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Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury
can lead to overestimation of the prevalence of symptoms or diagnoses in the TBI population. Symptom self-reporting might sometimes introduce another type of bias known as outcome misclassification, which leads to errors in how symptoms are classified into outcomes and analyzed.
Apart from some large population-based studies of mortality after TBI and a few others of neurologic outcomes, many of the studies evaluated by the committee had small samples. When a study sample is too small, it is possible to miss clinically important differences; this phenomenon is known in epidemiology as type II error. In such studies, attempts to examine even smaller subpopulations magnify the difficulties and reduce the likelihood of detecting meaningful differences. Of the studies examined by the committee, those with small samples were also sometimes hampered by other problems, including low participation rate, loss to followup, inadequate duration of followup, and self-reporting of symptoms.
An additional limitation of the studies reviewed is the lack of uniformity in defining the severity of TBI. Studies typically note whether the injury was a penetrating or a closed head injury but often use different criteria to assess severity. The committee found it difficult to compare outcomes among studies, particularly in the “moderate” TBI category, because researchers used different durations of LOC and of PTA to define severity. Similarly, the range of scores on the GCS was not always uniformly applied in defining mild, moderate, and severe TBI.
The committee focused on studies of people who had sustained TBI, followed the subjects to determine long-term sequelae, and generally asked whether a specific outcome was more likely in people with TBI than in controls without TBI. The committee discussed characteristics of the optimal control group for such studies because the type of controls could influence inferences drawn from the studies examined. When the outcome was a medical condition or a social outcome, the committee considered the best comparison group to be made up of people who had other traumatic injuries but without TBI (such as bone fractures) and were in the same facility as the subjects with TBI; such controls permit examination of the effects of TBI on outcome independently of the general effects of trauma and of the common risk factors that lead to trauma. When the outcome studied was death, the committee agreed that comparison with age- and sex-specific mortality in the general population provided the best comparison.
The committee found many studies for inclusion in its review. However, many excellent studies were excluded because they were not designed to answer the question posed to the committee: What are the long-term outcomes associated with sustaining TBI?
OVERVIEW OF HEALTH OUTCOMES
It is clear that TBI can have detrimental effects on a person, whether it is mild, moderate, or severe. The committee found many instances of long-term outcomes of TBI, although some acute outcomes resolved or lessened over time (such as some neurocognitive and psychosocial dysfunction) whereas other sequelae became more apparent several years after injury (such as psychiatric outcomes). Many studies found a dose–response relationship with regard to TBI severity and outcome: generally, the more severe the TBI, the more severe the outcome. For example, with regard to neurocognitive outcomes, the committee found sufficient evidence of an association between penetrating TBI and decline in neurocognitive function associated with the