Bloodstream infections in ICU with increased resistance: epidemiology and outcomes.

BACKGROUND: Aim of this study was to evaluate the epidemiology and outcomes of hospital-acquired bloodstream infections (HA-BSI) in Greek intensive care units (ICU). METHODS: Secondary analysis of data from 29 ICU collected during the EUROBACT study, a large prospective, observational, multination survey of HA-BSI. First episodes of HA-BSI acquired in the ICU or within 48 hours prior to admission were recorded. RESULTS: Gram-negative bacteria predominated namely Acinetobacter sp, Klebsiella sp, Pseudomonas sp (73.3% of monomicrobial infections) followed by Gram-positive cocci (18.3%); fungi (7.6%) and anaerobes (0.8%). Overall 73.3% of isolates were multidrug resistant (MDR), 47.1% extensively resistant (XDR) and 1.2% pan-drug resistant (PDR). Carbapenems were the most frequent empirically prescribed antibiotics, while colistin was the most frequently adequate; for both, calculated mean total daily doses were suboptimal. Overall 28-day all-cause mortality was 33.3%. In the multivariate analysis, factors adversely affecting outcome were higher SOFA score at HA-BSI onset (OR 1.19; 95% CI 1.08-1.31, P=0.0006), need for renal supportive therapy (OR 2.75; 95% CI 1.35-5.59, P=0.0053), and for vasopressors/inotropes (OR 2.68; CI 1.18-6.12, P=0.02); adequate empirical treatment had a protective effect (OR 0.48; CI 0.24-0.95, P=0.03). CONCLUSION: TIMELY administration of adequately dosed treatment regimens and early ICU admission of critically ill patients could help in improving outcomes.

Impact of contact isolation for multidrug-resistant organisms on the occurrence of medical errors and adverse events.

UNLABELLED: Contact isolation of infected or colonised hospitalised patients is instrumental to interrupting multidrug-resistant organism (MDRO) cross-transmission. Many studies suggest an increased rate of adverse events associated with isolation. We aimed to compare isolated to non-isolated patients in intensive care units (ICUs) for the occurrence of adverse events and medical errors. METHODS: We used the large database of the Iatroref III study that included consecutive patients from three ICUs to compare the occurrence of pre-defined medical errors and adverse events among isolated vs. non-isolated patients. A subdistribution hazard regression model with careful adjustment on confounding factors was used to assess the effect of patient isolation on the occurrence of medical errors and adverse events. RESULTS: Two centres of the Iatroref III study were eligible, an 18-bed and a 10-bed ICU (nurse-to-bed ratio 2.8 and 2.5, respectively), with a total of 1,221 patients. After exclusion of the neutropenic and graft transplant patients, a total of 170 isolated patients were compared to 980 non-isolated patients. Errors in insulin administration and anticoagulant prescription were more frequent in isolated patients. Adverse events such as hypo- or hyperglycaemia, thromboembolic events, haemorrhage, and MDRO ventilator-associated pneumonia (VAP) were also more frequent with isolation. After careful adjustment of confounders, errors in anticoagulant prescription [subdistribution hazard ratio (sHR) = 1.7, p = 0.04], hypoglycaemia (sHR = 1.5, p = 0.01), hyperglycaemia (sHR = 1.5, p = 0.004), and MDRO VAP (sHR = 2.1, p = 0.001) remain more frequent in isolated patients. CONCLUSION: Contact isolation of ICU patients is associated with an increased rate of some medical errors and adverse events, including non-infectious ones.

The ETHICA study (part I): elderly's thoughts about intensive care unit admission for life-sustaining treatments.

PURPOSE: To assess preferences among individuals aged ≥80 years for a future hypothetical critical illness requiring life-sustaining treatments. METHODS: Observational cohort study of consecutive community-dwelling elderly individuals previously hospitalised in medical or surgical wards and of volunteers residing in nursing homes or assisted-living facilities. The participants were interviewed at their place of residence after viewing films of scenarios involving the use of non-invasive mechanical ventilation (NIV), invasive mechanical ventilation (IMV), and renal replacement therapy after a period of invasive mechanical ventilation (RRT after IMV). Demographic, clinical, and quality-of-life data were collected. Participants chose among four responses regarding life-sustaining treatments: consent, refusal, no opinion, and letting the physicians decide. RESULTS: The sample size was 115 and the response rate 87 %. Mean participant age was 84.8 ± 3.5 years, 68 % were female, and 81 % and 71 % were independent for instrumental activities and activities of daily living, respectively. Refusal rates among the elderly were 27 % for NIV, 43 % for IMV, and 63 % for RRT (after IMV). Demographic characteristics associated with refusal were married status for NIV [relative risk (RR), 2.9; 95 % confidence interval (95 %CI), 1.5-5.8; p = 0.002] and female gender for IMV (RR, 2.4; 95 %CI, 1.2-4.5; p = 0.01) and RRT (after IMV) (RR, 2.7; 95 %CI, 1.4-5.2; p = 0.004). Quality of life was associated with choices regarding all three life-sustaining treatments. CONCLUSIONS: Independent elderly individuals were rather reluctant to accept life-sustaining treatments, especially IMV and RRT (after IMV). Their quality of life was among the determinants of their choices.

The ETHICA study (part II): simulation study of determinants and variability of ICU physician decisions in patients aged 80 or over.

PURPOSE: To assess physician decisions about ICU admission for life-sustaining treatments (LSTs). METHODS: Observational simulation study of physician decisions for patients aged ≥80 years. Each patient was allocated at random to four physicians who made decisions based on actual bed availability and existence of an additional bed before and after obtaining information on patient preferences. The simulations involved non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), and renal replacement therapy after a period of IMV (RRT after IMV). RESULTS: The physician participation rate was 100/217 (46 %); males without religious beliefs predominated, and median ICU experience was 9 years. Among participants, 85.7, 78, and 62 % felt that NIV, IMV, or RRT (after IMV) was warranted, respectively. By logistic regression analysis, factors associated with admission were age <85 years, self-sufficiency, and bed availability for NIV and IMV. Factors associated with IMV were previous ICU stay (OR 0.29, 95 % CI 0.13-0.65, p = 0.01) and cancer (OR 0.23, 95 % CI 0.10-0.52, p = 0.003), and factors associated with RRT (after IMV) were living spouse (OR 2.03, 95 % CI 1.04-3.97, p = 0.038) and respiratory disease (OR 0.42, 95 % CI 0.23-0.76, p = 0.004). Agreement among physicians was low for all LSTs. Knowledge of patient preferences changed physician decisions for 39.9, 56, and 57 % of patients who disagreed with the initial physician decisions for NIV, IMV, and RRT (after IMV) respectively. An additional bed increased admissions for NIV and IMV by 38.6 and 13.6 %, respectively. CONCLUSIONS: Physician decisions for elderly patients had low agreement and varied greatly with bed availability and knowledge of patient preferences.

Smoking history and lung carcinoma: KRAS mutation is an early hit in lung adenocarcinoma development.

BACKGROUND: In a European multicenter prospective study patients with lung cancer were interviewed for smoking history and biological samples centrally collected. The aim of this study was to compare KRAS mutation analysis with smoking status at the time of diagnosis. METHODS: A nested case-study was performed on 233 non-small cell lung carcinomas. Cases were selected on the basis of progressive disease or disease-free post surgery based on specific criteria. KRAS mutation analysis was performed with the point-EXACCT method. RESULTS: KRAS mutations were found in 39 adenocarcinomas and 1 squamous cell carcinoma in the 233 NSCLC. The median quitting smoking time (QST) for patients with and without KRAS mutations was 9 years, interquartile range [IQR 16-38] and 3 years, IQR [13-50], respectively (p=0.039). No difference was found for age at initiation of smoking, duration of smoking, average tobacco consumption, and smoking status at the time of diagnosis. CONCLUSION: The QST was longer for patients with KRAS mutations, supporting the notion that the presence of a KRAS mutation is a dominant early effect, supporting its role as a driver oncogen.

Primary lung adenocarcinoma: characteristics by smoking habit and sex.

The incidence of adenocarcinoma is increasing, particularly among females. We sought to assess the role of tobacco consumption in clinical presentation according to sex. In this retrospective study, 848 patients diagnosed between 1997 and 2006 at Grenoble University Hospital (Grenoble, France) were stratified into four groups according to smoking habits. Differences between sexes and two contrasting female profiles emerged. Female current smokers were younger than female never-smokers (median 51 versus 69 yrs; p < 0.001), more often had surgery (62.7% versus 39%; p = 0.01) and had a median (95% CI) estimated survival of 26.2 (18.1-49.2) versus 15.1 (12.8-22.2) months (p = 0.002). Both groups had similar survival when taking treatment into account. Among males, smoking did not influence presentation. Male current smokers were older than female current smokers (median 59 yrs; p < 0.001) and fewer had surgery (48.8%; p = 0.015), although the percentage of stage IIIb-IV disease was similar (53% and 46%; nonsignificant) and they had a poorer estimated survival of 14.3 (13.0-18.5) months (p = 0.0024). Males smoked more than females (median 41 versus 30 pack-yrs; p < 0.001). Quitting smoking delayed age at diagnosis by 11 yrs for females (p = 0.0035) and 8 yrs for males (p < 0.001). Our results support the hypothesis that carcinogenesis differs between males and females, and between female smokers and never-smokers.

Identifying adult asthma phenotypes using a clustering approach.

There is a need to improve asthma characterisation by integrating multiple aspects of the disease. The aim of the present study was to identify distinct asthma phenotypes by applying latent class analysis (LCA), a model-based clustering method, to two large epidemiological studies. Adults with asthma who participated in the follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2) (n = 641) and the European Community Respiratory Health Survey (ECRHSII) (n = 1,895) were included. 19 variables covering personal characteristics, asthma symptoms, exacerbations and treatment, age of asthma onset, allergic characteristics, lung function and airway hyperresponsiveness were considered in the LCA. Four asthma phenotypes were distinguished by the LCA in each sample. Two phenotypes were similar in EGEA2 and ECRHSII: active treated allergic childhood-onset asthma and active treated adult-onset asthma. The other two phenotypes were composed of subjects with inactive or mild untreated asthma, who differed by atopy status and age of asthma onset (childhood or adulthood). The phenotypes clearly discriminated populations in terms of quality of life, and blood eosinophil and neutrophil counts. The LCAs revealed four distinct asthma phenotypes in each sample. Considering these more homogeneous phenotypes in future studies may lead to a better identification of risk factors for asthma.

EUELC project: a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration.

The European Early Lung Cancer (EUELC) project aims to determine if specific genetic alterations occurring in lung carcinogenesis are detectable in the respiratory epithelium. In order to pursue this objective, nonsmall cell lung cancer (NSCLC) patients with a very high risk of developing progressive lung cancer were recruited from 12 centres in eight European countries: France, Germany, southern Ireland, Italy, the Netherlands, Poland, Spain and the UK. In addition, NSCLC patients were followed up every 6 months for 36 months. A European Bronchial Tissue Bank was set up at the University of Liverpool (Liverpool, UK) to optimise the use of biological specimens. The molecular-pathological investigations were subdivided into specific work packages that were delivered by EUELC Partners. The work packages encompassed mutational analysis, genetic instability, methylation profiling, expression profiling utilising immunohistochemistry and chip-based technologies, as well as in-depth analysis of FHIT and RARbeta genes, the telomerase catalytic subunit hTERT and genotyping of susceptibility genes in specific pathways. The EUELC project engendered a tremendous collaborative effort, and it enabled the EUELC Partners to establish protocols for assessing molecular biomarkers in early lung cancer with the view to using such biomarkers for early diagnosis and as intermediate end-points in future chemopreventive programmes.