Fiona Lecky

Derivation of the children’s head injury algorithm for the prediction of important clinical events decision rule for head injury in children

Background: A quarter of all patients presenting to emergency departments are children. Although there are several large, well-conducted studies on adults enabling accurate selection of patients with head injury at high risk for computed tomography scanning, no such study has derived a rule for children. Aim: To conduct a prospective multicentre diagnostic cohort study to provide a rule for selection of high-risk children with head injury for computed tomography scanning. Design: All children presenting to the emergency departments of 10 hospitals in the northwest of England with any severity of head injury were recruited. A tailor-made proforma was used to collect data on around 40 clinical variables for each child. These variables were defined from a literature review, and a pilot study was conducted before the children’s head injury algorithm for the prediction of important clinical events (CHALICE) study. All children who had a clinically significant head injury (death, need for neurosurgical intervention or abnormality on a computed tomography scan) were identified. Recursive partitioning was used to create a highly sensitive rule for the prediction of significant intracranial pathology. Results: 22 772 children were recruited over 2½ years. 65% of these were boys and 56% were <5 years old. 281 children showed an abnormality on the computed tomography scan, 137 had a neurosurgical operation and 15 died. The CHALICE rule was derived with a sensitivity of 98% (95% confidence interval (CI) 96% to 100%) and a specificity of 87% (95% CI 86% to 87%) for the prediction of clinically significant head injury, and requires a computed tomography scan rate of 14%. Conclusion: A highly sensitive clinical decision rule is derived for the identification of children who should undergo computed tomography scanning after head injury. This rule has the potential to improve and standardise the care of children presenting with head injuries. Validation of this rule in new cohorts of patients should now be undertaken.

Trends in head injury outcome from 1989 to 2003 and the effect of neurosurgical care: An observational study

BACKGROUND Case fatality rates after all types of blunt injury have not improved since 1994 in England and Wales, possibly because not all patients with severe head injury are treated in a neurosurgical centre. Our aims were to investigate the case fatality trends in major trauma patients with and without head injury, and to establish the effect of neurosurgical care on mortality after severe head injury. METHODS We analysed prospectively collected data from the Trauma Audit and Research Network database for patients presenting between 1989 and 2003. Mortality and odds of death adjusted for case mix were compared for patients with and without head injury, and for those treated in a neurosurgical versus a non-neurosurgical centre. FINDINGS Patients with head injury (n=22,216) had a ten-fold higher mortality and showed less improvement in the adjusted odds of death since 1989 than did patients without head injury (n=154,231). 2305 (33%) of patients with severe head injury (presenting between 1996 and 2003) were treated only in non-neurosurgical centres; such treatment was associated with a 26% increase in mortality and a 2.15-fold increase (95% CI 1.77-2.60) in the odds of death adjusted for case mix compared with patients treated at a neurosurgical centre. INTERPRETATION Since 1989 trauma system changes in England and Wales have delivered greater benefit to patients without head injury. Our data lend support to current guidelines, suggesting that treatment in a neurosurgical centre represents an important strategy in the management of severe head injury.

The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013

Background The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. Methods Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. Results In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. Conclusions Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.

The Glasgow Coma Scale at 40 years: standing the test of time

Since 1974, the Glasgow Coma Scale has provided a practical method for bedside assessment of impairment of conscious level, the clinical hallmark of acute brain injury. The scale was designed to be easy to use in clinical practice in general and specialist units and to replace previous ill-defined and inconsistent methods. 40 years later, the Glasgow Coma Scale has become an integral part of clinical practice and research worldwide. Findings using the scale have shown strong associations with those obtained by use of other early indices of severity and outcome. However, predictive statements should only be made in combination with other variables in a multivariate model. Individual patients are best described by the three components of the coma scale; whereas the derived total coma score should be used to characterise groups. Adherence to this principle and enhancement of the reliable practical use of the scale through continuing education of health professionals, standardisation across different settings, and consensus on methods to address confounders will maintain its role in clinical practice and research in the future.

Prediction of outcome after moderate and severe traumatic brain injury: External validation of the International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models*

Objective: The International Mission on Prognosis and Analysis of Clinical Trials and Corticoid Randomisation After Significant Head injury prognostic models predict outcome after traumatic brain injury but have not been compared in large datasets. The objective of this is study is to validate externally and compare the International Mission on Prognosis and Analysis of Clinical Trials and Corticoid Randomisation after Significant Head injury prognostic models for prediction of outcome after moderate or severe traumatic brain injury. Design: External validation study. Patients: We considered five new datasets with a total of 9,036 patients, comprising three randomized trials and two observational series, containing prospectively collected individual traumatic brain injury patient data. Measurements and Main Results: Outcomes were mortality and unfavorable outcome, based on the Glasgow Outcome Score at 6 months after injury. To assess performance, we studied the discrimination of the models (by area under the receiver operating characteristic curves), and calibration (by comparison of the mean observed to predicted outcomes and calibration slopes). The highest discrimination was found in the Trauma Audit and Research Network trauma registry (area under the receiver operating characteristic curves between 0.83 and 0.87), and the lowest discrimination in the Pharmos trial (area under the receiver operating characteristic curves between 0.65 and 0.71). Although differences in predictor effects between development and validation populations were found (calibration slopes varying between 0.58 and 1.53), the differences in discrimination were largely explained by differences in case mix in the validation studies. Calibration was good, the fraction of observed outcomes generally agreed well with the mean predicted outcome. No meaningful differences were noted in performance between the International Mission on Prognosis and Analysis of Clinical Trials and Corticoid Randomisation After Significant Head injury models. More complex models discriminated slightly better than simpler variants. Conclusions: Since both the International Mission on Prognosis and Analysis of Clinical Trials and the Corticoid Randomisation After Significant Head injury prognostic models show good generalizability to more recent data, they are valid instruments to quantify prognosis in traumatic brain injury.

Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (Center-tbi): A Prospective Longitudinal Observational Study

BACKGROUND: Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies. OBJECTIVE: To improve characterization and classification of TBI and to identify best clinical care, using comparative effectiveness research approaches. METHODS: This multicenter, longitudinal, prospective, observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting patients, presenting within 24 hours of injury, with a clinical diagnosis of TBI and an indication for computed tomography. Broader registry-level data collection in approximately 20 000 patients will assess generalizability. Cross sectional comprehensive outcome assessments, including quality of life and neuropsychological testing, will be performed at 6 months. Longitudinal assessments will continue up to 24 months post TBI in patient subsets. Advanced neuroimaging and genomic and biomarker data will be used to improve characterization, and analyses will include neuroinformatics approaches to address variations in process and clinical care. Results will be integrated with living systematic reviews in a process of knowledge transfer. The study initiation was from October to December 2014, and the recruitment period was for 18 to 24 months. EXPECTED OUTCOMES: Collaborative European NeuroTrauma Effectiveness Research in TBI should provide novel multidimensional approaches to TBI characterization and classification, evidence to support treatment recommendations, and benchmarks for quality of care. Data and sample repositories will ensure opportunities for legacy research. DISCUSSION: Comparative effectiveness research provides an alternative to reductionistic clinical trials in restricted patient populations by exploiting differences in biology, care, and outcome to support optimal personalized patient management.BACKGROUND Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies. OBJECTIVE To improve characterization and classification of TBI and to identify best clinical care, using comparative effectiveness research approaches. METHODS This multicenter, longitudinal, prospective, observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting patients, presenting within 24 hours of injury, with a clinical diagnosis of TBI and an indication for computed tomography. Broader registry-level data collection in approximately 20,000 patients will assess generalizability. Cross sectional comprehensive outcome assessments, including quality of life and neuropsychological testing, will be performed at 6 months. Longitudinal assessments will continue up to 24 months post TBI in patient subsets. Advanced neuroimaging and genomic and biomarker data will be used to improve characterization, and analyses will include neuroinformatics approaches to address variations in process and clinical care. Results will be integrated with living systematic reviews in a process of knowledge transfer. The study initiation was from October to December 2014, and the recruitment period was for 18 to 24 months. EXPECTED OUTCOMES Collaborative European NeuroTrauma Effectiveness Research in TBI should provide novel multidimensional approaches to TBI characterization and classification, evidence to support treatment recommendations, and benchmarks for quality of care. Data and sample repositories will ensure opportunities for legacy research. DISCUSSION Comparative effectiveness research provides an alternative to reductionistic clinical trials in restricted patient populations by exploiting differences in biology, care, and outcome to support optimal personalized patient management.

Effect of tranexamic acid on mortality in patients with traumatic bleeding: prespecified analysis of data from randomised controlled trial

Objectives To examine whether the effect of tranexamic acid on the risk of death and thrombotic events in patients with traumatic bleeding varies according to baseline risk of death. To assess the extent to which current protocols for treatment with tranexamic acid maximise benefits to patients. Design Prespecified stratified analysis of data from an international multicentre randomised controlled trial (the CRASH-2 trial) with an estimation of the proportion of premature deaths that could potentially be averted through the administration of tranexamic acid. Participants 13 273 trauma patients in the CRASH-2 trial who were treated with tranexamic acid or placebo within three hours of injury and trauma patients enrolled in UK Trauma and Audit Research Network, stratified by risk of death at baseline (<6%, 6-20%, 21-50%, >50%). Intervention Tranexamic acid (1 g over 10 minutes followed by 1 g over eight hours) or matching placebo. Main outcome measure Odds ratios and 95% confidence intervals for death in hospital within four weeks of injury, deaths from bleeding, and fatal and non-fatal thrombotic events associated with the use of tranexamic acid according to baseline risk of death. Unless there was strong evidence against the null hypothesis of homogeneity of effects (P<0.001), the overall odds ratio was used as the most reliable guide to the odds ratios in all strata. Results Tranexamic acid was associated with a significant reduction in all cause mortality and deaths from bleeding. In each stratum of baseline risk, there were fewer deaths among patients treated with tranexamic acid. There was no evidence of heterogeneity in the effect of tranexamic acid on all cause mortality (P=0.96 for interaction) or deaths from bleeding (P=0.98) by baseline risk of death. In those treated with tranexamic acid there was a significant reduction in the odds of fatal and non-fatal thrombotic events (odds ratio 0.69, 95% confidence interval 0.53 to 0.89; P=0.005) and a significant reduction in arterial thrombotic events (0.58, 0.40 to 0.83; P=0.003) but no significant reduction in venous thrombotic events (0.83, 0.59 to 1.17; P=0.295). There was no evidence of heterogeneity in the effect of tranexamic acid on the risk of thrombotic events (P=0.74). If the effect of tranexamic acid is assumed to be the same in all risk strata (<6%, 6-20%, 21-50%, >50% risk of death at baseline), the percentage of deaths that could be averted by administration of tranexamic acid within three hours of injury in each group is 17%, 36%, 30%, and 17%, respectively. Conclusions Tranexamic acid can be administered safely to a wide spectrum of patients with traumatic bleeding and should not be restricted to the most severely injured. Trial registration ISRCTN86750102.

Vital signs and estimated blood loss in patients with major trauma: testing the validity of the ATLS classification of hypovolaemic shock.

AIM The Advanced Trauma Life Support (ATLS) system classifies the severity of shock. The aim of this study is to test the validity of this classification. METHODS Admission physiology, injury and outcome variables from adult injured patients presenting to hospitals in England and Wales between 1989 and 2007 and stored on the Trauma Audit and Research Network (TARN) database, were studied. For each patient, the blood loss was estimated and patients were divided into four groups based on the estimated blood loss corresponding to the ATLS classes of shock. The median and interquartile ranges (IQR) of the heart rate (HR) systolic blood pressure (SBP), respiratory rate (RR) and Glasgow Coma Score (GCS) were calculated for each group. RESULTS The median HR rose from 82 beats per minute (BPM) in estimated class 1 shock to 95 BPM in estimated class 4 shock. The median SBP fell from 135 mm Hg to 120 mm Hg. There was no significant change in RR or GCS. CONCLUSION With increasing estimated blood loss there is a trend to increasing heart rate and a reduction in SBP but not to the degree suggested by the ATLS classification of shock.

A major trauma centre is a specialty hospital not a hospital of specialties

High estimates of preventable death rates have renewed the impetus for national regionalization of trauma care. Institution of a specialist multidisciplinary trauma service and performance improvement programme was hypothesized to have resulted in improved outcomes for severely injured patients.

Predictors of persistent neck pain after whiplash injury

Objective: To establish the aetiological influences of persistent neck pain following a motor vehicle collision and to construct a model for use in the emergency department for identifying patients at high risk of persistent symptoms. Design: Prospective cohort study. Patients recruited from hospital emergency departments were sent a questionnaire to gather information on various exposures. They were followed up at 1, 3, and 12 months to identify those with persistent symptoms. Main outcome measure: Persistent neck pain (pain at 1, 3, and 12 months after collision). Results: The baseline survey included 765 patients. Subsequently, 480 completed a questionnaire at each follow up time point, of whom 128 (27%) reported neck pain on each occasion. Few collision specific factors predicted persistent neck pain. In contrast, a high level of general psychological distress, pre-collision history of widespread body pain, type of vehicle, whiplash associated symptoms, and initial neck disability best predicted the persistence of symptoms. Furthermore, these factors, in combination, accounted for more than a fivefold increase in the risk of persistent neck pain. Conclusion: The greatest predictors of persistent neck pain following a motor vehicle collision relate to psychological distress and aspects of pre-collision health rather than to various attributes of the collision itself. With these factors, and those relating to initial injury severity, it is possible to identify a subgroup of patients presenting with neck pain with the highest risk of persistent symptoms. Thus, it is possible to identify whiplash patients with a poor prognosis and to provide closer follow up and specific attention to management in these individuals.