Risk factors associated with the development of delirium in general ICU patients. A prospective observational study.

OBJECTIVE: We aimed to analyze risk factors related to the development of delirium, aiming for early intervention in patients with greater risk. MATERIAL AND METHODS: Observational study, including prospectively collected patients treated in a single general ICU. These were classified into two groups, according to whether they developed delirium or not (screening performed using CAM-ICU tool). Demographics and clinical data were analyzed. Multivariate logistic regression analyses were performed to quantify existing associations. RESULTS: 1462 patients were included. 93 developed delirium (incidence: 6.3%). These were older, scored higher on the Clinical Frailty Scale, on the risk scores on admission (SAPS-3 and SOFA), and had a greater number of organ failures (OF). We observed more incidence of delirium in patients who (a) presented more than two OF (20.4%; OR 4.9; CI95%: 2.9-8.2), and (b) were more than 74 years old albeit having <2 OF (8.6%; OR 2.1; CI95%: 1.3-3.5). Patients who developed delirium had longer ICU and hospital length-of-stays and a higher rate of readmission. CONCLUSIONS: The highest risk observed for developing delirium clustered in patients who presented more than 2 OF and patients over 74 years old. The detection of patients at high risk for developing delirium could imply a change in management and improved quality of care.

[Functional status as an independent risk factor in elderly patients admitted to an Intensive Care Unit]. / Situación funcional como factor independiente asociado con el mal pronóstico de pacientes ancianos ingresados en Cuidados Intensivos.

OBJECTIVE: To assess the association of previous functional status in elderly patients admitted to the ICU, estimated by the Barthel and Short Form-Late Life Function and Disability instrument scales, and the relationship with prognosis and functional capacity at hospital discharge. MATERIAL AND METHODS: Observational prospective study of ICU-admitted patients older than 74 years, with a length of stay greater than 48hours. Demographic data, social background, comorbidities, disability questionnaire (Barthel, Short Form-Late Life Function and Disability instrument), main diagnosis and severity (SAPS 3) on ICU admission were recorded. Factors associated with mortality or poor functional status at hospital discharge (Barthel Index less than 35) were established by multivariate analysis. RESULTS: During the study period, 219 elderly patients were admitted in ICU, of whom 129 (15%) had an ICU length of stay greater than 48hours. The median age was 80 years (77-83), with 52% women. Main diagnoses on admission included ischaemic heart disease (19%), another medical diagnosis (38%), and surgical procedure (43%). A Barthel score <36 (median 95, 85-100) was observed in 3% of the patients on admission. The median ICU length of stay was 5 days (4-8). ICU mortality was 6% (hospital mortality: 10%). On hospital discharge, 7% had severe dependence (Barthel <36). In this population, factors independently associated with mortality or poor functional status at hospital discharge were the pre-admission functional status, based on Short Form-Late Life Function and Disability instrument (OR 0.95, 95% CI, 0.91 to 0.98), and the severity on admission assessed by SAPS 3 (OR 1.10, 95% CI, 1.02 to 1.18), p=.0007. CONCLUSIONS: In elderly patients requiring ICU admission, a higher SAPS 3 score and functional impairment on admission were associated with mortality or severe dependence upon discharge.

Limitation of life support techniques at admission to the intensive care unit: a multicenter prospective cohort study.

PURPOSE: To determine the frequency of limitations on life support techniques (LLSTs) on admission to intensive care units (ICU), factors associated, and 30-day survival in patients with LLST on ICU admission. METHODS: This prospective observational study included all patients admitted to 39 ICUs in a 45-day period in 2011. We recorded hospitals' characteristics (availability of intermediate care units, usual availability of ICU beds, and financial model) and patients' characteristics (demographics, reason for admission, functional status, risk of death, and LLST on ICU admission (withholding/withdrawing; specific techniques affected)). The primary outcome was 30-day survival for patients with LLST on ICU admission. Statistical analysis included multilevel logistic regression models. RESULTS: We recruited 3042 patients (age 62.5 ± 16.1 years). Most ICUs (94.8%) admitted patients with LLST, but only 238 (7.8% [95% CI 7.0-8.8]) patients had LLST on ICU admission; this group had higher ICU mortality (44.5 vs. 9.4% in patients without LLST; p < 0.001). Multilevel logistic regression showed a contextual effect of the hospital in LLST on ICU admission (median OR = 2.30 [95% CI 1.59-2.96]) and identified the following patient-related variables as independent factors associated with LLST on ICU admission: age, reason for admission, risk of death, and functional status. In patients with LLST on ICU admission, 30-day survival was 38% (95% CI 31.7-44.5). Factors associated with survival were age, reason for admission, risk of death, and number of reasons for LLST on ICU admission. CONCLUSIONS: The frequency of ICU admission with LLST is low but probably increasing; nearly one third of these patients survive for ≥ 30 days.

Human betacellulin structure modeled from other members of EGF family.

We have modeled betacellulin (BTC) to gain insight into the structural elements that can explain its properties. The epidermal growth factor (EGF) signal transduction pathway, a significant mediator of several cell functions, is based on four closely related tyrosine kinase receptors. The ErbB receptors are transmembrane glycoproteins and signal transduction is initiated by ligand binding that induces receptor homo- or heterodimerization to form a complex containing two molecules of ligand and two molecules of receptor. The EGF family of ligands can be divided into three groups based on their ability to bind and activate distinct ErbB receptor homo- and heterodimers. Each member of the group formed by BTC, heparin binding EGF (HB-EGF) and epiregulin (EP) can interact with both the EGF receptor (EGFR) and heregulin receptors (ErbB-3 and ErbB-4), and are hence called "bispecific" ligands. BTC and EP also present the distinctive feature that they activate all possible heterodimeric ErbB receptors. BTC has been modeled with the program MODELLER, using human EGF, human transforming growth factor alpha (hTGFalpha), human HB-EGF and human heregulin one alpha (hHRG-1alpha) as templates. The structure of the model as well as that of the templates were optimized and a simulation of 100 ps was run for all. The main structural properties of the model and the templates were compared and in conclusion the hBTC conformation was closely similar to that of hTGFalpha.