Establishment of urinary exosome-like vesicles isolation protocol for FHHNC patients and evaluation of different exosomal RNA extraction methods.

BACKGROUND: Molecular and cellular pathophysiological events occurring in the majority of rare kidney diseases remain to be elucidated. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder caused by mutations in either CLDN16 or CLDN19 genes. This disease is characterized by massive urinary wasting of magnesium and calcium, osmosis deregulation and polyuria. Patients with p.G20D homozygous mutation in CLDN19 gene exhibit different progression to kidney failure suggesting that beyond the pathogenic mutation itself, other molecular events are favoring disease progression. Due to the fact that biopsy is not clinically indicated in these patients, urinary exosome-like vesicles (uEVs) can be envisioned as a valuable non-invasive source of information of events occurring in the kidney. Exosome research has increased notably to identify novel disease biomarkers but there is no consensus standardized protocols for uEVs isolation in patients with polyuria. For this reason, this work was aimed to evaluate and refine different uEVs isolation methods based on differential centrifugation, the gold standard method. RESULTS: Characterization by NTA, cryo-TEM and immunoblotting techniques identified the most appropriate protocol to obtain the highest yield and purest uEVs enriched fraction possible from urine control samples and FHHNC patients. Moreover, we tested five different RNA extraction methods and evaluated the miRNA expression pattern by qRT-PCR. CONCLUSIONS: In summary, we have standardized the conditions to proceed with the identification of differentially expressed miRNAs in uEVs of FHHNC patients, or other renal diseases characterized by polyuria.

Immune checkpoint inhibitor-related hypophysitis and endocrine dysfunction: clinical review.

Immune checkpoint inhibitors are a new and effective class of cancer therapy, with ipilimumab being the most established drug in this category. The drugs' mechanism of action includes promoting the effector T cell response to tumours and therefore increased autoimmunity is a predictable side effect. The endocrine effects of these drugs include hypophysitis and thyroid dysfunction, with rare reports of adrenalitis. The overall incidence of hypophysitis with these medications is up to 9%. Primary thyroid dysfunction occurs in up to 15% of patients, with adrenalitis reported in approximately 1%. The mean onset of endocrine side effects is 9 weeks after initiation (range 5-36 weeks). Investigation and/or screening for hypophysitis requires biochemical and radiological assessment. Hypopituitarism is treated with replacement doses of deficient hormones. Since the endocrine effects of immune checkpoint inhibitors are classed as toxic adverse events, most authors recommend both discontinuation of the immune checkpoint inhibiting medication and 'high-dose' glucocorticoid treatment. However, this has been challenged by some authors, particularly if the endocrine effects can be managed (e.g. pituitary hormone deficiency), and the therapy is proving effective as an anticancer agent. This review describes the mechanism of action of immune checkpoint inhibitors and details the key clinical endocrine-related consequences of this novel class of immunotherapies.

Characteristics and outcomes of patients admitted to Spanish ICU: A prospective observational study from the ENVIN-HELICS registry (2006-2011).

OBJECTIVE: To describe the case-mix of patients admitted to intensive care units (ICUs) in Spain during the period 2006-2011 and to assess changes in ICU mortality according to severity level. DESIGN: Secondary analysis of data obtained from the ENVN-HELICS registry. Observational prospective study. SETTING: Spanish ICU. PATIENTS: Patients admitted for over 24h. INTERVENTIONS: None. VARIABLES: Data for each of the participating hospitals and ICUs were recorded, as well as data that allowed to knowing the case-mix and the individual outcome of each patient. The study period was divided into two intervals, from 2006 to 2008 (period 1) and from 2009 to 2011 (period 2). Multilevel and multivariate models were used for the analysis of mortality and were performed in each stratum of severity level. RESULTS: The study population included 142,859 patients admitted to 188 adult ICUs. There was an increase in the mean age of the patients and in the percentage of patients >79 years (11.2% vs. 12.7%, P<0.001). Also, the mean APACHE II score increased from 14.35±8.29 to 14.72±8.43 (P<0.001). The crude overall intra-UCI mortality remained unchanged (11.4%) but adjusted mortality rate in patients with APACHE II score between 11 and 25 decreased modestly in recent years (12.3% vs. 11.6%, odds ratio=0.931, 95% CI 0.883-0.982; P=0.008). CONCLUSION: This study provides observational longitudinal data on case-mix of patients admitted to Spanish ICUs. A slight reduction in ICU mortality rate was observed among patients with intermediate severity level.

[Comparative analysis of patients admitted to Spanish Intensive Care Units due to medical and surgical disease]. / Análisis comparativo de pacientes ingresados en Unidades de Cuidados Intensivos españolas por causa médica y quirúrgica.

OBJECTIVE: To describe the characteristics of the patients case-mix admitted to ICUs due to medical and surgical disease, and to compare both groups. DESIGN: Analysis of data covering the period 2006-2011 in the ENVIN-HELICS registry. An observational, prospective, multicenter and voluntary participation study. SETTING: A total of 188 Spanish ICUs. PATIENTS: All patients admitted for more than 24 hours. MAIN VARIABLES: Demographic data, cause of admission, severity scores, length of stay, mortality. RESULTS: A total of 138,999 patients were analyzed. Of these, 65,467 (47.1%) were admitted due to a non-coronary medical cause, 27,785 (20,0%) due to coronary-related illness, 28,044 (20,2%) after elective surgery and 17,613 (12.7%) after urgent surgery. Use of devices, nosocomial infections and isolation of multirresistant organisms were more prevalent in urgent surgery patients. Longer length of stay (median 5 days; interquartile range 2-11) as well as higher severity scale values (APACHE II and SAPS II) corresponded to this same group of patients. Mortality was higher in non-coronay medical patients. On categorizing the patients according to the APACHE II score, mortality was seen to be higher in urgent surgery cases than in elective surgery patients in all groups. The largest difference was observed in the APACHE II score 6-10 group (3% vs. 0.9%) (OR: 2.14, 95% CI 1.825-2.513; p<0.001). CONCLUSIONS: The mortality rate is higher in non-coronary medical patients, though resource use per patient is greater in the urgent surgery cases. The APACHE II scale underestimates mortality in emergency surgery patients.

Quality indicators on the use of antimicrobials in critically ill patients.

Quality indicators have been applied to many areas of health care in recent years, including intensive care. However, they have not been specifically developed and validated for antimicrobial use in critically ill patients. Antimicrobials play a key role in intensive care units not only in the prognosis of each individual patient, but also in the development of resistance and changes in the flora in this setting. Evaluating the use of these agents is complex in the intensive care unit, however, because the indications vary greatly and antimicrobial treatment is often changed during admission. We designed and developed specific quality indicators regarding the use of antimicrobials in critically ill patients admitted to the intensive care unit. These indicators are proposed as a tool for application in intensive care units to detect problems in the use of antimicrobials. Future trials are needed, however, to validate these indicators in a large population over time.

Epidemiological study of Clostridium difficile infection in critical patients admitted to the Intensive Care Unit.

UNLABELLED: Data on the epidemiology of infections caused by Clostridium difficile (CDI) in critically ill patients are scarce and center on studies with a limited time framework and/or epidemic outbreaks. OBJECTIVE: To describe the characteristics and risk factors of critically ill patients admitted to the ICU with CDI, as well as the treatments used for the control of such infections. MATERIAL AND METHODS: A retrospective study was made of patients included in the ENVIN-ICU registry with CDI in 2012. Patients were followed up to 72 h after discharge from the ICU. A case report form was used to record the following data: demographic variables, risk factors related to CDI, treatment and outcome. Infections were classified as community-acquired, nosocomial out-ICU and nosocomial in-ICU, according to the day on which Clostridium difficile isolates were obtained. Infection rates as episodes per 10,000 days of ICU stay are presented. The global in-ICU and hospital mortality rates were calculated. RESULTS: Sixty-eight episodes of CDI in 33 out of a total of 173 ICUs participating in the registry were recorded (19.1%) (2.1 episodes per 10,000 days of ICU stay). Forty-five patients were men (66.2%), with a mean (SD) age of 63.4 (16.4) years, a mean APACHE II score on ICU admission of 19.9 (7.4), and an underlying medical condition in 44 (64.7%). Sixty-two patients (91.2%) presented more than 3 liquid depositions/day, 40 (58.8%) in association with severe sepsis or septic shock. Community-acquired infection occurred in 13 patients (19.1%), nosocomial out-ICU infection in 13 (19.1%), and in-ICU infection in 42 (61.8%). Risk factors included age>64 years in 39 cases (57.4%), previous hospital admission (3 months) in 32 (45.6%), use of antimicrobials (previous 7 days) in 57 (83.8%), enteral nutrition in 23 (33.8%), and the use of H2 inhibitors in 39 (57.4%). Initial combined treatment was administered to 18 patients (26.5%). Metronidazole was used in 60 (88.2%) and vancomycin in 31 (45.6%). The in-ICU mortality rate was 25.0% (n=17), with a hospital mortality 27.9% (n=19). CONCLUSIONS: The rate of ICD in ICU patients is low, the infection affects severely ill patients, and is associated with high mortality. The presence of CDI is a marker of poor prognosis.

Guidelines for the prevention of ventilator-associated pneumonia and their implementation. The Spanish "Zero-VAP" bundle.

BACKGROUND: "Zero-VAP" is a proposal for the implementation of a simultaneous multimodal intervention in Spanish intensive care units (ICU) consisting of a bundle of ventilator-associated pneumonia (VAP) prevention measures. METHODS/DESIGN: An initiative of the Spanish Societies of Intensive Care Medicine and of Intensive Care Nurses, the project is supported by the Spanish Ministry of Health, and participation is voluntary. In addition to guidelines for VAP prevention, the "Zero-VAP" Project incorporates an integral patient safety program and continuous online validation of the application of the bundle. For the latter, VAP episodes and participation indices are entered into the web-based Spanish ICU Infection Surveillance Program "ENVIN-HELICS" database, which provides continuous information about local, regional and national VAP incidence rates. Implementation of the guidelines aims at the reduction of VAP to less than 9 episodes per 1000 days of mechanical ventilation. A total of 35 preventive measures were initially selected. A task force of experts used the Grading of Recommendations, Assessment, Development and Evaluation Working Group methodology to generate a list of 7 basic "mandatory" recommendations (education and training in airway management, strict hand hygiene for airway management, cuff pressure control, oral hygiene with chlorhexidine, semi-recumbent positioning, promoting measures that safely avoid or reduce time on ventilator, and discouraging scheduled changes of ventilator circuits, humidifiers and endotracheal tubes) and 3 additional "highly recommended" measures (selective decontamination of the digestive tract, aspiration of subglottic secretions, and a short course of iv antibiotic). DISCUSSION: We present the Spanish VAP prevention guidelines and describe the methodology used for the selection and implementation of the recommendations and the organizational structure of the project. Compared to conventional guideline documents, the associated safety assurance program, the online data recording and compliance control systems, as well as the existence of a pre-defined objective are the distinct features of "Zero VAP".

Effects of dietary free fatty acid content and degree of fat saturation on tibia bone properties of laying hens.

Acid oils and fatty acid distillates are fat by-products of the refining process of edible oils and are characterized by their high proportion of free fatty acids (FFA). While lipids are essential in poultry diets, their chemical structure may interfere with calcium absorption. Therefore, this study investigated the effects of dietary FFA content and the degree of fat saturation on bone metabolism in commercial layers. For 15-wk, a total of 144 laying hens (19-wk-old) were randomly assigned to 8 treatments (6 replicates with 3 birds each), which were obtained by gradually replacing crude soybean oil (rich in unsaturated fatty acids [UFA]) with soybean acid oil (rich in UFA and FFA), or crude palm oil (rich in saturated fatty acids [SFA]) with palm fatty acid distillate (rich in SFA and FFA). Following a 2 × 4 factorial design, 4 UFA-rich and 4 SFA-rich diets were created with varying FFA content: 10, 20, 30, and 45%. Tibiae (6 birds/treatment) were collected at the end of the trial for the assessment of mineral composition, morphological properties, and mechanical characteristics. The data were analyzed using a 2-way ANOVA with the GLM procedure. Orthogonal polynomial contrasts were employed to determine the linear effect of increasing %FFA, with statistical significance set at P < 0.05. The degree of saturation was found to negatively impact on calcium and phosphorus bone content, with higher levels found in soybean-based diets (P < 0.001). A significant interaction was observed for medullary bone mineral content, showing a linear decrease as the dietary %FFA increased (P < 0.05) in palm diets. In contrast, morphological and mechanical bone traits, total ash content, and cortical bone mineral composition remained unaffected (P > 0.05). These results suggest that the degree of fat saturation exerts a greater impact than FFA content on bone mineral metabolism, supporting the commercial use of fat by-products rich in FFA in laying hen diets, at least during the early stages of the laying cycle.

Invasive device-related infections after heart surgery.

OBJECTIVE: To analyze postoperative infections in critically ill patients undergoing heart surgery. SETTING: Intensive care units (ICUs). DESIGN: An observational, prospective, multicenter study was carried out. PATIENTS: Patients in the postoperative period of heart surgery admitted to the ICU and included in the ENVIN-HELICS registry between 2005 and 2011. MAIN OUTCOME VARIABLES: Mechanical ventilation associated pneumonia (MVP), urinary catheter-related infection (UCI), primary bacteremia (PB), PB related to vascular catheters (PB-VC) and secondary bacteremia. RESULTS: Of a total of 97,692 patients included in the study, 9089 (9.3%) had undergone heart surgery. In 440 patients (4.8%), one or more infections were recorded. Infection rates were 9.94 episodes of MVP per 1000 days of mechanical ventilation, 3.4 episodes of UCI per 1000 days of urinary catheterization, 3.10 episodes of BP-VC per 1000 days of central venous catheter, and 1.84 episodes of secondary bacteremia per 1000 days of ICU stay. Statistically significant risk factors for infection were ICU stay (odds ratio [OR] 1.18, 95%CI 1.16-1.20), APACHE II upon admission to the ICU (OR 1.05, 95%CI 1.03-1.07), emergency surgery (OR 1.67, 95%CI 1.13-2.47), previous antibiotic treatment (OR 1.38, 95%CI 1.04-1.83), and previous colonization by Pseudomonas aeruginosa (OR 18.25, 95%CI 3.74-89.06) or extended spectrum beta-lactamase producing enterobacteria (OR 16.97, 95%CI 5.4-53.2). The overall ICU mortality rate was 4.1% (32.2% in patients who developed one or more infections and 2.9% in uninfected patients) (P < .001). CONCLUSIONS: Of the patients included in the ENVIN-HELICS registry, 9.3% were postoperative heart surgery patients. The overall mortality was low but increased significantly in patients who developed one or more infection episodes.

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.

Influence of free fatty acid content and degree of fat saturation in laying hen diets on egg quality, yolk fatty acid profile, and cholesterol content.

The aim of the present study was to evaluate the effect of dietary free fatty acid (FFA) content and the degree of saturation on egg quality, yolk fatty acid (FA) profile, and yolk cholesterol content. For a 15-wk period, a total of 144 laying hens (19-wk-old) were randomly assigned to 8 treatments arranged in a 2 × 4 factorial design, with 2 sources of crude oil (soybean oil and palm oil) and 4 levels of FFA (10, 20, 30, and 45%). The dietary treatments were achieved by progressively substituting the original oils with equivalent amounts of their corresponding acid oils (soybean acid oil and palm fatty acid distillate, respectively). No differences in ADFI or egg mass were found. However, dietary FFA reduced egg production (linear, P < 0.05) and increased the feed conversion ratio (linear, P < 0.05). Higher levels of FFA in soybean diets resulted in higher egg weight with higher albumen and yolk weights (linear, P < 0.01). Palm diets presented higher yolk:albumen ratio than soybean diets (P < 0.001), but the effect of FFA did not follow a linear trend. Hens fed soybean diets laid eggs with higher Haugh units (HU) than palm diets (P < 0.001), although increasing the dietary FFA% reduced the HU values in both (linear, P < 0.001). Palm diets enhanced shell quality with greater resistance to breakage, and higher dry matter and ash content than soybean diets (P < 0.05). No differences in egg chemical composition and yolk cholesterol content were found (P > 0.05). The saturation degree had a significant effect on all the analyzed yolk FA (P < 0.001) except for arachidonic acid (C20:4 n-6), whereas increasing the FFA content did not affect to a great extent. These results show that varying dietary FFA level did not affect egg quality and yolk composition as much as the dietary fat source did, supporting the use of acid oils and fatty acid distillates as fat ingredients for feed.

STAT3 phosphorylation at serine 727 activates specific genetic programs and promotes clear cell renal cell carcinoma (ccRCC) aggressiveness.

The signal transducer and activator of transcription 3 (STAT3) is a transcription factor mainly activated by phosphorylation in either tyrosine 705 (Y705) or serine 727 (S727) residues that regulates essential processes such as cell differentiation, apoptosis inhibition, or cell survival. Aberrant activation of STAT3 has been related to development of nearly 50% of human cancers including clear cell renal cell carcinoma (ccRCC). In fact, phosho-S727 (pS727) levels correlate with overall survival of ccRCC patients. With the aim to elucidate the contribution of STAT3 phosphorylation in ccRCC development and progression, we have generated human-derived ccRCC cell lines carrying STAT3 Y705 and S727 phosphomutants. Our data show that the phosphomimetic substitution Ser727Asp facilitates a pro-tumoral phenotype in vitro, in a Y705-phosphorylation-independent manner. Moreover, we describe that STAT3 phosphorylation state determines the expression of different subsets of target genes associated with distinct biological processes, being pS727-dependent genes the most related to cellular hallmarks of cancer. In summary, the present study constitutes the first analysis on the role of overall STAT3 phosphorylation state in ccRCC and demonstrates that pS727 promotes the expression of a specific subset of target genes that might be clinically relevant as novel biomarkers and potential therapeutic targets for ccRCC.

Implementing strategic bundles for infection prevention and management.

Healthcare-associated infections (HAI) are considered to be the most frequent adverse event in healthcare delivery. Active efforts to curb HAI have increased across Europe thanks to the growing emphasis on patient safety and quality of care. Recently, there has been dramatic success in improving the quality of patient care by focusing on the implementation of a group or "bundle" of evidenced-based preventive practices to achieve a better outcome than when implemented individually. The project entitled IMPLEMENT is designed to spread and test knowledge on how to implement strategic bundles for infection prevention and management in a diverse sample of European hospitals. The general goal of this project is to provide evidence on how to decrease the incidence of HAI and to improve antibiotic use under routine conditions.

[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.

Methicillin-resistant Staphylococcus aureus (MRSA) in Europe: which infection control measures are taken?

BACKGROUND: The prevalence of hospital-acquired Methicillin-resistant Staphylococcus aureus (MRSA) infections shows a huge variety across Europe. Some countries reported a reduction in MRSA frequency, while in others countries increasing MRSA rates have been observed. To reduce the spread of MRSA in the healthcare setting, a sufficient MRSA management is essential. In order to reflect the MRSA management across Europe, MRSA prevention policies were surveyed in ten countries. MATERIALS AND METHODS: The survey was performed by questionnaires in European intensive care units (ICUs) and surgical departments (SDs) in 2004. Questionnaires asked for availability of bedside alcohol hand-disinfection, isolation precautions, decolonization and screening methods. The study was embedded in the Hospital in Europe Link for Infection Control through Surveillance (HELICS) Project, a European collaboration of national surveillance networks. HELICS was initiated in order to harmonize the national surveillance activities in the individual countries. Therefore, HELICS participants developed surveillance modules for nosocomial infections in ICUs and for surgical site infections (SSI). The coordination of this surveillance has now been transferred to the European Centre for Disease Prevention and Control (ECDC). RESULTS: A total of 526 ICUs and 223 SDs from ten countries sent data on organisational characteristics and policies, demonstrating wide variations in care. Substantial variation existed in availability of bedside alcohol hand-disinfection, which was much higher in participating ICUs rather than in SDs (86 vs. 59%). Surveillance cultures of contact patients were obtained in approximately three-fourths of all SDs (72%) and ICUs (75%). Countries with decreasing MRSA proportions showed especially strict implementation of various prevention measures. CONCLUSION: The data obtained regarding MRSA prevention measures should stimulate infection control professionals to pursue further initiatives. Particularly, the vigorous MRSA management in countries with decreasing MRSA proportions should encourage hospitals to implement preventive measures in order to reduce the spread of MRSA.

National influences on catheter-associated bloodstream infection rates: practices among national surveillance networks participating in the European HELICS project.

This study was performed to evaluate associations between organisational characteristics, routine practices and the incidence densities of central venous catheter-associated bloodstream infections (CVC-BSI rates) in European intensive care units (ICUs) as part of the HELICS project (Hospitals in Europe Link for Infection Control through Surveillance). Questionnaires were sent to ICUs participating in the national nosocomial infection surveillance networks in 2004. The national networks were asked for the CVC-BSI rates of the ICUs participating for the time period 2003--2004. Univariate and multivariate risk factor analyses were performed to identify which practices had the greatest impact on CVC-BSI rates. A total of 526 ICUs from 10 countries sent data on organisational characteristics and practices, demonstrating wide variation in care. CVC-BSI rates were also provided for 288 ICUs from five countries. This made it possible to include 1383444 patient days, 969897 CVC days and 1935 CVC-BSI cases in the analysis. Adjusted logistic regression analysis showed that the categorical variables of country [odds ratio (OR) varying per country from OR: 2.3; 95% confidence interval (CI): 0.5-10.2; to OR: 12.8; 95% CI: 4.4-37.5; in reference to the country with the lowest CVC-BSI rates] and type of hospital 'university' (OR: 2.08; 95% CI: 1.02-4.25) were independent risk factors for high CVC-BSI rates. Substantial variation existed in CVC-BSI prevention activities, surveillance methods and estimated CVC-BSI rates among the European countries. Differences in cultural, social and legal perspectives as well as differences between healthcare systems are crucial in explaining these differences.

Fungal colonization and/or infection in non-neutropenic critically ill patients: results of the EPCAN observational study.

The purpose of this paper is to determine the incidence of fungal colonization and infection in non-neutropenic critically ill patients and to identify factors favoring infection by Candida spp. A total of 1,655 consecutive patients (>18 years of age) admitted for > or = 7 days to 73 medical-surgical Spanish intensive care units (ICUs) participated in an observational prospective cohort study. Surveillance samples were obtained once a week. One or more fungi were isolated in different samples in 59.2% of patients, 94.2% of which were Candida spp. There were 864 (52.2%) patients with Candida spp. colonization and 92 (5.5%) with proven Candida infection. In the logistic regression analysis risk factors independently associated with Candida spp. infection were sepsis (odds ratio [OR] = 8.29, 95% confidence interval [CI] 5.07-13.6), multifocal colonization (OR = 3.49, 95% CI 1.74-7.00), surgery (OR = 2.04, 95% CI 1.27-3.30), and the use of total parenteral nutrition (OR = 4.37, 95% CI 2.16-8.33). Patients with Candida spp. infection showed significantly higher in-hospital and intra-ICU mortality rates than those colonized or non-colonized non-infected (P < 0.001). Fungal colonization, mainly due to Candida spp., was documented in nearly 60% of non-neutropenic critically ill patients admitted to the ICU for more than 7 days. Proven candidal infection was diagnosed in 5.5% of cases. Risk factors independently associated with Candida spp. infection were sepsis, multifocal colonization, surgery, and the use of total parenteral nutrition.

[Recommendations of antimicrobial treatment in patients allergic to beta-lactam antibiotics]. / Recomendaciones del tratamiento antimicrobiano en pacientes alérgicos a antibióticos betalactámicos.

Beta-lactam antibiotics are the cornerstone of most of the severe bacterial infections. However, their use can be limited by resistances and allergic reactions. Allergic reactions to beta-lactam antibiotics account for only a small proportion of reported adverse drug reactions, but they are related with an important morbidity, mortality and increase of the health care costs. Drug-specific IgE antibodies cause early reactions, whereas T cells play a predominant role in delayed hypersensitivity reactions. For penicillin a major antigenic determinant and several minor determinants have been identified. Clinical assessment is mandatory by medical history, skin and other testing, including provocation. If the beta-lactam should be avoided or a desensitization procedure should be performed depends on the nature and severity of the reaction. Several new antibiotics are currently available (tigecycline, linezolid, daptomycin, etc.) that are as effective and safe as beta-lactams. In this article we have developed a few recommendations for the management of patients with allergy to beta-lactams on the basis of evidence and expert opinion.

[Nosocomial infection indicators]. / Indicadores de infección nosocomial.

Nosocomial infection indicators are a reflection of healthcare quality and patient safety in hospitals. Infection indicators are calculated using surveillance programs and/or systems. Current nosocomial infection surveillance systems are based on both prevalence and incidence studies. Since 1990 the EPINE prevalence study, promoted by the Spanish Society for Preventive Medicine, Public Health and Hygiene, has developed 25 nosocomial infection indicators in hospital patients in Spain. And since 1994 the ENVIN-HELICS incidence study, promoted by the Infectious Diseases Working Group of the Spanish Society for Intensive and Critical Care Medicine and Coronary Units, has developed nine ICU-acquired infection indicators in critical patients. Participation in both surveillance systems is voluntary and has gradually increased over the years. These two control systems present the results of two different situations in the area of nosocomial infection and each complements the other; in addition, they have helped to train health professionals and to raise their awareness of nosocomial infection and patient safety. This article presents the indicators obtained in 2007 through both surveillance programs as well as their standards of reference.