Background: Severe traumatic injury continues to present challenges to healthcare systems around the world, and post-traumatic bleeding remains a leading cause of potentially preventable death among injured patients. Now in its fifth edition, this document aims to provide guidance on the management of major bleeding and coagulopathy following traumatic injury and encourages adaptation of the guiding principles described here to individual institutional circumstances and resources. Methods: The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004, and the current author group included representatives of six relevant European professional societies. The group applied a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reexamined and revised based on scientific evidence that has emerged since the previous edition and observed shifts in clinical practice. New recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. Results: Advances in our understanding of the pathophysiology of post-traumatic coagulopathy have supported improved management strategies, including evidence that early, individualised goal-directed treatment improves the outcome of severely injured patients. The overall organisation of the current guideline has been designed to reflect the clinical decision-making process along the patient pathway in an approximate temporal sequence. Recommendations are grouped behind the rationale for key decision points, which are patient-or problem-oriented rather than related to specific treatment modalities. While these recommendations provide guidance for the diagnosis and treatment of major bleeding and coagulopathy, emerging evidence supports the author group's belief that the greatest outcome improvement can be achieved through education and the establishment of and adherence to local clinical management algorithms. Conclusions: A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. If incorporated into local practice, these clinical practice guidelines have the potential to ensure a uniform standard of care across Europe and beyond and better outcomes for the severely bleeding trauma patient.

BackgroundSevere trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution.MethodsThe pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013.ResultsThe guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome.ConclusionsA multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1265-x) contains supplementary material, which is available to authorized users.

IntroductionEvidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved.MethodsThe multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.ResultsKey changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.ConclusionsA comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.Please see related letter by Morel et alhttp://ccforum.com/content/17/4/442

IntroductionEvidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes.MethodsThe multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.ResultsKey changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.ConclusionsThis guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.

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FOR THE BRESCIA HCC STUDY risk (RR) estimates for these factors. The relationships beWe performed a case-control study to assess the association tween HBV and HCV infections, and between these infections of hepatocellular carcinoma (HCC) with hepatitis B virus and alcohol drinking, may be of relevance and may contrib-(HBV) and hepatitis C virus (HCV) infection and alcohol ute to the discrepancies observed. Mutual negative confounddrinking. We recruited as cases 172 subjects with an initial ing interactions between HBV and HCV infections have been diagnosis of HCC, who were admitted to the two major hospifound in most studies, 3-6 whereas positive interactions have tals in the province of Brescia, northern Italy, and 332 subbeen observed in a few. 3,4 Positive interaction between HBV jects, sex-, age-, and hospital-matched, who were admitted to infection and alcohol intake as a cause of liver injury has the Departments of Ophthalmology, Dermatology, Urology, been suggested in some studies but has not been confirmed Cardiology, and Internal Medicine, as controls. Of the HCC by others. 7,8 Few studies have yet documented the joint effect cases, 23.8% were positive for HBsAg and 37.8% for HCV of HCV infection and alcohol drinking: some data suggest RNA; among the controls, 5.4% were positive for HBsAg and synergism between the two, but further research is needed 4.8% for HCV RNA. History of heavy alcohol intake (ú80 g to clarify the relationship. 9 of ethanol per day for at least 5 years) was found amongIn this study, we address the role of HBV, HCV infection 58.1% of the cases and among 36.4% of the controls. The and its genotypes, and alcohol drinking, and their interacrelative risks (RRs) for HBsAg, HCV RNA positivity, and tions in HCC causation, through a case-control study perheavy alcohol intake were, respectively: 11.4 (95% confidence formed in Brescia, North Italy. This locality showed a high interval: 5.7-22.8), 23.2 (95% confidence interval: 11.8-45.7), incidence of liver cancer as compared with the nine Italian and 4.6 (95% confidence interval: 2.7-7.8). Positive interacareas covered by a Cancer Registry, especially in men: the tions (synergisms) between both HBsAg positivity and HCV incidence rate, age-standardized on the Italian population, RNA positivity and heavy alcohol intake were found, sugwas 32.2 per 100,000 in Brescia versus 15 per 100,000 in gesting more than additive effects of viral infections and alcothe provinces of Turin and Varese, North Italy. 10 hol drinking on the risk of HCC. Infection with HCV genotype 1b showed a higher risk than type 2 (RR Å 2.9; 95% confi-PATIENTS AND METHODS dence interval: 0.9-10), suggesting a major role for the former type in causing HCC. On the basis of population attributable Design and Subjects risks (AR), heavy alcohol intake seems to be the single mostThe study base was the population resident in the province of relevant cause of HCC in this area (AR: 45%), followed by Brescia, North Italy. The province includes the city of Brescia (about HCV (AR: 36%), a...

SummaryBackgroundIntensive care units (ICUs) are high-risk areas for transmission of antimicrobial-resistant bacteria, but no controlled study has tested the effect of rapid screening and isolation of carriers on transmission in settings with best-standard precautions. We assessed interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in European ICUs.MethodsWe did this study in three phases at 13 ICUs. After a 6 month baseline period (phase 1), we did an interrupted time series study of universal chlorhexidine body-washing combined with hand hygiene improvement for 6 months (phase 2), followed by a 12–15 month cluster randomised trial (phase 3). ICUs were randomly assigned by computer generated randomisation schedule to either conventional screening (chromogenic screening for meticillin-resistant Staphylococcus aureus [MRSA] and vancomycin-resistant enterococci [VRE]) or rapid screening (PCR testing for MRSA and VRE and chromogenic screening for highly resistant Enterobacteriaceae [HRE]); with contact precautions for identified carriers. The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk, for which we calculated step changes and changes in trends after the introduction of each intervention. We assessed acquisition by microbiological surveillance and analysed it with a multilevel Poisson segmented regression model. We compared screening groups with a likelihood ratio test that combined step changes and changes to trend. This study is registered with ClinicalTrials.gov, number NCT00976638.FindingsSeven ICUs were assigned to rapid screening and six to conventional screening. Mean hand hygiene compliance improved from 52% in phase 1 to 69% in phase 2, and 77% in phase 3. Median proportions of patients receiving chlorhexidine body-washing increased from 0% to 100% at the start of phase 2. For trends in acquisition of antimicrobial-resistant bacteria, weekly incidence rate ratio (IRR) was 0·976 (0·954–0·999) for phase 2 and 1·015 (0·998–1·032) for phase 3. For step changes, weekly IRR was 0·955 (0·676–1·348) for phase 2 and 0·634 (0·349–1·153) for phase 3. The decrease in trend in phase 2 was largely caused by changes in acquisition of MRSA (weekly IRR 0·925, 95% CI 0·890–0·962). Acquisition was lower in the conventional screening group than in the rapid screening group, but did not differ significantly (p=0·06).InterpretationImproved hand hygiene plus unit-wide chlorhexidine body-washing reduced acquisition of antimicrobial-resistant bacteria, particularly MRSA. In the context of a sustained high level of compliance to hand hygiene and chlorhexidine bathings, screening and isolation of carriers do not reduce acquisition rates of multidrug-resistant bacteria, whether or not screening is done with rapid testing or conventional testing.FundingEuropean Commission.

IMPORTANCEThe effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown. OBJECTIVETo determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance. DESIGN, SETTING, AND PARTICIPANTS Randomized trial conducted from December 1, 2013, to May 31, 2017 European ICUs where at least 5% of bloodstream infections are caused by extendedspectrumβ-lactamase-producingEnterobacteriaceae.Patientswithanticipatedmechanicalventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017.INTERVENTIONS Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily. MAIN OUTCOMES AND MEASURESThe occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period. RESULTS A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, −0.6% to 1.1%), 0.6% (95% CI, −0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline. CONCLUSIONS AND RELEVANCE Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care.