86.0% (95% CI 80.0-92.0), 98.7% (95% CI 82.19-93.6), 87.9% (95% CI 82.19-93.6) and 98.5% (95% CI 97.8-99.2), respectively, with a kappa index of 0.85 (95% CI 0.79-0.92). Secondary bloodstream infection had the lowest sensitivity (59.3%), and intubation-associated pneumonia had the highest sensitivity (86.3%). CONCLUSION: There was good correlation between data reported by the registrars and data validated by auditors, confirming the reliability of the ENVIN-HELICS registry.

Morbidity and mortality associated with primary and catheter-related bloodstream infections in critically ill patients.

PURPOSE: To analyze the impact of primary and catheterrelated bloodstream infections (PBSI/CRBSI) on morbidity and mortality. METHODS: A matched case-control study (1:4) was carried out on a Spanish epidemiological database of critically ill patients (ENVIN-HELICS). To determine the risk of death in patients with PBSI/CRBSI a matched Cox proportional hazard regression analysis was performed. RESULTS: Out of the 74,585 registered patients, those with at least one episode of monomicrobial PBSI/CRBSI were selected and paired with patients without PBSI/CRBSI for demographic and diagnostic criteria and seriousness of their condition on admission to the Intensive Care Unit (ICU). for mortality analysis, 1,879 patients with PBSI/CRBSI were paired with 7,516 controls. The crude death rate in the ICU was 28.1% among the cases and 18.7% among the controls. Attributable mortality 9.4% (HR:1.20; 95% confidence interval: 1.07-1.34; p<0.001). Risk of death varied according to the source of infection, aetiology, moment of onset of bloodstream infection and severity on admission to the ICU. The median stay in the ICU of patients who survived PBSI/CRBSI was 13 days longer than the controls, also varying according to aetiology, moment of onset of bloodstream infection and severity on admission. CONCLUSIONS: Acquisition of PBSI/CRBSI in critically ill patients significantly increases mortality and length of ICU stay, which justifies prevention efforts.

Morbidity and mortality associated with primary and catheter-related bloodstream infections in critically ill patients

Objetivos. El propósito de este estudio es analizar el impacto de la bacteriemia primaria y relacionada con catéter (BP/ BRC) en la morbilidad y mortalidad. Métodos. Con datos pertenecientes a la base de datos epidemiológica de pacientes críticos en España ENVIN-HELICS, se realiza un estudio casos controles (1:4). Para analizar el riesgo de muerte en pacientes con BP/BRC se realiza un estudio emparejado de riesgos proporcionales de Cox. Resultados. De 74.585 pacientes registrados, se buscó pacientes con al menos un episodio de BP/BRC monomicrobiana y fueron emparejados con pacientes sin BP/BRC por criterios demográficos, diagnósticos y de gravedad al ingreso en la Unidad de Cuidados Intensivos (UCI). Para el análisis de mortalidad 1.879 pacientes con BP/BRC fueron emparejados con 7.516 controles. La mortalidad cruda en UCI fue del 28,1 % en los casos y 18,7 % en los controles. Mortalidad atribuida 9,4 %. (HR:1,20; intervalo confianza 95 %: 1,07 - 1,34; p<0,001). El riesgo de muerte varía de acuerdo a la fuente de la infección, la etiología, el momento de aparición de la bacteriemia y la gravedad al ingreso en UCI. Los pacientes que sobreviven y sufren una BP/BRC tienen una estancia en UCI 13 días de mediana más prolongada que los controles, variando también según la etiología, el momento de aparición de la bacteriemia y la gravedad al ingreso en UCI. Conclusiones. En pacientes críticos, la adquisición de una BP/BRC produce un significativo incremento de la mortalidad y la estancia, lo que justifica los esfuerzos de prevención(AU)

Purpose. To analyze the impact of primary and catheterrelated bloodstream infections (PBSI/CRBSI) on morbidity and mortality. Methods. A matched case-control study (1:4) was carried out on a Spanish epidemiological database of critically ill patients (ENVIN-HELICS). To determine the risk of death in patients with PBSI/CRBSI a matched Cox proportional hazard regression analysis was performed. Results. Out of the 74,585 registered patients, those with at least one episode of monomicrobial PBSI/CRBSI were selected and paired with patients without PBSI/CRBSI for demographic and diagnostic criteria and seriousness of their condition on admission to the Intensive Care Unit (ICU). For mortality analysis, 1,879 patients with PBSI/CRBSI were paired with 7,516 controls. The crude death rate in the ICU was 28.1% among the cases and 18.7% among the controls. Attributable mortality 9.4% (HR:1.20; 95% confidence interval: 1.07-1.34; p<0.001). Risk of death varied according to the source of infection, aetiology, moment of onset of bloodstream infection and severity on admission to the ICU. The median stay in the ICU of patients who survived PBSI/CRBSI was 13 days longer than the controls, also varying according to aetiology, moment of onset of bloodstream infection and severity on admission. Conclusions. Acquisition of PBSI/CRBSI in critically ill patients significantly increases mortality and length of ICU stay, which justifies prevention efforts(AU)

[Cigarette smoking prevalence and associated factors in secondary school children in Catalunya]. / Prevalencia y factores asociados al consumo de tabaco en alumnos de enseñanza secundaria de Cataluña.

OBJECTIVE: The aim of this study was to analyze those factors associated with cigarette smoking in adolescent school children, in order to plan future school interventions for promoting good health strategies developed by the schools and Primary Health Care professionals. DESIGN: Cross-sectional study with a two-stage cluster sampling. SETTING: The study included 97 schools, and was carried out in 2005-06 in Catalonia (Spain). PARTICIPANTS: 14-16 year-old secondary school children. MAIN MEASURES: The survey was based on a self-administered paper-based questionnaire that collected sociodemographic variables, academic level, health status, family variables, sexual relations, addictive substances, mood state, and variables related to opinions on cigarette smoking The association between these variables and smoker/non-smoker variable was analyzed, as well as factors that could increase the probability of becoming a smoker using multilevel models. RESULTS: A total of 9340 completed questionnaires, including 4653 from males, were received from the pupils, with a mean age of 15.2 years. The results showed that 71.1% of pupils were non-smokers, 75% of whom were males and 67.3% of females. The following factors increased the probability of becoming a smoker (OR and 95%CI): being a female 0.60 (0.53-0.68), being in the 4(th) year 1.27 (1.12-1.43), low academic performance 3.38 (2.74-4.17), self-reported regular/poor health status 2.81 (2.21-3.58), smoking parents 1.68 (1.45-1.95), alcohol consumption 5.05 (4.35-5.86), having 3 or more problems of mood state 1.22 (1.05-1.41), living without parents 1.59 (1.07-2.38), agreeing with tobacco industry advertising 1.64 (1.45-1.85) and believing that tobacco acts as a relaxant 3.57 (3.23-4.17). CONCLUSIONS: Although the majority of pupils were non-smokers, smoking was more prevalent among females. The factors associated with cigarette smoking in the adolescents included sociodemographic, sociocultural, and personal environmental factors, as well as their opinions on the habit.

Gender differences in negative mood states in secondary school students: health survey in Catalonia (Spain)

Objective: To determine the prevalence of negative mood states in adolescents according to gender, toanalyze variability among schools, and to evaluate the associated factors.Methods: A cross-sectional study with a cluster design was carried out. We administered the High-schoolstudents health survey to a sample of 9,340 students (aged 14-16 years) in the third and fourth year ofCompulsory Secondary Education in Catalonia, Spain, during the 2005-6 academic year. The main outcome measure was evidence of a negative mood state. A multilevel logistic regression model stratified bygender was used to identify the factors associated with negative mood states and to determine variabilityamong distinct schools.Results: Approximately 19% of adolescents reported evidence of a negative mood state, with a higherprevalence in girls (25%). The most significant factors associated with negative mood states were “useof tranquilizers” and “having eating disorders” in girls and “not exercising” and “poor self-perception ofhealth status” in boys. In both genders, variability was found among schools in the prevalence of negativemood states (girls: variance = 0.078; p <0.001; boys: variance = 0.079; p = 0.012).Conclusions: The prevalence of negative mood states in adolescent boys and girls was high. Differenceswere observed between genders in the factors related to these health states. The variability observedin the prevalence of negative mood states among distinct schools could not be explained by the studyvariables. Our results emphasize the association between the use of tranquilizers and negative moodstates (AU)

Objetivos: Determinar la prevalencia del estado de ánimo negativo entre alumnos adolescentes segúnsexo, analizar la variabilidad entre escuelas y evaluar los factores asociados.Métodos: Estudio transversal basado en un muestreo por conglomerados bietápico. Administramos unaencuesta de salud a 9340 estudiantes de tercero y cuarto curso de Educación Secundaria Obligatoriade 14 a 16 anos de edad, en Catalu ˜ na, durante el curso escolar 2005-06. La variable principal fue el ˜estado de ánimo negativo. Se usó un modelo de regresión logística multinivel estratificado por sexopara identificar los factores asociados al estado de ánimo negativo y determinar la variabilidad entre lasdiferentes escuelas.Resultados: Aproximadamente el 19% de los adolescentes refirieron un estado de ánimo negativo, siendomás prevalente entre las chicas (25%). En ellas, los factores asociados significativamente con estadosde ánimo negativo fueron «tomar tranquilizantes» y tener trastornos alimentarios, mientras que en loschicos fueron no realizar deporte y tener una mala percepción de su estado de salud. Hay variabilidad enla prevalencia del estado de ánimo negativo según las escuelas en ambos sexos (chicas: varianza = 0,078,p <0,001; chicos: varianza = 0,079, p = 0,012).Conclusiones: La prevalencia del estado de ánimo negativo entre los adolescentes fue alta. Se observarondiferencias entre sexos respecto a los factores relacionados con este estado de salud. Destacó la asociacióndel uso de tranquilizantes con el estado de ánimo negativo. Se observó una variabilidad de la prevalenciadel estado de ánimo negativo entre las diferentes escuelas no explicada por las variables de estudio (AU)

Urethral catheter-related urinary infection in critical patients admitted to the ICU. Descriptive data of the ENVIN-UCI study.

OBJECTIVE: To describe trends in national catheter-related urinary tract infection (CRUTI) rates, as well as etiologies and multiresistance markers. DESIGN: An observational, prospective, multicenter voluntary participation study was conducted from 1 April to 30 June in the period between 2005 and 2010. SETTING: Intensive Care Units (ICUs) that participated in the ENVIN-ICU registry during the study period. PATIENTS: We included all patients admitted to the participating ICUs and patients with urinary catheter placement for more than 24 hours (78,863 patients). INTERVENTION: Patient monitoring was continued until discharge from the ICU or up to 60 days. VARIABLES OF INTEREST: CRUTIs were defined according to the CDC system, and frequency is expressed as incidence density (ID) in relation to the number of urinary catheter-patients days. RESULTS: A total of 2329 patients (2.95%) developed one or more CRUTI. The ID decreased from 6.69 to 4.18 episodes per 1000 days of urinary catheter between 2005 and 2010 (p<0.001). In relation to the underlying etiology, gramnegative bacilli predominated (55.6 to 61.6%), followed by fungi (18.7 to 25.2%) and grampositive cocci (17.1 to 25.9%). In 2010, ciprofloxacin-resistant E. coli strains (37.1%) increased, as well as imipenem-resistant (36.4%) and ciprofloxacin-resistant (37.1%) strains of P. aeruginosa. CONCLUSIONS: A decrease was observed in CRUTI rates, maintaining the same etiological distribution and showing increased resistances in gramnegative pathogens, especially E. coli and P. aeruginosa.

Evolución del consumo de antifúngicos en pacientes críticos. Estudio multicéntrico observacional, 2006-2010 / Trends in systemic antifungal use in critically ill patients. Multicenter observational study, 2006-2010

Hay poca información sobre el consumo de antifúngicos (AF) en pacientes críticos y las variaciones temporales desde la introducción de nuevos AF. Este consumo puede tener influencia en la aparición de resistencias. Métodos Estudio observacional prospectivo del consumo de AF sistémicos en pacientes ingresados en unidades de cuidados intensivos (UCI) españolas del registro ENVIN-HELICS durante los años 2006 a 2010. Se compara la utilización anual, el consumo según prescripciones y para infecciones intra-UCI, el calculado por tamaño de hospital y por 1.000 días de estancia. Resultados De 8.240 prescripciones de AF registradas, los AF más frecuentemente empleados fueron el fluconazol y la caspofungina (55 y 19,5%, respectivamente). Existió un incremento del consumo hasta el año 2008 y una estabilización posterior. Anualmente, se comprobó la disminución del uso de fluconazol y el crecimiento del consumo de equinocandinas. Predominó la utilización de fluconazol en hospitales de tamaño mediano con respecto a hospitales grandes (60,4% versus 53,3%; p=0,036), y lo contrario con respecto a la utilización de caspofungina (15,8% versus 21,8%; p<0,001). El fluconazol se empleó más precozmente (mediana desde el ingreso en UCI: 12 días) y durante un tiempo similar a otros AF (mediana: 8 días). El total de días de tratamiento fue de 39,51 días por 1.000 estancias, con predominio de fluconazol (21,48 días por 1.000 estancias).Conclusiones El fluconazol es el AF más utilizado en pacientes críticos en cualquiera de las indicaciones, aunque se constata un progresivo descenso en su consumo y un incremento proporcional del empleo de equinocandinas (AU)

Introduction: There are limited data about the use of antifungal agents (AF) in critically ill patients and treatment trends since the inclusion of the new generation AF. The use of these agents may have a significant influence on the development of new resistances. Methods: Observational prospective study of the systemic use of AF in patients admitted to Spanish intensive care units (ICU) participating in the ENVIN-HELICS register, from 2006 to 2010. The annual use, the indications that led to that use and, the intra-ICU infections, the AF employment related to the hospital size, and per 1000 patients/day, were compared. Results: Of the 8240 prescriptions for AF, fluconazole and caspofungin were the most often employed (55%and 19.5%, respectively). An increase in use was observed to the year 2008, with subsequent stabilisation. A decrease in the use of fluconazole and an increase in echinocandins consumption was observed overtime. As regards the intra-ICU infections, the AF were ordered empirically in 47.9% of the indications. Fluconazole was more frequently used in medium size hospitals than in the large ones (60.4% versus 53.3%;P = .036) and the opposite occurred in the case of caspofungin (15.8% versus 21.8%; P < .001). Fluconazole was more prematurely employed (median 12 days since ICU admission) and the duration of the therapy was similar to the other AF (median 8 days). The total therapy days were 39.51 per 1000 patient/day, with predominance in fluconazole use (21.48 per 1000 patients/day).Conclusions: Fluconazole is the most used antifungal agent in critically ill patients in any of the indications, although a progressive decrease in its use is observed, with a proportional increase in the use of echinocandins (AU)

[Trends in systemic antifungal use in critically ill patients. Multicenter observational study, 2006-2010]. / Evolución del consumo de antifúngicos en pacientes críticos. Estudio multicéntrico observacional, 2006-2010.

INTRODUCTION: There are limited data about the use of antifungal agents (AF) in critically ill patients and treatment trends since the inclusion of the new generation AF. The use of these agents may have a significant influence on the development of new resistances. METHODS: Observational prospective study of the systemic use of AF in patients admitted to Spanish intensive care units (ICU) participating in the ENVIN-HELICS register, from 2006 to 2010. The annual use, the indications that led to that use and, the intra-ICU infections, the AF employment related to the hospital size, and per 1000 patients/day, were compared. RESULTS: Of the 8240 prescriptions for AF, fluconazole and caspofungin were the most often employed (55% and 19.5%, respectively). An increase in use was observed to the year 2008, with subsequent stabilisation. A decrease in the use of fluconazole and an increase in echinocandins consumption was observed over time. As regards the intra-ICU infections, the AF were ordered empirically in 47.9% of the indications. Fluconazole was more frequently used in medium size hospitals than in the large ones (60.4% versus 53.3%; P=.036) and the opposite occurred in the case of caspofungin (15.8% versus 21.8%; P<.001). Fluconazole was more prematurely employed (median 12 days since ICU admission) and the duration of the therapy was similar to the other AF (median 8 days). The total therapy days were 39.51 per 1000 patient/day, with predominance in fluconazole use (21.48 per 1000 patients/day). CONCLUSIONS: Fluconazole is the most used antifungal agent in critically ill patients in any of the indications, although a progressive decrease in its use is observed, with a proportional increase in the use of echinocandins.

[Recommendations of the Infectious Diseases Work Group (GTEI) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) and the Infections in Critically Ill Patients Study Group (GEIPC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) for the diagnosis and treatment of influenza A/H1N1 in seriously ill adults admitted to the Intensive Care Unit]. / Recomendaciones del Grupo de Trabajo Enfermedades Infecciosas (GTEI) de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) y el Grupo de Estudio de Infecciones en el Paciente Crítico (GEIPC) de la Sociedad Española de Enfermedades Infecciosas y Microbiología clínica (SEIMC) para el diagnóstico y tratamiento de la gripe A/H1N1 en pacientes adultos graves hospitalizados en las Unidades de Cuidados Intensivos.

The diagnosis of influenza A/H1N1 is mainly clinical, particularly during peak or seasonal flu outbreaks. A diagnostic test should be performed in all patients with fever and flu symptoms that require hospitalization. The respiratory sample (nasal or pharyngeal exudate or deeper sample in intubated patients) should be obtained as soon as possible, with the immediate start of empirical antiviral treatment. Molecular methods based on nucleic acid amplification techniques (RT-PCR) are the gold standard for the diagnosis of influenza A/H1N1. Immunochromatographic methods have low sensitivity; a negative result therefore does not rule out active infection. Classical culture is slow and has low sensitivity. Direct immunofluorescence offers a sensitivity of 90%, but requires a sample of high quality. Indirect methods for detecting antibodies are only of epidemiological interest. Patients with A/H1N1 flu may have relative leukopenia and elevated serum levels of LDH, CPK and CRP, but none of these variables are independently associated to the prognosis. However, plasma LDH> 1500 IU/L, and the presence of thrombocytopenia <150 x 10(9)/L, could define a patient population at risk of suffering serious complications. Antiviral administration (oseltamivir) should start early (<48 h from the onset of symptoms), with a dose of 75 mg every 12h, and with a duration of at least 7 days or until clinical improvement is observed. Early antiviral administration is associated to improved survival in critically ill patients. New antiviral drugs, especially those formulated for intravenous administration, may be the best choice in future epidemics. Patients with a high suspicion of influenza A/H1N1 infection must continue with antiviral treatment, regardless of the negative results of initial tests, unless an alternative diagnosis can be established or clinical criteria suggest a low probability of influenza. In patients with influenza A/H1N1 pneumonia, empirical antibiotic therapy should be provided due to the possibility of bacterial coinfection. A beta-lactam plus a macrolide should be administered as soon as possible. The microbiological findings and clinical or laboratory test variables may decide withdrawal or not of antibiotic treatment. Pneumococcal vaccination is recommended as a preventive measure in the population at risk of suffering severe complications. Although the use of moderate- or low-dose corticosteroids has been proposed for the treatment of influenza A/H1N1 pneumonia, the existing scientific evidence is not sufficient to recommend the use of corticosteroids in these patients. The treatment of acute respiratory distress syndrome in patients with influenza A/H1N1 must be based on the use of a protective ventilatory strategy (tidal volume <10 ml / kg and plateau pressure <35 mmHg) and positive end-expiratory pressure set to high patient lung mechanics, combined with the use of prone ventilation, muscle relaxation and recruitment maneuvers. Noninvasive mechanical ventilation cannot be considered a technique of choice in patients with acute respiratory distress syndrome, though it may be useful in experienced centers and in cases of respiratory failure associated with chronic obstructive pulmonary disease exacerbation or heart failure. Extracorporeal membrane oxygenation is a rescue technique in refractory acute respiratory distress syndrome due to influenza A/H1N1 infection. The scientific evidence is weak, however, and extracorporeal membrane oxygenation is not the technique of choice. Extracorporeal membrane oxygenation will be advisable if all other options have failed to improve oxygenation. The centralization of extracorporeal membrane oxygenation in referral hospitals is recommended. Clinical findings show 50-60% survival rates in patients treated with this technique. Cardiovascular complications of influenza A/H1N1 are common. Such problems may appear due to the deterioration of pre-existing cardiomyopathy, myocarditis, ischemic heart disease and right ventricular dysfunction. Early diagnosis and adequate monitoring allow the start of effective treatment, and in severe cases help decide the use of circulatory support systems. Influenza vaccination is recommended for all patients at risk. This indication in turn could be extended to all subjects over 6 months of age, unless contraindicated. Children should receive two doses (one per month). Immunocompromised patients and the population at risk should receive one dose and another dose annually. The frequency of adverse effects of the vaccine against A/H1N1 flu is similar to that of seasonal flu. Chemoprophylaxis must always be considered a supplement to vaccination, and is indicated in people at high risk of complications, as well in healthcare personnel who have been exposed.

[Role of paediatrics in primary care and coordination with specialist care]. / Papel del pediatra de atención primaria y coordinación con atención especializada.

OBJECTIVES: Primary care (PC) paediatricians are trained mainly in the hospital setting, with little contact with PC. This study aimed to find out what perceptions and experiences they have on the attributes of PC (first contact, comprehensiveness and continuity of care) that are assumed and performed by PC paediatricians. MATERIAL AND METHODS: A qualitative study was performed based on focus groups and semi-structured individual interviews with paediatricians with pre-defined sociodemographic and speciality training characteristics. Two focus groups (5 and 4 people each) and 5 interviews were made. Participants responded to two questions: how would you explain your function as a primary care paediatrician? and what is your opinion on the relationship between primary care paediatricians and the specialists to whom your patients are referred? The conversations of the groups and interviews were recorded and transcribed, and a content analysis was performed. RESULTS: Paediatricians assume that PC must be comprehensive, and take into account the context of the child. Paediatricians declare a lack in their training and poor social and institutional recognition. Coordination with specialists and the transfer of information are not satisfactory. Helpful factors are personal knowledge, the shared training and the face-to-face clinical sessions. CONCLUSION: Despite their hospital-based training, paediatricians assume the attributes of PC. Difficulties in performing their function include poor adaptation of their training to PC, and little institutional and social recognition. Coordination with specialists is not satisfactory. Approaching these difficulties can help maintaining a high quality level in the care of the paediatric population.

Multirresistencia antibiótica en unidades de críticos / Antibiotic multiresistance in critical care units

La presencia de microorganismos con resistencia adquirida a múltiples antibióticos complica el manejo y la evolución de los pacientes críticos. El intensivista, en su actividad diaria, se enfrenta a este problema desde la responsabilidad de la prevención y control y desde el reto de prescribir el tratamiento antibiótico apropiado ante una posible infección. Se realiza una revisión de la bibliografía en lo concerniente a definición, conceptos importantes relacionados con la transmisión, recomendaciones sobre medidas generales de control en las unidades y opciones de tratamiento. Además se presentan datos epidemiológicos sobre la situación en nuestro país obtenidos, fundamentalmente, a través del ENVIN-UCI. El abordaje de la multirresistencia antibiótica requiere formación adecuada, trabajo en equipo con otros profesionales y conocimiento de la epidemiología local (AU)

The presence of microorganisms with acquired resistance to multiple antibiotics complicates the management and outcome of critically ill patients. The intensivist, in his/her daily activity, is responsible for the prevention and control of the multiresistance and the challenge of prescribing the appropriate treatment in case of an infection by these microorganisms. We have reviewed the literature regarding the definition, important concepts related to transmission, recommendations on general measures of control in the units and treatment options. We also present data on the situation in our country known primarily through the ENVIN-UCI register. Addressing the multiresistance not only requires training but also teamwork with other specialists and adaptation to the local environment (AU)

[Antibiotic multiresistance in critical care units]. / Multirresistencia antibiótica en unidades de críticos.

The presence of microorganisms with acquired resistance to multiple antibiotics complicates the management and outcome of critically ill patients. The intensivist, in his/her daily activity, is responsible for the prevention and control of the multiresistance and the challenge of prescribing the appropriate treatment in case of an infection by these microorganisms. We have reviewed the literature regarding the definition, important concepts related to transmission, recommendations on general measures of control in the units and treatment options. We also present data on the situation in our country known primarily through the ENVIN-UCI register. Addressing the multiresistance not only requires training but also teamwork with other specialists and adaptation to the local environment.

[Impact of primary and intravascular catheter-related bacteremia due to coagulase-negative staphylococci in critically ill patients]. / Impacto de la bacteriemia primaria y relacionada con catéter intravascular causada por Staphylococcus coagulasa negativo en pacientes críticos.

OBJECTIVE: To study the impact of coagulase-negative staphylococcal (CNS) primary and intravascular catheter-related bloodstream infection (PBSI/CRBSI) on mortality and morbidity in critically-ill patients. DESIGN: We performed a double analysis using data from the ENVIN-HELICS registry data (years 1997 to 2008): 1) We studied the clinical characteristics and outcomes of patients with CNS-induced PBSI/CRBSI and compared them with those of patients with PBSI/CRBSI caused by other pathogens; and 2) We analyzed the impact of CNS-induced PBSI/CRBSI using a case-control design (1:4) in patients without other nosocomial infections. SETTING: 167 Spanish Intensive Care Units. PATIENTS: Patients admitted to ICU for more than 24 hours. RESULTS: 2,252 patients developed PBSI/CRBSI, of which 1,133 were caused by CNS. The associated mortality for PBSI/CRBSI caused by non-CNS pathogens was higher than that of the CNS group (29.8% vs. 25.9%; P=.039) due exclusively to the mortality of patients with candidemia (mortality: 45.9%). In patients without other infections, PBSI/CRBSI caused by CNS (414 patients) is an independent risk factor for a higher than average length of ICU stay (OR: 5.81, 95% CI: 4.31-7.82; P<.001). CONCLUSION: Crude mortality of patients with CNS-induced BPSI/CRBSI is similar to that of patients with BPSI/CRBSI caused by other bacteria, but lower than that of patients with candidemia. Compared to patients without nosocomial infections, CNS-induced PBSI/CRBSI is associated with a significant increase in length of ICU stay.