Functional Status Examination Yields Higher Measurement Precision than the Glasgow Outcome Scale-Extended after Moderate-to-Severe Traumatic Brain Injury.

A limited evidence base supports the Functional Status Examination (FSE) as superior to the more commonly used Glasgow Outcome Scale-Extended (GOSE) for precisely characterizing injury-related functional limitations. The aim of this study was to use modern psychometric tools to test the hypothesis that the FSE is more precise than the GOSE in characterizing individual differences in functional limitations after moderate-to-severe traumatic brain injury (TBI). Secondarily, we sought to confirm that the type of interviewee (patient, significant other) does not affect the test performance of the FSE. Using data from 357 individuals with TBI who participated in the Magnesium Sulfate clinical trial and had six-month outcome data, we performed item response theory (IRT) analyses comparing the FSE and GOSE at six months post-injury. Results showed that the FSE yielded higher measurement precision (IRT test information) than the GOSE across most of the disability severity spectrum. The GOSE yielded more information than the FSE at a very high level of disability, because of the GOSE's assignment of a unique score for individuals who are in a vegetative state. Finally, the FSE showed no evidence of differential item functioning by interviewee, indicating it is appropriate to interview either persons with TBI or significant others and combine data across respondents as is typically done. The findings support the FSE as a viable and oftentimes advantageous substitute for the GOSE in clinical trials and translational studies of TBI.

The Glasgow Outcome Scale-Extended Pediatric Scores of Intracranial Bleeding Patients with Acquired Prothrombin Complex Deficiency Post Craniotomy and Duraplasty.

INTRODUCTION: Surgical evacuation of intracranial bleeding in pediatric patients due to acquired prothrombin complex deficiency (APCD) is a life-saving surgery when conservative treatment insufficient and impending brain herniation. This study aimed to evaluate the Glasgow outcome scale-extended pediatric (GOS-ePed) score of the pediatric intracranial bleeding patients with APCD after craniotomy and duraplasty. METHOD: This was a retrospective study in the last 5 years of our experience. All of the pediatric patients with intracranial bleeding due to APCD who needed surgery were investigated. The data were collected from medical records after their parents have given their written informed concern and approved by the Ethics Review Committee, Faculty of Medicine, Universitas Kristen Indonesia. The inclusion criteria were patients who operated on by craniotomy and duraplasty. The patient with a second disease was excluded. Blood tests include hemoglobin, prothrombin time, activated prothrombin time, and platelets were investigated before and after intravenous vitamin K injection, transfusion packed red cells (PRCs), and fresh frozen plasma (FFP) administration. The Glasgow coma scale (GCS) pre- and postoperatively was evaluated using a modified GCS for infants and children. The outcome was evaluated by the GOS-ePed score. All data were analyzed with the normality test and paired t test. RESULTS: There were 5 patients age between 37 and 60 days, and all patients did not get vitamin K prophylaxis after birth. The blood tests of all patients revealed anemia, prothrombin, and activated prothrombin time increased, but platelets were normal. All these values returned to normal after vitamin K injection, transfusion of PRCs, and FFP. The paired t tests were p < 0.05. The GCS of all patients before surgery was 8 or below. After surgery, the GCS of 4 patients was increased become 12 and 15. One patient did not change significantly. The GOS-ePed score showed 4 patients (80%) had upper or lower good recovery, and 1 patient (20%) was in a vegetative state. CONCLUSIONS: The GOS-ePed score of the pediatric intracranial bleeding with APCD after craniotomy and duraplasty was mostly in upper or lower good recovery.

Reliability of the Glasgow Antipsychotic Side-effects Scale for Clozapine Japanese version (GASS-C-J).

The purpose of this study was to develop the Glasgow Antipsychotic Side effects Scale for Clozapine Japanese version (GASS-C-J) and examine its reliability to assess clozapine-related side effects. We developed the GASS-C-J using forward and backward translation. Semantic equivalence of the GASS-C-J to the GASS-C was confirmed by the original author. We then administered the GASS-C-J twice to 109 patients on clozapine treatment at two psychiatric hospitals in Japan. We assessed the internal consistency and test-retest reliability of the GASS-C-J using Cronbach's alpha and weighted kappa coefficient, respectively. We also examined if discrepancies in each GASS-C-J item score between the first and second rating were correlated with items of the Brief Evaluation of Psychosis Symptom Domains (BE-PSD). The Cronbach's alpha coefficient of the GASS-C-J at the first and second rating was 0.78 (95% CI: 0.72 to 0.84) and 0.82 (95% CI: 0.76 to 0.88), respectively. The weighted kappa coefficient of individual and total GASS-C-J item scores ranged from 0.45 to 0.88. Some symptom domains were correlated with discrepancies in specific items of the GASS-C-J: psychotic symptoms and nausea/vomiting (rs = 0.27), thirst (rs = 0.31), and appetite/weight gain (rs = 0.27); disorganized thinking and urinary incontinence (rs = 0.26); depression/anxiety and myoclonus (rs = 0.25), hypersalivation (rs = -0.27), and blurred vision (rs = -0.22). These findings demonstrate that the GASS-C-J can be used in clinical and research settings as a reliable scale to assess clozapine-related side effects.

Study Design Features Associated with Patient Attrition in Studies of Traumatic Brain Injury: A Systematic Review.

Loss to follow-up or patient attrition is common in longitudinal studies of traumatic brain injury (TBI). Lack of understanding exists between the relation of study design and patient attrition. This review aimed to identify features of study design that are associated with attrition. We extended the analysis of a previous systematic review on missing data in 195 TBI studies using the Glasgow Outcome Scale Extended (GOSE) as an outcome measure. Studies that did not report attrition or had heterogeneous methodology were excluded, leaving 148 studies. Logistic regression found seven of the 14 design features studied to be associated with patient attrition. Four features were associated with an increase in attrition: greater follow-up frequency (odds ratio [OR]: 1.2, 95% confidence interval [CI]: 1.0-1.3), single rather than multi-center design (OR: 1.6, 95% CI: 1.2-2.2), enrollment of exclusively mild TBI patients (OR: 2.8, 95% CI: 1.6-4.9), and collection of the GOS by post or telephone without face-to-face contact (OR: 1.6, 95% CI:1.1-2.4). Conversely, two features were associated with a reduction in attrition: recruitment in an acute care setting defined as the ward or intensive care unit (OR: 0.58, 95% CI: 0.47-0.72) and a greater duration of time between injury and follow-up (OR: 0.93, 95% CI: 0.88-0.99). This review highlights design features that are associated with attrition and could be considered when planning for patient retention. Further work is needed to establish the mechanisms between the observed associations and potential remedies.

Monitoring Outcome after Hospital-Presenting Milder Spectrum Pediatric Traumatic Brain Injury Using the Glasgow Outcome Scale-Extended, Pediatric Revision.

The Glasgow Outcome Scale, Pediatric Revision (GOSE-P) is an assessment of "global outcome" designed as a developmentally appropriate version of the Glasgow Outcome Scale-Extended for use in clinical trials of children with traumatic brain injury (TBI). Initial testing describes validity across a wide age and injury severity spectrum, yet the GOSE-P's utility for monitoring children with milder injuries is less clear. We examined the level of agreement between the GOSE-P and the Health and Behavior Inventory (HBI), a TBI-related symptom checklist used to assess children with mild TBI for clinical and research purposes. Participants included children and adolescents 3-16 years of age (n = 50) who presented to two level 1 trauma centers within 24 h of injury, with a GCS of 13-15, who underwent clinical neuroimaging. Outcome was assessed 2 weeks and 3 months following injury. We examined the severity of TBI-related symptoms across disability categories identified using the GOSE-P, and the level of agreement between the two measures in identifying deficits 2 weeks following injury and improvement from 2 weeks to 3 months. Using the GOSE-P, 62% had deficits at 2 weeks, and 42% improved from 2 weeks to 3 months. Agreement between the GOSE-P and HBI was fair 2 weeks after TBI (k = 0.24-0.33), and poor for identifying subsequent improvement (k = 0.10-0.16). Modest agreement between the GOSE-P and the HBI may reflect restricted participation from diverse causes, including TBI, other bodily injuries, and prescribed activity restrictions, and highlights the need for multi-dimensional outcome batteries.

Global outcome after traumatic brain injury in a prospective cohort.

OBJECTIVES: Traumatic Brain Injury(TBI) is one of the most common neurosurgical emergencies but the long-term outcome remains unclear. This study investigated the global outcome and return to work after TBI and tried to identify any relationships that exist with injury and demographic features. PATIENTS & METHODS: 1322 consecutive TBI admissions over 4 years, assessed at a specialist neurorehabilitation clinic at 10weeks and 1 yr. The outcomes were Extended Glasgow Outcome Scale(GOSE), return to work, Rivermead Head Injury Follow-up Questionnaire, Rivermead Post-Concussion Symptoms and the Hospital Anxiety and Depression Score. RESULTS: 1 year follow-up was achieved in 1207(91.3%). Mean age was 46.9(SD17.3) and 49.2% had mild TBI. The proportion attaining Good Recovery increased from 25.1% to 42.9% by 1 year. However 11.4% deteriorated in GOSE. Only 28.1% of individuals returned to the same pre-morbid level of work by 10 weeks, improving to 45.9% at 1 year. Over a quarter (25.6%) at 1 year were unable to make any return to work or study. Several demographic and injury variables were associated with these outcomes including TBI severity, social class, past psychiatric history and alcohol intoxication. These may allow targeting of vulnerable individuals. CONCLUSIONS: In a largely representative TBI population including predominantly mild injury, there is still considerable functional disability at 1 year and many individuals are unable to make any return to pre-morbid vocation.

Diagnosing the GOSE: Structural and Psychometric Properties Using Item Response Theory, a TRACK-TBI Pilot Study.

The Glasgow Outcome Scale-Extended (GOSE) was designed to assess global outcome after traumatic brain injury (TBI). Since its introduction, several empirically founded criticisms of the GOSE have been raised, including poor reliability; an insensitivity to small, but potentially meaningful, changes; a tendency to produce ceiling effects; inconsistent associations with neurocognitive, psychological, and quality-of-life measures; and an inability to assess the multi-dimensional nature of TBI outcome. The current project took a diagnostic approach to identifying the underlying causes of reported limitations by exploring the internal construct validity of the GOSE at 3 and 6 months post-injury using item response theory (IRT) techniques. Data were from the TRACK-TBI Pilot Study, a large (N = 586), prospective, multi-site project that included TBI cases of all injury severity levels. To assess the level of latent functional "impairment" captured by GOSE items independent of the assigned outcome category or GOSE total score, items were modified so that higher scores reflected greater impairment. Results showed that although the GOSE's items capture varying levels of impairment across a broad disability spectrum at 3 and 6 months, there was also evidence at each time point of item redundancy (multiple items capturing similar levels of impairment), item deficiency (lack of items capturing lower levels of impairment), and item inefficiency (items only capturing minimal impairment information). The findings illustrate the value of IRT to illuminate strengths and weaknesses of clinical outcome assessment measures and provide a framework for future measure refinement.

Matching early arterial oxygenation to long-term outcome in severe traumatic brain injury: target values.

OBJECTIVE: The aim of this study was to examine the relationship between early arterial oxygenation thresholds and long-term outcome after severe traumatic brain injury (TBI). METHODS: In a post hoc analysis of a randomized trial, adults with severe TBI were classified based on exposure to different levels of arterial oxygenation as measured using the average of arterial partial pressure of oxygen (PaO2) values obtained within 24 hours of admission. Potentially important PaO2 thresholds were defined a priori. The primary outcome was Glasgow Outcome Scale-Extended (GOSE) score at 6 months. Secondary outcomes were cognitive outcomes measured using a battery of 9 neuropsychological tests administered at 6 months, and 6-month mortality. RESULTS: In adjusted analyses, oxygenation thresholds of 150 and 200 mm Hg were associated with better functional outcome at 6 months (adjusted OR for better functional outcome on GOSE 1.82 [95% CI 1.12-2.94] and 1.59 [95% CI 1.06-2.37], respectively) and improved cognitive outcome at 6 months (adjusted beta coefficients for better cognitive percentile across 9 neuropsychological tests: 6.9 [95% CI 1.3-12.5] and 6.8 [95% CI 2.4-11.3], respectively). There was no significant association between oxygenation level and 6-month mortality except at a PaO2 threshold of 200 mm Hg (OR for death 0.36, 95% CI 0.18-0.71). Higher or lower oxygenation thresholds were not associated with functional or cognitive outcome. CONCLUSIONS: In this observational study, the relationship between early arterial oxygenation and long-term functional and cognitive TBI outcomes appears to be U-shaped. Mild levels of hyperoxemia within the first 24 hours after injury were associated with better long-term functional and cognitive outcomes. These findings highlight the importance of examining balanced oxygen supplementation as a potential strategy to improve TBI outcomes in future research.

Inflammation-based Glasgow Prognostic Score in patients with acute ST-segment elevation myocardial infarction: A prospective cohort study.

The inflammation-based Glasgow Prognostic Score (GPS), which involves C-reactive protein and serum albumin levels, has been reported to be a strong independent predictor of mortality in many cancers. This study aimed to investigate whether the GPS is associated with mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).In this study, 406 consecutive patients with STEMI at our emergency department (ED) who were undergoing pPCI were prospectively enrolled and assigned a GPS of 0, 1, or 2. Kaplan-Meier survival and multivariable Cox regression analyses were used to evaluate the associations between the GPS and long-term mortality.Twenty-three patients (5.7%) died at the hospital, and 37 (9.7%) died during follow-up (14.4 [9.3-17.6] months). Compared with patients with a lower GPS, those with a higher GPS had significantly higher in-hospital mortality (GPS = 0 vs GPS = 1 vs GPS = 2: 3.3% vs 6.3% vs 28.0%, P < .001), follow-up mortality (4.6% vs 14.3% vs 55.6%, P < .001), and cumulative mortality (9.6% vs 21.1% vs 71.1%, P < .001). Multivariable Cox regression analysis revealed that in patients with a GPS of 1 and 2 (versus 0), the multivariable adjusted hazard ratios (HR) for all-cause mortality were 2.068 (95% CI: 1.082-3.951, P = .028) and 8.305 (95% CI: 4.017-17.171, P < .001), respectively, after controlling for all of the confounding factors. Subgroup analysis showed that a higher GPS was associated with an increased risk of cumulative mortality in the different subgroups.The GPS on admission may be useful for stratifying the risk of adverse outcomes in patients with STEMI undergoing pPCI in the ED.

Evaluation of Short-Term Neurological Outcomes in Children with Brain Abscesses.

AIM: To evaluate the neurological outcomes of children diagnosed with brain abscesses in the early post-treatment period. < b > MATERIAL and METHODS: This study was a retrospective analysis of pediatric brain abscess patients between January 2000 and December 2015, during a 16-years period. Patients were divided into two groups according to their outcome at the end of the treatment. The patients with "good outcome" were the ones without any neurological sequelae [Glasgow Outcome Scale (GOS) score 5]. "Unfavorable outcome" was defined as having any kind of neurological deficit (GOS score 1-4). RESULTS: A total number of 31 patients (22 male, 71%) with the median age at diagnosis of 84 months (range, 1-202 months) were enrolled in this study. The most common presenting symptom was fever being encountered in 71% of the patients (n=22), followed by focal neurological deficit (FND)(n=17, 54.8%), vomiting (n=14, 45.2%), headache (n=13, 41.9%), seizure (n=13, 41.9%), change in mental status (n=12, 38.7%) and visual disturbance (n=2, 6.5%). Twenty-four patients (77.4%) had predisposing factors. The most common pathogens were gram-positive cocci (n=9, 29%). Seventeen patients (54.8%) had unfavorable outcome; 2 patients (6.4%) died. All patients were treated with parenteral antibiotherapy with median duration of 73 days (range, 28-540 days). Surgical procedures were performed in 83.9% (n=26) of patients [isolated aspiration (n=19, 61.3%), only resection (n=5, 16.1%), aspiration and resection (n=2, 6.5%)]. CONCLUSION: Glasgow coma scale score below 12 and the presence of FND on admission were found to be independent risk factors for unfavourable neurological outcome in children with brain abscesses.

Developing a Cognition Endpoint for Traumatic Brain Injury Clinical Trials.

Cognitive impairment is a core clinical feature of traumatic brain injury (TBI). After TBI, cognition is a key determinant of post-injury productivity, outcome, and quality of life. As a final common pathway of diverse molecular and microstructural TBI mechanisms, cognition is an ideal endpoint in clinical trials involving many candidate drugs and nonpharmacological interventions. Cognition can be reliably measured with performance-based neuropsychological tests that have greater granularity than crude rating scales, such as the Glasgow Outcome Scale-Extended, which remain the standard for clinical trials. Remarkably, however, there is no well-defined, widely accepted, and validated cognition endpoint for TBI clinical trials. A single cognition endpoint that has excellent measurement precision across a wide functional range and is sensitive to the detection of small improvements (and declines) in cognitive functioning would enhance the power and precision of TBI clinical trials and accelerate drug development research. We outline methodologies for deriving a cognition composite score and a research program for validation. Finally, we discuss regulatory issues and the limitations of a cognition endpoint.

The Glasgow Outcome Scale - 40 years of application and refinement.

The Glasgow Outcome Scale (GOS) was first published in 1975 by Bryan Jennett and Michael Bond. With over 4,000 citations to the original paper, it is the most highly cited outcome measure in studies of brain injury and the second most-cited paper in clinical neurosurgery. The original GOS and the subsequently developed extended GOS (GOSE) are recommended by several national bodies as the outcome measure for major trauma and for head injury. The enduring appeal of the GOS is linked to its simplicity, short administration time, reliability and validity, stability, flexibility of administration (face-to-face, over the telephone and by post), cost-free availability and ease of access. These benefits apply to other derivatives of the scale, including the Glasgow Outcome at Discharge Scale (GODS) and the GOS paediatric revision. The GOS was devised to provide an overview of outcome and to focus on social recovery. Since the initial development of the GOS, there has been an increasing focus on the multidimensional nature of outcome after head injury. This Review charts the development of the GOS, its refinement and usage over the past 40 years, and considers its current and future roles in developing an understanding of brain injury.

Comparative study of outcome measures and analysis methods for traumatic brain injury trials.

Batteries of functional and cognitive measures have been proposed as alternatives to the Extended Glasgow Outcome Scale (GOSE) as the primary outcome for traumatic brain injury (TBI) trials. We evaluated several approaches to analyzing GOSE and a battery of four functional and cognitive measures. Using data from a randomized trial, we created a "super" dataset of 16,550 subjects from patients with complete data (n=331) and then simulated multiple treatment effects across multiple outcome measures. Patients were sampled with replacement (bootstrapping) to generate 10,000 samples for each treatment effect (n=400 patients/group). The percentage of samples where the null hypothesis was rejected estimates the power. All analytic techniques had appropriate rates of type I error (≤5%). Accounting for baseline prognosis either by using sliding dichotomy for GOSE or using regression-based methods substantially increased the power over the corresponding analysis without accounting for prognosis. Analyzing GOSE using multivariate proportional odds regression or analyzing the four-outcome battery with regression-based adjustments had the highest power, assuming equal treatment effect across all components. Analyzing GOSE using a fixed dichotomy provided the lowest power for both unadjusted and regression-adjusted analyses. We assumed an equal treatment effect for all measures. This may not be true in an actual clinical trial. Accounting for baseline prognosis is critical to attaining high power in Phase III TBI trials. The choice of primary outcome for future trials should be guided by power, the domain of brain function that an intervention is likely to impact, and the feasibility of collecting outcome data.

Representing the Glasgow Coma Scale in IT: Proper Specification is Required for Assessment Scales.

In healthcare a huge amount of assessment scales and score systems are in use to abbreviate and summarize the results of clinical observations to interpret a patient's condition in a valid and reliable manner. It is challenging to convey the information in a semantic interoperable form to other systems. A bad approach would be to invent individual models for each of them. Within this paper we would like to demonstrate that a generic model is sufficient by demonstrating the realization with the Glasgow Coma Scale.

External validation of the CRASH and IMPACT prognostic models in severe traumatic brain injury.

An accurate prognostic model is extremely important in severe traumatic brain injury (TBI) for both patient management and research. Clinical prediction models must be validated both internally and externally before they are considered widely applicable. Our aim is to independently externally validate two prediction models, one developed by the Corticosteroid Randomization After Significant Head injury (CRASH) trial investigators, and the other from the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) group. We used a cohort of 300 patients with severe TBI (Glasgow Coma Score [GCS] ≤8) consecutively admitted to the National Neuroscience Institute (NNI), Singapore, between February 2006 and December 2009. The CRASH models (base and CT) predict 14 day mortality and 6 month unfavorable outcome. The IMPACT models (core, extended, and laboratory) estimate 6 month mortality and unfavorable outcome. Validation was based on measures of discrimination and calibration. Discrimination was assessed using the area under the receiving operating characteristic curve (AUC), and calibration was assessed using the Hosmer-Lemeshow (H-L) goodness-of-fit test and Cox calibration regression analysis. In the NNI database, the overall observed 14 day mortality was 47.7%, and the observed 6 month unfavorable outcome was 71.0%. The CRASH base model and all three IMPACT models gave an underestimate of the observed values in our cohort when used to predict outcome. Using the CRASH CT model, the predicted 14 day mortality of 46.6% approximated the observed outcome, whereas the predicted 6 month unfavorable outcome was an overestimate at 74.8%. Overall, both the CRASH and IMPACT models showed good discrimination, with AUCs ranging from 0.80 to 0.89, and good overall calibration. We conclude that both the CRASH and IMPACT models satisfactorily predicted outcome in our patients with severe TBI.

Neurological outcome scale for traumatic brain injury: III. Criterion-related validity and sensitivity to change in the NABIS hypothermia-II clinical trial.

The neurological outcome scale for traumatic brain injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. Participants were 16-45 years of age with severe TBI assessed at 1, 3, 6, and 12 months postinjury. For analysis of criterion-related validity (concurrent and predictive), Spearman's rank-order correlations were calculated between the NOS-TBI and the glasgow outcome scale (GOS), GOS-extended (GOS-E), disability rating scale (DRS), and neurobehavioral rating scale-revised (NRS-R). Concurrent validity was demonstrated through significant correlations between the NOS-TBI and GOS, GOS-E, DRS, and NRS-R measured contemporaneously at 3, 6, and 12 months postinjury (all p<0.0013). For prediction analyses, the multiplicity-adjusted p value using the false discovery rate was <0.015. The 1-month NOS-TBI score was a significant predictor of outcome in the GOS, GOS-E, and DRS at 3 and 6 months postinjury (all p<0.015). The 3-month NOS-TBI significantly predicted GOS, GOS-E, DRS, and NRS-R outcomes at 6 and 12 months postinjury (all p<0.0015). Sensitivity to change was analyzed using Wilcoxon's signed rank-sum test of subsamples demonstrating no change in the GOS or GOS-E between 3 and 6 months. The NOS-TBI demonstrated higher sensitivity to change, compared with the GOS (p<0.038) and GOS-E (p<0.016). In summary, the NOS-TBI demonstrated adequate concurrent and predictive validity as well as sensitivity to change, compared with gold-standard outcome measures. The NOS-TBI may enhance prediction of outcome in clinical practice and measurement of outcome in TBI research.

Relating quality of life to Glasgow outcome scale health states.

There has recently been a call for the adoption of comparative effectiveness research (CER) and related research approaches for studying traumatic brain injury (TBI). These methods allow researchers to compare the effectiveness of different therapies in producing patient-oriented outcomes of interest. Heretofore, the only measures by which to compare such therapies have been mortality and rate of poor outcome. Better comparisons can be made if parametric, preference-based quality-of-life (QOL) values are available for intermediate outcomes, such as those described by the Glasgow Outcome Scale Extended (GOSE). Our objective was therefore to determine QOL for the health states described by the GOSE. We interviewed community members at least 18 years of age using the standard gamble method to assess QOL for descriptions of GOSE scores of 2-7 derived from the structured interview. Linear regression analysis was also performed to assess the effect of age, gender, and years of education on QOL. One hundred and one participants between the ages of 18 and 83 were interviewed (mean age 40 ± 19 years), including 55 men and 46 women. Functional impairment and QOL showed a strong inverse relationship, as assessed by both linear regression and the Spearman rank order coefficient. No consistent effect or age, gender, or years of education was seen. As expected, QOL decreased with functional outcome as described by the GOSE. The results of this study will provide the groundwork for future groups seeking to apply CER methods to clinical studies of TBI.

Impact of GOS misclassification on ordinal outcome analysis of traumatic brain injury clinical trials.

This study extends our previous investigation regarding the effect of nondifferential dichotomous Glasgow Outcome Scale (GOS) misclassification in traumatic brain injury (TBI) clinical trials to the effect of GOS misclassification on ordinal analysis in TBI clinical trials. The impact of GOS misclassification and ordinal outcome analysis was explored via probabilistic sensitivity analyses using TBI patient datasets from the IMPACT database (n = 9205). Three patterns of misclassification were explored given the pre-specified misclassification distributions. For the random pattern, we specified a trapezoidal distribution (minimum: 80%, mode: 85%, and 95%, maximum: 100%) for both sensitivity and specificity; for the upward pattern, the same trapezoidal distribution for sensitivity but with a perfect specificity; and for the downward pattern, the same trapezoidal distribution for specificity but with a perfect sensitivity. The conventional 95% confidence intervals and simulation intervals, which accounts for the misclassification and random errors together, were reported. The results showed that given the specified misclassification distributions, the misclassification with a random or upward pattern would have caused a slightly underestimated outcome in the observed data. However, the misclassification with a downward pattern would have resulted in an inflated estimation. Thus the sensitivity analysis suggests that the nondifferential misclassification can cause uncertainties on the primary outcome estimation in TBI trials. However, such an effect is likely to be small when ordinal analysis is applied, compared with the impact of dichotomous GOS misclassifications. The result underlines that the ordinal GOS analysis may gain from both statistical efficiency, as suggested by several recent studies, and a relatively smaller impact from misclassification as compared with conventional binary GOS analysis.

Biochemical markers and somatosensory evoked potentials in patients after cardiac arrest: the role of neurological outcome scores.

Biochemical markers, e.g. NSE or S100B, and somatosensory evoked potentials (SSEP) are considered promising candidates for neurological prognostic predictors in patients after cardiac arrest (CA). The Utstein Templates recommend the use of the Glasgow-Pittsburgh Cerebral Performance Categories (GP-CPC) to divide patients according to their neurological outcome. However, several studies investigating biochemical markers and SSEP are based on the Glasgow Outcome Score (GOS). We noticed that many studies failed to exclude patients who died without certified brain damage from patients classified as poor outcome, instead including all patients who died into this category. Therefore, we summarized the published NSE cut-off values and the derived sensitivity and specificity to predict poor outcome of those studies which only included patients with certified brain death in GOS-1 or GP-CPC-5 (group A) vs. those studies which did not differentiate between death from any cause or death due to primary brain damage (group B). On average, mean NSE cut-off values and sensitivity were higher (56 ± 35 ng/ml, 56 ± 18%) in group A than in group B (41 ± 17 ng/ml, 44 ± 25%), respectively. The specificity remained equally high in both groups. In analogy, the average sensitivity of SSEP to predict poor outcome was higher in group A (76 ± 11%) than in group B (50 ± 15%), while the specificity was similar in both groups. Conclusively, inclusion of deaths without certified brain damage after CA in neurological outcome studies will lead to underestimation of the prognostic power of biochemical or electrophysiological markers for brain damage. A modified GOS and GP-CPC score might help to avoid this bias.

A method for reducing misclassification in the extended Glasgow Outcome Score.

The eight-point extended Glasgow Outcome Scale (GOSE) is commonly used as the primary outcome measure in traumatic brain injury (TBI) clinical trials. The outcome is conventionally collected through a structured interview with the patient alone or together with a caretaker. Despite the fact that using the structured interview questionnaires helps reach agreement in GOSE assessment between raters, significant variation remains among different raters. We introduce an alternate GOSE rating system as an aid in determining GOSE scores, with the objective of reducing inter-rater variation in the primary outcome assessment in TBI trials. Forty-five trauma centers were randomly assigned to three groups to assess GOSE scores on sample cases, using the alternative GOSE rating system coupled with central quality control (Group 1), the alternative system alone (Group 2), or conventional structured interviews (Group 3). The inter-rater variation between an expert and untrained raters was assessed for each group and reported through raw agreement and with weighted kappa (kappa) statistics. Groups 2 and 3 without central review yielded inter-rater agreements of 83% (weighted kappa = 0.81; 95% CI 0.69, 0.92) and 83% (weighted kappa = 0.76, 95% CI 0.63, 0.89), respectively, in GOS scores. In GOSE, the groups had an agreement of 76% (weighted kappa = 0.79; 95% CI 0.69, 0.89), and 63% (weighted kappa = 0.70; 95% CI 0.60, 0.81), respectively. The group using the alternative rating system coupled with central monitoring yielded the highest inter-rater agreement among the three groups in rating GOS (97%; weighted kappa = 0.95; 95% CI 0.89, 1.00), and GOSE (97%; weighted kappa = 0.97; 95% CI 0.91, 1.00). The alternate system is an improved GOSE rating method that reduces inter-rater variations and provides for the first time, source documentation and structured narratives that allow a thorough central review of information. The data suggest that a collective effort can be made to minimize inter-rater variation.