Death after head injury: the 13 year outcome of a case control study.

BACKGROUND: Head injury is common, and the risk of subsequent disability and death is high. Increased risk of death years after injury might be explained by factors associated with, but not a consequence of, the head injury. This unique prospective study investigates mortality over 13 years after injury. METHODS: A cohort of n=767 with head injury was compared with two case control groups, matched for age, gender and deprivation, and in one control group, matched for duration of hospital admission following (non-head) injury. RESULTS: Two-fifths of the head injury cohort had died. The death rate (30.99 per 1000 per year) was much higher than in community controls (13.72 per 1000 per year). More than 1 year after injury, the death rate in younger (15-54 years) adults was much higher than in community controls (17.36 vs. 2.36 per 1000 per year) whereas in older adults the difference was more marginal (61.47 vs. 42.36). Death rate was elevated after mild and after more severe head injury, including in younger adults after mild head injury (14.82 per 1000 per year mild head injury vs. 2.21 community). Female gender and greater deprivation were not associated with increased death rates after head injury. Late after injury, deaths occurred from the same main causes as for the general population. CONCLUSION: Head injury is associated with increased vulnerability to death from a variety of causes for at least 13 years after hospital admission. There is a need to understand how head injury influences mortality, particularly in younger adults and after mild head injury.

Quality in healthcare and the quest for improvement.

Improvement in the quality of healthcare is desired by everyone. Delivering this however, is hindered by lack of clear, widely embraced perceptions of what is encompassed within quality and how improvement can best be brought about. This paper, written from the viewpoint of a clinician now with a responsibility for this field in Scotland, presents a multidimensional concept of quality, as encompassing effectiveness, safety, patient centeredness, timeliness, efficiency and equity. This approach allows views about the relative importance of the various components to differ but also to be reconciled and the different standpoints made coherent. The principal kinds of interventions, aimed to improve one or more aspects of quality, are presented and the need for much greater evidence about their value, alone or in combination is noted. Nevertheless, there is increasing recognition of the importance of emphasising the human factors of attitude, culture and behaviour that provide the best assurance of quality of care to individuals. NHS Quality Improvement Scotland has a key role in searching out knowledge about how improvement is achieved and in engaging with patients and NHS staff to ensure that the necessary advances are achieved in Scotland.

Death rate is increased for at least 7 years after head injury: a prospective study.

Although a high mortality rate among patients recently admitted to hospital with severe head injury is well recognized, less is known about their later mortality and very little about the ensuing lifestyle and less-severe injuries that lead to death. The aims of this study were to determine the rate of death in the first and six subsequent years after head injury, in a prospectively identified cohort admitted to hospital, and investigate the factors associated with death--comparing these with general death rates in Scottish populations. A structured sample of 767 patients aged 14 years and over was identified at the time of admission to hospital after a head injury and followed up 7 years later. A trace exercise was conducted to identify those deceased. The General Register of Scotland confirmed death and provided information about cause of death. Seven years after head injury, 206/767 (27%) people had died. Compared to the Glasgow population, risk of death was high after head injury in months 1-2 (23 times), 3-12 (3 times) and 13-84 (2 times), and overall was especially raised in younger people, even late (13-84 months) after injury (7 times). Mortality was only associated with greater severity of head injury during year 1. Pre-injury medical history was associated both with earlier and later deaths, but risk of death remained higher in those with no such history. Later deaths were often associated with lifestyle post-injury. The primary causes of death after head injury were the same as those in the general population. Compared to the general population, the death rate after admission to hospital with head injury remains high for at least 7 years, and is particularly high for those aged under 55 years. Interventions aimed at change in lifestyle may reduce this continuing excess mortality.

Decompressive craniectomy in traumatic brain injury: the randomized multicenter RESCUEicp study (www.RESCUEicp.com).

The RESCUEicp (Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of intracranial pressure) study has been established to determine whether decompressive craniectomy has a role in the management of patients with traumatic brain injury and raised intracranial pressure that does not respond to initial treatment measures. We describe the concept of decompressive craniectomy in traumatic brain injury and the rationale and protocol of the RESCUEicp study.

Disability in young people and adults after head injury: 5-7 year follow up of a prospective cohort study.

BACKGROUND: Improvement 1-2 years after head injury is well established but the pattern thereafter is unclear. Past studies have not examined representative head injury populations and typically report findings in terms of functioning across social, psychological, neurobehavioural, or cognitive domains rather than global outcome. OBJECTIVE: To determine the late outcome of a representative cohort of participants admitted to hospital after a head injury 5-7 years previously and to identify early and late factors correlating with persisting disability and change between one and 5-7 years. METHODS: A representative cohort of head injured people whose outcome one year after injury was reported previously, were followed up 5-7 years after injury. Participants were assessed using structured and validated measures of global outcome (Glasgow Outcome Scale Extended), cognitive impairment, psychological wellbeing, health status, and social factors. RESULTS: Of 475 survivors studied at one year, 115 (24%) had died by seven years. In survivors at 5-7 years, disability remained frequent (53%); and the rate, similar to that found at one year (57%). Sixty three participants (29%) had improved but 55 (25%) deteriorated. The persistence of disability and its development after previous recovery each showed stronger associations with indices of depression, anxiety, and low self-esteem than with initial severity of injury or persisting cognitive impairment. CONCLUSIONS: Admission to hospital after head injury is followed 5-7 years later by disability in a high proportion of survivors. Persistence of disability and development of new disability are strongly associated with psychosocial factors that may be open to remediation, even late after injury.

The association between APOE epsilon4, age and outcome after head injury: a prospective cohort study.

Previous preliminary studies have suggested that possession of the APOE epsilon4 allele is associated with a poor outcome after head injury. This study was designed to confirm and extend those observations in a larger study with examination of additional variables. We prospectively identified admissions to a Neurosurgical Unit for head injury, collected demographic and clinical data, determined APOE genotypes and obtained follow-up information at 6 months. A total of 1094 subjects were enrolled (age range: 0-93 years, mean 37 years). Outcome was assessed using the Glasgow Outcome Scale. There was no overall association between APOE genotype and outcome, with 36% of APOE epsilon4 carriers having an unfavourable outcome compared with 33% of non-carriers of APOE epsilon4. However, there was evidence of an interaction between age and APOE genotype on outcome (P = 0.007) such that possession of APOE epsilon4 reduced the prospect of a favourable outcome in children and young adults. The influence of APOE genotype in younger patients after head injury can be expressed as, at age <15 years, carriage of APOE epsilon4 being equivalent to ageing by 25 years. This finding is consistent with experimental data suggesting that the effect of APOE genotype on outcome after head injury may be expressed through the processes of repair and recovery.

Ethical considerations on consent procedures for emergency research in severe and moderate traumatic brain injury.

Therapeutic trials in TBI are subject to principles of Good Clinical Practice (GCP), to national legislation, and to international and European ethical concepts and regulations [e.g. 13]. The guiding principles underlying these investigations of treatment are respect for autonomy of research subjects, protection against discomfort, risk, harm and exploitation and the prospect of some benefit. Patients with significant TBI are mentally incapacitated, thus prohibiting obtaining consent directly from the subject. Various approaches to consent procedures are used as surrogate to subject consent: proxy consent, consent by an independent physician and waiver of consent. These approaches are reviewed. A questionnaire soliciting opinions was mailed to 148 EBIC (European Brain Injury Consortium) associated neuro-trauma centers in 19 European countries. 48% respondents believe that relatives were not able to make a balanced decision, 72% believed that consent procedures are a significant factor causing decrease in enrollment rate and 83% stated that consent procedures delay initiation of study treatment, resulting in possible harm if the agent has shown to be effective. 64% of the respondents considered TBI an emergency situation in which clinical research could be initiated under the emergency exception for consent. In new European legislation, emergency research under waiver of consent is not permitted. Nevertheless, we consider that randomising patients with TBI into carefully evaluated trial protocols without prior consent may be considered ethically justified.

Acquired prolactin deficiency (APD) after treatment for Cushing's disease is a reliable marker of irreversible severe GHD but does not reflect disease status.

OBJECTIVE: We have previously reported that acquired prolactin deficiency (APD) is a marker for severe hypopituitarism and observed a high prevalence of APD in patients treated for Cushing's disease. Recovery of GH secretion is recognized to occur in a proportion of patients treated for Cushing's disease after the effects of glucocorticoid excess on GH secretion have subsided. The aim of this study was to investigate further the association between APD, treated Cushing's disease and, in particular, to determine whether recovery of GH secretion may occur in these patients. METHODS: Fifty-seven patients (42 female), in remission after treatment for Cushing's disease, were studied. The cohort comprised 13 patients with, and 44 without APD. APD was defined as a serum prolactin persistently below the detection limit of the assay. Severe GH deficiency was defined as a peak GH response of less than 9 mU/l during a GH stimulation test. Age and gender did not significantly differ between subgroups. RESULTS: Of the 13 patients with APD, a macroadenoma was present in one patient, a microadenoma was present in 10, no lesion was detected in one, and in one patient (treated with an yttrium implant) the size of the tumour was unknown. Of the 28 patients who did not have APD, who were treated with primary surgery a microadenoma was present in 23 and a macroadenoma was present in five. Detailed pituitary imaging was not available in 16 patients who did not have APD, who were treated with primary external XRT. Deficiencies of GH, TSH, LH/FSH (P < 0.0001) and ADH (P = 0.006) status, by conventional testing, were present more frequently in the APD subgroup. In contrast, the prevalence of ACTH deficiency after treatment was not different between the APD and non-APD groups. However, the requirement for additional therapy, targeting the pituitary or adrenal gland, after primary treatment, in those patients not rendered ACTH-deficient, was significantly greater in the APD compared with the non-APD groups (P = 0.003). After pituitary surgery, a significant correlation between peak GH response and interval since remission of Cushing's syndrome was found in the subgroup without APD (r = 0.4, P = 0.04). Four patients who did not have APD, who had documented severe GHD in the immediate postoperative period displayed normalization of GH secretion, when re-tested after a mean interval of 27.2 months. In contrast, no patient with APD after pituitary surgery demonstrated a detectable GH response after up to 132 months of follow-up. No patient with APD showed recovery of prolactin secretion by the time of the most recent measurement (mean 57 months). All 10 patients who developed APD immediately after pituitary surgery had undergone a radical procedure (either a subtotal or total hypophysectomy). In contrast, of 28 patients with Cushing's disease who did not develop APD, only four underwent radical surgery (P < 0.0001). Seven of 14 patients (50%) who underwent a radical operation and two of 20 treated by selective adenomectomy (10%) required additional treatment to achieve control of Cushing's syndrome (P = 0.04). CONCLUSION: In the presence of APD, patients with Cushing's disease do not experience recovery of GH secretion after treatment, even after the effects of glucocorticoid excess subside. In the absence of APD, GH status may normalize after successful surgical treatment. Although a marker for severe hypopituitarism, APD does not indicate success of treatment of Cushing's disease and may be associated with detectable ACTH secretion from residual corticotroph adenoma activity. APD after pituitary surgery for Cushing's disease occurs only after a radical operation. When a selective adenomectomy is not possible, control of Cushing's disease by operation is less frequent and when achieved, is more often at the cost of hypopituitarism. The optimal management of such patients requires further study.

Calcium channel blockers for acute traumatic brain injury.

BACKGROUND: Acute traumatic brain injury is a major cause of death and disability. Calcium channel blockers (calcium antagonists) have been used in an attempt to prevent cerebral vasospasm after injury, maintain blood flow to the brain, and so prevent further damage. OBJECTIVES: To estimate the effects of calcium channel blockers in patients with acute traumatic brain injury, and in a subgroup of brain injury patients with traumatic subarachnoid haemorrhage. SEARCH STRATEGY: Handsearching and electronic searching for randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials in patients with all levels of severity of clinically diagnosed acute traumatic brain injury. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the identified studies for eligibility and extracted data from each study. Summary odds ratios were calculated using the Mantel-Haenszel method. MAIN RESULTS: Six RCTs were identified as eligible for inclusion in the systematic review. The effect of calcium channel blockers on the risk of death was reported in five of the RCTs. The pooled odds ratio (OR) for the five studies was 0.91 (95% confidence interval [95%CI] 0.70-1.17). For the four RCTs that reported death and severe disability (unfavourable outcome), the pooled odds ratio was 0.85 (95%CI 0.68-1.07). In the two RCTs which reported the risk of death in a subgroup of traumatic subarachnoid haemorrhage patients, the pooled odds ratio was 0.59 (95%CI 0.37-0.94). Three RCTs reported death and severe disability as an outcome in this subgroup, and the pooled odds ratio was 0.67 (95%CI 0.46-0.98). REVIEWER'S CONCLUSIONS: This systematic review of randomised controlled trials of calcium channel blockers in acute traumatic head injury patients shows that considerable uncertainty remains over their effects. The effect of nimodipine in a subgroup of brain injury patients with subarachnoid haemorrhage shows a beneficial effect, though the increase in adverse reactions suffered by the intervention group may mean that the drug is harmful for some patients.

Genetic variation of the APOE promoter and outcome after head injury.

The APOE-epsilon4 allele is associated with risk for Alzheimer's disease (AD) and poorer outcome after head injury. Several studies show that polymorphisms in the promoter that influence APOE expression also increase risk for AD. The authors' data from a study of 92 patients are consistent with a possible influence of the G-219T promoter polymorphism on outcome after head injury. The group with unfavorable outcome had a genotype frequency distribution similar to that found in AD.

Long term neuropsychological outcome after head injury: relation to APOE genotype.

BACKGROUND: Existing evidence suggests that some patients who sustain a head injury suffer cognitive decline many years later, and that head injury and possession of the APOE epsilon 4 allele are each risk factors for Alzheimer's disease. OBJECTIVE: To determine whether late cognitive decline after head injury is more prevalent among carriers of APOE epsilon 4. METHODS: A database of head injured patients was used. Initial assessment was at the time of their injury, between 1968 and 1985, and outcome data at six months were available. Their ages at the time of injury ranged between 2 and 70 years. A cohort of 396 subjects was reassessed at a mean of 18 years later, with determination of APOE genotype and detailed neuropsychological testing. RESULTS: Judging by the Glasgow outcome scale, twice as many patients had deteriorated as improved between six months after injury and the late assessment; 22.2% of APOE epsilon 4 carriers had a good late outcome compared with 30.5% of non-carriers (95% confidence interval for the difference, -0.7% to 17.2%; p = 0.084). There were no clear differences between epsilon 4 carriers and non-carriers in detailed neuropsychological assessments. CONCLUSIONS: Although this study provides additional evidence that a late decline may occur after head injury, there was no clear relation to APOE genotype. Despite the follow up interval of 15 to 25 years, the cohort is still too young (mean age 42.1 years) to assess the risk of Alzheimer's disease.

Reliability of postal questionnaires for the Glasgow Outcome Scale.

The purpose of the study was to investigate if a questionnaire sent by mail can give a reliable assessment of outcome on the Glasgow Outcome Scale. A questionnaire was developed for the Glasgow Outcome Scale (GOS) and a second questionnaire for the Extended Glasgow Outcome Scale (GOSE). The questionnaires were self-contained and designed to be completed by either a head-injured person or a proxy. The questionnaires were studied in two ways: each questionnaire was administered twice (at an interval of approximately 2 weeks), and ratings from the postal questionnaires were compared to ratings from a structured interview conducted by telephone. The four studies were carried out in separate groups of head-injured participants consisting of 32-38 individuals. For the test-retest comparison, k(w) (quadratic weights) was 0.94 for the GOS questionnaire and 0.98 for the GOSE questionnaire. For the comparison with the telephone interview, k(w) was 0.67 for the GOS and 0.92 for the GOSE. The values of k(w) indicate good agreement for all comparisons. We conclude that it is possible to obtain reliable outcome data after head injury using postal questionnaires.

Head injury in the United Kingdom.

This paper reviews aspects of head injury management and research in the United Kingdom (UK). We discuss evidence about the scale and etiology of head injury in Britain and how this information has supported a triage-based approach, incorporating risk analysis. A Cohesive organization based upon nationally accepted, yet regionally flexible head injury management guidelines is important. Research in the United Kingdom has clarified the effect of head injury on the brain and how this can be reduced. This clarification follows from improved understanding of the neurobiology of injury, of secondary damage and recovery, and information gained from new techniques aimed at investigating events in patients. Outcome is an important perspective and we highlight the increasing focus upon recovery and the extent of disability after so called mild head injury. Although we retain a UK perspective, comparisons with aspects of European head injury emphasize the increasing importance of an international approach in the future.