A Model Predicting the 6-Month Disability of Patients With Traumatic Brain Injury to Assess the Quality of Care in Intensive Care Units: Results from the CREACTIVE Study.

Assessing quality of care is essential for improving the management of patients experiencing traumatic brain injury (TBI). This study aimed at devising a rigorous framework to evaluate the quality of TBI care provided by intensive care units (ICUs) and applying it to the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) consortium, which involved 83 ICUs from seven countries. The performance of the centers was assessed in terms of patients' outcomes, as measured by the 6-month Glasgow Outcome Scale-Extended (GOS-E). To account for the between-center differences in the characteristics of the admitted patients, we developed a multinomial logistic regression model estimating the probability of a four-level categorization of the GOS-E: good recovery (GR), moderate disability (MD), severe disability (SD), and death or vegetative state (D/VS). A total of 5928 patients admitted to the participating ICUs between March 2014 and March 2019 were analyzed. The model included 11 predictors and demonstrated good discrimination (area under the receiver operating characteristic [ROC] curve in the validation set for GR: 0.836, MD: 0.802, SD: 0.706, D/VS: 0.890) and calibration, both overall (Hosmer-Lemeshow test p value: 0.87) and in several subgroups, defined by prognostically relevant variables. The model was used as a benchmark for assessing quality of care by comparing the observed number of patients experiencing GR, MD, SD, and D/VS to the corresponding numbers expected in each category by the model, computing observed/expected (O/E) ratios. The four center-specific ratios were assembled with polar representations and used to provide a multidimensional assessment of the ICUs, overcoming the loss of information consequent to the traditional dichotomizations of the outcome in TBI research. The proposed framework can help in identifying strengths and weaknesses of current TBI care, triggering the changes that are necessary to improve patient outcomes.

An Interactive E-learning Platform-Based Training to Improve Intensive Care Professionals' Knowledge Regarding Central Venous Catheter-Related Infections.

Introduction The presence of a central venous catheter (CVC) leads to a high risk for blood infections, which are associated with increases in morbidity, mortality, and costs. This study aims to assess intensive care unit (ICU) nurses' and physicians' knowledge regarding the Centers for Disease Control and Prevention (CDC) guidelines for preventing CVC-related infections before and after an interactive distance education delivered through the e-learning platform Teleprometheus. Materials and methods The study was conducted among 85 nurses and physicians in Nicosia's General Hospital Intensive Care Unit (NGH-ICU) and high dependency unit (HDU). A validated questionnaire was used to assess nurses' and physicians' knowledge. Results Prior to the online interactive distance education, the mean total knowledge score was x̄ = 4.8 (SD = 2.46), while after, the mean total knowledge score increased to x̄ = 8.9 (SD = 2.38) (p<0.001). ICU physicians had a higher mean total knowledge score (x̄ = 10.20) than ICU nurses (x̄ = 8.75) after the intervention. There was no correlation between years of experience in the ICU and the level of knowledge (r = 0.048). The interactive distance education was positively evaluated by the participants, through a questionnaire, specially designed for this study. Discussion The most important findings were that (a) the level of knowledge of the participants improved with a statistically significant difference after the completion of the e-course, (b) the level of knowledge of the participants, after the completion of the e-course, was much higher from other studies, (c) there was no correlation between the years of experience of ICU health professionals and their level of knowledge, and (d) the interactive distance e-course was positively evaluated and satisfied the participants. Conclusion The current study demonstrates that in high-intensity work environments, such as ICUs, adopting e-learning approaches seems more necessary than ever.

Comparative Effectiveness of Intracranial Pressure Monitoring on 6-Month Outcomes of Critically Ill Patients With Traumatic Brain Injury.

Importance: While the relationship between persistent elevations in intracranial pressure (ICP) and poorer outcomes is well established for patients with traumatic brain injury (TBI), there is no consensus on how ICP measurements should drive treatment choices, and the effectiveness of ICP monitoring remains unknown. Objective: To evaluate the effectiveness of ICP monitoring on short- and mid-term outcomes of patients with TBI. Design, Setting, and Participants: CREACTIVE was a prospective cohort study that started in March 2014 and lasted 5 years. More than 8000 patients with TBI were enrolled at 83 intensive care units (ICUs) from 7 countries who joined the CREACTIVE Consortium. Patients with TBI who met the Brain Trauma Foundation guidelines for ICP monitoring were selected for the current analyses, which were performed from January to November 2022. Exposure: Patients who underwent ICP monitoring within 2 days of injury (exposure group) were propensity score-matched to patients who were not monitored or who underwent monitoring 2 days after the injury (control group). Main Outcome and Measure: Functional disability at 6 months as indicated by Glasgow Outcome Scale-Extended (GOS-E) score. Results: A total of 1448 patients from 43 ICUs in Italy and Hungary were eligible for analysis. Of the patients satisfying the ICP-monitoring guidelines, 503 (34.7%) underwent ICP monitoring (median [IQR] age: 45 years [29-61 years]; 392 males [77.9%], 111 females [22.1%]) and 945 were not monitored (median [IQR] age: 66 years [48-78 years]; 656 males [69.4%], 289 females [30.6%]). After matching to balance the variables, worse 6-month recovery was observed for monitored patients compared with nonmonitored patients (death/vegetative state: 39.2% vs 40.6%; severe disability: 33.2% vs 25.4%; moderate disability: 15.7% vs 14.9%; good recovery: 11.9% vs 19.1%, respectively; P = .005). Monitored patients received medical therapies significantly more frequently. Conclusions and Relevance: In this cohort study, ICP monitoring was associated with poorer recovery and more frequent medical interventions with their relevant adverse effects. Optimizing the value of ICP monitoring for TBI requires further investigation on monitoring indications, clinical interventions, and management protocols.

Correlation Between Teamwork and Patient Safety in a Tertiary Hospital in Cyprus.

Background Over time, the multidimensional nature of the safety culture in the healthcare field has led to great efforts to improve quality and create tools aiming at enhancing safety. In particular, emphasis has been placed on teamwork and the safety climate. There is a strong relationship between these two complex elements, which interact to improve the safety climate and reduce patient-safety issues. In this study, "teamwork" includes the perceptions of the health professionals collaborating within a health team to provide safe patient care, and "safety climate" refers to the professional commitment to patient safety. Objective This article assesses health professionals' perceptions of both patient-safety issues and teamwork in their hospital work environment after the development and implementation of a comprehensive quality-assurance system. Methods This descriptive correlation study is based on anonymous and self-completed questionnaires obtained after the development and implementation of a comprehensive quality assurance system in the wards and departments of Nicosia General Hospital. The research sample consisted of the health professionals who participated in the working groups that implemented the quality assurance system. We used the questionnaire's sociodemographic data and the Safety Attitudes Questionnaire (SAQ) developed in the Deepening our Understanding of Quality Improvement in Europe program, focusing on two factors: Teamwork and the safety climate. Results While teamwork received a positive score (>75%), the same did not occur for the safety climate (68.60%). Women typically rated the safety climate more positively than men, who mostly gave negative ratings (p = 0.005). There was a statistically significant difference (p = 0.011) in the scores between participants aged 24-44 and those aged 45-54, with the latter reporting higher teamwork scores. The participants' educational levels also played important roles in their responses, with university graduates (BSc) providing more positive teamwork scores than those with a master's degree (p = 0.018). Conclusions Our research revealed that the health professionals of Nicosia General Hospital perceived the teamwork climate as positive, in contrast to the safety climate. The results highlight the need not only to intervene in all the areas covered by the SAQ to improve the safety climate but also to keep encouraging teamwork to obtain better results.

Hospitals with and without neurosurgery: a comparative study evaluating the outcome of patients with traumatic brain injury.

BACKGROUND: We leveraged the data of the international CREACTIVE consortium to investigate whether the outcome of traumatic brain injury (TBI) patients admitted to intensive care units (ICU) in hospitals without on-site neurosurgical capabilities (no-NSH) would differ had the same patients been admitted to ICUs in hospitals with neurosurgical capabilities (NSH). METHODS: The CREACTIVE observational study enrolled more than 8000 patients from 83 ICUs. Adult TBI patients admitted to no-NSH ICUs within 48 h of trauma were propensity-score matched 1:3 with patients admitted to NSH ICUs. The primary outcome was the 6-month extended Glasgow Outcome Scale (GOS-E), while secondary outcomes were ICU and hospital mortality. RESULTS: A total of 232 patients, less than 5% of the eligible cohort, were admitted to no-NSH ICUs. Each of them was matched to 3 NSH patients, leading to a study sample of 928 TBI patients where the no-NSH and NSH groups were well-balanced with respect to all of the variables included into the propensity score. Patients admitted to no-NSH ICUs experienced significantly higher ICU and in-hospital mortality. Compared to the matched NSH ICU admissions, their 6-month GOS-E scores showed a significantly higher prevalence of upper good recovery for cases with mild TBI and low expected mortality risk at admission, along with a progressively higher incidence of poor outcomes with increased TBI severity and mortality risk. CONCLUSIONS: In our study, centralization of TBI patients significantly impacted short- and long-term outcomes. For TBI patients admitted to no-NSH centers, our results suggest that the least critically ill can effectively be managed in centers without neurosurgical capabilities. Conversely, the most complex patients would benefit from being treated in high-volume, neuro-oriented ICUs.

Prevention of Central Line-Associated Bloodstream Infections Through Educational Interventions in Adult Intensive Care Units: A Systematic Review.

Central line-associated bloodstream infections (CLABSIs) represent a severe systemic threat to patients admitted in ICUs and contribute to increased mortality, prolonged length of stay in ICUs, and increased costs. The majority of CLABSIs are preventable. The current systematic review aimed to investigate the effectiveness of educational methods on CLABSI rates in adult ICUs. A systematic literature search was conducted using the electronic databases of Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, and Cochrane Database of Systematic Reviews for studies published from the beginning of 1995 to March 2020. The terms used for the search were as follows: central venous catheters, infection, central line-associated bloodstream infections, intensive care unit, and education intervention in all possible combinations and using the word 'and' between them. Data were extracted independently and crosschecked by two authors using a standard data collection form. The quality of the studies included in the review was assessed using the Methodological Index for Non-randomized Studies (MINORS). The current systematic review included 27 interventional studies of central line insertion or maintenance or both in adult ICU settings with documentation of the CLABSI incidence expressed per 1,000 catheter days. A large deviation between the length of time and type of educational interventions was found. Statistical significance was found in all studies (except one) in terms of CLABSI reduction despite the large variation of the length or the type of the educational intervention. Continuing education on infection prevention may be necessary to maintain the post-intervention results and improve clinical outcomes.

Prognostic Value of a Combination of Circulating Biomarkers in Critically Ill Patients with Traumatic Brain Injury: Results from the European CREACTIVE Study.

Individualized patient care is essential to reduce the global burden of traumatic brain injury (TBI). This pilot study focused on TBI patients admitted to intensive care units (ICUs) and aimed at identifying patterns of circulating biomarkers associated with the disability level at 6 months from injury, measured by the extended Glasgow Outcome Scale (GOS-E). The concentration of 107 biomarkers, including proteins related to inflammation, innate immunity, TBI, and central nervous system, were quantified in blood samples collected on ICU admission from 80 patients. Patients were randomly selected among those prospectively enrolled in the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) observational study. Six biomarkers were selected to be associated with indicators of primary or secondary brain injury: three glial proteins (glial cell-derived neurotrophic factor, glial fibrillary acidic protein, and S100 calcium-binding protein B) and three cytokines (stem cell factor, fibroblast growth factor [FGF] 23 and FGF19). The subjects were grouped into three clusters according to the expression of these proteins. The distribution of the 6-month GOS-E was significantly different across clusters (p < 0.001). In two clusters, the number of 6-month deaths or vegetative states was significantly lower than expected, as calculated according to a customization of the corticosteroid randomization after significant head injury (CRASH) scores (observed/expected [O/E] events = 0.00, 95% confidence interval [CI]: 0.00-0.90 and 0.00, 95% CI: 0.00-0.94). In one cluster, less-than-expected unfavorable outcomes (O/E = 0.50, 95% CI: 0.05-0.95) and more-than-expected good recoveries (O/E = 1.55, 95% CI: 1.05-2.06) were observed. The improved prognostic accuracy of the pattern of these six circulating biomarkers at ICU admission upon established clinical parameters and computed tomography results needs validation in larger, independent cohorts. Nonetheless, the results of this pilot study are promising and will prompt further research in personalized medicine for TBI patients.

Multi-omics data integration and network-based analysis drives a multiplex drug repurposing approach to a shortlist of candidate drugs against COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is undeniably the most severe global health emergency since the 1918 Influenza outbreak. Depending on its evolutionary trajectory, the virus is expected to establish itself as an endemic infectious respiratory disease exhibiting seasonal flare-ups. Therefore, despite the unprecedented rally to reach a vaccine that can offer widespread immunization, it is equally important to reach effective prevention and treatment regimens for coronavirus disease 2019 (COVID-19). Contributing to this effort, we have curated and analyzed multi-source and multi-omics publicly available data from patients, cell lines and databases in order to fuel a multiplex computational drug repurposing approach. We devised a network-based integration of multi-omic data to prioritize the most important genes related to COVID-19 and subsequently re-rank the identified candidate drugs. Our approach resulted in a highly informed integrated drug shortlist by combining structural diversity filtering along with experts' curation and drug-target mapping on the depicted molecular pathways. In addition to the recently proposed drugs that are already generating promising results such as dexamethasone and remdesivir, our list includes inhibitors of Src tyrosine kinase (bosutinib, dasatinib, cytarabine and saracatinib), which appear to be involved in multiple COVID-19 pathophysiological mechanisms. In addition, we highlight specific immunomodulators and anti-inflammatory drugs like dactolisib and methotrexate and inhibitors of histone deacetylase like hydroquinone and vorinostat with potential beneficial effects in their mechanisms of action. Overall, this multiplex drug repurposing approach, developed and utilized herein specifically for SARS-CoV-2, can offer a rapid mapping and drug prioritization against any pathogen-related disease.

Negative drift of sedation depth in critically ill patients receiving constant minimum alveolar concentration of isoflurane, sevoflurane, or desflurane: a randomized controlled trial.

BACKGROUND: Intensive care unit (ICU) physicians have extended the minimum alveolar concentration (MAC) to deliver and monitor long-term volatile sedation in critically ill patients. There is limited evidence of MAC's reliability in controlling sedation depth in this setting. We hypothesized that sedation depth, measured by the electroencephalography (EEG)-derived Narcotrend-Index (burst-suppression N_Index 0-awake N_Index 100), might drift downward over time despite constant MAC values. METHODS: This prospective single-centre randomized clinical study was conducted at a University Hospital Surgical Intensive Care Unit and included consecutive, postoperative ICU patients fulfilling the inclusion criteria. Patients were randomly assigned to receive uninterrupted inhalational sedation with isoflurane, sevoflurane, or desflurane. The end-expiratory concentration of the anaesthetics and the EEG-derived index were measured continuously in time-stamped pairs. Sedation depth was also monitored using Richmond-Agitation-Sedation-Scale (RASS). The paired t-test and linear models (bootstrapped or multilevel) have been employed to analyze MAC, N_Index and RASS across the three groups. RESULTS: Thirty patients were recruited (female/male: 10/20, age 64 ± 11, Simplified Acute Physiology Score II 30 ± 10). In the first 24 h, 21.208 pairs of data points (N_Index and MAC) were recorded. The median MAC of 0.58 ± 0.06 remained stable over the sedation time in all three groups. The t-test indicated in the isoflurane and sevoflurane groups a significant drop in RASS and EEG-derived N_Index in the first versus last two sedation hours. We applied a multilevel linear model on the entire longitudinal data, nested per patient, which produced the formula N_Index = 43 - 0.7·h (R2 = 0.76), showing a strong negative correlation between sedation's duration and the N_Index. Bootstrapped linear models applied for each sedation group produced: N_Index of 43-0.9, 45-0.8, and 43-0.4·h for isoflurane, sevoflurane, and desflurane, respectively. The regression coefficient for desflurane was almost half of those for isoflurane and sevoflurane, indicating a less pronounced time-effect in this group. CONCLUSIONS: Maintaining constant MAC does not guarantee stable sedation depth. Thus, the patients necessitate frequent clinical assessments or, when unfeasible, continuous EEG monitoring. The differences across different volatile anaesthetics regarding their time-dependent negative drift requires further exploration. TRIAL REGISTRATION: NCT03860129.

Nursing quality indicators for adult intensive care: A consensus study.

BACKGROUND: The selection of quality indicators demonstrating the efficiency and relevance of nursing practice in patient outcomes in the intensive care unit remains a challenge. AIM: The aim of this study was to develop a set of potential quality indicators to quantify nursing care provided to critically ill patients through a consensus method. DESIGN: This was a three-phase study including a European survey of intensive care unit (ICU) nurses (phase one) followed by a two-phase face-to-face consensus meeting of experts from Cyprus. METHOD: Two distinct panels of experts were asked to rate each quality indicator using a 4-point Likert scale in phases one and two. The level of consensus was set at 60%. In phase three, scores of the content validity index for items and scales were considered for the final selection of quality indicators. RESULTS: The phase one survey included 139 ICU nurses from 13 European countries, and phases two and three included seven ICU experts from Cyprus. "Consensus in" was achieved for 12 items at the end of phase two. Three of the quality indicators were significantly different by country: (a) falls (P = .006), (b) accidental removal of nasogastric tube (P < .001), and (c) accidental removal of intravascular catheters (P < .001). Only falls was significantly correlated with higher academic qualifications of the participants (P = .002). CONCLUSIONS: Fifteen items have been identified as potential indicators for adult ICU nursing quality. These need to be prospectively studied to determine the extent to which they can accurately capture nursing care quality in this setting. RELEVANCE TO CLINICAL PRACTICE: The study provides a set of relevant quality indicators. A nursing set for the ICU may serve as the basis for nursing management and facilitate the strategy dedicated to the vision of health care quality assurance.

PROSAFE: a European endeavor to improve quality of critical care medicine in seven countries.

BACKGROUND: Long-lasting shared research databases are an important source of epidemiological information and can promote comparison between different healthcare services. Here we present PROSAFE, an advanced international research network in intensive care medicine, with the focus on assessing and improving the quality of care. The project involved 343 ICUs in seven countries. All patients admitted to the ICU were eligible for data collection. METHODS: The PROSAFE network collected data using the same electronic case report form translated into the corresponding languages. A complex, multidimensional validation system was implemented to ensure maximum data quality. Individual and aggregate reports by country, region, and ICU type were prepared annually. A web-based data-sharing system allowed participants to autonomously perform different analyses on both own data and the entire database. RESULTS: The final analysis was restricted to 262 general ICUs and 432,223 adult patients, mostly admitted to Italian units, where a research network had been active since 1991. Organization of critical care medicine in the seven countries was relatively similar, in terms of staffing, case mix and procedures, suggesting a common understanding of the role of critical care medicine. Conversely, ICU equipment differed, and patient outcomes showed wide variations among countries. CONCLUSIONS: PROSAFE is a permanent, stable, open access, multilingual database for clinical benchmarking, ICU self-evaluation and research within and across countries, which offers a unique opportunity to improve the quality of critical care. Its entry into routine clinical practice on a voluntary basis is testimony to the success and viability of the endeavor.

Effects of controlled dehydration on sleep quality and quantity: A polysomnographic study in healthy young adults.

Dehydration is associated with several alternations in body homeostasis involving both physiological and mental aspects. In addition some studies have reported a negative effect of dehydration on subjectively assessed sleep-related parameters. The aim of the current study was to examine for the first time the effect of controlled dehydration on sleep quality and quantity using the gold-standard method of polysomnography. Twelve healthy male volunteers participated in this study (23.4 ± 0.8 years). Participants performed an in-house full polysomnographic assessment in two different occasions taking place in random order: (i) in a dehydrated state; and (ii) in a euhydrated state. In the dehydration scenario, the participants were allowed to consume only 1.25 L of non-caffeinated fluids, while during the euhydrated state participants had to drink at least 3 L of non-caffeinated fluids during the last 24 hr before the polysomnographic study. Urine specific gravity was assessed by refractrometry on collection day in order to assess hydration status. Participants who did not fulfil the hydration criteria were rescheduled. All participants successfully completed the two polysomnographic studies without any complaints or adverse effects reported. No significant differences were found in any of the examined indices of sleep quality and quantity between the dehydration and euhydration scenarios (p > .05). This is the first study to show that controlled mild dehydration does not seem to affect sleep quality and quantity in young healthy adults. More research is necessary to further verify these conclusions and assess whether other parameters are involved in the manifestation of sleep disturbances.

Proposal for an eHealth Based Ecosystem Serving National Healthcare.

The European Union (EU)'s keen concern about citizens' health and well-being advancement has been expressed at all levels. It has been understood that at present, these can only be achieved through coordinated actions at the individual member states' level based on EU directives, as well as through promoting and funding R&D and expanding the use of eHealth technologies. Despite the diversities and particularities among member states, common values such as universal access to good quality healthcare, equity, and solidarity have been widely accepted across EU. That demanded the adoption of policies and follow directives, which streamlined actions to bridge healthcare gaps, and facilitate cross-border healthcare. This paper articulates a framework for deriving a national healthcare system, based on interoperable Electronic Health Record (EHR) with safeguarding healthcare quality, enabling quadruple helix (Public, Academia, Industry, NGOs) driven R&D and guided by a patient-centered approach. A methodology to develop an integrated EHR at National level is proposed as a prerequisite for eHealth and put into perspective. Recommendations are given for the steps needed, from the managerial, legal, technical, and financial concerns in developing an open access, patient-centered national healthcare system based on the context and constraints of a country. The example of a small country to apply the proposed methodology is demonstrated. Stakeholders, including citizens, healthcare professionals, academia, and the industry are mobilized, enabled, and incentivized for implementing the methodology. Experiences are aspired to be offered as lessons learned for other countries to adapt on their environment.

A New Method for Diaphragmatic Maximum Relaxation Rate Ultrasonographic Measurement in the Assessment of Patients With Diaphragmatic Dysfunction.

Measurements of ultrasound diaphragmatic motion, amplitude, force, and velocity of contraction may provide important and essential information about diaphragmatic fatigue, weakness, or paralysis. In this paper, we propose and evaluate a semi-automated analysis system for measuring the diaphragmatic motion and estimating the maximum relaxation rate (MRR_SAUS) from ultrasound M-mode images of the diaphragmatic muscle. The system was evaluated on 27 M-mode ultrasound images of the diaphragmatic muscle [20 with no resistance (NRES) and 7 with resistance (RES)]. We computed semi-automated ultrasound MRR measurements on all NRES/RES images, using the proposed system (MRR_SAUS = 3.94 ± 0.91/4.98 ± 1.98 [1/s]), and compared them with the manual measurements made by a clinical expert (MRR_MUS = 2.36 ± 1.19/5.8 ± 2.1 [1/s],) and those made by a reference manual method (MRR_MB = 3.93 ± 0.89/3.73 ± 0.52 [1/sec], performed manually with the Biopac system. MRR_SAUS and MRR_MB measurements were not statistically significantly different for NRES and RES subjects but were significantly different with the MRR-MUS measurements made by the clinical expert. It is anticipated that the proposed system might be used in the future in the clinical practice in the assessment and follow up of patients with diaphragmatic weakness or paralysis. It may thus potentially help to understand post-operative pulmonary dysfunction or weaning failure from mechanical ventilation. Further validation and additional experimentation in a larger sample of images and different patient groups is required for further validating the proposed system.

Effects of an Integrative Nursing Intervention on Pain in Critically Ill Patients: A Pilot Clinical Trial.

BACKGROUND: Pain, a persistent problem in critically ill patients, adversely affects outcomes. Despite recommendations, no evidence-based nonpharmacological approaches for pain treatment in critically ill patients have been developed. OBJECTIVES: To investigate the effects of a multimodal integrative intervention on the incidence of pain and on secondary outcomes: intensity of pain, hemodynamic indices (systolic and mean arterial pressure, heart rate), anxiety, fear, relaxation, optimism, and sleep quality. METHODS: A randomized, controlled, double-blinded repeated-measures trial with predetermined eligibility criteria was conducted. The intervention included relaxation, guided imagery, moderate pressure massage, and listening to music. The primary outcome was incidence of pain (score on Critical Care Pain Observation Tool > 2). Other outcomes included pain ratings, hemodynamic measurements, self-reported psychological outcomes, and quality of sleep. Repeated-measures models with adjustments (baseline levels, confounders) were used. RESULTS: Among the 60 randomized critically ill adults in the sample, the intervention group experienced significant decreases in the incidence (P = .003) and ratings of pain (P < .001). Adjusted models revealed a significant trend for lower incidence (P = .002) and ratings (P < .001) of pain, systolic arterial pressure (P < .001), anxiety (P = .01), and improved quality of sleep (P = .02). CONCLUSION: A multimodal integrative intervention may be effective in decreasing pain and improving pain-related outcomes in critically ill patients.

Attitudes towards euthanasia among Greek intensive care unit physicians and nurses.

OBJECTIVES: To investigate the attitudes of Greek intensive care unit (ICU) medical and nursing staff towards euthanasia. BACKGROUND: ICU physicians and nurses deal with end-of-life dilemmas on a daily basis. Therefore, the exploration of their stances on euthanasia is worthwhile. METHODS: This was a descriptive quantitative study conducted in three ICUs in Athens. The convenience sample included 39 physicians and 107 nurses. RESULTS: Of respondents, 52% defined euthanasia inaccurately, as withholding or withdrawal of treatment, while 15% ranked limitation of life-support among the several forms of euthanasia, together with active shortening of the dying process and physician - assisted suicide. Only one third of participants defined euthanasia correctly. While 59% of doctors and 64% of nurses support the legalization of active euthanasia, just 28% and 26% of them, respectively, agree with it ethically. CONCLUSIONS: Confusion prevails among Greek ICU physicians and nurses regarding the definition of euthanasia. The majority of staff disagrees with active euthanasia, but upholds its legalization.

Novel biomarkers of acute kidney injury in the general adult ICU: a review.

Acute kidney injury is one of the most frequent problems occurring in the critically ill patients of the intensive care units and it is well established that it increases both morbidity and mortality in these patients. Moreover, despite technological and pharmaceutical advances during the last decades, the incidence as well as the mortality associated with acute kidney injury in these patients remains unchanged. Creatinine, the most common renal dysfunction biomarker in use, has many disadvantages, such as time delay in its increase and the influence by other factors on its serum concentration, such as age, gender, muscle mass, etc. Hence, the need for better renal biomarkers in order to timely intervene for acute kidney injury prevention is imperative. The lack of an early biomarker is an obstacle for the development of new acute kidney injury prevention strategies. With the incidence of acute kidney injury reaching epidemic dimensions, the need for novel markers is urgent. During the last years, the research for finding such biomarkers has been intense. The purpose of the present article is to review the studies which have tested the predictive ability of those markers (in urine and/or plasma) for early detection of acute kidney injury in the mixed adult intensive care unit population and underline the potential limitations encountered in the various studies.

Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects.

Circulating bone-marrow-derived cells, named endothelial progenitor cells (EPCs), are capable of maintaining, generating, and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury. Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role. Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk. In this review, we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension, obstructive sleep-apnea syndrome, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease, pulmonary hypertension, and heart failure. Recent studies have introduced the novel concept that physical activity, either performed as a single exercise session or performed as part of an exercise training program, results in a significant increase of circulating EPCs. In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations.

Combination of renal biomarkers predicts acute kidney injury in critically ill adults.

OBJECTIVE: Most studies so far have focused on the performance of individual biomarkers to detect early acute kidney injury (AKI) in the adult intensive care unit (ICU) patients; however, they have not determined the predictive ability of their combinations. The aim of this study was to compare the predictive abilities of plasma neutrophil gelatinase-associated lipocalin (pNGAL), urine neutrophil gelatinase-associated lipocalin (uNGAL), plasma cystatin C (pCysC), serum creatinine (sCr), and their combinations in detecting AKI in an adult general ICU population. METHODS: A total of 100 consecutive ICU patients were included in the analysis. AKI was defined according to RIFLE criteria. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: AKI occurred in 36% of patients 7 days post-admission. All three novel biomarkers as well as sCr had moderate predictive abilities for AKI occurrence. The most efficient combinations (pNGAL + sCr and pNGAL + uNGAL + sCr) were selected to participate in the subsequent analyses. Both combinations, when added to a reference clinical model, increased its AUC significantly (0.858, p = 0.04). Their NRI (0.78, p = 0.0002) was equal to that of pNGAL, but higher than that of the other three biomarkers, whereas their IDI was higher than that of any individual biomarker (0.23, p = 0.0001). Both combinations had better specificities, positive likelihood ratios, and positive predictive values than those of any individual biomarker. CONCLUSION: The biomarker combinations had better predictive characteristics compared with those of each biomarker alone.