Revue universitaire; éducation--enseignement--administration--préparation aux examens et concours, lettres et langues vivantes. Devoirs de classe--bibliographie.

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Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: Results from the Metocard-CNIC trial (Effect of Metoprolol in Cardioprotection during an Acute Myocardial Infarction)

The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions.

Timing-dependent protection of hypertonic saline solution administration in experimental liver ischemia/reperfusion injury

Background. Diving liver ischemia, the decrease in mitochondrial energy causes cellular damage that is aggravated after reperfusion. This injury can trigger a systemic inflammatory syndrome, also producing remote organ damage. Several substances have been employed to decrease this inflammatory response during liver transplantation, liver resections, and hypovolemic shock. The aim of this study was to evaluate the effects of hypertonic saline solution and the best timing of administration to prevent organ injury during experimental liver ischemia/reperfusion. Methods. Rats underwent 1 hr of warm liver ischemia followed by reperfusion. Eighty-four rats Were allocated into 6 groups: sham group, control of ischemia group) (C), pre-ischemia treated NaCl 0.9% (ISS) and NaCl 7.5% (HTS) groups, pre-repefusion ISS, and HTS groups. Blood and tissue samples were collected 4 hr after reperfusion. Results. HTS showed beneficial effects in prevention of live ischemia/reperfusion injury. HTS groups developed increases in AST and ALT levels that were significantly less than ISS groups; however, the HTS pre-reperfusion group showed levels significantly less than the HTS pre-ischemia group. No differences in IL-6 and IL-10 levels, were observed. A significant decrease in mitochondrial dysfunction as well as hepatic edema was observed in the HTS pre-reperfusion group. Pulmonary vascular permeability Was significantly less in the pre-reperfusion HTS group compared to the ISS group. No differences in myeloperoxidase activity were observed. The liver histologic score was significantly less in the pre-reperfusion HTS group compared to the pre-ischemia I-ITS group. Conclusion. HTS ameliorated local and systemic injuries in experimental liver ischemia/reperfusion. Infusion of HTS in the pre-reperfusion period may be an important adjunct to accomplish the best results. (Surgery 2010;147:415-23.)

Reforms of the pre-graduate curriculum for medical students: the Bologna process and beyond.

For several years, all five medical faculties of Switzerland have embarked on a reform of their training curricula for two reasons: first, according to a new federal act issued in 2006 by the administration of the confederation, faculties needed to meet international standards in terms of content and pedagogic approaches; second, all Swiss universities and thus all medical faculties had to adapt the structure of their curriculum to the frame and principles which govern the Bologna process. This process is the result of the Bologna Declaration of June 1999 which proposes and requires a series of reforms to make European Higher Education more compatible and comparable, more competitive and more attractive for Europeans students. The present paper reviews some of the results achieved in the field, focusing on several issues such as the shortage of physicians and primary care practitioners, the importance of public health, community medicine and medical humanities, and the implementation of new training approaches including e-learning and simulation. In the future, faculties should work on several specific challenges such as: students' mobility, the improvement of students' autonomy and critical thinking as well as their generic and specific skills and finally a reflection on how to improve the attractiveness of the academic career, for physicians of both sexes.

Speech by Mr Micheál Martin TD at Launch of Pre-Registration Nursing Degree Programme

Good afternoon ladies and gentlemen. I am very pleased that you were all able to accept my invitation to join me here today on this landmark occasion for nursing education. It is fitting that all of the key stakeholders from the health and education sectors should be so well represented at the launch of an historic new development. Rapid and unpredictable change throughout society has been the hallmark of the twenty-first century, and healthcare is no exception. Regardless of what change occurs, no one doubts that nursing is intrinsic to the health of this nation. However, significant changes in nurse education are now needed if the profession is to deliver on its social mandate to promote people´s health by providing excellent and sensitive care. As science, technology and the demands of the public for sophisticated and responsive health care become increasingly complex, it is essential that the foundation of nursing education is redesigned. Pre-registration nursing education has already undergone radical change over the past eight years, during which time it has moved from an apprenticeship model of education and training to a diploma based programme firmly rooted in higher education. The Secretary General of my Department, Michael Kelly, played a leading role in bringing about this transformation, which has greatly enhanced the way students are prepared for entry to the nursing profession. The benefits of the revised model of education are clearly evident from the quality of the nurses graduating from the diploma programme. The Commission on Nursing examined the whole area of nursing education, and set out a very convincing case for educating nursing students to degree level. It argued that nurses of the future would be required to possess increased flexibility and the ability to work autonomously. A degree programme would provide nurses with a theoretical underpinning that would enable them to develop their clinical skills to a greater extent and to respond to future challenges in health care, for the benefit of patients and clients of the health services. The Commission has provided a solid framework for the professional development of nurses and midwives, including a process that is already underway for the creation of clinical nurse specialist and advanced nurse practitioner posts. This process will facilitate the transfer of skills across divisions of nursing. In this scenario, it is clearly desirable that the future benchmark qualification for registration as a nurse should be a degree in nursing studies. A Nursing Education Forum was established in early 1999 to prepare a strategic framework for the implementation of a nursing degree programme. When launching the Forum´s report last January, I indicated that the Government had agreed in principle to the introduction of the proposed degree programme next year. At the time two substantial outstanding issues had yet to be resolved, namely the basis on which nurse teachers would transfer from the health sector to the education sector and the amount of capital and revenue funding required to operate the degree programme. My Department has brokered agreements between the Nursing Alliance and the Higher Education Institutions for the assimilation of nurse teachers as lecturers into their affiliated institutions. The terms of these agreements have been accepted by all four nursing unions following a ballot of their nurse teacher members. I would like to pay particular tribute to all nurse teachers who have contributed to shaping the position, relevance and visibility of nursing through leadership, which embodies scholarship and excellence in the profession of nursing itself. In response to a recommendation of the Nursing Education Forum, I established an Inter-Departmental Steering Committee, chaired by Bernard Carey of my Department, to consider all the funding and policy issues. This Steering Committee includes representatives of the Department of Finance and the Department of Education and Science as well as the Higher Education Authority. The Steering Committee has been engaged in intensive negotiations with representatives of the Conference of Heads of Irish Universities and the Institutes of Technology in relation to their capital and revenue funding requirements. These negotiations were successfully concluded within the past few weeks. The satisfactory resolution of the industrial relations and funding issues cleared the way for me to go to the Government with concrete proposals for the implementation of degree level education for nursing students. I am delighted to announce here today that the Government has approved all of my proposals, and that a four-year undergraduate pre-registration nursing degree programme will be implemented on a nation-wide basis at the start of the next academic year, 2002/2003. The Government has approved the provision of capital funding totalling £176 million pounds for a major building and equipment programme to facilitate the full integration of nursing students into the higher education sector. This programme is due to be completed by September 2004, and will ensure that nursing students are accommodated in purpose built schools of nursing studies with state of the art clinical skills and human science laboratories at thirteen higher education sites throughout the country. The Government has also agreed to make available the substantial additional revenue funding required to support the nursing degree programme. By 2006, the full year cost of operating the programme will rise to some £43 million pounds. The scale of this investment in pre-registration nursing education is enormous by any yardstick. It demonstrates the firm commitment of myself and my Government colleagues to the full implementation of the recommendations of the Commission on Nursing, of which the introduction of pre-registration degree level education is arguably the most important. This historic decision, and it is truly historic, will finally put the education of nurses on a par with the education of other health care professionals. The nursing profession has long been striving for parity, and my own involvement in the achievement of it is a matter of deep personal satisfaction to me. I am also pleased to announce that the Government has approved my plans for increasing the number of nursing training places to coincide with the implementation of the degree programme next year. Ninety-three additional places in mental handicap and psychiatric nursing will be created at Athlone, Letterkenny, Tralee and Waterford Institutes of Technology. This will yield 392 extra places over the four years of the degree programme. A total of 1,640 places annually on the new degree programme will thus be available. This is an all-time record, and maintaining the annual student intake at this level for the foreseeable future is a key element of my overall strategy for ensuring that we produce sufficient “home-grown” nurses for our health services. I am aware that the Nursing Alliance were anxious that some funding would be provided for the further academic career development of nurse teachers who transfer to one of the six Universities that will be involved in the delivery of the degree programme. I am happy to confirm that up to £300,000 in total per year will be available for this purpose over the first four years of the degree programme. In line with a recommendation of the Commission on Nursing, my Department will have responsibility for the administration of the nursing degree budget until the programme has been bedded down in the higher education sector. A primary concern will be to ensure that the substantial capital and revenue funding involved is ring-fenced for nursing studies. It is intended that responsibility for the budget will be transferred to the Department of Education and Science after the first cohort of nursing degree students have graduated in 2006. In the context of today´s launch, it is relevant to refer to a special initiative that I introduced last year to assist registered nurses wishing to undertake part-time nursing degree courses. Under this initiative, nurses are entitled to have their course fees paid by their employers in return for a commitment to continue working in the public health service for a period following completion of the course. This initiative has proved extremely popular with large numbers of nurses availing of it. I want to confirm here today that the free fees initiative will continue in operation until 2005, at a total cost of at least £15 million pounds. I am giving this commitment in order to assure this year´s intake of nursing students to the final diploma programmes that fee support for a part-time nursing degree course will be available to them when they graduate in three years time. The focus of today´s celebration is rightly on the landmark Government decision to implement the nursing degree programme next year. As Minister for Health and Children, and as a former Minister for Education, I also have a particular interest in the educational opportunities available to other health service workers to upgrade their skills. I am pleased to announce that the Government has approved my proposals for the introduction of a sponsorship scheme for suitable, experienced health care assistants who wish to become nurses. This new scheme will commence next year and will be administered by the health boards. Successful applicants will be allowed to retain their existing salaries throughout the four years of the degree programme in return for a commitment to work as nurses for their health service employer for a period of five years following registration. Up to forty sponsorships will be available annually. The new scheme will enable suitable applicants to undertake nursing education and training without suffering financial hardship. The greatest advantage of the scheme will be the retention by the public health service of staff who are supported under it, since they will have had practical experience of working in the service and their own personal commitment to upgrading their skills will be informed by that experience. I am confident that the sponsorship scheme will be warmly welcomed by health service unions representing care assistants as providing an exciting new career development path for their members. Education and health are now the two pillars upon which the profession of nursing rests. We must continue to build bridges, even tunnels where needed to strengthen this partnership. We must all understand partnerships donâ?Tt just happen they are designed and must be worked at. The changes outlined here today are powerful incentives for those in healthcare agencies, academic institutions and regulatory bodies to design revolutionary programmes capable of shaping a critical mass of excellent practitioners. You have an opportunity, greater perhaps than has been granted to any other generation in history to make certain those changes are for the good. Ultimately changes that will make the country a healthier and more equitable place to live. The challenge relates to building a seamless preparatory programme which equally respects both education and practise as an indivisible duo whilst ensuring that high tech does not replace the human touch. This is a special day in the history of the development of the Irish nursing profession, and I would like to thank everybody for their contribution. I want to express my particular appreciation of two people who by this stage are well known to all of you – Bernard Carey of my Department and Siobhán O´Halloran of the National Implementation Committee. Bernard and Siobhán have devoted considerable time and energy to the project on my behalf over the past fourteen months or so. That we are here today celebrating the launch of degree level education is due in no small part to their successful execution of the mandate that I gave them. We live in a rapidly changing world, one in which nursing can no longer rely on systems of the past to guide it through the new millennium. In terms of contemporary healthcare, nursing is no longer just a reciprocal kindness but rather a highly complex set of professional behaviours, which require serious educational investment. Pre-registration nurse education will always need development and redesign to ensure our health care system meets the demands of modern society. Nothing is finite. Today more than ever the health system is dependent on the resourcefulness of nursing. I have no doubt that the new educational landscape painted will ensure that nurses of the future will be increasingly innovative, independent and in demand. The unmistakable message from my Department is that nursing really matters. Thank you.

Effects of colostrum feeding and glucocorticoid administration on insulin-dependent glucose metabolism in neonatal calves

Colostrum feeding and glucocorticoid administration affect glucose metabolism and insulin release in calves. We have tested the hypothesis that dexamethasone as well as colostrum feeding influence insulin-dependent glucose metabolism in neonatal calves using the euglycemic-hyperinsulinemic clamp technique. Newborn calves were fed either colostrum or a milk-based formula (n=14 per group) and in each feeding group, half of the calves were treated with dexamethasone (30 microg/[kg body weight per day]). Preprandial blood samples were taken on days 1, 2, and 4. On day 5, insulin was infused for 3h and plasma glucose concentrations were kept at 5 mmol/L+/-10%. Clamps were combined with [(13)C]-bicarbonate and [6,6-(2)H]-glucose infusions for 5.5h (i.e., from -150 to 180 min, relative to insulin infusion) to determine glucose turnover, glucose appearance rate (Ra), endogenous glucose production (eGP), and gluconeogenesis before and at the end of the clamp. After the clamp liver biopsies were taken to measure mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC). Dexamethasone increased plasma glucose, insulin, and glucagon concentrations in the pre-clamp period thus necessitating a reduction in the rate of glucose infusion to maintain euglycemia during the clamp. Glucose turnover and Ra increased during the clamp and were lower at the end of the clamp in dexamethasone-treated calves. Dexamethasone treatment did not affect basal gluconeogenesis or eGP. At the end of the clamp, dexamethasone reduced eGP and PC mRNA levels, whereas mitochondrial PEPCK mRNA levels increased. In conclusion, insulin increased glucose turnover and dexamethasone impaired insulin-dependent glucose metabolism, and this was independent of different feeding.

Pre-hospital antibiotic treatment and mortality caused by invasive meningococcal disease, adjusting for indication bias.

Background: Mortality from invasive meningococcal disease (IMD) has remained stable over the last thirty years and it is unclear whether pre-hospital antibiotherapy actually produces a decrease in this mortality. Our aim was to examine whether pre-hospital oral antibiotherapy reduces mortality from IMD, adjusting for indication bias. Methods: A retrospective analysis was made of clinical reports of all patients (n = 848) diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain, and of the relationship between the use of pre-hospital oral antibiotherapy and mortality. Indication bias was controlled for by the propensity score technique, and a multivariate analysis was performed to determine the probability of each patient receiving antibiotics, according to the symptoms identified before admission. Data on in-hospital death, use of antibiotics and demographic variables were collected. A logistic regression analysis was then carried out, using death as the dependent variable, and prehospital antibiotic use, age, time from onset of symptoms to parenteral antibiotics and the propensity score as independent variables. Results: Data were recorded on 848 patients, 49 (5.72%) of whom died. Of the total number of patients, 226 had received oral antibiotics before admission, mainly betalactams during the previous 48 hours. After adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment, pre-hospital oral antibiotherapy remained a significant protective factor (Odds Ratio for death 0.37, 95% confidence interval 0.15–0.93). Conclusion: Pre-hospital oral antibiotherapy appears to reduce IMD mortality.

Schistogram changes after administration of antischistosomal drugs in mice at the early phase of Schistosoma mansoni infection

Mice infected with Schistosoma mansoni were treated with oxamniquine, praziquantel, artesunate at the pre-patent phase, aiming at observing schistogram alterations. Half of the animals were perfused five days post-treatment for counting and classification of immature worms, based on pre-established morphological criteria (schistogram); the remaining animals were evaluated 42 or 100 days after infection and perfusion of the portal-system was performed for collection and counting of adult worms and oogram. It was observed that oxamniquine and artesunate treatment administered at the pre-postural phase causes significant reduction in the number of immature and adult worms. However, there was little reduction with praziquantel when used at the dose of 400 mg/kg for treatments administered 14, 15, 21 or 23 days post-infection. Artesunate was responsible for significant alterations in development of young worms, as well as for a higher number of worms presenting intestinal damages. Immature adult worms were detected in mice treated with artesunate or oxamniquine at the pre-patent phase of infection and recovered by perfusion 100 days after infection. Schistogram proved to be a very useful tool for experimental evaluation of the activity of antischistosomal drugs and a good model to identify the most sensitive stages to drugs.

Influences of β-HCG administration on carbon isotope ratios of endogenous urinary steroids.

Several factors influencing the carbon isotope ratios (CIR) of endogenous urinary steroids have been identified in recent years. One of these should be the metabolism of steroids inside the body involving numerous different enzymes. A detailed look at this metabolism taking into account differences found between steroids excreted as glucuronides or as sulphates and hydrogen isotope ratios of different steroids pointed out possibility of unequal CIR at the main production sites inside the male body - the testes and the adrenal glands. By administration of β-HCG it is possible to strongly stimulate the steroid production within the testes without influencing the production at the adrenal glands. Therefore, this treatment should result in changed CIR of urinary androgens in contrast to the undisturbed pre-treatment values. Four male volunteers received three injections of β-HCG over a time course of 5 days and collected their urine samples at defined intervals after the last administration. Those samples showing the largest response in contrast to the pre-administration urines were identified by steroid profile measurements and subsequent analysed by GC/C/IRMS. CIR of androsterone, etiocholanolone, testosterone, 5α- and 5β-androstanediol and pregnanediol were compared. While pregnanediol was not influenced, most of the investigated androgens showed depleted values after treatment. The majority of differences were found to be statistically significant and nearly all showed the expected trend towards more depleted δ(13)C-values. These results support the hypothesis of different CIR at different production sites inside the human body. The impact of these findings on doping control analysis will be discussed.

La chaîne des secours: le modèle vaudois [An efficient example of a Swiss pre-hospital chain of survival: the state of Vaud model].

The state of Vaud model of the pre-hospital chain of survival is an example of an efficient way to deal with pre-hospital emergencies. It revolves around a centrally located dispatch center managing emergencies according to specific key words, allowing dispatchers to send out resources among which we find general practitioners, ambulances, physician staffed fast response cars or physician staffed helicopters and specific equipment. The Vaud pre-hospital chain of survival has been tailored according to geographical, demographical and political necessities. It undergoes constant reassessment and needs continuous adaptations to the ever changing demographics and epidemiology of pre-hospital medicine.

Entrepreneurial structure of the mercantile company in pre-industrial Catalonia

The mercantile company was the basic form of enterprise in pre-industrial Catalonia. The aim of this paper is to study the formation and development of the mercantile companies in Barcelona whose end was the wholesale and retail sale of textiles in the botigues de teles (textile retail shops) throughout the eighteenth century. These firms were officially registered before a notary and their deeds reveal how these establishments were administered and managed.The study covers a sample of 121 mercantile companies, and the articles and documentation that were put into effect by 32 notaries who were active in Barcelona in the 18th century have been consulted in their entirety. From an initial selection of documentation, a total of 228 deeds registering companies have been found, 107 of which (47%) relate to the creation of companies whose various activities were centred in taverns, textile manufacturing, braiding.... While the 121 companies, which make up our sample and which account for 53% of the deeds registered with the notaries mentioned above, focused exclusively on the management of textile retail shops located in the commercial heart of the city. Thus one point of interest that the documentation reveals is that the majority of the mercantile companies registered by Barcelona notaries throughout the 18th century were establishments which traded in textiles. The first part of the article focuses on the structural characteristics of these enterprises, the number and socio-professional status of the partners and the extent of each partner s involvement in the administration and management. The second part of the article examines the capital investment made by each partner, their rights and obligations agreed on, the sharing out of profits and possible losses and the duration of the companies. The final aim of the paper is to highlight the evolution of these companies through one specific case.

The Reliability of Pre-travel History to Decide on Appropriate Counseling and Vaccinations: A Prospective Study.

BACKGROUND: Although medical and travel plans gathered from pre-travel interviews are used to decide the provision of specific pre-travel health advice and vaccinations, there has been no evaluation of the relevance of this strategy. In a prospective study, we assessed the agreement between pre-travel plans and post-travel history and the effect on advice regarding the administration of vaccines and recommendations for malaria prevention. METHODS: We included prospectively all consenting adults who had not planned an organized tour. Pre- and post-travel information included questions on destination, itineraries, departure and return dates, access to bottled water, plan of bicycle ride, stays in a rural zone, and close contact with animals. The outcomes measured included: agreement between pre- and post-travel itineraries and activities; and the effect of these differences on pre-travel health recommendations, had the traveler gone to the actual versus intended destinations for actual versus intended duration and activities. RESULTS: Three hundred and sixty-five travelers were included in the survey, where 188 (52%) were males (median age 38 years). In 81(23%) travelers, there was no difference between pre- and post-travel history. Disagreement between pre- and post-travel history were the highest for stays in rural zones or with local people (66% of travelers), close contact with animals (33%), and bicycle riding (21%). According to post-travel history, 125 (35%) travelers would have needed rabies vaccine and 9 (3%) typhoid fever vaccine. Potential overprovision of vaccine was found in <2% of travelers. A change in the malaria prescription would have been recommended in 18 (5%) travelers. CONCLUSIONS: Pre-travel history does not adequately reflect what travelers do. However, difference between recommendations for the actual versus intended travel plans was only clinically significant for the need for rabies vaccine. Particular attention during pre-travel health counseling should focus on the risk of rabies, the need to avoid close contact with animals and to seek care for post-exposure prophylaxis following an animal bite.

Pre-hospital tracheal intubation in patients with traumatic brain injury: systematic review of current evidence.

BACKGROUND: We reviewed the current evidence on the benefit and harm of pre-hospital tracheal intubation and mechanical ventilation after traumatic brain injury (TBI). METHODS: We conducted a systematic literature search up to December 2007 without language restriction to identify interventional and observational studies comparing pre-hospital intubation with other airway management (e.g. bag-valve-mask or oxygen administration) in patients with TBI. Information on study design, population, interventions, and outcomes was abstracted by two investigators and cross-checked by two others. Seventeen studies were included with data for 15,335 patients collected from 1985 to 2004. There were 12 retrospective analyses of trauma registries or hospital databases, three cohort studies, one case-control study, and one controlled trial. Using Brain Trauma Foundation classification of evidence, there were 14 class 3 studies, three class 2 studies, and no class 1 study. Six studies were of adults, five of children, and three of both; age groups were unclear in three studies. Maximum follow-up was up to 6 months or hospital discharge. RESULTS: In 13 studies, the unadjusted odds ratios (ORs) for an effect of pre-hospital intubation on in-hospital mortality ranged from 0.17 (favouring control interventions) to 2.43 (favouring pre-hospital intubation); adjusted ORs ranged from 0.24 to 1.42. Estimates for functional outcomes after TBI were equivocal. Three studies indicated higher risk of pneumonia associated with pre-hospital (when compared with in-hospital) intubation. CONCLUSIONS: Overall, the available evidence did not support any benefit from pre-hospital intubation and mechanical ventilation after TBI. Additional arguments need to be taken into account, including medical and procedural aspects.