Int. J. Epidemiol. Advance Access published September 9, 2008 Published by Oxford University Press on behalf of the International Epidemiological Association ß The Author 2008; all rights reserved.
International Journal of Epidemiology 2008;1–7 doi:10.1093/ije/dyn189
Patient outcome after traumatic brain injury in high-, middle- and low-income countries: analysis of data on 8927 patients in 46 countries Mary J De Silva,1* Ian Roberts,1 Pablo Perel,1 Phil Edwards,1 Michael G Kenward,1 Janice Fernandes,2 Haleema Shakur1 and Vikram Patel1 on behalf of the CRASH Trial Collaborators
Accepted
13 August 2008
Background Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. The burden of TBI is greatest in low- and middle-income countries (LAMIC), yet little is known about patient outcomes in these settings. Methods
Complete data on 8927 patients from 46 countries from the corticosteroid randomization after significant head injury (CRASH) trial were analysed to explore whether outcomes 6 months after TBI differed between high-income countries and LAMIC.
Results
Just under half of patients experienced a good recovery, one-third moderate or severe disability and one-quarter died within 6 months of their injury. Univariate analyses showed that patients in LAMIC were more likely to die following severe TBI, but were less likely to be disabled following mild and moderate TBI. These results were confirmed in multivariate analyses. Compared to patients in high-income countries, patients in LAMIC have over twice the odds of dying following severe TBI (OR 2.23, 95% CI 1.51–3.30) but half the odds of disability following mild (OR 0.41, 95% CI 0.23–0.72) and moderate TBI (OR 0.53, 95% CI 0.35–0.81). There were no differences between settings in the odds of death following either mild or moderate TBI.
Conclusions Reduced death rates following severe TBI in patients from highincome countries may be due to differences in medical care which may result in a higher proportion of patients surviving with a disability. Socio-cultural factors may explain the lower levels of disability after mild and moderate TBI in LAMIC. Keywords
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Traumatic brain injury, Glasgow Outcome Score, high-income countries, middle-income countries, low-income countries
Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, London, UK. Centre for Brain and Cognitive Development, School of Psychology, Birkbeck, University of London, Malet Street, WC1E 7HX, London, UK.
* Corresponding author. Dr Mary J De Silva, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, London, UK. E-mail:
[email protected]
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INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
Introduction Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Every year, millions of people receive emergency medical treatment for TBI and an estimated 1.5 million die.1 TBI is the leading cause of disability in people under 40, severely disabling 150–200 people per million annually.2,3 The burden of TBI is greatest in low- and middleincome countries (LAMIC), where 85% of the world’s population live. The World Health Organization (WHO) estimates that almost 90% of deaths due to injuries occur in these settings.1,4 Despite this, very little is known about patient outcomes after TBI in LAMIC. For example, a systematic review of prognostic models after TBI found that only 7% of the 102 included models were based on data from LAMIC.5 This may be a consequence of the 10/90 gap whereby 1 to ≤3 h, >3 to ≤8 h) - Intervention group (placebo/intervention)
Figure 1 Analytical framework
Statistical analysis Unordered multinomial regression models with robust standard errors were used. These were chosen because we did not wish to treat the categories of the outcome variable as strictly ordered and therefore base the analysis on cumulative probabilities, and because patients were clustered within hospitals. All variables which were thought to confound the relationship between country-income group and 6-month outcome were included in the model irrespective of statistical significance. As we hypothesized that the severity of initial injury (GCS) may modify the effect of country-income group on outcome, interactions between GCS and countryincome group were tested. Additional analyses examined the impact of some key assumptions on the conclusions reached. First, the consequence of departures from complete randomness of the missing data was explored using multiple imputation.13 This allows the incorporation of subjects with incomplete data into the analysis in a statistically principled way, allowing for possible dependence of the probability of a value being missing on other observed variables. The imputation model contained all the variables which were included in the final model, plus those variables which may predict them. Secondly, the model was re-fitted with a binary 6-month outcome variable (favourable outcome: good recovery or moderate disability; unfavourable outcome: severe disability or death), and with a finer categorization of country-income group (high-, upper-middle-, lower-middle- and low-income country). All analyses were conducted using Stata 9.0.14
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Results Sample selection and description of sample Figure 2 outlines the sample selection of patients for the analysis. A total of 10 008 patients from 239 hospitals in 48 countries were enrolled in the trial. In order to restrict the analysis to adults, 67 patients who were under 16 were excluded. In addition, 270 patients who had a disability which was not caused by their TBI were excluded as these patients cannot inform us about outcomes caused by TBI. In total, 7.5% of the sample was excluded due to missing data. A total of 8927 patients from 46 countries were included in the final analysis. Due to differences between countries in the numbers and sizes of participating hospitals, the numbers of patients from each country ranged from 1 to 1044 (mean 194; see Supplementary Data). A full description of the sample has been provided elsewhere.8 The mean age of the patients is 37, and over 81% are male. Patients from LAMIC were younger and more likely to be male than patients from high-income countries (Table 1). Three-quarters live in LAMIC, and roughly a third suffered mild, moderate or severe TBI respectively. Patients in highincome countries suffered more mild and severe TBIs, but fewer moderate TBIs. One-fifth of patients suffered a major extra-cranial injury in addition to a TBI. Just under half of patients experienced a good recovery, one-third moderate or severe disability and one-quarter died within 6 months of their injury. Patients were more likely to experience a good recovery but were also more likely to die following TBI in LAMIC compared with high-income countries. The demographic, injury-related and treatment factors included in the analysis displayed the expected association with the GOS. As the association between these variables and the GOS has already been presented elsewhere,15 these results will not be discussed in detail here. Differences in 6-month outcomes by country-income group There were significant differences according to injury severity in outcomes 6 months after TBI between high-income countries and LAMIC (Table 2). Twentyone per cent more patients died following a severe TBI (GCS 3–8) in LAMIC compared with high-income countries (51%, n ¼ 1347 vs 30%, n ¼ 285; P < 0.001). However, patients in LAMIC had significantly better outcomes following mild (GCS 13–14) and moderate TBI (GCS 9–12) than patients in high-income countries. For example, 18% more patients had a good recovery following mild TBI in LAMIC compared with high-income countries (78%, n ¼ 1557 vs 60%, n ¼ 410; P < 0.001). Levels of moderate and severe disability were lower in LAMIC following severe TBI, though the proportion enjoying a good recovery did not differ between country groups.
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INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Table 1 Description of sample by setting
10,008 enrolled in trial
Mean age (years) 9941 adults
Male 270 disability not due to TBI 447 missing outcome data
% (n) LAMIC
HIC
67
