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G D Murray

Publications and source records attributed to G D Murray.

At least 37 records · Page 2Linked to original sources

The influence of apolipoprotein E genotype on outcome after spontaneous subarachnoid hemorrhage: a preliminary study.

OBJECTIVE: Possession of an apolipoprotein E (APOE)epsilon4 allele has been shown to be associated with a poor outcome after closed head injury and spontaneous intracerebral hemorrhage but not after ischemic stroke. This study assessed the influence of the APOE genotype on outcome in patients admitted to a neurosurgical unit with spontaneous subarachnoid hemorrhage. METHODS: A total of 100 patients with spontaneous subarachnoid hemorrhage were studied. Four patients were excluded because the diagnosis of subarachnoid hemorrhage was not confirmed. The incidence of rehemorrhage and delayed ischemia and the outcome at 6 months were determined using the Glasgow Outcome Scale. APOE genotypes were determined by polymerase chain reaction and restriction enzyme digestion. RESULTS: Allele frequencies in this patient group were 0.04 for epsilon2, 0.86 for epsilon3, and 0.1 for epsilon4. Of 96 patients, 72 had an aneurysmal hemorrhage and 1 had a hemorrhage from an arteriovenous malformation. In 14 patients, the results of angiography were negative, and in 9, no angiogram was performed. Of the 96 patients, 20 had one or more epsilon4 allele. Outcome at 6 months was no worse in patients with one or more epsilon4 allele than in those with no epsilon4 allele (odds ratio, 0.98; 95% confidence interval, 0.35-2.74). None of the 12 patients who experienced delayed ischemic deterioration had an epsilon4 allele. Of the 20 patients with an epsilon4 allele, 3 had a rehemorrhage, as compared with 6 of 76 patients without an epsilon4 allele. CONCLUSION: There was underrepresentation of the epsilon4 allele in this group when compared with previously studied cases of subarachnoid hemorrhage with a fatal outcome and with the general population. This suggests that patients with the epsilon4 allele who have a subarachnoid hemorrhage are less likely to be admitted to a neurosurgical unit. This study does not support an association between possession of an epsilon4 allele and poor outcome in patients admitted to a neurosurgical unit with spontaneous subarachnoid hemorrhage, although the wide confidence interval does not preclude a clinically relevant association between APOE genotype and outcome. The findings indicate that an association between genotype and the development of delayed ischemic complications after subarachnoid hemorrhage may be possible.

Adult↗

A unique insight into the incidence of rugby injuries using referee replacement reports.

OBJECTIVES: To obtain further information the incidence of injuries and playing positions affected in club rugby in Scotland. METHODS: Routine reports of injury (permanent) and blood (temporary) replacements occurring in competitive club rugby matches by referees to the Scottish Rugby Union during seasons 1990-1991 to 1996-1997 were analysed. RESULTS: A total of 3,513 injuries (87 per 100 scheduled matches) and 1,000 blood replacements (34 per 100 scheduled matches) were reported. Forwards accounted for 60% of the injury and 72% of the blood replacements. Flankers and the front row were the most commonly replaced forwards while wing and centre three quarters were the most vulnerable playing positions among backs. The incidence of injury replacements increased as the match progressed up until the last 10 minutes when the trend was reversed. Blood replacements showed a different pattern with 60% occurring during the first half of the match. CONCLUSION: The most important finding of the study was reliability of referees in documenting the vulnerability of certain playing positions, and the timing when injuries took place, thus assisting coaches and team selectors when choosing replacement players for competitive club and representative rugby matches. This study re-emphasises the need for continuing epidemiological research.

Football↗

Disability in young people and adults one year after head injury: prospective cohort study.

OBJECTIVE: To determine the frequency of disability in young people and adults admitted to hospital with a head injury and to estimate the annual incidence in the community. DESIGN: Prospective, hospital based cohort study, with one year follow up of sample stratified by coma score. SETTING: Five acute hospitals in Glasgow. SUBJECTS: 2962 patients (aged 14 years or more) with head injury; 549 (71%) of the 769 patients selected for follow up participated. MAIN OUTCOME MEASURES: Glasgow outcome scale and problem orientated questionnaire. RESULTS: Survival with moderate or severe disability was common after mild head injury (47%, 95% confidence interval 42% to 52%) and similar to that after moderate (45%, 35% to 56%) or severe injury (48%, 36% to 60%). By extrapolation from the population identified (90% of whom had mild injuries), it was estimated that annually in Glasgow (population 909 498) 1400 young people and adults are still disabled one year after head injury. CONCLUSION: The incidence of disability in young people and adults admitted with a head injury is higher than expected. This reflects the high rate of sequelae previously unrecognised in the large number of patients admitted to hospital with an apparently mild head injury.

Adolescent↗

Domiciliary occupational therapy for patients with stroke discharged from hospital: randomised controlled trial.

OBJECTIVE: To establish if a brief programme of domiciliary occupational therapy could improve the recovery of patients with stroke discharged from hospital. DESIGN: Single blind randomised controlled trial. SETTING: Two hospital sites within a UK teaching hospital. SUBJECTS: 138 patients with stroke with a definite plan for discharge home from hospital. INTERVENTION: Six week domiciliary occupational therapy or routine follow up. MAIN OUTCOME MEASURES: Nottingham extended activities of daily living score and "global outcome" (deterioration according to the Barthel activities of daily living index, or death). RESULTS: By eight weeks the mean Nottingham extended activities of daily living score in the intervention group was 4.8 points (95% confidence interval -0.5 to 10.0, P=0.08) greater than that of the control group. Overall, 16 (24%) intervention patients had a poor global outcome compared with 30 (42%) control patients (odds ratio 0.43, 0.21 to 0.89, P=0.02). These patterns persisted at six months but were not statistically significant. Patients in the intervention group were more likely to report satisfaction with a range of aspects of services. CONCLUSION: The functional outcome and satisfaction of patients with stroke can be improved by a brief occupational therapy programme carried out in the patient's home immediately after discharge. Major benefits may not, however, be sustained.

Activities of Daily Living↗

Effects of influenza vaccination of health-care workers on mortality of elderly people in long-term care: a randomised controlled trial.

BACKGROUND: Vaccination of health-care workers has been claimed to prevent nosocomial influenza infection of elderly patients in long-term care. Data are, however, limited on this strategy. We aimed to find out whether vaccination of health-care workers lowers mortality and the frequency of virologically proven influenza in such patients. METHODS: In a parallel-group study, health-care workers in 20 long-term elderly-care hospitals (range 44-105 patients) were randomly offered or not offered influenza vaccine (cluster randomisation, stratified for policy for vaccination of patients and hospital size). All deaths among patients were recorded over 6 months in the winter of 1996-97. We selected a random sample of 50% of patients for virological surveillance for influenza, with combined nasal and throat swabs taken every 2 weeks during the epidemic period. Swabs were tested by tissue culture and PCR for influenza viruses A and B. FINDINGS: Influenza vaccine uptake in health-care workers was 50.9% in hospitals in which they were routinely offered vaccine, compared with 4.9% in those in which they were not. The uncorrected rate of mortality in patients was 102 (13.6%) of 749 in vaccine hospitals compared with 154 (22.4%) of 688 in no-vaccine hospitals (odds ratio 0.58 [95% CI 0.40-0.84], p=0.014). The two groups did not differ for proportions of patients positive for influenza infection (5.4% and 6.7%, respectively); at necropsy, PCR was positive in none of 17 patients from vaccine hospitals and six (20%) of 30 from no-vaccine hospitals (p=0.055). INTERPRETATION: Vaccination of health-care workers was associated with a substantial decrease in mortality among patients. However, virological surveillance showed no associated decrease in non-fatal influenza infection in patients.

Aged↗

Public health implications of new guidelines for lead in drinking water: a case study in an area with historically high water lead levels.

Concern about the neurotoxicity of lead, particularly in infants and young children, has led to a revision of blood lead levels which are considered to involve an acceptable level of human exposure. Drinking water guidelines have also been reviewed in order to reduce this source of population exposure to lead. In the last 20 years, guidelines have been reduced from 100 to 50 to 10 microg/litre. Lead in tap water used to be a major public health problem in Glasgow because of the high prevalence of houses with lead service pipes, the low pH of the public water supply and the resulting high levels of lead in water used for public consumption. Following two separate programmes of water treatment, involving the addition of lime and, a decade later, lime supplemented with orthophosphate, it is considered that maximal measures have been taken to reduce lead exposure by chemical treatment of the water supply. Any residual problem of public exposure would require large scale replacement of lead service pipes. In anticipation of the more stringent limits for lead in drinking water, we set out to measure current lead exposure from tap water in the population of Glasgow served by the Loch Katrine water supply, to compare the current situation with 12 years previously and to assess the public health implications of different limits. The study was based on mothers of young children since maternal blood lead concentrations and the domestic water that mothers use to prepare bottle feeds are the principal sources of foetal and infant lead exposure. An estimated 17% of mothers lived in households with tap water lead concentrations of 10 microg/litre (the [WHO,] guideline) or above in 1993 compared with 49% in 1981. Mean maternal blood lead concentrations fell by 69% in 12 years. For a given water lead concentration, maternal blood lead concentrations were 67% lower. The mean maternal blood lead concentration was 3.7 microg/litre in the population at large, compared with 3.3 microg/litre in households with negligible or absent tap water lead. Nevertheless, between 63% and 76% of cases of mothers with blood lead concentrations of 10 microg/dl or above were attributable to tap water lead. The study found that maternal blood lead concentrations were well within limits currently considered safe for human health. About 15% of infants may be exposed via bottle feeds to tap water lead concentrations that exceed the WHO guideline of 10 microg/litre. In the context of the health and social problems which affect the well-being and development of infants and children in Glasgow, however, current levels of lead exposure are considered to present a relatively minor health problem.

Adult↗

Increased augmentation index and systolic stress in type 1 diabetes mellitus.

Type 1 diabetes mellitus is associated with endothelial dysfunction and increased arterial stiffness, both of which may contribute to the excess cardiovascular mortality in such patients. Arterial stiffening increases pulse wave velocity and wave reflection, which augments central systolic pressure and stress. Using the non-invasive technique of pulse wave analysis, we investigated aortic augmentation and central pressure in 35 patients with type 1 diabetes and 35 matched controls. Peripheral pulse waveforms were recorded from the radial artery. Central aortic waveforms were then generated, and augmentation index (AIx), ascending aortic pressure and tension time index (TTI), a measure of systolic load, were calculated. Peripheral and central blood pressure did not differ between the two groups. AIx was significantly elevated in the diabetic patients compared with controls (7.1+/-1.6% vs. 0.4+/-2.0%; p=0.01), as was the TTI (2307+/-51 mmHg x s x min(-1) vs. 2010+/-61 mmHg. s x min(-1); p<0.001). Estimated pulse wave velocity was also higher in the diabetic group. Type 1 diabetes is associated with an increased AIx and rate of wave travel, indicating enhanced wave reflection and increased systemic arterial stiffness, and elevation of the TTI. Such haemodynamic effects may contribute to the increased left ventricular mass and risk of cardiovascular disease associated with type 1 diabetes mellitus.

Adolescent↗

The value of the "worst" computed tomographic scan in clinical studies of moderate and severe head injury. European Brain Injury Consortium.

OBJECTIVE: Computed tomographic (CT) scanning can reveal the pattern and severity of structural brain damage after head injury. With the proliferation of CT scanners in general hospitals, and with improvements in patient transport, the interval from injury to the first CT scan is decreasing. The potential result is an "admission" scan missing an evolving and potentially operable lesion. Furthermore, the literature is confusing regarding the timing and coding of CT findings. We sought to establish the frequency of deterioration in CT appearance from an admission scan to subsequent scans and the prognostic significance of such deterioration. METHODS: In a survey organized by the European Brain Injury Consortium, data on initial severity, management, and subsequent outcome were gathered prospectively for 1005 patients with moderate or severe head injury admitted to one of 67 European neurosurgical units during a 3-month period in 1995. The findings of the initial and the final ("worst") CT scan were classified according to the Traumatic Coma Data Bank system and were related to outcome as assessed using the Glasgow Outcome Scale 6 months after injury. RESULTS: Data on an initial and a final CT scan were available for 897 patients; of these, 724 patients were assessed using the Glasgow Outcome Scale at 6 months. The initial CT findings were classified as a diffuse injury for 53% of the cohort, with 16% of these diffuse injuries demonstrating deterioration on a subsequent scan. In 56 (74%) of 76 deteriorations, the change was from a diffuse injury to a mass lesion. When the initial CT scan demonstrated a diffuse injury without swelling or shift, evolution to a mass lesion was associated with a statistically significant increase in the risk of an unfavorable outcome (62% versus 38%). When the initial scan demonstrated evidence of swelling or shift, there was a nonsignificant trend in the opposite direction, although the numbers were limited. CONCLUSION: When an admission CT scan demonstrates evidence of a diffuse injury, follow-up scans should be performed, because approximately one in six such patients will demonstrate significant CT evolution. In studies comparing series of head-injured patients, correspondence of timing of CT scans is necessary for valid comparison.

Brain Injuries↗

Genetic polymorphisms of cytochrome p4502E1 and susceptibility to alcoholic liver disease and hepatocellular carcinoma in a white population: a study and literature review, including meta-analysis.

AIMS: To investigate the associations between the Rsa I, Dra I, and Taq I genetic polymorphisms of cytochrome p4502E1 and susceptibility to alcoholic liver disease or to hepatocellular carcinoma. METHODS: DNA samples isolated from 61 patients with alcoholic liver disease, 46 patients with hepatocellular carcinoma, and 375 healthy controls were subjected to polymerase chain reaction amplification followed by digestion with the endonucleases Rsa I, Dra I, or Taq I. Meta-analysis was performed using data from previous studies of Rsa I polymorphism and the risk of alcoholic liver disease. RESULTS: No association was found between any of the three polymorphisms and susceptibility to hepatocellular carcinoma. The distributions of Rsa I and Dra I alleles among the patients with alcoholic liver disease were not significantly different from those among the control group. Meta-analysis of this data and previous data concerning Rsa I polymorphism and alcoholic liver disease risk failed to demonstrate any significant association between the two. However, the alcoholic liver disease group in this study showed a significantly lower frequency of the less common Taq I allele compared with the healthy control group (odds ratio, 0.33; 95% confidence interval, 0.12 to 0.78). CONCLUSIONS: Possession of the less common Taq I cytochrome p4502E1 allele is associated with reduced susceptibility to alcoholic liver disease. There is no existing evidence that the Taq I polymorphism is directly associated with altered alcohol metabolism, but it might be in linkage disequilibrium with as yet unidentified protective factors.

Adult↗

Promoting good research practice.

Embarking on a new millennium provides the stimulus both to take stock and also to look forward. In the field of medical statistics there is much to make us feel proud and excited. Rapid methodological developments together with parallel developments in computer technology have enormously expanded our statistical repertoire. At the same time, the high profile attained by the evidence-based medicine movement means that the importance of our discipline is recognized more widely then ever before. However, any medical statistician who is involved in medical publishing, or who is even a regular reader of the medical literature, must be aware of the yawning chasm between what is recognized as good statistical practice and what is actually published. Poor study design, inappropriate analysis and selective reporting are commonplace. In my opinion the most important challenge currently facing our profession is the task of bridging this chasm.

Consensus Statements as Topic↗

Efficacy and safety of the endothelin, receptor antagonist TAK-044 in treating subarachnoid hemorrhage: a report by the Steering Committee on behalf of the UK/Netherlands/Eire TAK-044 Subarachnoid Haemorrhage Study Group.

OBJECT: Delayed cerebral ischemia remains an important cause of death and disability in patients who have suffered subarachnoid hemorrhage (SAH). Endothelin (ET) has a potent contractile effect on cerebral arteries and arterioles and has been implicated in vasospasm. The authors administered ET(A/B) receptor antagonist (TAK-044) to patients suffering from aneurysmal SAH. They then assessed whether this agent reduced the occurrence of delayed cerebral ischemic events and examined its safety profile in this group of patients. METHODS: Four hundred twenty patients who had suffered an SAH were recruited into a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II trial. The primary end point was whether a delayed ischemic event occurred within 3 months after the first dose of the study drug and the secondary end points included determining whether a delayed ischemic event occurred by 10 days after the first dose of the study drug, whether a new cerebral infarct was demonstrated on a computerized tomography scan or at postmortem examination by 3 months after administration of the initial dose, the patient's Glasgow Outcome Scale scores at 3 months after the initial dose, and adverse events. There was a lower incidence of delayed ischemic events at 3 months in the TAK-044-treated group: 29.5% compared with 36.6% in a group of patients receiving placebo. The estimated relative risk was 0.8 with a 95% confidence interval of 0.61 to 1.06. There were no significant differences in the secondary end points, including clinical outcomes in the placebo-treated and TAK-044-treated groups. CONCLUSIONS: The TAK-044 was well tolerated by patients who had suffered an SAH, even though hypotension and headache--side effects compatible with the drug's vasodilatory properties--occurred. It would be valuable to proceed to a fully powered phase III trial of an ET receptor antagonist in treating aneurysmal SAH.

Adult↗

A comparison of reports from referees chosen by authors or journal editors in the peer review process.

The aim was to analyse the peer review process by comparing reports produced by referees selected by journal editors, with those of referees selected by the authors of a scientific manuscript. Some 104 consecutive papers from the UK submitted to the British Journal of Surgery (BJS) were included. Of these, 102 were reviewed blind both by referees chosen by the journal editors, and referees chosen by the paper's principal author. Manuscripts were marked using a standard sheet for four basic aspects: originality, clinical/scientific importance, clarity and analysis; a final overall recommendation about possible publication was given. The time taken and the number of completed referee reports were similar in each group. Referees chosen by the BJS editors were more critical (scored higher) of the submitted articles. Mean scores for all domains were higher than for authors' referees, significantly for scientific importance (p = 0.009) and decision to publish (p = 0.029). In conclusion, reports produced by referees selected by BJS editors were more critical than those chosen by authors of the papers. Authors might argue that this reduced their chance of publication but constructive criticism might improve the final article and assist editors to make decisions about acceptance or rejection.

Authorship↗

Using routine data to complement and enhance the results of randomised controlled trials.

BACKGROUND: Randomised controlled trials (RCTs) are widely accepted as the best way to assess the outcomes and safety of medical interventions, but are sometimes not ethical, not feasible, or limited in the generalisability of their results. In such circumstances, routinely available data could help in several ways. Routine data could be used, for example, to conduct 'pseudo-trials', to estimate likely outcomes and required sample size to help design and conduct trials, or to examine whether the expected outcomes observed in an RCT will be realised in the general population. OBJECTIVES: The project was undertaken to explore how routinely assembled hospital data might complement or supplement RCTs to evaluate medical interventions: in contexts where RCTs are not feasible for defining the context and design of an RCT for assessing whether the benefits indicated by RCTs are achieved in wider clinical practice. METHODS: The project was based on the system of linked Scottish morbidity records, which cover 100% of acute hospital care episodes and statutory death records from 1981 to 1995. Three case studies were undertaken as a way of investigating the utility of these records in different applications. First, an attempt was made to analyse the link between the timing of surgery for subarachnoid haemorrhage (SAH) and subsequent outcomes (a question not easily susceptible to RCT design). A subsample was derived by excluding patients for which a diagnosis of SAH may not have been established or that may not have been admitted to a neurosurgical unit, and the data were assessed to attempt to inform the design of a trial of early versus late surgery. Transurethral prostatectomy (TURP), the second case study, has become the surgery of choice for benign prostatic hyperplasia without systematic assessment of its effectiveness and safety, and an RCT would now be considered unethical. However, there is a need to investigate long-term effects and the influence of co-morbidities on outcomes. A retrospective comparison of mortality and re-operation following either open prostatectomy (OPEN) or TURP was, therefore, undertaken. Patients for whom it was not possible to establish the initial procedure were excluded. The third case study compared coronary artery bypass grafting (CABG) with percutaneous transluminal angioplasty (PTCA) for coronary revascularisation. RCTs have been conducted in limited patient subgroups with short follow-up periods. A meta-analysis of RCTs could be augmented by routine data, which are available for large populations. This would allow assessment of subgroup effects, and outcomes over a long period. A subgroup of patients was therefore constructed for whom relevant routine data were available and who reflected the entry criteria for major RCTs, thus enabling a comparison between the results expected from this subgroup and those of the general population. RESULTS AND CONCLUSIONS: The uses of routine data in these contexts had strengths and weaknesses. The SAH study suggested a means of assessing outcomes and survival rates following haemorrhage, which could have value in informing the design of more precise trials and in evaluating changes in outcome following the introduction of new treatments such as embolisation. However, the potential of the data was not realised because their scope and content were insufficient. For example, lack of data on the time of onset of symptoms and patients' conditions at hospital admission made it difficult to establish the link between timing of surgery and the outcome, and there was insufficient information on patients' conditions at discharge to enable a comparison of outcomes. The prostatectomy study was able to address questions not answered by RCT literature because the large number of cases it included allowed exploration of subgroup effects. (ABSTRACT TRUNCATED)

Adult↗

The European Brain Injury Consortium survey of head injuries.

To provide a picture of contemporary practice, a survey was carried out of severely and moderately head injured patients admitted to 67 'neuro' centres in 12 European countries. 1,005 adult head injuries were recruited over a three month period. Sixty items of information on demography, clinical features, investigations, management and early complications were captured on a simple, two-page questionnaire and, information on outcome at six months on a third page. The median age of the subjects was 38 years, 74% were male and 51% injured in road traffic accidents; 57% of patients were transferred to the 'neuro' centre from another hospital. Assessment of clinical responsiveness was limited by the use of sedation and intubation and information from four early time points (pre-hospital, arrival at the Accident and Emergency department, post-resuscitation, and arrival at the 'neuro' unit) was combined to stratify the subjects as severe (58%), moderate (17%) or intermediate (19%). In 48% of patients classified the CT scan showed features of a 'mass lesion' and in 40% showed a subarachnoid haemorrhage. Fifty-five centres provided the data on outcome for 94% of the cases recruited in these centres six months after injury. 31% died, 3% were vegetative, 16% severely disabled, 20% moderately disabled and 31% had made a good recovery. Comparison of the data from different parts of Europe showed differences in the frequency of secondary transfer, cause of injury, occurrence of major extracranial injury, CT scan findings, intracranial operation, clinical severity of injury and utilisation of the components of intensive care and the occurrence of a favourable outcome, although the latter difference was not statistically significant when variations in the initial severity of injury were taken into account. The findings in the present survey are compared with newly analysed information for three previous large series: the International Data Bank involving the UK, the Netherlands and the USA, the North American Traumatic Coma Data Bank, and data from four centres in the UK. The comparisons showed substantial similarities and also differences that may reflect variations in policy for admission of the head injury to 'neuro' units, and evolution in methods of assessment, investigation and management. The effects of these differences on outcome requires further, rigorous prospective study.

Adolescent↗

Comparing outcomes of percutaneous transluminal coronary angioplasty with coronary artery bypass grafting; can routine health service data complement and enhance randomized controlled trials?

AIM: To compare outcomes of percutaneous transluminal coronary angioplasty (PTCA) with coronary artery bypass graft surgery (CABG) for a population stemming from routinely collected data, in order to assess the merits of such data sources as a complement, and possible enhancement, to randomized controlled trial results. METHODS AND RESULTS: A population of Scottish patients were taken from a routine discharge summary and from this data source patients comparable to those from randomized controlled trial settings were identified. Between 1989 and 1995, 12 238 pseudo randomized controlled trial patients were identified from the routine data set, of which 3714 (30.3%) received PTCA and 8524 (69.7%) received CABG. The baseline characteristics of the pseudo randomized controlled trial and randomized controlled trial patients were similar. The evidence from both the randomized controlled trials and routine data indicate that for 1 year follow-up the risk of cardiac death and/or non-fatal myocardial infarction is not significantly different between the two treatment groups. CONCLUSION: The outcomes expected of PTCA and CABG following trial evidence have been realized in the routine data which are representative of a complete, non-selective population. Due to the size of the routine data set it would be possible to set up hypotheses for potential subgroup effects at the outset.

Angioplasty, Balloon, Coronary↗

Head injuries in four British neurosurgical centres.

An issue in the design of trials in traumatic brain injury is whether variation amongst centres in 'conventional' management could mask the impact of a powerful new pharmacological agent. We report the results of an observational study of 988 patients admitted to one of four British neurosurgical units between 1986 and 1988 within 3 days of a severe head injury. The centres fell into two pairs on the basis of the 'intensity' of management. In Edinburgh and Southampton, more frequent use of intracranial pressure monitoring, ventilation and osmotic diuretics was made than in Glasgow and Liverpool. The odds ratio for an independent outcome at 6 months in Edinburgh or Southampton, relative to Glasgow or Liverpool, controlling for case mix, was 1.43 (95% CI, 1.03-1.98, p = 0.033). Thus, there is weak evidence of an association between the approach to management and clinical outcome at 6 months.

Accidents, Traffic↗

Evaluation of designs for clinical trials of neuroprotective agents in head injury. European Brain Injury Consortium.

In a study involving the statistical modeling of potential head injury trials, we explore approaches to trial design that could enhance their power to detect treatment-related effects on clinical outcome. The study uses a survey organized by the European Brain Injury Consortium of over 1,000 head-injured patients to characterize the population from which trial participants can be selected. A variety of models are postulated for the effects of "neuroprotective" treatment on outcome, and their interaction with a range of strategies for targeting patients for inclusion in the trial is evaluated. A very simple strategy of targeting patients with an intermediate prognosis was found to allow a reduction in sample size by 30%, with no reduction in statistical power. This paper illustrates an important methodology for studying the characteristics of competing trial designs.

Adolescent↗