Clinicopathological profile and management challenges of congenital encephaloceles in a tertiary hospital in southwest Nigeria.

PURPOSE: A congenital encephalocele is the herniation of intracranial contents through skull defects of various sizes. Depending on the site, content, and size, it is associated with significant morbidity and mortality in children. There is a paucity of recent and comprehensive local clinical data regarding this anomaly. Understanding the peculiarities, clinical-pathologic profiles, and management challenges will help prevent and effectively manage congenital encephalocele to improve outcomes. METHODS: This was a retrospective study of all cases of congenital encephalocele managed between July 2000 and December 2023 at a tertiary hospital in the southwest region of Nigeria. Relevant demographic, clinicopathological, and management data were retrieved and analysed. RESULTS: There were 31 females and 11 males. Their ages ranged from 3 hours to 24 years. Sixteen (35.3%) were delivered in a non-health facility. Birth asphyxia was reported in 5 babies. Few mothers (4.8%) used preconception folic acid. Anaemia (n = 5) and sepsis (n = 4) were the common preoperative morbidities. All patients had definitive surgery, with 18 operated on within the first month of life. Cerebrospinal fluid (CSF) leak was the most common postoperative complication and was significantly observed in the sincipital group (p = 0.018). Thirty-one patients (73.8%) presented for follow-up after surgery, and the mean follow-up duration was 26.6 weeks. Mortality was recorded in a patient (2.4%) due to Klebsiella meningitis. CONCLUSION: Congenital encephaloceles are relatively common in our setting. Therefore, there is a need to address the associated poor maternal and neonatal health conditions. Early surgery can be performed with a favourable outcome.

Hydrocephalus Management Challenges in a Low-income Country: A Review Article.

Hydrocephalus is a very common brain disorder affecting both children and adult populations. Its global burden has been well documented in the literature, and its management is not without challenges and complications, especially in low-income countries. This study aims at reviewing the management of hydrocephalus in a tertiary hospital in Nigeria and illustrating two cases managed with peculiar challenges. This study is a retrospective clinical review of 170 patients with hydrocephalus amenable to ventriculoperitoneal shunting as primary treatment. Two cases of hydrocephalus with peculiar management challenges were illustrated. The first case was that of an abandoned infant with hydrocephalus. The second case was that of a 5-year-old boy with post-meningitic hydrocephalus with delays in having cerebrospinal fluid (CSF) shunting. Majority of the patients with hydrocephalus were infants (71.2%), and the top two most common etiologies were aqueductal stenosis (64.7%) and post-meningitic hydrocephalus (11.2%), respectively. Shunt infection was the most common complication (9.4%), which was within the lower limit of rates reported in the literature (8.6%-50%). Approximately 84% of shunting had no complication. In conclusion, ventriculoperitoneal shunting is the preferred treatment option for hydrocephalus in low-income countries, and it is not without management challenges that are peculiar to these climes. Shunt infection appeared to be the most common complication.

Clinicopathological Profile of Central Nervous System Tumors in a Tertiary Hospital in Southwest Nigeria.

Background: Central nervous system tumors are a complex heterogeneous group of neoplasm comprising both benign and malignant tumors with varied patterns in clinical picture and histologic profile. There have been some similarities and differences seen in the pattern of clinicopathological profile worldwide, however, there is a paucity of study to show the pattern in Nigeria. Aim: This study aimed at describing the clinical and histopathological pattern of central nervous system tumors in our institution. Materials and Methods: This was a retrospective review of cases of central nervous tumors from 2010 to 2021. Information on clinical presentations and histopathology of the tumors were reviewed and analyzed. Results: We found 115 cases of central nervous system tumor with a mean age of 43.7 years and female preponderance. The most common presentations were headache (59 cases, 55.5%) for brain tumors and neck/back pain (16 cases, 100%) for spinal tumors. Supratentorial tumors were the most common accounting for (69 cases, 60%), and sellar region, the commonest site accounting for (25 cases, 29%) of primary brain tumors. Neuroepithelial tumors accounted for the majority (35 cases, 30.4%). Conclusion: Central nervous system tumors were most common in the 5th decade with female preponderance. Neuroepithelial tumors have the highest incidence in the tumor groups.

Developing a Guideline for Neurotrauma in Nigeria.

BACKGROUND: The Nigerian Academy of Neurological Surgeons in 2019 resolved to standardize the practice of neurosurgery in Nigeria. It set up committees to standardize the various aspects of neurosurgery, such as neurotrauma, pediatrics, functional, vascular, skull base, brain tumor, and spine. The Committee on Neurotrauma convened and resolved to study most of the available protocols and guidelines in use in different parts of the world. OBJECTIVE: To formulate a standard protocol for the practice of neurotrauma care within the Nigerian locality. METHODS: The Committee split its membership into 3 subcommittees to cover the various aspects of the Neurotrauma Guidelines, such as neurotrauma curriculum, standard neurotrauma management protocols, and neurotrauma registry. Each subcommittee was to research on available models and formulate a draft for Nigerian neurotrauma. RESULTS: All the 3 subcommittees had their reports ready on schedule. Each concurred that neurotrauma is a major public health challenge in Nigeria. They produced 3 different drafts on the 3 thematic areas of the project. The subcommittees are: 1. Subcommittee on Fellowship, Training and Research Curriculum; 2. Subcommittee on Standard Protocols and Management Guidelines; and 3. Subcommittee of the Nigerian Neurotrauma Registry. CONCLUSION: The committee concluded that a formal protocol for neurotrauma care is long overdue in Nigeria for the standardization of all aspects of neurotrauma. It then recommended the adoption of these guidelines by all institutions offering services in Nigeria using the management protocols, opening a registry, and mounting researches on the various aspects of neurotrauma.

Idiopathic intracranial hypertension: Proposal of a stratification strategy for monitoring risk of disease progression.

OBJECTIVES: A general consensus based on a multidisciplinary perspective involving an international panel was recently developed for management of patients with idiopathic intracranial hypertension (IIH). In this paper, the authors sought to develop further on the aspect of this consensus that concerns monitoring progression of the disease. PATIENTS AND METHODS: A systematic literature review of previous publications on monitoring disease progression in IIH and a meta-analysis to examine efficacy of method of monitoring employed in each study. The authors present a brief descriptive analysis of challenges with monitoring progression of the disease and propose a risk stratification to aid monitoring. RESULTS: Of a total of 382 publications identified from the literature search, only 8 studies (144 patients) satisfied inclusion criteria and were included for analysis. Among these, 3 were based on ICP monitoring while the remaining 5 focused on ophthamological evaluation. Interestingly, there were neither any studies on monitoring with progression of clinical features nor any study on monitoring with symptomatology associated with IIH among the selected studies. CONCLUSION: There is a paucity of studies in the literature on methods of monitoring disease progression in IIH. Though close attention to adequate evaluation and proper care of patients with IIH remains the key in managing this problem, this proposed risk stratification will be an objective tool and useful guide to better monitor these patients according to their extent of risk from the disease and possibly for planning treatment and intervention.

The pattern, peculiarities, and management challenges of spina bifida in a teaching hospital in Southwest Nigeria.

PURPOSE: Spina bifida is a common congenital anomaly of the nervous system. It is frequently associated with significant morbidity and sometimes mortality in affected children. In this paper, we review the clinico-epidemiological pattern, peculiarities, and therapeutic challenges of this condition in our practice setting. METHODS: This is a retrospective study of all cases of spina bifida managed from July 2000 to March 2016 at a tertiary health facility located in the southwest region of Nigeria. Relevant information was retrieved from the medical records. The data was collected using a pro forma and analyzed with SPSS version 22. RESULTS: Data from 148 patients was reviewed and analyzed. There were 78 males and 70 females. Only 5.8% of these children were delivered at the health institution. A fifth (20%) of the patients were first born of their mothers. The mean maternal age was 29 years. Few (10.1%) mothers use folate medication prior to conception and only 58% of the mothers use folate during antenatal care. Mean duration of pregnancy was 38 weeks. The most common anatomical site was lumbosacral region (74.3%) while the most common pathology was myelomeningocele 80.4%. Mean age at surgery was 88.68 h. Mean duration of surgery was 92.8 min. Mean follow-up duration was 46.8 weeks. As many as 59% of the patients had some neurologic improvement noticed during follow-up clinic visits. CONCLUSION: Spina bifida occurs frequently in our environment. Low socio-economic status and poor antenatal clinic visits contributes significantly to its occurrence.

Patterns of pre-hospital events and management of motorcycle-related injuries in a tropical setting.

This study sought to highlight associated factors and evaluate outcomes of motorcycle-related injuries (MCRI) among adults managed in a university teaching hospital in south-western Nigeria. The study was a cross-sectional descriptive study of 150 adult patients presenting with MCRI at the adult accident and emergency unit of the hospital. Information on the use of helmet, alcohol intake, number of pillion passengers, type of collision and time of arrival at hospital was collected. Patients were followed up and questionnaires were completed after discharge, referral or death. The male to female ratio was 4:1 with patients aged 20-29 years (n = 44, 29.3%) having the highest incidence of MCRI. Only 4 (2.7%) patients used helmet at the time of injury. About one-third of the patients (n = 59, 39.3%) arrived at the hospital within 1-6 hours after injury. The limbs were the most frequently involved site of injury, hence orthopaedic procedures constituted the highest number of interventions. Mortality rate was 10.7% (16 out of 150) with head injury being the leading cause. MCRI requires more emphasis on preventive measures. This will play a crucial role in the reduction of the associated morbidity and mortality.

Neurosurgery in rural Nigeria: A prospective study.

BACKGROUND: Africa has very few neurosurgeons. These are almost exclusively in urban centers. Consequently, people in rural areas, most of the African population, have poor or no access to neurosurgical care. We have recently pioneered rural neurosurgery in Nigeria. OBJECTIVES: This report details our initial experiences and the profile of neurosurgical admissions in our center. METHODS: A prospective observational study of all neurosurgical patients managed at a rural tertiary health institution in Nigeria from December 2010 to May 2012 was done. Simple descriptive data analysis was performed. RESULTS: A total of 249 males (75.2%) and 82 females (24.8%) were managed. The median age was 37 years (range: Day of birth - 94 years). Trauma was the leading cause of presentation with 225 (68.0%) and 35 (10.6%) having sustained head and spinal injuries, respectively. Operative intervention was performed in 54 (16.3%). Twenty-four (7.2%) patients discharged against medical advice, mostly for economic reasons. Most patients (208, 63.4%) had satisfactory outcome while 30 (9.1%) died. CONCLUSION: Trauma is the leading cause of rural neurosurgical presentations. There is an urgent need to improve access to adequate neurosurgical care in the rural communities.

Paediatric day-case neurosurgery in a resource challenged setting: Pattern and practice.

BACKGROUND: It has been generally observed that children achieve better convalescence in the home environment especially if discharged same day after surgery. This is probably due to the fact that children generally tend to feel more at ease in the home environment than in the hospital setting. Only few tertiary health institutions provide routine day-case surgery for paediatric neurosurgical patients in our sub-region. OBJECTIVE: To review the pattern and practice of paediatric neurosurgical day-cases at our hospital. PATIENTS AND METHODS: A prospective study of all paediatric day-case neurosurgeries carried out between June 2011 and June 2014. RESULTS: A total of 53 patients (34 males and 19 females) with age ranging from 2 days to 14 years were seen. Majority of the patients (77.4%) presented with congenital lesions, and the most common procedure carried out was spina bifida repair (32%) followed by ventriculoperitoneal shunt insertion (26.4%) for hydrocephalus. Sixty-eight percentage belonged to the American Society of Anesthesiologists physical status class 2, whereas the rest (32%) belonged to class 1. General anaesthesia was employed in 83% of cases. Parenteral paracetamol was used for intra-operative analgesia for most of the patients. Two patients had post-operative nausea and vomiting and were successfully managed. There was no case of emergency re-operation, unplanned admission, cancellation or mortality. CONCLUSION: Paediatric day-case neurosurgery is feasible in our environment. With careful patient selection and adequate pre-operative preparation, good outcome can be achieved.

Optic nerve sonography: A noninvasive means of detecting raised intracranial pressure in a resource-limited setting.

OBJECTIVE: The aim was to assess the use of optic nerve sonography (ONS) as a quick, noninvasive diagnostic test tool for detecting raised the intracranial pressure (ICP). MATERIALS AND METHODS: A prospective blinded observational study was conducted at Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife, Nigeria. The study population consisted of 160 adult patients referred to the radiology department for cranial computed tomography (CT) scan. There were 80 subjects and 80 controls. Optic nerve sheath diameter (ONSD) was measured by a radiologist using a 7.5 Megahertz ultrasound probe while cranial CT was reviewed by other radiologists blinded to the ONSD. RESULTS: Sixty-nine subjects (86.3%) had intracranial space occupying lesions (SOL) with cranial CT confirmed features of increased ICP, mean binocular ONSD of 5.7 ± 0.59 mm while 11 (13.7%) had intracranial SOL without any cranial CT evidence of increased ICP, mean binocular ONSD of 4.8 ± 0.39 mm. The difference of mean ONSD of the two groups was statistically significant (P = 0.0001). The controls had a mean binocular ONSD of 4.5 ± 0.22 mm and the difference in mean binocular ONSD for subjects with raised ICP and the controls were also statistically significant (P = 0.0001). A cut-off value of 5.2 mm (sensitivity 81.2% [95% confidence interval (CI): 69.9-89.6], specificity 100% [95% CI: 71.5-100]) was obtained from the receiver operator characteristics curve as the mean binocular ONSD that best predicts raised ICP confirmed by at least a sign on cranial CT. CONCLUSIONS: Optic nerve sonography can differentiate between normal and elevated ICP and may serve as a useful screening tool in resource-limited practice.

Outcome of a posterior spinal fusion technique using spinous process wire and vertical strut.

BACKGROUND/OBJECTIVE: Spinal fusion is a rapidly developing area of spine surgery. Many of the implants often used are not within the reach of the patients in the developing world. In this study, we describe the outcome of a novel technique of posterior spinal fusion using the rush nail and spinous process wire. MATERIALS AND METHODS: We prospectively evaluated patients who underwent the technique since October 2006. We reviewed the patients' biodata, clinical diagnosis, imaging studies, indications for surgery, type of operations, and complications related to the implants and the technique. Clinical test of instability was also determined. RESULTS: The technique was used in 11 female and 19 male patients. The age range was 11-82 years. The indication for surgery was trauma in 15 patients, degenerative disease in seven patients, tuberculosis of the spine in four patients, and four patients had neoplasms. Occipitocervical fusion was performed in three patients, cervical fusion in six patients, thoracic fusion in 10 patients, thoracolumbar fusion in seven patients, lumbar fusion in three patients, and lumbosacral fusion in one patient. The distal segment of the implant backed out in one patient following fracture of the spinal process. The implant was eventually removed. Clinical evidence of instability necessitating external orthotics was also seen in one patient. Two patients had wound infection. These were managed without removing the implants. We did not observe significant complications in other patients. CONCLUSION: The technique appears safe and effective in carefully selected cases. The technique needs further evaluation in a larger patient population and with a longer duration of follow-up.

Epidemiology of neurotrauma in Ife-Ijesha zone of Nigeria.

BACKGROUND AND OBJECTIVE: Trauma remains one of the important causes of severe disability and high mortality. In this study, we looked at the epidemiology of neurotrauma in our region so as to highlight essential factors for trauma prevention program. METHODOLOGY: This is a cross-sectional study of all neurotrauma cases admitted to the neurosurgery service of our hospital over an 18-month period. Information was obtained on patients' demographic data, etiology of injury, duration of injury, site, and cause of accident among others. RESULTS: One hundred forty-three patients were included in the study. The injuries occurred mostly in males and in the third decade. Most of the patients were students and traders. Eighty-one percent of the accidents were due to road traffic crash (RTC), and the most common contributory factors were head-on collision (46.2%) and overtaking (28.6%). Five of six patients who had RTC in the first decade of life were pedestrians. There were more crashes within the cities. None of the patients who had motorcycle accidents used helmet and only four patients used seatbelts at the time of the accident. Transfer to hospital was mostly in vehicles other than ambulance. CONCLUSION: Neurotrauma in our study was mostly due to RTC and it is most common in young male students. Contributory factors were head on collision and overtaking.

Predicting intracranial hemorrhage after traumatic brain injury in low and middle-income countries: a prognostic model based on a large, multi-center, international cohort.

BACKGROUND: Traumatic brain injury (TBI) affects approximately 10 million people annually, of which intracranial hemorrhage is a devastating sequelae, occurring in one-third to half of cases. Patients in low and middle-income countries (LMIC) are twice as likely to die following TBI as compared to those in high-income countries. Diagnostic capabilities and treatment options for intracranial hemorrhage are limited in LMIC as there are fewer computed tomography (CT) scanners and neurosurgeons per patient as in high-income countries. METHODS: The Medical Research Council CRASH-1 trial was utilized to build this model. The study cohort included all patients from LMIC who received a CT scan of the brain (n = 5669). Prognostic variables investigated included age, sex, time from injury to randomization, pupil reactivity, cause of injury, seizure and the presence of major extracranial injury. RESULTS: There were five predictors that were included in the final model; age, Glasgow Coma Scale, pupil reactivity, the presence of a major extracranial injury and time from injury to presentation. The model demonstrated good discrimination and excellent calibration (c-statistic 0.71). A simplified risk score was created for clinical settings to estimate the percentage risk of intracranial hemorrhage among TBI patients. CONCLUSION: Simple prognostic models can be used in LMIC to estimate the risk of intracranial hemorrhage among TBI patients. Combined with clinical judgment this may facilitate risk stratification, rapid transfer to higher levels of care and treatment in resource-poor settings.

CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial.

BACKGROUND: Worldwide, over 10 million people are killed or hospitalized because of traumatic brain injury each year. About 90% of deaths occur in low- and middle-income countries. The condition mostly affects young adults, and many experience long lasting or permanent disability. The social and economic burden is considerable. Tranexamic acid (TXA) is commonly given to surgical patients to reduce bleeding and the need for blood transfusion. It has been shown to reduce the number of patients receiving a blood transfusion by about a third, reduces the volume of blood transfused by about one unit, and halves the need for further surgery to control bleeding in elective surgical patients. METHODS/DESIGN: The CRASH-3 trial is an international, multicenter, pragmatic, randomized, double-blind, placebo-controlled trial to quantify the effects of the early administration of TXA on death and disability in patients with traumatic brain injury. Ten thousand adult patients who fulfil the eligibility criteria will be randomized to receive TXA or placebo. Adults with traumatic brain injury, who are within 8 h of injury and have any intracranial bleeding on computerized tomography (CT scan) or Glasgow Coma Score (GCS) of 12 or less can be included if the responsible doctor is substantially uncertain as to whether or not to use TXA in this patient. Patients with significant extracranial bleeding will be excluded since there is evidence that TXA improves outcome in these patients. Treatment will entail a 1 g loading dose followed by a 1 g maintenance dose over 8 h.The main analyses will be on an 'intention-to-treat' basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses for the primary outcome will be based on time from injury to randomization, the severity of the injury, location of the bleeding, and baseline risk. Interaction tests will be used to test whether the effect of treatment differs across these subgroups. A study with 10,000 patients will have approximately 90% power to detect a 15% relative reduction from 20% to 17% in all-cause mortality. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15088122; Clinicaltrials.gov NCT01402882.

The social and economic impacts of epilepsy on women in Nigeria.

BACKGROUND: Persons with epilepsy in sub-Saharan Africa experience stigma and social marginalization. There is paucity of data on the social and economic impacts of epilepsy in these patients and in particular, groups like women. We sought to determine the social and economic impacts of epilepsy on Nigerian women and especially how it affects their treatment and outcomes. METHODS: We carried out a cross-sectional survey of 63 women with epilepsy (WWE) and 69 controls matched for age, social status and site of care. A structured questionnaire was used to document information on demographic characteristics, education, employment status, economic status, health care use, personal safety and perceived stigma. The data were collated and analyzed with SPSS version 15. RESULTS: Unemployment, fewer years of formal education, lower marriage rates and higher stigma scores were more frequent among WWE than controls. Physical and sexual abuse with transactional sex was also reported among WWE. We also noted poorer environmental and housing conditions and lower mean personal and household incomes among WWE compared to the control group. CONCLUSION: WWE in this sample from Nigeria have worse social and economic status when compared with women with other non-stigmatized chronic medical conditions.

The International Tethered Cord Partnership: Beginnings, process, and status.

BACKGROUND: Spina bifida presents a significant cause of childhood morbidity in lower- and middle-income nations. Unfortunately, there is a paucity of literature examining outcomes among children with spina bifida in these countries. The goal of the International Tethered Cord Parternship is twofold: (1) to establish an international surveillance database to examine the correlation between time of repair and clinical outcomes in children with spina bifida and tethered cord; and (2) to foster collaboration among international institutions around pediatric neurosurgical concerns. METHODS: Twelve institutions in 7 countries committed to participating in the International Tethered Cord Partnership. A neurosurgeon at each institution will evaluate all children presenting with spina bifida and/or tethered cord using the survey instrument after appropriate consent is obtained. The instrument was developed collaboratively and based on previous measures of motor and sensory function, ambulation, and continence. All institutions who have begun collecting data received appropriate Institutional Review Board approval. All data will be entered into a Health Insurance Portability and Accountability Act (HIPAA) compliant database. In addition, a participant restricted internet forum was created to foster communication and includes non-project-specific communications, such as case and journal article discussion. RESULTS: From October 2010 to December 2010, 82 patients were entered from the various study sites. CONCLUSION: To our knowledge this is the first international pediatric neurosurgical database focused on clinical outcomes and predictors of disease progression. The collaborative nature of the project will not only increase knowledge of spina bifida and tethered cord, but also foster discussion and further collaboration between neurosurgeons internationally.

The technique of using rigid vertical strut and spinal process wire for posterior spinal stabilization.

BACKGROUND AND OBJECTIVE: High cost of conventional spinal instrumentation and the need for intraoperative imaging have forced us to consider other methods of spinal stabilization especially suitable in low-income societies. In this article, we describe our technique of spinal fusion using spinous process wiring and rigid vertical strut. TECHNIQUE AND METHODOLOGY: Vertical strut which has been bent at one end is passed through loops of wire introduced into the base of the spinous processes to be instrumented. Another vertical strut is passed through the loose ends of the loops. We currently use Rush nail as the vertical strut. RESULTS: The loose ends of the loops of wire are pulled snugly and twisted. This results in immediate rigid stabilization of the spine. CONCLUSIONS: The technique seems safe and efficient in stabilizing the spine pending definitive bony fusion.

Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial.

BACKGROUND: Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients. METHODS: This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919. FINDINGS: 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077). INTERPRETATION: Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients. FUNDING: UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.