Evaluation of Outcomes Among Patients With Traumatic Intracranial Hypertension Treated With Decompressive Craniectomy vs Standard Medical Care at 24 Months: A Secondary Analysis of the RESCUEicp Randomized Clinical Trial.

Importance: Trials often assess primary outcomes of traumatic brain injury at 6 months. Longer-term data are needed to assess outcomes for patients receiving surgical vs medical treatment for traumatic intracranial hypertension. Objective: To evaluate 24-month outcomes for patients with traumatic intracranial hypertension treated with decompressive craniectomy or standard medical care. Design, Setting, and Participants: Prespecified secondary analysis of the Randomized Evaluation of Surgery With Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUEicp) randomized clinical trial data was performed for patients with traumatic intracranial hypertension (>25 mm Hg) from 52 centers in 20 countries. Enrollment occurred between January 2004 and March 2014. Data were analyzed between 2018 and 2021. Eligibility criteria were age 10 to 65 years, traumatic brain injury (confirmed via computed tomography), intracranial pressure monitoring, and sustained and refractory elevated intracranial pressure for 1 to 12 hours despite pressure-controlling measures. Exclusion criteria were bilateral fixed and dilated pupils, bleeding diathesis, or unsurvivable injury. Interventions: Patients were randomly assigned 1:1 to receive a decompressive craniectomy with standard care (surgical group) or to ongoing medical treatment with the option to add barbiturate infusion (medical group). Main Outcomes and Measures: The primary outcome was measured with the 8-point Extended Glasgow Outcome Scale (1 indicates death and 8 denotes upper good recovery), and the 6- to 24-month outcome trajectory was examined. Results: This study enrolled 408 patients: 206 in the surgical group and 202 in the medical group. The mean (SD) age was 32.3 (13.2) and 34.8 (13.7) years, respectively, and the study population was predominantly male (165 [81.7%] and 156 [80.0%], respectively). At 24 months, patients in the surgical group had reduced mortality (61 [33.5%] vs 94 [54.0%]; absolute difference, -20.5 [95% CI, -30.8 to -10.2]) and higher rates of vegetative state (absolute difference, 4.3 [95% CI, 0.0 to 8.6]), lower or upper moderate disability (4.7 [-0.9 to 10.3] vs 2.8 [-4.2 to 9.8]), and lower or upper severe disability (2.2 [-5.4 to 9.8] vs 6.5 [1.8 to 11.2]; χ27 = 24.20, P = .001). For every 100 individuals treated surgically, 21 additional patients survived at 24 months; 4 were in a vegetative state, 2 had lower and 7 had upper severe disability, and 5 had lower and 3 had upper moderate disability, respectively. Rates of lower and upper good recovery were similar for the surgical and medical groups (20 [11.0%] vs 19 [10.9%]), and significant differences in net improvement (≥1 grade) were observed between 6 and 24 months (55 [30.0%] vs 25 [14.0%]; χ22 = 13.27, P = .001). Conclusions and Relevance: At 24 months, patients with surgically treated posttraumatic refractory intracranial hypertension had a sustained reduction in mortality and higher rates of vegetative state, severe disability, and moderate disability. Patients in the surgical group were more likely to improve over time vs patients in the medical group. Trial Registration: ISRCTN Identifier: 66202560.

A practical method for dealing with missing Glasgow Coma Scale verbal component scores.

OBJECTIVE: The Glasgow Coma Scale (GCS) is used for the assessment of impaired consciousness; however, it is not always possible to test each component, most commonly the verbal component. This affects the derivation of the GCS sum score, which has a role in systems for predicting patient outcome. Imputation of missing scores does not add extra information, but it does allow use of tools for predicting outcome that require complete data. The authors devised a simple and practical tool to employ when verbal component data are missing. They then assessed the tool's utility by application to the GCS-Pupils plus age plus CT findings (GCS-PA CT) prognostic model. METHODS: The authors inspected data from the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) cohort to characterize the frequency of missing verbal scores. The authors identified a single verbal score to impute for each eye and motor combined sum (EM) score from distributions of verbal scores in a published database of 54,069 patients. The effectiveness of the imputed verbal score was assessed using a dataset containing information from the IMPACT and Corticosteroid Randomisation After Significant Head Injury (CRASH) databases. The authors compared the performance of the prognostic model using actual verbal scores with the performance using imputed verbal scores and assessed the information yield using Nagelkerke's R2 statistic. RESULTS: Verbal data were most commonly missing in patients with no eye opening and with a motor score of 4 or less. The "simple" imputation model that was developed performed as well as a more complex model involving distinct combinations of eye and motor scores. The imputation model consisted of the following: EM scores 2-6, add 1; EM score 7, add 2; EM score 8 or 9, add 4; and EM score 10, add 5 to provide the GCS sum score. Modeling without information about the verbal score reduced the R2 from 32.1% to 31.4% and from 34.9% to 34.0% for predictions of death and favorable outcome at 6 months, respectively, compared with using full verbal score information. CONCLUSIONS: This strategy is particularly valuable for imputation in clinical practice, enabling clinicians to make a rapid and reliable determination of the GCS sum score when the verbal component is not testable. This will support clinical communication and decisions based on estimates of injury severity as well as enable estimation of prognosis. The authors suggest that external validation of their imputation strategy and the performance of the GCS-PA charts should be undertaken in other clinical populations.

The Story of the Development and Adoption of the Glasgow Coma Scale: Part I, The Early Years.

The Glasgow Coma Scale and its derived Score have been adopted worldwide for assessing the degree of impaired responsiveness in traumatic brain injury and other kinds of acute brain damage. In this historical vignette, we describe how the foundations for their enduring success were laid during their initial development. To provide a unique additio nal background and context, the material from interviews with one of the originators of the scale was brought together with information from key publications in the early years after the first description of the scale in 1974. This historical investigation shows how the contents of the eye, verbal, and motor components of the scale were assembled through analysis of previous systems, guided by early clinimetric principles. Its reproducibility as a tool for clinical communication was confirmed through innovative studies of interobserver variability. To test its validity, international collaborations linking units in Britain, the Netherlands, and the United States were pursued. These collaborations were accompanied by the creation of the total Glasgow Coma Score with a 6-point motor subdivision. The observation that outcomes after severe head injury were similar in the different countries, despite marked variations in management, stimulated controversy that promoted further interest in traumatic brain injury research and a recommendation for the worldwide use of the scale as a common severity marker. Inclusion of the scale in major developments such as the Advanced Trauma Life Support (ATLS) and the National Traumatic Coma Databank cemented its influential position in clinical care and research for the succeeding decades.

Simplifying the use of prognostic information in traumatic brain injury. Part 1: The GCS-Pupils score: an extended index of clinical severity.

Objective: Glasgow Coma Scale (GCS) scores and pupil responses are key indicators of the severity of traumatic brain damage. The aim of this study was to determine what information would be gained by combining these indicators into a single index and to explore the merits of different ways of achieving this. Methods: METHODS Information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality were obtained at the individual patient level by reviewing data from the CRASH (Corticosteroid Randomisation After Significant Head Injury; n = 9,045) study and the IMPACT (International Mission for Prognosis and Clinical Trials in TBI; n = 6855) database. These data were combined into a pooled data set for the main analysis. Methods of combining the Glasgow Coma Scale and pupil response data varied in complexity from using a simple arithmetic score (GCS score [range 3-15] minus the number of nonreacting pupils [0, 1, or 2]), which we call the GCS-Pupils score (GCS-P; range 1-15), to treating each factor as a separate categorical variable. The content of information about patient outcome in each of these models was evaluated using Nagelkerke's R2. Results: Separately, the GCS score and pupil response were each related to outcome. Adding information about the pupil response to the GCS score increased the information yield. The performance of the simple GCS-P was similar to the performance of more complex methods of evaluating traumatic brain damage. The relationship between decreases in the GCS-P and deteriorating outcome was seen across the complete range of possible scores. The additional 2 lowest points offered by the GCS-Pupils scale (GCS-P 1 and 2) extended the information about injury severity from a mortality rate of 51% and an unfavorable outcome rate of 70% at GCS score 3 to a mortality rate of 74% and an unfavorable outcome rate of 90% at GCS-P 1. The paradoxical finding that GCS score 4 was associated with a worse outcome than GCS score 3 was not seen when using the GCS-P. Conclusions: A simple arithmetic combination of the GCS score and pupillary response, the GCS-P, extends the information provided about patient outcome to an extent comparable to that obtained using more complex methods. The greater range of injury severities that are identified and the smoothness of the stepwise pattern of outcomes across the range of scores may be useful in evaluating individual patients and identifying patient subgroups. The GCS-P may be a useful platform onto which information about other key prognostic features can be added in a simple format likely to be useful in clinical practice.

Simplifying the use of prognostic information in traumatic brain injury. Part 2: Graphical presentation of probabilities.

OBJECTIVE Clinical features such as those included in the Glasgow Coma Scale (GCS) score, pupil reactivity, and patient age, as well as CT findings, have clear established relationships with patient outcomes due to neurotrauma. Nevertheless, predictions made from combining these features in probabilistic models have not found a role in clinical practice. In this study, the authors aimed to develop a method of displaying probabilities graphically that would be simple and easy to use, thus improving the usefulness of prognostic information in neurotrauma. This work builds on a companion paper describing the GCS-Pupils score (GCS-P) as a tool for assessing the clinical severity of neurotrauma. METHODS Information about early GCS score, pupil response, patient age, CT findings, late outcome according to the Glasgow Outcome Scale, and mortality were obtained at the individual adult patient level from the CRASH (Corticosteroid Randomisation After Significant Head Injury; n = 9045) and IMPACT (International Mission for Prognosis and Clinical Trials in TBI; n = 6855) databases. These data were combined into a pooled data set for the main analysis. Logistic regression was first used to model the combined association between the GCS-P and patient age and outcome, following which CT findings were added to the models. The proportion of variability in outcomes "explained" by each model was assessed using Nagelkerke's R2. RESULTS The authors observed that patient age and GCS-P have an additive effect on outcome. The probability of mortality 6 months after neurotrauma is greater with increasing age, and for all age groups the probability of death is greater with decreasing GCS-P. Conversely, the probability of favorable recovery becomes lower with increasing age and lessens with decreasing GCS-P. The effect of combining the GCS-P with patient age was substantially more informative than the GCS-P, age, GCS score, or pupil reactivity alone. Two-dimensional charts were produced displaying outcome probabilities, as percentages, for 5-year increments in age between 15 and 85 years, and for GCS-Ps ranging from 1 to 15; it is readily seen that the movement toward combinations at the top right of the charts reflects a decreasing likelihood of mortality and an increasing likelihood of favorable outcome. Analysis of CT findings showed that differences in outcome are very similar between patients with or without a hematoma, absent cisterns, or subarachnoid hemorrhage. Taken in combination, there is a gradation in risk that aligns with increasing numbers of any of these abnormalities. This information provides added value over age and GCS-P alone, supporting a simple extension of the earlier prognostic charts by stratifying the original charts in the following 3 CT groupings: none, only 1, and 2 or more CT abnormalities. CONCLUSIONS The important prognostic features in neurotrauma can be brought together to display graphically their combined effects on risks of death or on prospects for independent recovery. This approach can support decision making and improve communication of risk among health care professionals, patients, and their relatives. These charts will not replace clinical judgment, but they will reduce the risk of influences from biases.

Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension.

BACKGROUND: The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear. METHODS: From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 6 months. The primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. If the model was rejected, that would indicate a significant difference in the GOS-E distribution, and results would be reported descriptively. RESULTS: The GOS-E distribution differed between the two groups (P<0.001). The proportional-odds assumption was rejected, and therefore results are reported descriptively. At 6 months, the GOS-E distributions were as follows: death, 26.9% among 201 patients in the surgical group versus 48.9% among 188 patients in the medical group; vegetative state, 8.5% versus 2.1%; lower severe disability (dependent on others for care), 21.9% versus 14.4%; upper severe disability (independent at home), 15.4% versus 8.0%; moderate disability, 23.4% versus 19.7%; and good recovery, 4.0% versus 6.9%. At 12 months, the GOS-E distributions were as follows: death, 30.4% among 194 surgical patients versus 52.0% among 179 medical patients; vegetative state, 6.2% versus 1.7%; lower severe disability, 18.0% versus 14.0%; upper severe disability, 13.4% versus 3.9%; moderate disability, 22.2% versus 20.1%; and good recovery, 9.8% versus 8.4%. Surgical patients had fewer hours than medical patients with intracranial pressure above 25 mm Hg after randomization (median, 5.0 vs. 17.0 hours; P<0.001) but had a higher rate of adverse events (16.3% vs. 9.2%, P=0.03). CONCLUSIONS: At 6 months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative state, lower severe disability, and upper severe disability than medical care. The rates of moderate disability and good recovery were similar in the two groups. (Funded by the Medical Research Council and others; RESCUEicp Current Controlled Trials number, ISRCTN66202560 .).

Lack of Standardization in the Use of the Glasgow Coma Scale: Results of International Surveys.

The Glasgow Coma Scale (GCS) was introduced 40 years ago and has received world-wide acceptance. The GCS rates eye, motor, and verbal responses to assess the level of consciousness. Concerns have been expressed with regard to reliability and consistency of assessments. We considered that lack of standardization in application techniques and reporting of the GCS may have contributed to these concerns, and aimed to assess current procedures in its use. Questionnaire-based assessments were conducted by an online survey and during neurosurgical training courses. Overall, 616 participants were recruited, representing 48 countries and including physicians and nurses from different disciplines. Use of the GCS was reported by nearly all participants for assessment of patients with traumatic brain injury, but not for all patients with a reduced level of consciousness from other causes (78%). Major differences were found regarding the type of stimulus applied when patients do not obey commands: Nail bed pressure, supraorbital pressure, trapezius or pectoralis pinch, and sternal rub were all frequently used, whereas 25% of responders reported to never use a peripheral stimulus. Strategies for reporting the GCS varied greatly, and 35% of participants limited the reporting to a summary score. Moreover, different approaches were used when one of the components could not be assessed. Overall, the surveys have identified a general lack of standardization in assessment and reporting of the GCS. The results illustrate the need for continued education to improve reliability of assessments through guidance to a standard approach.

Mortality from Head Injury over Four Decades in Scotland.

Although the causes of head injury, the population at risk, and approaches to prevention and treatment are continually evolving, there is little information about how these are reflected in patterns of mortality over time. We used population-based comprehensive data uniquely available in Scotland to investigate changes in the total numbers of deaths from 1974 to 2012, as well as the rates of head injury death, from different causes, overall and in relation to age and gender. Total mortality fell from an annual average of 503 to 339 with a corresponding annual decrease in rate from 9.6 to 6.4 per 100,000 population, the decline substantially occurring between 1974 and 1990. Deaths in children fell strikingly, but rose in older people. Deaths in males fell to a greater extent than females, but remained at a higher rate overall. Initially, a transport accident accounted for most deaths, but these fell by 80%, from 325 per year to 65 per year over the 39-year period. Deaths from falling and all other causes did not decline, coming to outnumber transport accident deaths by 1998, which accounts for the overall absence of change in total mortality in recent years. In order to reduce mortality in the future, more-effective measures to prevent falls are needed and these strategies will vary in younger adults (where alcohol is often a factor), as well as in older adults where infirmity can be a cause. In addition, measures to sustain reductions in transport accidents need to be maintained and further developed.

Cytokine gene polymorphisms and outcome after traumatic brain injury.

Clinical outcome after traumatic brain injury (TBI) is variable and cannot easily be predicted. There is increasing evidence to suggest that there may be genetic influences on outcome. Cytokines play an important role in mediating the inflammatory response provoked within the central nervous system after TBI. This study was designed to identify associations between cytokine gene polymorphisms and clinical outcome 6 months after head injury. A prospectively identified cohort of patients (n=1096, age range 0-93 years, mean age 37) was used. Clinical outcome at 6 months was assessed using the Glasgow Outcome Scale. In an initial screen of 11 cytokine gene single nucleotide polymorphisms (SNPs) previously associated with disease susceptibility or outcome (TNFA -238 and -308, IL6 -174, -572 and -597, IL1A -889, IL1B -31, -511 and +3953, and TGFB -509 and -800), TNFA -308 was identified as having a likely association. The TNFA -308 SNP was further evaluated, and a significant association was identified, with 39% of allele 2 carriers having an unfavorable outcome compared with 31% of non-carriers (adjusted odds ratio 1.67, confidence interval 1.19-2.35, p=0.003). These findings are consistent with experimental and clinical data suggesting that neuroinflammation has an impact on clinical outcome after TBI and that tumor necrosis factor alpha plays an important role in this process.

Disability in young people and adults after head injury: 12-14 year follow-up of a prospective cohort.

BACKGROUND: There is a need to establish how long term outcome evolves after head injury (HI) and factors related to this, to inform opportunities for intervention. OBJECTIVE: To determine late outcome in adults 12-14 years after hospital admission for HI and to examine relationships between injury, early and late factors, and disability. METHODS: A prospective cohort with HI, whose outcome was reported previously at 1 and 5-7 years after injury, were followed up after 12-14 years. Participants were assessed using structured and validated measures of disability (Glasgow Outcome Scale-Extended), psychological well being, alcohol use and health status. RESULTS: Of 219 survivors followed-up at 5-7 years, 34 (15.5%) had died by 12-14 years. Disability remained common in survivors at 12-14 years (51%), as found at 1 and 5-7 years (53%). For those disabled at 1 year, outcome was poor, with 80% dead or disabled at 12-14 years. Older age at injury, a premorbid history of brain illness or physical disability and post-injury low self-esteem and stress were associated with disability at 12-14 years. Disability changed between 5-7 and 12-14 years in 55% of survivors, improving in 23%. Late changes in disability between 5-7 and 12-14 years were associated with self-perceptions of locus of control as being 'powerful others' at 5-7 years. CONCLUSIONS: Disability is common 12-14 years after hospital admission with a HI. For some there is a dynamic process of change in disability over time that is associated with self-perceptions of control that could be a target for intervention based research.

Neuropathological findings in disabled survivors of a head injury.

We investigated how the occurrence and severity of the main neuropathological types of traumatic brain injury (TBI) influenced the severity of disability after a head injury. Eighty-five victims, each of whom had lived at least a month after a head injury but then died, were studied. Judged by the Glasgow Outcome Scale (GOS), before death 35 were vegetative, 30 were severely and 20 were moderately disabled. Neuropathological assessment showed that 71 (84%) victims had sustained cerebral contusions, 49 (58%) had diffuse axonal injury (DAI), 57 (67%), had ischemic brain damage (IBD), 58 (68%) had symmetrical ventricular enlargement, and in 47 (55%) intracranial pressure (ICP) had been increased. Thirty-five (41%) had undergone evacuation of an intracranial hematoma. Brainstem damage was seen in only 11 (13%). Analysis (χ(2) test for trends) of the relationship between these features and outcome showed that findings of DAI, raised ICP, thalamic damage, or ventricular enlargement (all p<0.005), and IBD (p=0.04) were associated with an increasingly worse outcome. Conversely, moderate or severe contusions (p=0.001) were increasingly associated with better outcomes, and evacuation of a hematoma was associated (p=0.001) with outcomes likely to be better than vegetative. We conclude that diffuse or multifocal neuropathological patterns of TBI from primary axonal injury or secondary ischemic damage are most likely to be associated with the most severely impaired outcomes after a head injury.

The management of patients with intradural post-traumatic mass lesions: a multicenter survey of current approaches to surgical management in 729 patients coordinated by the European Brain Injury Consortium.

OBJECTIVE: Controversy exists about the indications and timing for surgery in head injured patients with an intradural mass lesion. The aim of this study was to survey contemporary approaches to the treatment of head injured patients with an intradural lesion, placing a particular focus on the utilization of decompressive craniectomy. METHODS: A prospective international survey was conducted over a 3-month period in 67 centers from 24 countries on the neurosurgical management of head injured patients with an intradural mass lesion and/or radiological signs of raised intracranial pressure. Information was obtained about demographic, clinical, and radiological features; surgical management, and mortality at discharge. RESULTS: Over the period of the study, data were collected about 729 patients consecutively admitted to one of the participating centers. The survey included 397 patients with a severe head injury (Glasgow Coma Scale [GCS] 3-8), 155 with a moderate head injury (GCS 9-12) and 143 patients with a mild head injury (GCS 13-15). An operation was performed on 502 patients (69%). Emergency surgery (<24 h) was most frequently performed for patients with an extracerebral mass lesions (subdural hematomas) whereas delayed surgery was most frequently performed for an intracerebral hematoma or contusion. Decompressive craniectomy was performed in a substantial number of patients, either during an emergency procedure (n = 134, 33%) or a delayed procedure (n = 47, 31%). The decompressive procedure was nearly always combined with evacuation of a mass lesion. The size of the decompression was however considered too small in 25% of cases. CONCLUSION: The results provide a contemporary picture of neurosurgical surgical approaches to the management of head injured patients with an intradural mass lesion and/or signs of raised intracranial pressure in some Neurosurgical Units across the world. The relative benefits of early versus delayed surgery in patients with intraparenchymal lesions and on the indications, technique and benefits of decompressive craniectomy could be topics for future head injury research.

The management of patients with intradural post-traumatic mass lesions: a multicenter survey of current approaches to surgical management in 729 patients coordinated by the European Brain Injury Consortium.

OBJECTIVE: Controversy exists about the indications and timing for surgery in head injured patients with an intradural mass lesion. The aim of this study was to survey contemporary approaches to the treatment of head injured patients with an intradural lesion, placing a particular focus on the utilization of decompressive craniectomy. METHODS: A prospective international survey was conducted over a 3-month period in 67 centers from 24 countries on the neurosurgical management of head injured patients with an intradural mass lesion and/or radiological signs of raised intracranial pressure. Information was obtained about demographic, clinical, and radiological features; surgical management, and mortality at discharge. RESULTS: Over the period of the study, data were collected about 729 patients consecutively admitted to one of the participating centers. The survey included 397 patients with a severe head injury (Glasgow Coma Scale [GCS] 3-8), 155 with a moderate head injury (GCS 9-12) and 143 patients with a mild head injury (GCS 13-15). An operation was performed on 502 patients (69%). Emergency surgery (<24 h) was most frequently performed for patients with an extracerebral mass lesions (subdural hematomas) whereas delayed surgery was most frequently performed for an intracerebral hematoma or contusion. Decompressive craniectomy was performed in a substantial number of patients, either during an emergency procedure (n = 134, 33%) or a delayed procedure (n = 47, 31%). The decompressive procedure was nearly always combined with evacuation of a mass lesion. The size of the decompression was however considered too small in 25% of cases. CONCLUSION: The results provide a contemporary picture of neurosurgical surgical approaches to the management of head injured patients with an intradural mass lesion and/or signs of raised intracranial pressure in some Neurosurgical Units across the world. The relative benefits of early versus delayed surgery in patients with intraparenchymal lesions and on the indications, technique and benefits of decompressive craniectomy could be topics for future head injury research.

Premorbid intelligence and brain injury.

OBJECTIVES: To determine whether NART scores are associated with severity of brain injury and therefore presumably affected by brain injury. In addition, to compare the Cambridge Contextual Reading Test (CCRT) with injury severity in head-injured individuals. DESIGN AND METHODS: Participants were 55 survivors of traumatic head injury, who completed the NART and the CCRT. The scores on these premorbid measures were then compared with indices of injury severity from their initial neurosurgical admission. RESULTS: The NART was significantly correlated with Glasgow coma scale, with greater severity of injury associated with poorer performance. Poorer NART performance was also significantly more likely amongst those whose injury resulted in coma. The CCRT was preferred by patients, though it was also significantly associated with Glasgow coma scale and presence of coma. CONCLUSIONS: The data suggest that performance on both the NART and the CCRT are affected by brain injury severity and thus may underestimate true premorbid ability in these individuals. Similar findings would be likely with the conceptually identical WTAR measure. These measures should be used with appropriate caution and may be usefully supplemented by predictions based on demographic information.

Design and analysis of phase III trials with ordered outcome scales: the concept of the sliding dichotomy.

The conventional approach to the analysis of a Phase III trial in head injury or stroke takes an ordered scale measuring functional outcome and collapses the scale to a binary outcome of favorable versus unfavorable. This discards potentially relevant information which limits statistical power and moreover is not in accord with clinical practice. We propose an alternative approach where a favorable outcome is defined as better than would be expected, taking account of each individual patient's baseline prognosis. This is illustrated through a worked example based on data from a Phase III trial in head injury. The approach is also compared with the proportional odds model, which is another statistical approach that can exploit an ordered outcome scale. The approach raises issues of clinical, statistical, and regulatory importance, and we initiate what we believe needs to become a widespread debate amongst the community involved in clinical research in head injury and stroke.

The familial risk of subarachnoid haemorrhage.

Relatives of people with aneurysmal subarachnoid haemorrhage (SAH) may be at increased risk of SAH, but precise data on the level of risk and which relatives are most likely to be affected are lacking. We studied two samples: 5478 relatives of patients from the whole of Scotland who had a SAH in one year and 3213 relatives of patients with a SAH admitted to the West of Scotland regional neurosurgical unit 10 years previously. Overall, 2% of all relatives in each sample had a SAH. In the Scotland-wide sample, the absolute lifetime risk of SAH (from birth to 70 years) was higher for first-degree relatives [4.7%; 95% confidence interval (CI): 3.1-6.3%] than for second-degree (1.9%; 95% CI: 1.0-2.9%). In the West of Scotland sample, the lifetime risks were very similar to the Scotland-wide sample. The 10-year prospective risk for first-degree relatives alive at the time of the index patient's SAH was 1.2% (95% CI: 0.4-2%) and for second-degree was 0.5% (95% CI: 0.1-0.8%). There was a trend for risk to be highest in families with two first-degree relatives affected and lowest with only one second-degree affected. Most living relatives of patients who suffer a SAH are at low absolute risk of a future haemorrhage; screening is inappropriate except for the few families in whom two or more first-degree relatives, i.e. index case plus one extra have been affected.

Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial.

BACKGROUND: Spontaneous supratentorial intracerebral haemorrhage accounts for 20% of all stroke-related sudden neurological deficits, has the highest morbidity and mortality of all stroke, and the role of surgery remains controversial. We undertook a prospective randomised trial to compare early surgery with initial conservative treatment for patients with intracerebral haemorrhage. METHODS: A parallel-group trial design was used. Early surgery combined haematoma evacuation (within 24 h of randomisation) with medical treatment. Initial conservative treatment used medical treatment, although later evacuation was allowed if necessary. We used the eight-point Glasgow outcome scale obtained by postal questionnaires sent directly to patients at 6 months follow-up as the primary outcome measure. We divided the patients into good and poor prognosis groups on the basis of their clinical status at randomisation. For the good prognosis group, a favourable outcome was defined as good recovery or moderate disability on the Glasgow outcome scale. For the poor prognosis group, a favourable outcome also included the upper level of severe disability. Analysis was by intention to treat. FINDINGS: 1033 patients from 83 centres in 27 countries were randomised to early surgery (503) or initial conservative treatment (530). At 6 months, 51 patients were lost to follow-up, and 17 were alive with unknown status. Of 468 patients randomised to early surgery, 122 (26%) had a favourable outcome compared with 118 (24%) of 496 randomised to initial conservative treatment (odds ratio 0.89 [95% CI 0.66-1.19], p=0.414); absolute benefit 2.3% (-3.2 to 7.7), relative benefit 10% (-13 to 33). INTERPRETATION: Patients with spontaneous supratentorial intracerebral haemorrhage in neurosurgical units show no overall benefit from early surgery when compared with initial conservative treatment.