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Elana Farace and Wayne M. Alves

Object. The purpose of this metaanalysis was to investigate possible gender differences in traumatic brain injury (TBI) sequelae. The case fatality rates in patients after TBI have previously been shown to be significantly higher in women as compared with men.

Methods. A quantitative review of published studies of TBI outcome revealed eight studies (20 outcome variables) of TBI, in which outcome was reported separately for men and women.

Conclusions. Outcome was worse in women than in men for 85% of the measured variables, with an average effect size of −0.15. Although clinical opinion is often that women tend to experience better outcomes than men after TBI, the opposite pattern was suggested in the results of this metaanalysis. However, this conclusion is limited by the fact that, in only a small percentage of the total published reports on TBI outcome, was outcome described separately for each sex. A careful, prospective study of sex differences in TBI outcome is clearly needed.

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Elana Farace and Wayne M. Alves

The purpose of this metaanalysis was to investigate possible gender differences in TBI sequelae. The case fatality rates in patients after TBI have previously been shown to be significantly higher in women as compared with men. A quantitative review of published studies of TBI outcome revealed eight studies (20 outcome variables) of TBI in which outcome was reported separately for men and women. Outcome was worse in women than in men for 85% of the measured variables, with an average effect size of −0.15. Although clinical opinion is often that women tend to experience better outcomes than do men after TBI, the opposite pattern was suggested in the results of this metaanalysis. However, this conclusion is limited by the fact that in only a small percentage of the total published reports on TBI outcome was outcome described separately for each sex. A careful, prospective study of sex differences in TBI outcome is clearly needed.

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Mark E. Shaffrey, Elana Farace, David Schiff, James M. Larner, Melike Mut and M. Beatriz S. Lopes

Object. This study was conducted to determine whether proliferative tumor activity, as assessed using the Ki-67 immunohistochemical labeling index (LI), has prognostic utility for patients with Grade II oligoastrocytomas.

Methods. The study period spans the years 1988 to 2000. In a retrospective analysis, the authors selected cases with biopsy-proven diagnoses of Grade II oligoastrocytomas on initial presentation. The authors added new patients to this group and followed all patients prospectively at the University of Virginia Neuro-Oncology Center.

Twenty-three adult patients were followed for at least 1 year (median 40.3 months). Eleven patients with Grade II tumors and initial Ki-67 LIs less than 10% had a significantly longer median time to tumor progression (TTP, 51.8 months compared with 9.9 months) and a longer median survival (93.1 months compared with 16.1 months) than 12 patients with initial Ki-67 LIs of 10% or greater. Twelve patients with Grade III oligoastrocytomas had a mean TTP that was similar to the TTP of patients with Grade II tumors and high Ki-67 LIs (mean 4 months compared with 9.9 months) and duration of survival (13.3 months compared with 16.1 months).

Conclusions. Patients with a Grade II oligoastrocytoma and a Ki-67 LI of 10% or greater have a much shorter TTP and potentially a poorer disease prognosis than expected—more similar to patients with a Grade III oligoastrocytoma. These results indicate that in the future a measure of proliferative activity should be taken into consideration along with the World Health Organization grading criteria for oligoastrocytomas.

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Elana Farace and Lawrence F. Marshall

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Chantal W. P. M. Hukkelhoven, Ewout W. Steyerberg, Elana Farace, J. Dik F. Habbema, Lawrence F. Marshall and Andrew I. R. Maas

Object. Regional differences have been shown in patient characteristics and case management within multiple unselected series of patients suffering from traumatic brain injury (TBI). One might expect that such regional heterogeneity would be small in a more selected population of a randomized clinical trial. The goal of this study was to examine what regional differences in patient characteristics, case management, and outcomes exist between continents and among countries within a patient population included in a randomized clinical trial.

Methods. Data were extracted from two concurrently conducted randomized clinical trials of the drug tirilazad; the designs of these studies were similar. The studies included 1701 patients with severe and 476 patients with moderate TBI. Differences were primarily investigated between studies performed in Europe and North America, but also among European regions and between Canada and the United States. Associations among regions and outcomes (6-month mortality rate and Glasgow Outcome Scale scores) were studied using multivariable logistic regression analysis.

Comparisons between continents and among regions within Europe showed differences in the distribution of patient ages, causes of injury, and several clinical characteristics (motor score, pupillary reactivity, hypoxia, hypotension, intracranial pressure [ICP]), and findings on computerized tomography scans. Secondary referrals occurred 2.5 times more frequently in Europe. Within Europe secondary referral was mainly associated with an increased proportion of patients with mass lesions (46% in the European Study compared with 40% in the North American Study). Therapy for lowering ICP was more frequently applied in North America. After adjustments for case mix and management, mortality and unfavorable outcomes were significantly higher in Europe (odds ratios = 1.58 and 1.46, respectively). Significant differences in outcome between regions within Europe or within North America were not observed.

Conclusions. Despite the use of a strict study protocol, considerable differences in patient characteristics and case management exist between continents and among countries, reflecting variations in social, cultural, and organizational aspects. Outcomes of TBI may be worse in Europe compared with North America, but this finding requires further study.

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Chantal W. P. M. Hukkelhoven, Ewout W. Steyerberg, Anneke J. J. Rampen, Elana Farace, J. Dik F. Habbema, Lawrence F. Marshall, Gordon D. Murray and Andrew I. R. Maas

Object. Increasing age is associated with poorer outcome in patients with closed traumatic brain injury (TBI). It is uncertain whether critical age thresholds exist, however, and the strength of the association has yet to be investigated across large series. The authors studied the shape and strength of the relationship between age and outcome, that is, the 6-month mortality rate and unfavorable outcome based on the Glasgow Outcome Scale.

Methods. The shape of the association was examined in four prospective series with individual patient data (2664 cases). All patients had a closed TBI and were of adult age (96% < 65 years of age). The strength of the association was investigated in a metaanalysis of the aforementioned individual patient data (2664 cases) and aggregate data (2948 cases) from TBI studies published between 1980 and 2001 (total 5612 cases). Analyses were performed with univariable and multivariable logistic regression.

Proportions of mortality and unfavorable outcome increased with age: 21 and 39%, respectively, for patients younger than 35 years and 52 and 74%, respectively, for patients older than 55 years. The association between age and both mortality and unfavorable outcome was continuous and could be adequately described by a linear term and expressed even better statistically by a linear and a quadratic term. The use of age thresholds (best fitting threshold 39 years) in the analysis resulted in a considerable loss of information. The strength of the association, expressed as an odds ratio per 10 years of age, was 1.47 (95% confidence interval [CI] 1.34–1.63) for death and 1.49 (95% CI 1.43–1.56) for unfavorable outcome in univariable analyses, and 1.39 (95% CI 1.3–1.5) and 1.46 (95% CI 1.36–1.56), respectively, in multivariable analyses. Thus, the odds for a poor outcome increased by 40 to 50% per 10 years of age.

Conclusions. An older age is continuously associated with a worsening outcome after TBI; hence, it is disadvantageous to define the effect of age on outcome in a discrete manner when we aim to estimate prognosis or adjust for confounding variables.