Edward O Komolafe

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 AL analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.gov NCT00375258, and South African Clinical Trial Register DOH-27-0607-1919. RESULTS 10096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10060 and 10067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [160%] placebo group; relative risk 0.91, 95% CI 085-097; p = 00035). The risk of death due to bleeding was significantly reduced (489 [49%] vs 574 [5-7%]; relative risk 0-85, 95% CI 0.76-0.96; p = 0-0077). CONCLUSION 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.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.

Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial.

BACKGROUND Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment. METHODS 10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797. FINDINGS Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05). INTERPRETATION Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear.

Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients.

Objective To develop and validate practical prognostic models for death at 14 days and for death or severe disability six months after traumatic brain injury. Design Multivariable logistic regression to select variables that were independently associated with two patient outcomes. Two models designed: “basic” model (demographic and clinical variables only) and “CT” model (basic model plus results of computed tomography). The models were subsequently developed for high and low-middle income countries separately. Setting Medical Research Council (MRC) CRASH Trial. Subjects 10 008 patients with traumatic brain injury. Models externally validated in a cohort of 8509. Results The basic model included four predictors: age, Glasgow coma scale, pupil reactivity, and the presence of major extracranial injury. The CT model also included the presence of petechial haemorrhages, obliteration of the third ventricle or basal cisterns, subarachnoid bleeding, midline shift, and non-evacuated haematoma. In the derivation sample the models showed excellent discrimination (C statistic above 0.80). The models showed good calibration graphically. The Hosmer-Lemeshow test also indicated good calibration, except for the CT model in low-middle income countries. External validation for unfavourable outcome at six months in high income countries showed that basic and CT models had good discrimination (C statistic 0.77 for both models) but poorer calibration. Conclusion Simple prognostic models can be used to obtain valid predictions of relevant outcomes in patients with traumatic brain injury.

Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months.

MRC CRASH is a randomised controlled trial (ISRCTN74459797) of the effect of corticosteroids on death and disability after head injury. We randomly allocated 10,008 adults with head injury and a Glasgow Coma Scale score of 14 or less, within 8 h of injury, to a 48-h infusion of corticosteroid (methylprednisolone) or placebo. Data at 6 months were obtained for 9673 (96.7%) patients. The risk of death was higher in the corticosteroid group than in the placebo group (1248 [25.7%] vs 1075 [22.3%] deaths; relative risk 1.15, 95% CI 1.07-1.24; p=0.0001), as was the risk of death or severe disability (1828 [38.1%] vs 1728 [36.3%] dead or severely disabled; 1.05, 0.99-1.10; p=0.079). There was no evidence that the effect of corticosteroids differed by injury severity or time since injury. These results lend support to our earlier conclusion that corticosteroids should not be used routinely in the treatment of head injury.

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

BackgroundWorldwide, 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/designThe 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 registrationCurrent 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.

Symptomatic pleural effusion without intrathoracic migration of ventriculoperitoneal shunt catheter.

BackgroundSymptomatic pleural effusion following ventriculoperitoneal (VP) shunt insertion is very rare. The patient was an 8-year-old girl who had VP shunt for hydrocephalus as a result of aqueductal stenosis. Six weeks after surgery, she presented with headache, vomiting and drowsiness. She developed respiratory distress with pain in the right lower chest region and right hypochondrium on admission.MethodsChest X-ray confirmed right hydrothorax and showed the tip of the peritoneal catheter in the right suprahepatic subphrenic space. Her symptoms abated after the catheter was repositioned from the subphrenic region to the general peritoneal cavity. Repeat chest X-ray confirmed the resolution of the hydrothorax.DiscussionShunt review without thoracocentesis or thoracostomy is an effective treatment of symptomatic hydrothorax following VP shunt, especially when there is no intrathoracic shunt migration.

New onset neuromyelitis optica in a young Nigerian woman with possible antiphospholipid syndrome: a case report

IntroductionDevics neuromyelitis optica is an inflammatory demyelinating disease that targets the optic nerves and spinal cord. It has a worldwide distribution and distinctive features that distinguish it from multiple sclerosis. There has been no previous report of neuromyelitis optica from our practice environment, and we are not aware of any case associated with antiphospholipid syndrome in an African person.Case presentationWe report the case of a 28-year-old Nigerian woman who presented with neck pain, paroxysmal tonic spasms, a positive Lhermittes sign and spastic quadriplegia. She later developed bilateral optic neuritis and had clinical and biochemical features of antiphospholipid syndrome. Her initial magnetic resonance imaging showed a central linear hyperintense focus in the intramedullary portion of C2 to C4. Repeat magnetic resonance imaging after treatment revealed resolution of the signal intensity noticed earlier.ConclusionNeuromyelitis optica should be considered in the differential diagnoses of acute myelopathy in Africans. We also highlight the unusual association with antiphospholipid syndrome. Physicians should screen such patients for autoimmune disorders.

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.

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

BackgroundTraumatic 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.MethodsThe 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.ResultsThere 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.ConclusionSimple 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.