Management of bleeding and coagulopathy following major trauma: an updated European guideline.

INTRODUCTION: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved. METHODS: The 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. RESULTS: Key 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. CONCLUSIONS: A 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.

The STOP the Bleeding Campaign.

According to the World Health Organization, traumatic injuries worldwide are responsible for over 5 million deaths annually. Post-traumatic bleeding caused by traumatic injury-associated coagulopathy is the leading cause of potentially preventable death among trauma patients. Despite these facts, awareness of this problem is insufficient and treatment options are often unclear. The STOP the Bleeding Campaign therefore aims to increase awareness of the phenomenon of post-traumatic coagulopathy and its appropriate management by publishing European guidelines for the management of the bleeding trauma patient, by promoting and monitoring the implementation of these guidelines and by preparing promotional and educational material, organising activities and developing health quality management tools. The campaign aims to reduce the number of patients who die within 24 hours after arrival in the hospital due to exsanguination by a minimum of 20% within the next 5 years.

Wireless capsule endoscopy: perspectives beyond gastrointestinal bleeding.

Wireless capsule endoscopy (CE) is a technology developed for the endoscopic exploration of the small bowel. The first capsule model was approved by the Food and Drug Administration in 2001, and its first and essential indication was occult gastrointestinal (GI) bleeding. Over subsequent years, this technology has been refined to provide superior resolution, increased battery life, and capabilities to view different parts of the GI tract. Indeed, cases for which CE proved useful have increased significantly over the last few years, with new indications for the small bowel and technical improvements that have expanded its use to other parts of the GI tract, including the esophagus and colon. The main challenges in the development of CE are new devices with the ability to provide therapy, air inflation for a better vision of the small bowel, biopsy sampling systems attached to the capsule and the possibility to guide and move the capsule with an external motion control. In this article we review the current and new indications of CE, and the evolving technological changes shaping this technology, which has a promising potential in the coming future of gastroenterology.

New insights to occult gastrointestinal bleeding: From pathophysiology to therapeutics.

Obscure gastrointestinal bleeding is still a clinical challenge for gastroenterologists. The recent development of novel technologies for the diagnosis and treatment of different bleeding causes has allowed a better management of patients, but it also determines the need of a deeper comprehension of pathophysiology and the analysis of local expertise in order to develop a rational management algorithm. Obscure gastrointestinal bleeding can be divided in occult, when a positive occult blood fecal test is the main manifestation, and overt, when external sings of bleeding are visible. In this paper we are going to focus on overt gastrointestinal bleeding, describing the physiopathology of the most usual causes, analyzing the diagnostic procedures available, from the most classical to the novel ones, and establishing a standard algorithm which can be adapted depending on the local expertise or availability. Finally, we will review the main therapeutic options for this complex and not so uncommon clinical problem.

Peut-on évaluer te risque hémorragique tors d'anticoagutation orale [Oral anticoagulation and the risk of major bleeding]

Oral anticoagulants are frequently used in clinical practice. The most important complication of oral anticoagulation is major bleeding. The incidence of major bleeding is about 2-3%/year in randomized controlled trials but may be considerably higher under real life conditions. Major bleeding risk in patients receiving oral anticoagulants depends on factors related to anticoagulation itself (intensity and quality), patient-related factors (demographic characteristics and comorbid diseases), and concomitant treatments with antiplatelet or non-steroidal anti-inflammatory drugs. The role of clinical prediction rules for major bleeding is discussed.

Management of bleeding following major trauma: an updated European guideline.

INTRODUCTION Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes. METHODS The 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. RESULTS Key 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. CONCLUSIONS This guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.

Missed opportunities among HIV-positive women to control viral replication during pregnancy and to have a vaginal delivery.

INTRODUCTION: Most national guidelines for the prevention of mother-to-child transmission of HIV in Europe updated between 2001 and 2010 recommend vaginal deliveries for women with undetectable or very low viral load (VL). Our aim was to explore the impact of these new guidelines on the rates of vaginal deliveries among HIV-positive women in Europe. METHODS: In a pooled analysis of data on HIV-positive pregnant women enrolled in the Swiss Mother & Child HIV Cohort Study and the European Collaborative Study 2000 to 2010, deliveries were classified as occurring pre- or postpublication of national guidelines recommending vaginal delivery. RESULTS: Overall, 2663 women with 3013 deliveries were included from 10 countries; 28% women were diagnosed with HIV during pregnancy. Combination antiretroviral therapy was used in most pregnancies (2020, 73%), starting during the first or second trimester in 78% and during the third trimester in 22%; in 25% pregnancies, the woman conceived on combination antiretroviral therapy. Overall, in 86% pregnancies, a VL < 400 copies per milliliter was achieved before delivery. The proportion of vaginal deliveries increased from 17% (414/2377) before the change in guidelines to 52% (313/600) after; elective Caesarean section rates decreased from 65% to 27%. The proportion of women with undetectable VL having a Caesarean section was 55% after implementation of new guidelines. We observed a decrease of late preterm deliveries from 16% (377/2354) before to 7% (42/599) after the change in guidelines (P < 0.001). CONCLUSION: There are still missed opportunities for women with HIV to fully suppress their VL and to deliver vaginally in Europe.

A comparison of dequalinium chloride vaginal tablets (Fluomizin®) and clindamycin vaginal cream in the treatment of bacterial vaginosis: a single-blind, randomized clinical trial of efficacy and safety.

AIMS: To investigate if vaginal application of dequalinium chloride (DQC, Fluomizin®) is as effective as vaginal clindamycin (CLM) in the treatment of bacterial vaginosis (BV). METHODS: This was a multinational, multicenter, single-blind, randomized trial in 15 centers, including 321 women. They were randomized to either vaginal DQC tablets or vaginal CLM cream. Follow-up visits were 1 week and 1 month after treatment. Clinical cure based on Amsel's criteria was the primary outcome. Secondary outcomes were rate of treatment failures and recurrences, incidence of post-treatment vulvovaginal candidosis (VVC), lactobacillary grade (LBG), total symptom score (TSC), and safety. RESULTS: Cure rates with DQC (C1: 81.5%, C2: 79.5%) were as high as with CLM (C1: 78.4%, C2: 77.6%). Thus, the treatment with DQC had equal efficacy as CLM cream. A trend to less common post-treatment VVC in the DQC-treated women was observed (DQC: 2.5%, CLM: 7.7%; p = 0.06). Both treatments were well tolerated with no serious adverse events occurring. CONCLUSION: Vaginal DQC has been shown to be equally effective as CLM cream, to be well tolerated with no systemic safety concerns, and is therefore a valid alternative therapy for women with BV [ClinicalTrials.gov, Med380104, NCT01125410].

Rectal and vaginal immunization of mice with human papillomavirus L1 virus-like particles.

Human papillomavirus (HPV) vaccines based on L1 virus-like particle (VLP) can prevent genital HPV infection and associated lesions after three intramuscular injections. Needle-free administration might facilitate vaccine implementation, especially in developing countries. Here we have investigated rectal and vaginal administration of HPV16 L1 VLPs in mice and their ability to induce anti-VLP and HPV16-neutralizing antibodies in serum and in genital, rectal and oral secretions. Rectal and vaginal immunizations were not effective in the absence of adjuvant. Cholera toxin was able to enhance systemic and mucosal anti-VLPs responses after rectal immunization, but not after vaginal immunization. Rectal immunization with Resiquimod and to a lesser extent Imiquimod, but not monophosphoryl lipid A, induced anti-HPV16 VLP antibodies in serum and secretions. Vaginal immunization was immunogenic only if administered in mice treated with nonoxynol-9, a disrupter of the cervico-vaginal epithelium. Our findings show that rectal and vaginal administration of VLPs can induce significant HPV16-neutralizing antibody levels in secretions, despite the fact that low titers are induced in serum. Imidazoquinolines, largely used to treat genital and anal warts, and nonoxonol-9, used as genital microbicide/spermicide were identified as adjuvants that could be safely used by the rectal or vaginal route, respectively.

Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

OBJECTIVE: To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING: Twenty-nine centres in Switzerland and Argentina. POPULATION: A total of 385 women with preterm labour (24(0/7) to 33(6/7)  weeks of gestation) treated with acute tocolysis. METHODS: Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. MAIN OUTCOME MEASURES: Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. RESULTS: Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. CONCLUSION: There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour.

Major bleeding risk in anticoagulated patients receiving concomitant antiplatelet therapy: A prospective study.

INTRODUCTION: Current literature suggesting a higher bleeding risk during combination therapy compared to oral anticoagulation alone is primarily based on retrospective studies or specific populations. We aimed to prospectively evaluate whether unselected medical patients on oral anticoagulation have an increased risk of bleeding when on concomitant antiplatelet therapy. MATERIAL AND METHODS: We prospectively studied consecutive adult medical patients who were discharged on oral anticoagulants between 01/2008 and 03/2009 from a Swiss university hospital. The primary outcome was the time to a first major bleed on oral anticoagulation within 12months, adjusted for age, international normalized ratio target, number of medications, and history of myocardial infarction and major bleeding. RESULTS: Among the 515 included anticoagulated patients, the incidence rate of a first major bleed was 8.2 per 100 patient-years. Overall, 161 patients (31.3%) were on both anticoagulant and antiplatelet therapy, and these patients had a similar incidence rate of major bleeding compared to patients on oral anticoagulation alone (7.6 vs. 8.4 per 100 patient-years, P=0.81). In a multivariate analysis, the association of concomitant antiplatelet therapy with the risk of major bleeding was not statistically significant (hazard ratio 0.89, 95% confidence interval, 0.37-2.10). CONCLUSIONS: The risk of bleeding in patients receiving oral anticoagulants combined with antiplatelet therapy was similar to patients receiving oral anticoagulants alone, suggesting that the incremental bleeding risk of combination therapy might not be clinically significant.