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Purpose: The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in comatose patients with severe AKI., Methods: We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale [RASS] < - 3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < - 3), incomplete awakening (RASS [- 3; - 2]), awakening (RASS [- 1; + 1] two consecutive days), and agitation (RASS >  + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization., Results: A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio [HR] = 0.36 [0.17-0.78]; p = 0.010). Time spent awake was 10.11 days [8.11-12.15] and 7.63 days [5.57-9.64] in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results., Conclusion: In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Pulmonary embolism (PE) is a frequent complication in COVID19 hospitalized patients. Inflammatory storm and endothelial dysfunction due to the virus seem to be the two major risk factors for PE. Consequently, PE related to COVID19 could be consider as triggered by a transient inflammatory acute phase and treated for no longer than 3 months. However, few data are available on management of anticoagulation and risk of venous thromboembolic (VTE) recurrences in these patients and guidelines are still undefined. Aim of the present study is to evaluate the long-term follow-up of a cohort of covid-19 patients with PE., Methods: We conducted a retrospective multicenter study in four Italian hospitals between March 1st, 2020, and May 31st, 2021 in patients who experienced a PE during hospitalization for a COVID-19 pneumonia, excluding patients who died during hospitalization. Baseline characteristics were collected and patients were grouped according to duration of anticoagulant treatment (< 3 months or > 3 months). The primary outcome was incidence of VTE recurrence while secondary outcome was the composite of deaths, major hemorrhages and VTE recurrence during follow-up., Results: 106 patients with PE were discharged, of these 95 (89.6 %) had follow up longer than 3 months (seven patients were lost to follow up and four died within three months). The median follow-up was 13 months (IQR 1-19). Overall, 23 % of subjects (22/95) were treated for 3 months or less and 76.8 % (73/95) received anticoagulation for >3 months. Of patients in the short treatment group, 4.5 % died, compared with 5.5 % of those in the longer treatment group (p = NS); no difference was shown in risk of VTE recurrence (0 % vs 4.1 %, p = NS), major bleeding (4.5 % vs 4.1 %, p = NS) or in composite outcome (9.1 % vs 11 %, p = NS). No difference was found between the two treatment groups for composite outcome using the Kaplan-Meier analysis (Log Rank Test p = 0.387)., Conclusion: In our retrospective multi-center cohort, prolongation of duration of anticoagulation seems not to affect risk of VTE recurrences, deaths and bleeding after a PE related to COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To show the impact of problematic social media use (PSMU) on the 4 domains of emotional intelligence (emotional management, emotional awareness, social emotional awareness, and relationship management) among the Lebanese population., Methods: This cross-sectional study enrolled 466 adults (January-May 2019). The Social Media Disorder Scale and Quick Emotional Intelligence Self-Assessment were used to assess problematic social media use and emotional intelligence, respectively., Results: Higher PSMU was significantly associated with lower emotional management scores (β = -0.13), but not emotional awareness, social emotional awareness, relationship management, or total emotional intelligence scores. Female sex and older age were associated with higher social emotional awareness (β = 2.63 and β = 0.10, respectively) and relationship management (β = 2.12 and β = 0.13, respectively) scores., Conclusions: This study showed that higher PSMU was related to lower emotional intelligence. Future prospective studies are needed to gain an understanding of the relationship between PSMU and each component of emotional intelligence, as well as the mediating factors in such associations., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Background: Intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) are the two main RRT modalities in patients with severe acute kidney injury (AKI). Meta-analyses conducted more than 10 years ago did not show survival difference between these two modalities. As the quality of RRT delivery has improved since then, we aimed to reassess whether the choice of IHD or CRRT as first modality affects survival of patients with severe AKI., Methods: This is a secondary analysis of two multicenter randomized controlled trials (AKIKI and IDEAL-ICU) that compared an early RRT initiation strategy with a delayed one. We included patients allocated to the early strategy in order to emulate a trial where patients would have been randomized to receive either IHD or CRRT within twelve hours after the documentation of severe AKI. We determined each patient's modality group as the first RRT modality they received. The primary outcome was 60-day overall survival. We used two propensity score methods to balance the differences in baseline characteristics between groups and the primary analysis relied on inverse probability of treatment weighting., Results: A total of 543 patients were included. Continuous RRT was the first modality in 269 patients and IHD in 274. Patients receiving CRRT had higher cardiovascular and total-SOFA scores. Inverse probability weighting allowed to adequately balance groups on all predefined confounders. The weighted Kaplan-Meier death rate at day 60 was 54·4% in the CRRT group and 46·5% in the IHD group (weighted HR 1·26, 95% CI 1·01-1·60). In a complementary analysis of less severely ill patients (SOFA score: 3-10), receiving IHD was associated with better day 60 survival compared to CRRT (weighted HR 1.82, 95% CI 1·01-3·28; p < 0.01). We found no evidence of a survival difference between the two RRT modalities in more severe patients., Conclusion: Compared to IHD, CRRT as first modality seemed to convey no benefit in terms of survival or of kidney recovery and might even have been associated with less favorable outcome in patients with lesser severity of disease. A prospective randomized non-inferiority trial should be implemented to solve the persistent conundrum of the optimal RRT technique., (© 2022. The Author(s).)

Background: Trials comparing early and delayed strategies of renal replacement therapy in patients with severe acute kidney injury may have missed differences in survival as a result of mixing together patients at heterogeneous levels of risks. Our aim was to evaluate the heterogeneity of treatment effect on 60-day mortality from an early vs a delayed strategy across levels of risk for renal replacement therapy initiation under a delayed strategy., Methods: We used data from the AKIKI, and IDEAL-ICU randomized controlled trials to develop a multivariable logistic regression model for renal replacement therapy initiation within 48 h after allocation to a delayed strategy. We then used an interaction with spline terms in a Cox model to estimate treatment effects across the predicted risks of RRT initiation., Results: We analyzed data from 1107 patients (619 and 488 in the AKIKI and IDEAL-ICU trial respectively). In the pooled sample, we found evidence for heterogeneous treatment effects (P = 0.023). Patients at an intermediate-high risk of renal replacement therapy initiation within 48 h may have benefited from an early strategy (absolute risk difference, - 14%; 95% confidence interval, - 27% to - 1%). For other patients, we found no evidence of benefit from an early strategy of renal replacement therapy initiation but a trend for harm (absolute risk difference, 8%; 95% confidence interval, - 5% to 21% in patients at intermediate-low risk)., Conclusions: We have identified a clinically sound heterogeneity of treatment effect of an early vs a delayed strategy of renal replacement therapy initiation that may reflect varying degrees of kidney demand-capacity mismatch., (© 2022. The Author(s).)

Objective: Attention-deficit/hyperactivity disorder (ADHD) has been recognized as a clinically diverse condition with elevated rates of comorbidities with other psychiatric conditions. The consequences of social media are gaining attention worldwide due to its rapidly increased use. The objective of this study was to identify an association between problematic social media use and ADHD in a Lebanese sample and determine whether depression or anxiety could be considered as mediators of this association., Methods: This cross-sectional study was conducted between January and May 2019. Proportionate random-sampling techniques were applied on all Lebanese governorates, which resulted in the recruitment of 466 community-dwelling participants. Adult ADHD was identified using the Adult ADHD Self-Report Scale., Results: Higher problematic social media use (adjusted odds ratio [aOR] = 1.065) was significantly associated with higher odds of having ADHD. When anxiety was added as an independent variable, the results showed that higher anxiety (aOR = 1.043) was significantly associated with higher odds of ADHD. Anxiety mediated the association between problematic social media use and ADHD by 26.75%., Conclusions: A clear correlation was demonstrated in this study linking problematic social media use to anxiety and ADHD symptoms. This correlation was explained by the finding that constant stimulation provided by the social network sites significantly decreased attention. Future studies should evaluate the possible mechanisms and methods to increase awareness of problematic social media use, especially among the younger generation., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Background: The prevalence of pressure injuries (PIs) in critically ill patients has been extensively studied, but there is uncertainty regarding the risk factors. The main objective of this study was to describe the prevalence of PIs in critically ill patients. Secondary objectives were to describe PI, use of preventive measures for PI, and factors associated with occurrence of PI in the intensive care unit (ICU)., Material and Methods: This was a 1-day point-prevalence study performed on a weekday in June 2017 in ICUs in France. On the same day, we noted the presence or absence of PI in all hospitalised patients of the participating ICUs, data on the ICUs, and the characteristics of patients and of PI., Results: Eighty-six participating ICUs allowed the inclusion of 1228 patients. The prevalence of PI on the study day was 18.7% (95% confidence interval: 16.6-21.0). PIs acquired in the ICU were observed in 12.5% (95% confidence interval: 10.6-14.3) of critically ill patients on the study day. The most frequent locations of PI were the sacrum (57.4%), heel (35.2%), and face (8.7%). Severe forms of PI accounted for 40.8% of all PIs. Antiulcer mattresses were used in 91.5% of the patients, and active and/or passive mobilisation was performed for all the patients. Multiple logistic regression analysis identified longer length of stay in the ICU, a higher Simplified Acute Physiology Score, higher body weight, motor neurological disorder, high-dose steroids, and absence of oral nutrition on the study day as factors independently associated with occurrence of PI in the ICU., Conclusion: This large point-prevalence study shows that PIs are found in about one of five critically ill patients despite extensive use of devices for preventing PI. Acquisition of PI in the ICU is strongly related to the patient's severity of illness on admission to the ICU and length of stay in the ICU., (Copyright © 2020 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess the relationship of smoking (cigarettes or waterpipe), alcohol drinking, alexithymia, self-esteem, anxiety, depression, stress, social phobia, emotional intelligence, impulsivity, insomnia, physical health, and loneliness with problematic social media use (PSMU) in a sample of Lebanese citizens., Methods: This cross-sectional study enrolled 466 participants (January-May 2019)., Results: Higher anxiety, alcohol use disorder, and social phobia were correlated with elevated PSMU, while older age was associated with lower PSMU. Emotional intelligence partially mediated the association between alexithymia and PSMU by 4.55%., Practical Implications: Since these manifestations are preventable, spreading awareness through our schools, educational programs, and even healthcare professionals would considerably reduce the pace at which young adults are transforming into anxious and distorted individuals., (© 2020 Wiley Periodicals LLC.)

The present work aims to identify the predictors of COVID-19 in-hospital mortality testing a set of Machine Learning Techniques (MLTs), comparing their ability to predict the outcome of interest. The model with the best performance will be used to identify in-hospital mortality predictors and to build an in-hospital mortality prediction tool. The study involved patients with COVID-19, proved by PCR test, admitted to the "Ospedali Riuniti Padova Sud" COVID-19 referral center in the Veneto region, Italy. The algorithms considered were the Recursive Partition Tree (RPART), the Support Vector Machine (SVM), the Gradient Boosting Machine (GBM), and Random Forest. The resampled performances were reported for each MLT, considering the sensitivity, specificity, and the Receiving Operative Characteristic (ROC) curve measures. The study enrolled 341 patients. The median age was 74 years, and the male gender was the most prevalent. The Random Forest algorithm outperformed the other MLTs in predicting in-hospital mortality, with a ROC of 0.84 (95% C.I. 0.78-0.9). Age, together with vital signs (oxygen saturation and the quick SOFA) and lab parameters (creatinine, AST, lymphocytes, platelets, and hemoglobin), were found to be the strongest predictors of in-hospital mortality. The present work provides insights for the prediction of in-hospital mortality of COVID-19 patients using a machine-learning algorithm.

Background: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy., Methods: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed., Findings: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups., Interpretation: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm., Funding: Programme Hospitalier de Recherche Clinique., Competing Interests: Declaration of interests The authors declare no competing interests. The AKIKI 2 trial was promoted by the Assistance Publique—Hôpitaux de Paris and funded by a grant of the French Ministry of Health (Programme Hospitalier de Recherche Clinique 2016; AOM16278)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To examine the association between problematic social media use with depression, anxiety, insomnia, and stress in a sample of young Lebanese adults., Methods: This cross-sectional study was achieved between January and May 2019; 466 out of 600 adults completed the questionnaire., Results: Higher problematic social media use was significantly associated with higher depression, anxiety, and insomnia, but not stress. Stress mediated the relation between depression, anxiety, insomnia, and problematic social media use., Practical Implications: This study showed that problematic social media use was associated with psychological disorders. Additional research is needed to identify and describe the potential causality between the use of social media and various mental health issues and the interplay between the social media network and other mental health factors., (© 2020 Wiley Periodicals LLC.)

Background: Psychological factors such as depression, anxiety, stress and insomnia and problematic social media use are able to alter our memories and might have an impact on memory function and retrieval. More studies are needed to better understand the relationship between memory performance and mental health disorders, especially the ones that could be related to problematic social media use. The objective of this study was to evaluate any association between problematic social media use, depression, anxiety, stress, and insomnia vs memory performance among a representative sample of Lebanese people., Methods: This cross-sectional study, conducted between January and May 2019, enrolled 466 community dwelling participants using a proportionate random sample from all Lebanese governorates. The questionnaire consisted of the following measures: the Memory Awareness Rating Scale (MARS) to assesses views of memory performance, the problematic social media use scale to measure the degree of addiction to social media, the Hamilton depression rating scale and Hamilton anxiety scale to assess depression and anxiety respectively, the Beirut Distress Scale to assess stress and the Lebanese Insomnia sale to assess insomnia. The data analysis was performed using the SPSS software version 25. A linear regression was conducted, taking the memory performance scale as the dependent variable. A mediation analysis was performed to test the effect of problematic social media use on memory performance mediated by depression, anxiety, stress and insomnia., Results: Higher problematic social media use (Beta = - 0.21) and higher anxiety (Beta = - 0.25) were significantly associated with lower memory performance. The association between problematic social media use and memory performance was partially mediated by anxiety (21.19%) but not depression, stress or insomnia., Conclusion: Concerning problematic social media use, a clear correlation was demonstrated in this study linking it to lower memory performances. Future studies should evaluate the possible mechanisms and methods for effective awareness especially towards the younger generation.

Objectives: Standard nursing interventions, especially bed-baths, in ICUs can lead to complications or adverse events defined as a physiologic change that can be life-threatening or that prolongs hospitalization. However, the frequency and type of these adverse events are rarely reported in the literature. The primary objective of our study was to describe the proportion of patients experiencing at least one serious adverse event during bed-bath. The secondary objectives were to determine the incidence of each type of serious adverse event and identify risk factors for these serious adverse events., Design: Prospective multicenter observational study., Setting: Twenty-four ICUs in France, Belgium, and Luxembourg., Patients: The patients included in this study had been admitted to an ICU for less than 72 hours and required at least one of the following treatments: invasive ventilation, vasopressors, noninvasive ventilation, high-flow oxygen therapy. Serious adverse events were defined as cardiac arrest, accidental extubation, desaturation and/or mucus plugging/inhalation, hypotension and/or arrhythmia and/or agitation requiring therapeutic intervention, acute pain, accidental disconnection or dysfunction of equipment, and patient fall requiring additional assistance., Interventions: None., Measurements and Main Results: The study included 253 patients from May 1, 2018, to July 31, 2018 in 24 ICUs, representing 1,529 nursing procedures. The mean Simplified Acute Physiology Score II was 54 ± 19. Nursing care was administered by an average of 2 ± 1 caregivers and lasted between 11 and 20 minutes. Of the 253 patients included, 142 (56%) experienced at least one serious adverse event. Of the 1,529 nursing procedures, 295 (19%) were complicated by at least one serious adverse event. In multivariate analysis, the factors associated with serious adverse event were as follows: presence of a specific protocol (p = 0.011); tracheostomy (p = 0.032); administration of opioids (p = 0.007); presence of a physician (p = 0.0004); duration of nursing care between 6 and 10 minutes (p = 0.003), duration of nursing care between 11 and 20 minutes (p = 0.005), duration of nursing care greater than 40 minutes (p = 0.04) with a reference duration of nursing care between 20 and 40 minutes., Conclusions: Serious adverse events were observed in one-half of patients and concerned one-fifth of nurses, confirming the need for caution. Further studies are needed to test systematic serious adverse event prevention strategies., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

The present study assessed the proportion of intensive care unit (ICU) patients who had a vancomycin serum concentration between 20 and 25 mg/L after 24-48 h of intravenous vancomycin administration. From 2016 to 2018, adult ICU patients with vancomycin continuous infusion (CI) for any indication were included. The primary outcome was the proportion of patients with a first-available vancomycin serum concentration between 20-25 mg/L at 24 h (D2) or 48 h (D3). Of 3894 admitted ICU patients, 179 were included. A median loading dose of 15.6 (interquartile range (IQR) = (12.5-20.8) mg/kg) was given in 151/179 patients (84%). The median daily doses of vancomycin infusion for D1 and D2 were 2000 [(IQR (1600-2000)) and 2000 (IQR (2000-2500)) mg/d], respectively. The median duration of treatment was 4 (2-7) days. At D2 or D3, the median value of first serum vancomycin concentration was 19.8 (IQR (16.0-25.1)) with serum vancomycin concentration between 20-25 mg/L reported in 43 patients (24%). Time spent in the ICU before vancomycin initiation was the only risk factor of non-therapeutic concentration at D2 or D3. Acute kidney injury occurred significantly more when vancomycin concentration was supra therapeutic at D2 or D3. At D28, 44 (26%) patients had died. These results emphasize the need of appropriate loading dose and regular monitoring to improve vancomycin efficacy and avoid renal toxicity.

Objectives: Data about end-stage kidney disease patients admitted to the ICU are scarce, dated, and mostly limited to short-term survival. The aim of this study was to assess the short- and long-term outcome and to determine the prognostic factors for end-stage kidney disease patients admitted to the ICU., Design: Prospective observational study., Setting: Medical ICUs in two university hospitals., Patients: Consecutive end-stage kidney disease patients admitted in two ICUs between 2012 and 2017., Intervention: None., Measurements and Main Results: Renal replacement therapy variables, demographic, clinical, and biological data were collected. The requirement of mechanical ventilation and vasopressive drugs were also collected. In-ICU and one-year mortality were estimated and all data were analyzed in order to identify predictive factors of short and long-term mortality. A total of 140 patients were included, representing 1.7% of total admissions over the study period. Septic shock was the main reason for admission mostly of pulmonary origin. Median Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score were at 63 and 6.7, respectively. In-ICU, hospital, and 1-year mortality were 41.4%, 46.4%, and 63%, respectively. ICU mortality was significantly higher as compared with ICU control group non-end-stage kidney disease (25% vs 41.4%; p = 0.005). By multivariate analysis, the short-term outcome was significantly associated with nonrenal Sequential Organ Failure Assessment score, and with the requirement of mechanical ventilation or/and vasoconstrictive agents during ICU stay. One-year mortality was associated with increased dialysis duration (> 3 yr) and phosphatemia (> 2.5 mmol/L), with lower albuminemia (< 30 g/L) and nonrenal Sequential Organ Failure Assessment greater than 8., Conclusions: End-stage kidney disease patients presented frequently severe complications requiring critical care that induced significant short- and long-term mortality. ICU and hospital mortality depended mainly on the severity of the critical event reflected by Sequential Organ Failure Assessment score and the need of mechanical ventilation and/or catecholamines. One-year mortality was associated with both albuminemia and phosphatemia and with prior duration of chronic dialysis treatment, and with organ failure at ICU admission.

Background: The timing of renal replacement therapy (RRT) for severe acute kidney injury is highly debated when no life-threatening complications are present. We assessed whether a strategy of delayed versus early RRT initiation affects 28-day survival in critically ill adults with severe acute kidney injury., Methods: In this systematic review and individual patient data meta-analysis, we searched MEDLINE (via PubMed), Embase, and the Cochrane Central Register of Controlled Trials for randomised trials published from April 1, 2008, to Dec 20, 2019, that compared delayed and early RRT initiation strategies in patients with severe acute kidney injury. Trials were eligible for inclusion if they included critically ill patients aged 18 years or older with acute kidney injury (defined as a Kidney Disease: Improving Global Outcomes [KDIGO] acute kidney injury stage 2 or 3, or, where KDIGO was unavailable, a renal Sequential Organ Failure Assessment score of 3 or higher). We contacted the principal investigator of each eligible trial to request individual patient data. From the included trials, any patients without acute kidney injury or who were not randomly allocated were not included in the individual patient data meta-analysis. The primary outcome was all-cause mortality at day 28 after randomisation. This study is registered with PROSPERO (CRD42019125025)., Findings: Among the 1031 studies identified, one study that met the eligibility criteria was excluded because the recruitment period was not recent enough, and ten (including 2143 patients) were included in the analysis. Individual patient data were available for nine studies (2083 patients), from which 1879 patients had severe acute kidney injury and were randomly allocated: 946 (50%) to the delayed RRT group and 933 (50%) to the early RRT group. 390 (42%) of 929 patients allocated to the delayed RRT group and who had available data did not receive RRT. The proportion of patients who died by day 28 did not significantly differ between the delayed RRT group (366 [44%] of 837) and the early RRT group (355 [43%] of 827; risk ratio 1·01 [95% CI 0·91 to 1·13], p=0·80), corresponding to an overall risk difference of 0·01 (95% CI -0·04 to 0·06). There was no heterogeneity across studies (I 2 =0%; τ 2 =0), and most studies had a low risk of bias., Interpretation: The timing of RRT initiation does not affect survival in critically ill patients with severe acute kidney injury in the absence of urgent indications for RRT. Delaying RRT initiation, with close patient monitoring, might lead to a reduced use of RRT, thereby saving health resources., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The simplified Geneva risk assessment model (RAM) predicts the risk of hospitalization-related venous thromboembolism (VTE) in medical inpatients in its developmental cohort but has not been validated., Objectives: To externally validate the simplified Geneva RAM., Patients/methods: For this secondary analysis of a prospective cohort set in Padua, we calculated the simplified Geneva RAM for all participants. They were followed up for 90 days for the occurrence of adjudicated VTE. Thirty- and 90-day risks of VTE were estimated by the Kaplan-Meier method, and categories of risks compared with a Cox regression model adjusted for the use of thromboprophylaxis., Results: Among 1180 medical inpatients, the 90-day risk of symptomatic VTE was 3.1%. The simplified Geneva RAM classified 56.9% as high risk (≥3 points; 90-day risk of VTE of 5.2%) and 43.1% as low risk (<3 points; 90-day risk of VTE of 0.4%). Compared with low-risk participants, high-risk participants had an 18-fold greater risk of VTE than low-risk participants (hazard ratio [HR] 17.9, 95% confidence interval [CI] 4.3-74.7). A very high-risk category (≥7 points) identified 5.3% of participants with a 9.5% probability of VTE at 90 days., Conclusions: In this external validation study, we confirm the excellent discrimination and clinically adequate calibration of the simplified Geneva RAM as a stratification tool to guide the use of thromboprophylaxis., (© 2019 International Society on Thrombosis and Haemostasis.)

Background: The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed "standard") with another in which RRT is further delayed for a longer period (termed "delayed strategy")., Methods/design: This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects., Discussion: The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019., Trial Registration: ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018.

We sought to better define the demographics and characteristics of post-transplant lymphoproliferative disorders (PTLD) in a cohort of paediatric OHT patients from a developing country. Data were collected from the Heart Institute, Sao Paulo, for all paediatric OHT recipients from October 1992 to October 2018. Group differences between the PTLD and non-PTLD cohorts were assessed by Fisher exact and Mann-Whitney U tests. Kaplan-Meier curves analysed the survival in each group. Data were reviewed for 202 paediatric OHT recipients. Overall 1-, 5- and 10-year survival for the entire cohort was 76.5%, 68.3% and 62.9%; 24 patients (11.9%) developed PTLD at a median 3.1 years (IQR 0.8-9.0) after OHT. Cases were evenly spread over the follow-up period, with PTLD diagnosed in 9.8% (n = 137) of patients who were alive at 3 years, 15.3% (n = 78) of patients who were alive at 5 years and 29.3% (n = 41) of patients who were alive at 10 years. The commonest form of PTLD was diffuse large B cell lymphoma (n = 9), and most patients received rituximab with immunosuppression and chemotherapy as treatment (n = 15). We identified no increased risk in mortality amongst the PTLD vs. non-PTLD cohorts in multivariate analysis (P = 0.365). PTLD after paediatric OHT had acceptable outcomes. However, risk factors for PTLD were not identified and warrant further investigation.

Background: The Bova score has shown usefulness in the identification of intermediate-high risk patients with acute pulmonary embolism (PE), but lacks prospective validation. The aim of this study was to prospectively validate the Bova score in different settings from the original derivation cohort., Methods: Consecutive, normotensive patients with acute PE recruited at 13 academic or general hospitals were stratified, using their baseline data, into the three Bova risk stages (I-III). The primary outcome was the 30-day composite of PE-related mortality, hemodynamic collapse and non-fatal PE recurrences in the three risk categories., Results: In the study period, 639 patients were enrolled. The primary end point occurred in 45 patients (7.0%; 95% Confidence Intervals, 5.2%-9.3%). Risk stage correlated with the PE-related complication rate (stage I, 2.9%; stage II, 17%; stage III, 27%). Patients classified as stage III by the Bova score had a 6.5-fold increased risk for adverse outcomes (3.1-13.5, p < 0.001) compared with stages I and II combined. Rescue thrombolysis increased from stage I to stage III (0.6%, 12% and 15% respectively). All-cause mortality (5.3%) did not substantially differ among the stages., Conclusions: The Bova score accurately stratifies normotensive patients with acute PE into stages of increasing risk of 30-day PE-related complications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Monitoring fungal ecology and resistance to antifungal agents within intensive care units (ICU) is essential for the management of invasive fungal infections. Therefore, a retrospective descriptive study was carried in the ICU of Nimes University Hospital, France, from 2007 to 2016. As the majority of invasive fungal infections in ICU are caused by Candida species, the study objectives were to describe Candida species distribution, to assess candidaemia incidence and to monitor the antifungal drug susceptibility of Candida isolates and the consumption of antifungal agents. Among the recorded invasive Candida infections (n=244), 43% were intra-abdominal and 22% bloodstream infections. Candida albicans was the most frequent species (55.8%), followed by Candida glabrata (14.1%), Candida tropicalis (10%), Candida parapsilosis (8%) and Candida krusei (5.3%). Candidaemia incidence was 4.49 per 1000 admissions. The mean consumption of antifungal agents was of 170.5 defined daily doses (DDD) for 1000 hospital days (HD) per year. Changes in antifungal drug consumption were observed, with an increased use of echinocandins (from 17.96 DDD/1000 HD in 2007 to 48.76 DDD/1000 HD in 2016), and the total treatment cost tripled during the study period. No significant change in fungal ecology or in the emergence of resistant species was observed; indeed, only 1.1% of isolates presented an unusual resistance to antifungal agents., (© 2017 Blackwell Verlag GmbH.)

Deep vein thrombosis and pulmonary embolism are associated with considerable morbidity and mortality in hospitalized patients, accounting for up to 10% of hospitalization-related deaths in both surgical and medical patients. Pharmacologic thromboprophylaxis has been demonstrated to be effective, safe, and cost-effective in preventing hospital-acquired venous thromboembolism (VTE) among medical inpatients, and clinician awareness of thrombotic risk promotes prescription of thromboprophylaxis. Guidelines recommend stratification of thrombotic risk for all patients and, unless contraindicated, administration of VTE prophylaxis. Based on several recognized predisposing and exposing risk factors for VTE, several scoring systems have been published in the past 15 years. Borrowing models developed in the surgical setting, recognized risk factors for VTE complications in medical inpatients have been combined in different weighted scores and derived and validated in heterogeneous medical populations. Although the perfect score, balancing thrombotic and hemorrhagic risk, has probably not yet been built, the adoption of an easy-to-use risk assessment model has the potential to support physicians in properly stratifying VTE risk in medical inpatients, tailoring thromboprophylaxis prescription., Competing Interests: Conflict of Interest: The authors declare no conflict of interest. Contribution S.B. and P.P. wrote the article and approved the final manuscript., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: The prevalence of pulmonary embolism among patients hospitalized for syncope is not well documented, and current guidelines pay little attention to a diagnostic workup for pulmonary embolism in these patients., Methods: We performed a systematic workup for pulmonary embolism in patients admitted to 11 hospitals in Italy for a first episode of syncope, regardless of whether there were alternative explanations for the syncope. The diagnosis of pulmonary embolism was ruled out in patients who had a low pretest clinical probability, which was defined according to the Wells score, in combination with a negative d-dimer assay. In all other patients, computed tomographic pulmonary angiography or ventilation-perfusion lung scanning was performed., Results: A total of 560 patients (mean age, 76 years) were included in the study. A diagnosis of pulmonary embolism was ruled out in 330 of the 560 patients (58.9%) on the basis of the combination of a low pretest clinical probability of pulmonary embolism and negative d-dimer assay. Among the remaining 230 patients, pulmonary embolism was identified in 97 (42.2%). In the entire cohort, the prevalence of pulmonary embolism was 17.3% (95% confidence interval, 14.2 to 20.5). Evidence of an embolus in a main pulmonary or lobar artery or evidence of perfusion defects larger than 25% of the total area of both lungs was found in 61 patients. Pulmonary embolism was identified in 45 of the 355 patients (12.7%) who had an alternative explanation for syncope and in 52 of the 205 patients (25.4%) who did not., Conclusions: Pulmonary embolism was identified in nearly one of every six patients hospitalized for a first episode of syncope. (Funded by the University of Padua; PESIT ClinicalTrials.gov number, NCT01797289 .).

Background: Lupeol and betulin are triterpenoids that are majorly found in dietary substances. The aim of present study was to investigate the inhibition and induction potential of lupeol and betulin on cytochrome P450 (CYP)1A2, CYP2C11, CYP2D6 and CYP3A2 activities in rat liver microsomes., Methods: The inhibition and induction studies were conducted using ethoxy resorufin-O-deethylase (CYP1A2), tolbutamide hydroxylase (CYP2C9), and midazolam hydroxylase (CYP3A4) activity assays. In vitro inhibition study was evaluated by incubating lupeol and betulin (1, 3, 10, 30 and 100 μM) with rat liver microsomes, and the metabolite formation was analyzed by high-performance liquid chromatography. The induction study was conducted by administering lupeol (20 mg/kg) and betulin (50 mg/kg) intraperitoneally for 14 days to rats followed by liver isolation and microsome preparation., Results: The IC50 values in inhibition studies were found to be 59.42 μM (CYP1A2), >100 μM (CYP2C11, CYP2D6, CYP3A2) for lupeol, 52.24 μM (CYP1A2), and >100 μM (CYP2C9, CYP2D6, CYP3A2) for betulin. There was no significant modification observed in the CYP450 isoforms, indicating neither inhibition nor induction potential of lupeol and betulin., Conclusions: Lupeol and betulin have very low propensity to interact with CYP enzyme, suggesting no CYP inhibitory and inducing potential in rat liver microsomes.

Low peak plasma concentrations (Cmax) of amikacin and gentamicin are reported in intensive care unit (ICU) patients after administration of the first dose. The present study aimed to describe the proportion of ICU patients in whom an adequate Cmax was achieved throughout the course of therapy. Septic ICU patients with an indication for intravenous amikacin or gentamicin were eligible for inclusion in this single-centre observational study. The first and subsequent doses and the corresponding Cmax values were recorded. The target Cmax was ≥60mg/L for amikacin and ≥30mg/L for gentamicin. Amikacin and gentamicin plasma concentrations were available in 66 and 24 patients, respectively (59±17 years; 79±19kg; height 169±12cm; SAPS II score 46±19). Pulmonary, abdominal and urinary tract infections were diagnosed in 64 patients. Culture-positive infection was confirmed in 65 patients (72%). A target first Cmax was achieved in 17/90 patients (19%). For amikacin, the target Cmax was achieved in 16/66 patients (24%) after the initial dose. In the 50 remaining patients, a change in dosing was performed in 14 patients, leading adequate peak plasma level in 2 patients. For gentamicin, the targeted Cmax was achieved in only 1/24 patient (4%) after the initial dose and was never achieved after the third dose. In conclusion, standard dosing of amikacin or gentamicin led to adequate Cmax in only 19% of patients. Subtherapeutic Cmax were not significantly corrected after subsequent doses., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Once anticoagulation is stopped, the risk of recurrent venous thromboembolism (VTE) over years after a first episode is consistently around 30%. This risk is higher in patients with unprovoked than in those with (transient) provoked VTE, and among the latter in patients with medical than in those with surgical risk factors. Baseline parameters that have been found to be related to the risk of recurrent VTE are the proximal location of deep-vein thrombosis, obesity, old age, male sex and non-0 blood group, whereas the role of inherited thrombophilia is controversial. The persistence of residual vein thrombosis at ultrasound assessment has consistently been shown to increase the risk, as do persistently high values of D-dimer and the early development of the post-thrombotic syndrome. Although the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, strategies that incorporate the assessment of residual vein thrombosis and D-dimer have the potential to identify subjects in whom anticoagulation can be safely discontinued. Moreover, new opportunities are offered by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving the same effectiveness; and by low-dose aspirin, which has the potential to prevent the occurrence of both venous and arterial thrombotic events.

The separate nature of venous and arterial thrombotic disorders has recently been challenged. Patients with venous thromboembolism (VTE) have an increased risk of subsequent symptomatic arterial cardiovascular events, the risk being higher in those with unexplained episodes. Among the implications of this association, there is the potential for old and new antithrombotic drugs to impact on the development of both venous and arterial cardiovascular events. According to the results of recent studies, aspirin in low doses, when administered for the long-term management of patients with unprovoked VTE, reduces by approximately 35% the risk of recurrent VTE while offering a considerable protection against the development of arterial cardiovascular events. By contrast, there is no room to expect a reduction in the risk of subsequent arterial cardiovascular events in patients treated with vitamin K antagonists (VKA) in comparison to patients in whom VKAs are discontinued. According to the results from recent randomized clinical trials, the likelihood of arterial cardiovascular events in patients on the novel direct factor Xa inhibitors is unlikely to differ from that of patients receiving conventional anticoagulation. As dabigatran has been associated with a slight increase in the risk of myocardial infarction over warfarin, its use should be discouraged in patients with coronary heart disease. The long-term use of low-dose apixaban beyond the first months in patients with unprovoked VTE may decrease the long-term risk of arterial, as well as venous, thrombotic events., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The introduction of factor Xa inhibitors advocated the initiation of clinical trials that addressed the value of anticoagulation in patients with hemodynamically stable primary pulmonary embolism (PE). In the Matisse trial in patients with PE, fondaparinux administered at therapeutic doses followed by vitamin K antagonists (VKA) has shown a comparable efficacy and safety profile to that seen with intravenous adjusted-dose unfractionated heparin/VKA. A long-acting derivative of fondaparinux, idraparinux, failed to achieve similar results. On the other hand, the Cassiopea study revealed that once weekly injections of idrabiotaparinux, a slightly modified form of idraparinux, have similar efficacy and better safety profile compared to VKAs in the long-term treatment of patients with PE. However, the inconvenient parenteral administration of both fondaparinux and idrabiotaparinux limits their routine clinical use. The availability of antithrombotic compounds that can be administered orally in fixed dose, owing to their predictable pharmacokinetics and pharmacodynamics, and have a lower potential for drug and food interactions has opened new horizons for the treatment of patients with PE. The Einstein PE, Amplify and Hokusai studies, conducted with rivaroxaban, apixaban and edoxaban, respectively, showed that for the treatment of PE they possess a more favorable benefit-to-risk profile than the conventional antithrombotic drugs. In addition, rivaroxaban and apixaban make it possible to treat uncomplicated PE patients from the beginning, without the need for the parenteral administration of heparins or fondaparinux, and edoxaban allows the treatment of fragile patients with lower doses. All of them cover a wide spectrum of clinical presentations, including PE patients at intermediate risk.

The risk of recurrent thromboembolic disorders in the 10-year period following an episode of unprovoked venous thromboembolism (VTE) ranges between 30 and 50%, the rate being higher in patients with primary deep venous thrombosis (DVT) than in those with primary pulmonary embolism (PE). The clinical presentation with primary PE increases by more than three times the risk of a new PE episode over that with isolated DVT. Baseline parameters that increase this risk are the proximal location of DVT, obesity, old age and male sex, whereas the role of thrombophilia is controversial. An increasing role is played by post-baseline parameters such as the ultrasound assessment of residual vein thrombosis and the determination of D-dimer. While the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, new scenarios are being offered by the identification of risk stratification models and by strategies that have the potential to help identify patients in whom anticoagulation can be safely discontinued, such as those that incorporate the assessment of D-dimer and residual vein thrombosis. New opportunities are being offered by low-dose aspirin, which has recently been reported to decrease by more than 30% the risk of recurrent events without increasing the bleeding risk; and especially by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving at least the same effectiveness, do not require laboratory monitoring, and can be used immediately after the thrombotic episode., (© 2013.)

Objectives: Antithrombotic treatment for retinal vein occlusion (RVO) is controversial, although RVO has been surmised as a predictor of a subsequent vascular event. We aimed to evaluate risk factors, the effects of antithrombotic therapy and the occurrence of subsequent vascular events in patients with a first episode of RVO, according to age of RVO onset., Methods: In this prospective cohort study, patients with central (CRVO) and branch RVO (BRVO) confirmed by fluorescein angiography were studied; they were divided according to age. Cardiovascular risk factors and thrombophilia were evaluated. Anticoagulants or aspirin were given for at least 3 months. Patients were followed every 6-12 months and vascular events were recorded., Results: One hundred CRVO and 32 BRVO patients were enrolled. Five of 60 (8.3%) patients <50 yr and 4/72 (5.5%) over 50 yr had a hereditary thrombophilic defect. One or more cardiovascular risk factors were found in 35 (58%) patients of the younger group, and in 66 (91%) of the older group (P < 0.001). Antithrombotic treatment led to both a satisfactory recanalization of occluded veins and visual acuity improvement especially in younger patients. Vascular events occurred in 19 (14%) cases after 4 ± 3.3 yr from RVO, more frequently in older than in younger patients (22% vs. 5%, P = 0.005)., Conclusions: Distribution of cardiovascular, but not of thrombophilic risk factors seems to be influenced by age in RVO patients. Patients with a first RVO, especially those >50 yr, are likely at risk of a subsequent vascular event., (© 2013 John Wiley & Sons A/S.)

Objectives: Cerebral vein thrombosis (CVT) is a potentially fatal disorder for which treatment guidelines are scanty. To assess the short- and long-term benefit of anticoagulant therapy, we performed a prospective cohort study on CVT patients., Methods: Forty-four consecutive CVT patients received conventional anticoagulation with heparin followed by warfarin for at least 3 months. Patients presenting with symptoms suggestive of pulmonary embolism (PE) underwent confirmatory objective tests. Acquired or inherited risk factors for thrombosis were investigated in all patients. Thrombotic and hemorrhagic events occurring during treatment, and the long-term outcome using the modified Rankin Scale (mRS) were recorded., Results: Congenital and/or acquired conditions predisposing to thrombosis were detected in 37 patients (84.1%), with a high prevalence of oral contraceptive use (66.7% of females) and thrombophilia (31.8%); more than one risk factor was seen in 31.8% of cases. At referral, six patients (13.6%) presented with symptoms of PE, which was confirmed in all. During the initial treatment period, two patients (4.5%) developed symptomatic progression of CVT, which was fatal in 1, and 2 (4.5%) developed major bleeding complications. A favorable outcome (mRS 0-2) at 6-12 months was recorded in 37 of the 43 patients who survived the acute phase (86%)., Conclusions: The outcome of CVT patients managed with conventional anticoagulation who survive the initial phase is favorable in the vast majority. The prevalence of concomitant PE is considerably high, supporting the need of anticoagulant therapy., (© 2012 John Wiley & Sons A/S.)

Background: Little information is available on the long-term clinical outcome of cerebral vein thrombosis (CVT)., Objectives and Methods: In an international, retrospective cohort study, we assessed the long-term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode., Results: Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient-years. Median follow-up was 40 months (range 6, 297 months). At the end of follow-up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Score [mRS] 0-1) and 3.8% had a partial recovery and were independent (mRS 2). Eighty-four per cent of patients were treated with oral anticoagulants and the mean treatment duration was 12 months. CVT recurred in 31 patients (4.4%), and 46 patients (6.5%) had a VTE in a different site, for an overall incidence of recurrence of 23.6 events per 1000 patient-years (95% confidence Interval [CI] 17.8, 28.7) and of 35.1 events/1000 patient-years (95% CI, 27.7, 44.4) after anticoagulant therapy withdrawal. A previous VTE was the only significant predictor of recurrence at multivariate analysis (hazard ratio [HR] 2.70; 95% CI 1.25, 5.83)., Conclusions: The long-term risk of mortality and recurrent VTE appears to be low in patients who survived the acute phase of CVT. A previous VTE history independently predicts recurrent events., (© 2012 International Society on Thrombosis and Haemostasis.)

Objectives: The benefit of arginine in intensive care unit patients with severe sepsis is still controversial. An excessive supply of arginine could lead to an overproduction of nitric oxide and could be responsible for septic shock and multiorgan failure. However, this claim is not supported by any experimental or clinical data. We set out to determine whether an enteral supply of arginine would modulate bacterial invasion in rats with head injury., Methods: Male Sprague-Dawley rats with head injury were randomized into two groups. Group 1 included rats with head injury fed a standard enteral nutrition (Sondalis HP, n = 10) and group 2 included rats with head injury fed the standard enteral nutrition plus arginine (4 g/kg/d, n = 11). Two days after head injury, the rats received a single enteral bolus of luminescent Escherichia coli Xen 14. Bacterial proliferation was evaluated in vivo at time + 2 hrs and time + 6 hrs after E. coli challenge. Four days after head injury, blood was sampled for arginine and fibrinogen assay. Muscles, intestine, spleen, and thymus were removed and weighed., Results: There was no mortality in either group. The luminescence signal was similar in the two groups at time +2 hrs (group 1: 414 [5-823] vs. group 2: 496 [0.1-993] (median value[min-max]; not significant) and was significantly lower at time +6 hrs in group 2 (group 1: 71 [0-142] vs. group 2: 8.5 [0-17]; p = .026). Arginine treatment did not improve any nutritional parameters., Conclusions: Arginine was not responsible for mortality in rats with head injury with infectious complications and reduced the intensity of bacterial invasion.

Purpose: Burnout syndrome (BOS) has frequently been reported in healthcare workers, and precipitating factors include communication problems in the workplace and stress related to end-of-life situations. We evaluated the effect of an intensive communication strategy on BOS among caregivers working in intensive care (ICU)., Methods: Longitudinal, monocentric, before-and-after, interventional study. BOS was evaluated using the Maslach Burnout Inventory (MBI) and depression using the Centre for Epidemiologic Studies Depression Scale (CES-D) in 2007 (period 1) and 2009 (period 2). Between periods, an intensive communication strategy on end-of-life practices was implemented, based on improved organisation, better communication, and regular staff meetings., Results: Among 62 caregivers in the ICU, 53 (85%) responded to both questionnaires in period 1 and 49 (79%) in period 2. We observed a significant difference between periods in all three components of the MBI (emotional exhaustion, p = 0.04; depersonalization p = 0.04; personal accomplishment, p = 0.01). MBI classified burnout as severe in 15 (28%) caregivers in period 1 versus 7 (14%) in period 2, p < 0.01, corresponding to a 50% risk reduction. Symptoms of depression as evaluated by the CES-D were present in 9 (17%) caregivers in period 1 versus 3 (6%) in period 2, p < 0.05, corresponding to a risk reduction of almost 60%., Conclusion: The implementation of an active, intensive communication strategy regarding end-of-life care in the ICU was associated with a significant reduction in the rate of burnout syndrome and depression in a stable population of caregiving staff.

Purpose: Since the 2005 French law on end of life and patients' rights, it is unclear whether practices have evolved. We investigated whether an intensive communication strategy based on this law would influence practices in terms of withholding and withdrawing treatment (WWT), and outcome of patients hospitalised in intensive care (ICU)., Methods: This was a single-centre, two-period study performed before and after the 2005 law. Between these periods, an intensive strategy for communication was developed and implemented, comprising regular meetings and modalities for WWT. We examined medical records of all patients who died in the ICU or in hospital during both periods., Results: In total, out of 2,478 patients admitted in period 1, 678 (27%) died in the ICU and 823/2,940 (28%) in period 2. In period 1, among patients who died in the ICU, 45% died subsequent to a decision to WWT versus 85% in period 2 (p < 0.01). Among these, median time delay between ICU admission and initiation of decision-making process was significantly different (6-7 days in period 1 vs. 3-5 days in period 2, p < 0.05). Similarly, median time from admission to actual WWT decision was significantly shorter in period 2 (11-13 days in period 1 vs. 4-6 days in period 2, p < 0.05). Finally, median time from admission to death in the ICU subsequent to a decision to WWT was 13-15 days in period 1 versus 7-8 days in period 2, p < 0.05. Reasons for WWT were not significantly different between periods., Conclusion: Intensive communication brings about quicker end-of-life decision-making in the ICU. The new law has the advantage of providing a legal framework.

Background: Prophylaxis of venous thromboembolism (VTE) in hospitalized medical patients is largely underused. We sought to assess the value of a simple risk assessment model (RAM) for the identification of patients at risk of VTE., Methods: In a prospective cohort study, 1180 consecutive patients admitted to a department of internal medicine in a 2-year period were classified as having a high or low risk of VTE according to a predefined RAM. They were followed-up for up to 90 days to assess the occurrence of symptomatic VTE complications. The primary study outcome was to assess the adjusted hazard ratio (HR) of VTE in high-risk patients who had adequate in-hospital thromboprophylaxis in comparison with those who did not, and that of VTE in the latter group in comparison with low-risk patients., Results: Four hundred and sixty-nine patients (39.7%) were labelled as having a high risk of thrombosis. VTE developed in four of the 186 (2.2%) who received thromboprophylaxis, and in 31 of the 283 (11.0%) who did not (HR of VTE, 0.13; 95% CI, 0.04-0.40). VTE developed also in two of the 711 (0.3%) low-risk patients (HR of VTE in high-risk patients without prophylaxis as compared with low-risk patients, 32.0; 95% CI, 4.1-251.0). Bleeding occurred in three of the 186 (1.6%) high-risk patients who had thromboprophylaxis., Conclusions: Our RAM can help discriminate between medical patients at high and low risk of VTE. The adoption of adequate thromboprophylaxis in high-risk patients during hospitalization leads to longstanding protection against thromboembolic events with a low risk of bleeding., (© 2010 International Society on Thrombosis and Haemostasis.)

Cancer produces a hypercoagulable state, which might lead to thrombosis, and on contrary, unprovoked venous thromboembolism might be the manifestation of an occult cancer. In this pilot case-control study, we assessed the risk of gynecological malignant diseases related to the presence of the factor V Leiden and prothrombin G20210A polymorphisms. Fifty-two women underwent an operation for gynecological malignancy and were enrolled in the study. Women who underwent an operation for gynecological nonmalignant disease in the same days of cases were considered as controls. The presence of factor V Leiden and prothrombin G20210A was assessed in case and control groups. In all, 7 out of 52 cases were carriers of the 2 polymorphisms compared with 20 out of 198 controls (odds ratio = 1.3; 95% confidence interval, 0.6-3.0). The results were also similar when the risk was considered separately for the site of cancer. As for advanced and metastatic malignancies, the odds ratios were 2.3 (95% confidence interval, 0.9-6.0) and 3.3 (95% confidence interval, 1.0-11), respectively, compared to noncancer patients. When these 2 groups were compared to nonadvanced cancer group, the odds ratios for carriers of polymorphisms were 2.7 (95%confidence interval, 0.7-11.0) and 3.9 (95%confidence interval, 0.8-18.6) for advanced cancer and metastatic malignancies, respectively. Women with factor V Leiden or prothrombin G20210A polymorphisms who developed gynecological malignancy might present with a higher stage of cancer at the time of surgery. Larger case-control studies in similar cohort of patients are needed to confirm these findings.

Purpose of Review: To discuss the risk factors and underlying illnesses that play a role in the pathophysiology of stress ulcer, and to evaluate the evidence pertaining to stress ulcer-related bleeding prophylaxis in critically ill patients., Recent Findings: The use of stress ulcer prophylaxis is common in critical care medicine and is a major challenge to physicians in the ICU. The mechanism of stress ulcer is believed to be multifactorial, yet remains incompletely understood. The most widely used drugs for stress ulcer prophylaxis are intravenous histamine2-receptor antagonists. They raise gastric pH, but are associated with the development of tolerance, possible drug interactions, and neurologic manifestations. Sucralfate, which can be administered by the nasogastric route, can protect the gastric mucosa without raising pH, but may decrease absorption of concomitantly administered oral medications. Proton pump inhibitors are the most potent acid-inhibiting pharmacologic agents available. Proton pump inhibitors are at least as effective as histamine2-receptor antagonists, as a limited number of clinical trials have demonstrated. However, these trials were small, lacked an active comparator, varied in the number of risk factors, and used a different definition of clinically important bleeding than previously established., Summary: Routine prophylaxis against stress ulcers in the ICU is not well justified by current evidence. Patients at risk of stress ulcer-related bleeding are most likely to benefit from prophylaxis. Thus, healthcare professionals should continue to evaluate risk and assess the need for stress ulcer-related prophylaxis.

Introduction: Management of the early stage of sepsis is a critical issue. As part of it, infection control including appropriate antibiotic therapy administration should be prompt. However, microbiological findings, if any, are generally obtained late during the course of the disease. The potential interest of procalcitonin (PCT) as a way to assess the clinical efficacy of the empirical antibiotic therapy was addressed in the present study., Methods: An observational cohort study including 180 patients with documented sepsis was conducted in our 15-bed medical intensive care unit (ICU). Procalcitonin measurement was obtained daily over a 4-day period following the onset of sepsis (day 1 (D1) to D4). The PCT time course was analyzed according to the appropriateness of the first-line empirical antibiotic therapy as well as according to the patient outcome., Results: Appropriate first-line empirical antibiotic therapy (n = 135) was associated with a significantly greater decrease in PCT between D2 and D3 (DeltaPCT D2-D3) (-3.9 (35.9) vs. +5.0 (29.7), respectively; P < 0.01). In addition, DeltaPCT D2-D3 was found to be an independent predictor of first-line empirical antibiotic therapy appropriateness. In addition, a trend toward a greater rise in PCT between D1 and D2 was observed in patients with inappropriate antibiotics as compared with those with appropriate therapy (+5.2 (47.4) and +1.7 (35.0), respectively; P = 0.20). The D1 PCT level failed to predict outcome, but higher levels were measured in the nonsurvivors (n = 51) when compared with the survivors (n = 121) as early as D3 (40.8 (85.7) and 21.3 (41.0), respectively; P = 0.04). Moreover, PCT kinetics between D2 and D3 were also found to be significantly different, since a decrease >or= 30% was expected in the survivors (log-rank test, P = 0.04), and was found to be an independent predictor of survival (odds ratio = 2.94; 95% confidence interval 1.22 to 7.09; P = 0.02)., Conclusions: In our study in an ICU, appropriateness of the empirical antibiotic therapy and the overall survival were associated with a greater decline in PCT between D2 and D3. Further studies are needed to assess the utility of the daily monitoring of PCT in addition to clinical evaluation during the early management of sepsis.

Purpose: To determine if the gadolinium-enhancement characteristics of magnetic resonance images (MRI) differ for acute and chronic benign retroperitoneal fibrosis (RPF)., Method: Seven male subjects, 3 with newly diagnosed nontreated RPF (acute group) and 4 with long-standing stable RPF (chronic group) who had been treated with steroids, ureteric stents or both, underwent MRI examinations with gadolinium enhancement. Patients in the acute group were examined again after treatment. Mean dynamic gadolinium-enhancement ratios (both dynamic and delayed) were calculated for each group., Results: The initial mean dynamic enhancement ratio for the acute group (mean 1.86, range 1.80-1.95) was significantly different (p = 0.005) from that of the chronic group (mean 1.37, range 1.26-1.61). The mean dynamic enhancement ratio for the acute group after treatment (4-8 months duration) was 1.40 (range 1.26-1.51). The mean delayed enhancement ratio (RPF/psoas muscle signal intensity) for the acute group was 1.41 (range 1.38-1.43, data from 2 patients) and for the chronic group was 1.29 (range 1.13-1.44)., Conclusion: Dynamic gadolinium enhancement was useful in differentiating newly diagnosed RPF from treated chronic disease and may have a role in assessing disease activity, monitoring response to treatment and detecting relapse.

Background: Elderly people frequently report the presence of chronically disturbed sleep. However, most data are derived from predominantly Caucasian populations. The current study is an investigation of the prevalence and correlates of sleep disturbances in a cohort of elderly Japanese American men residing in Hawaii. The importance of this population lies in its representation of an ethnic group living in a culture different from their ancestry., Methods: This study is a cross-sectional cohort analysis of data pertaining to sleep disturbances and their potential correlates from 3,845 elderly Japanese American men residing in Hawaii (mean age. 78 years; range, 71-93 years) who participated in the fourth survey of the Honolulu Heart Program (1991-1994), which is the baseline exam for the Honolulu-Asia Aging Study. Information collected included an extensive survey of medication use, medical history, and assessments of physical and mental function, quality of life, and sleep., Results: The prevalence of insomnia (DIMS) was 32.6%, a rate similar to that reported in predominantly Caucasian populations. Depression, benzodiazepine use, and several chronic health problems were the most important factors associated with DIMS. In contrast, excessive daytime sleepiness (EDS) had a prevalence of 8.9%, a rate lower than that found in elderly Caucasian populations but close to that reported among native Japanese. Important factors related to EDS were symptoms of nocturnal respiratory disturbance, depression, perception of adverse quality of life, Parkinson's disease, and digitalis use., Conclusions: Elderly Japanese men are less likely than elderly Caucasian men to report excessive daytime sleepiness. However, their insomnia rates are similar.