Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial

BACKGROUND: The CRASH-2 trial showed that early administration of tranexamic acid (TXA) safely reduces mortality in bleeding in trauma patients. Based on data from the CRASH-2 trial, global mortality data and a systematic literature review, we estimated the number of premature deaths that might be averted every year worldwide through the use of TXA. METHODS: We used CRASH-2 trial data to examine the effect of TXA on death due to bleeding by geographical region. We used WHO mortality data (2008) and data from a systematic review of the literature to estimate the annual number of in-hospital trauma deaths due to bleeding. We then used the relative risk estimates from the CRASH-2 trial to estimate the number of premature deaths that could be averted if all hospitalised bleeding trauma patients received TXA within one hour of injury, and within three hours of injury. Sensitivity analyses were used to explore the effect of uncertainty in the parameter estimates and the assumptions made in the model. RESULTS: There is no evidence that the effect of TXA on death due to bleeding varies by geographical region (heterogeneity p = 0.70). Based on WHO data and our systematic literature review, we estimate that each year worldwide there are approximately 400,000 in-hospital trauma deaths due to bleeding. If patients received TXA within one hour of injury then approximately 128,000 (uncertainty range [UR] ≈ 72,000 to 172,000) deaths might be averted. If patients received TXA within three hours of injury then approximately 112,000 (UR ≈ 68,000 to 148,000) deaths might be averted. Country specific estimates show that the largest numbers of deaths averted would be in India and China. CONCLUSIONS: The use of TXA in the treatment of traumatic bleeding has the potential to prevent many premature deaths every year. A large proportion of the potential health gains are in low and middle income countries

One-Step Purification of Recombinant Human Amelogenin and Use of Amelogenin as a Fusion Partner

Amelogenin is an extracellular protein first identified as a matrix component important for formation of dental enamel during tooth development. Lately, amelogenin has also been found to have positive effects on clinical important areas, such as treatment of periodontal defects, wound healing, and bone regeneration. Here we present a simple method for purification of recombinant human amelogenin expressed in Escherichia coli, based on the solubility properties of amelogenin. The method combines cell lysis with recovery/purification of the protein and generates a >95% pure amelogenin in one step using intact harvested cells as starting material. By using amelogenin as a fusion partner we could further demonstrate that the same method also be can explored to purify other target proteins/peptides in an effective manner. For instance, a fusion between the clinically used protein PTH (parathyroid hormone) and amelogenin was successfully expressed and purified, and the amelogenin part could be removed from PTH by using a site-specific protease

A systematic review of the effects of residency training on patient outcomes

<p>Abstract</p> <p>Background</p> <p>Residents are vital to the clinical workforce of today and tomorrow. Although in training to become specialists, they also provide much of the daily patient care. Residency training aims to prepare residents to provide a high quality of care. It is essential to assess the patient outcome aspects of residency training, to evaluate the effect or impact of global investments made in training programs. Therefore, we conducted a systematic review to evaluate the effects of relevant aspects of residency training on patient outcomes.</p> <p>Methods</p> <p>The literature was searched from December 2004 to February 2011 using MEDLINE, Cochrane, Embase and the Education Resources Information Center databases with terms related to residency training and (post) graduate medical education and patient outcomes, including mortality, morbidity, complications, length of stay and patient satisfaction. Included studies evaluated the impact of residency training on patient outcomes.</p> <p>Results</p> <p>Ninety-seven articles were included from 182 full-text articles of the initial 2,001 hits. All studies were of average or good quality and the majority had an observational study design.Ninety-six studies provided insight into the effect of 'the level of experience of residents' on patient outcomes during residency training. Within these studies, the start of the academic year was not without risk (five out of 19 studies), but individual progression of residents (seven studies) as well as progression through residency training (nine out of 10 studies) had a positive effect on patient outcomes. Compared with faculty, residents' care resulted mostly in similar patient outcomes when dedicated supervision and additional operation time were arranged for (34 out of 43 studies). After new, modified or improved training programs, patient outcomes remained unchanged or improved (16 out of 17 studies). Only one study focused on physicians' prior training site when assessing the quality of patient care. In this study, training programs were ranked by complication rates of their graduates, thus linking patient outcomes back to where physicians were trained.</p> <p>Conclusions</p> <p>The majority of studies included in this systematic review drew attention to the fact that patient care appears safe and of equal quality when delivered by residents. A minority of results pointed to some negative patient outcomes from the involvement of residents. Adequate supervision, room for extra operation time, and evaluation of and attention to the individual competence of residents throughout residency training could positively serve patient outcomes. Limited evidence is available on the effect of residency training on later practice. Both qualitative and quantitative research designs are needed to clarify which aspects of residency training best prepare doctors to deliver high quality care.</p

Pharmacological adjuncts to stop bleeding: options and effectiveness

Severe trauma and massive haemorrhage represent the leading cause of death and disability in patients under the age of 45 years in the developed world. Even though much advancement has been made in our understanding of the pathophysiology and management of trauma, outcomes from massive haemorrhage remain poor. This can be partially explained by the development of coagulopathy, acidosis and hypothermia, a pathological process collectively known as the “lethal triad” of trauma. A number of pharmacological adjuncts have been utilised to stop bleeding, with a wide variation in the safety and efficacy profiles. Antifibrinolytic agents in particular, act by inhibiting the conversion of plasminogen to plasmin, therefore decreasing the degree of fibrinolysis. Tranexamic acid, the most commonly used antifibrinolytic agent, has been successfully incorporated into most trauma management protocols effectively reducing mortality and morbidity following trauma. In this review, we discuss the current literature with regard to the management of haemorrhage following trauma, with a special reference to the use of pharmacological adjuncts. Novel insights, concepts and treatment modalities are also discussed