The cost-effectiveness of newer drugs as add-on therapy for children with focal epilepsies.

PURPOSE: Epilepsies in children are complex diseases. Guidelines are needed on the appropriate use of newer versus older anti-epileptic drugs (AEDs). This paper presents an individual patient-sampling model to assess the cost-effectiveness of using newer AEDs as add-on therapy in line with UK prescribing guidance. METHODS: Identification of the relevant parameters and treatment pathways for the model were achieved by a systematic review of the literature and discussions with clinical experts. Data were obtained from the literature and supplemented with data elicited from paediatric neurologists. The model considered paediatric patients over the period of childhood from the age of diagnosis to 18 years. RESULTS: The results suggest that the older and newer AEDs are similar in terms of drug retention rates and the average time in 'good' treatment outcomes. In terms of cost, the results indicate a consistent increase in cost (compared to older AEDs) when all of the newer AEDs are considered. The decision analysis results indicate that there are no important health benefits from the use of newer AEDs when used as add-on therapy. However, the analysis also reveals that the uncertainties in the model are greater than the differences between the drug strategies. CONCLUSIONS: To develop guidelines on the appropriate use of newer AEDs, better information is required from randomised controlled trials as there is insufficient data available in the public domain to accurately estimate the nature of the trade off between older versus newer AEDs.     

A prospective audit of the use and costs of myelography in a regional neuroscience unit.

A consecutive series of 397 myelograms performed in 385 patients over a six month period at the Mersey Regional Neurosciences Unit is reported. The reasons for performing the myelogram were to identify the cause of a radicular lesion in 54% of patients, a chronic spinal cord lesion in 30%, an acute cord lesion in 9%, suspected disease at the level of the foramen magnum 6%, and for a variety of other conditions in 8%. For the 385 patients undergoing a myelogram in the study period, the median interval from admission to request, request to myelography and from myelography to discharge was nought, one and three days respectively. The proportion of patients submitted to myelography by individual consultants ranged from 7% to 28%. There was a two-fold variation in the delays in the time to requesting and performing myelograms. There was room for improvement in the clinical information supplied on the myelography request form. The role of ancillary investigations and their effect on myelography was unclear. Only 16 of the patients with suspected cord disease had visual evoked responses performed before myelography. Five of them had myelography after an abnormal result. The estimated annual direct cost of myelography in the unit was at least 486,000 pounds. Reorganisation might have yielded hypothetical "savings" of between 30,000 pounds (6%) and 155,000 pounds (32%), though in practical terms these "savings" represented resources which might have been freed for use in other higher priority clinical problems within the unit, rather than true reductions in monetary cost.     

Value of computed tomography in patients with stroke: Oxfordshire Community Stroke Project

The usefulness of computed tomography (CT) was assessed in 325 consecutive patients with a "clinically definite first stroke" from a community stroke register. CT detected five "non-stroke" lesions (two cerebral gliomas, one cerebral metastasis, and two subdural haematomas), a frequency of 1.5%. Five patients were identified with cerebellar haemorrhage, but only one survived long enough to have a CT scan. CT was useful in excluding intracranial haemorrhage as the cause of the stroke in four patients receiving anticoagulants and seven receiving antiplatelet treatment; it showed intracranial haemorrhage in one patient taking aspirin. Forty six patients were in atrial fibrillation at the time of their stroke; four had intracranial haemorrhages and three had haemorrhagic cerebral infarcts. Nineteen patients with presumed ischaemic minor stroke were considered suitable for carotid endarterectomy; CT showed small haemorrhages in two. The CT scan provides very useful information in a minority (up to 28%) of patients with first stroke, who can be selected on quite simple criteria: (a) doubt (usually because of an inadequate history) whether the patient has stroke or a treatable intracranial lesion; (b) the possibility of cerebellar haemorrhage or infarction; (c) the exclusion of intracranial haemorrhage in patients who either are already taking or likely to need antihaemostatic drugs or are being considered for carotid endarterectomy; (d) if the patient deteriorates in a fashion atypical of stroke.     

The natural history of lacunar infarction: the Oxfordshire Community Stroke Project

In a consecutive series of 515 first-ever strokes in a community-based study of stroke that combined prompt clinical assessment by a study neurologist with a high rate of confirmed pathologic diagnosis, 108 cases (21%) had a lacunar syndrome. A computed tomography (CT) scan was performed in 104 (96%) of these cases. Only 3 cases had primary intracerebral hemorrhage, and another 3 had "inappropriate" areas of infarcts were seen in 34 of the remaining 98 (35%) CT scans. The crude annual incidence of lacunar infarction was 0.33/1,000. There was no excess risk among men. The case fatality rates were 1% at 1 month and 9.8% at 1 year. The rate of recurrent strokes was 11.8% in the first year. Among patients surviving 1 year, 66% were capable of independent existence.     

A simple method to improve the accuracy of non-invasive ultrasound in selecting TIA patients for cerebral angiography.

A prospective study is reported of the ability of B mode ultrasound imaging and continuous wave Doppler flow studies to detect different degrees of stenosis of the extracranial internal carotid artery (ICA) in 186 arteries in 99 patients with transient ischaemic attacks (TIA) and minor ischaemic stroke. A simple mathematical equation has been developed which combines the image and flow data to provide a single predictor of the degree of angiographic stenosis which has advantages over either ultrasonic modality used alone. The sensitivity and specificity of the predictive model in the detection of stenosis greater than or equal to 25% was 73% and 98%, of stenosis greater than or equal to 50% was 90% and 93%, of stenosis greater than or equal to 75%, 65% and 99% and occlusion 100% and 94% respectively. The principal clinical value of ultrasound screening is to spare patients with "non-significant" stenosis the risk of unnecessary angiography. Thus a simple measure of the Duplex screening tests' performance is the proportion of all strokes occurring as a complication of angiography that are avoided by changing the investigation policy from "angiograms for all carotid TIA and minor ischaemic stroke patients" to "angiograms for all patients with abnormal ultrasound results". If Duplex scanning were used to select patients most likely to have a significant abnormality on angiography, depending on the degree of stenosis to be detected, 52-85% of angiographic strokes might be avoided. If the predictive equation were used 62-88% of angiographic strokes might be avoided.     

Are the modified "simple questions" a valid and reliable measure of health related quality of life after stroke?

OBJECTIVES: Two "simple questions" were developed as a minimalist measurement tool to assess outcome in large trials and epidemiological studies after stroke. A previous study of their validity had disclosed ambiguities in their wording. In this study, the clarity, validity, and reliability of a modified version of these simple questions were examined. The relation between patients' responses to these questions and two widely used generic measures of health related quality of life were also studied. METHODS: A hospital based stroke register cohort of 152 patients, who were all visited at home by a study nurse, was used to study validity. A cohort of 1753 patients derived from the International Stroke Trial was used to study the relation with measures of quality of life. The sensitivity, specificity, and accuracy with which responses to each question predicted the patients' outcome measured using standard instruments was assessed. The distribution of scores for the EuroQol and SF-36 was examined for patients classified as dependent, independent, and fully recovered by the combined use of the modified simple questions. RESULTS: The modified "dependency" question had excellent sensitivity (>85%), specificity (>79%), and accuracy (>82%) for identifying dependency after stroke. The "problems" question had good sensitivity (65-88%) and moderate specificity (36-72%) for the detection of problems in a broad range of domains. The combined use of the modified dependency and problems questions provided a valid, simple, and reliable overall indicator of health related quality of life after stroke. CONCLUSIONS: The modified simple questions have excellent face validity and good measurement properties for the assessment of outcome after stroke. They are particularly well suited for large epidemiological studies and randomised trials.     

Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups

BACKGROUND AND PURPOSE: Long-term daily aspirin is of benefit in the years after ischemic stroke, and 2 large randomized trials (the Chinese Acute Stroke Trial [CAST] and the International Stroke Trial [IST]), with 20 000 patients in each, have shown that starting daily aspirin promptly in patients with suspected acute ischemic stroke also reduces the immediate risk of further stroke or death in hospital and the overall risk of death or dependency. However, some uncertainty remains about the effects of early aspirin in particular categories of patient with acute stroke. METHODS: To assess the balance of benefits and risks of aspirin in particular categories of patient with acute stroke (eg, the elderly, those without a CT scan, or those with atrial fibrillation), a prospectively planned meta-analysis is presented of the data from 40 000 individual patients from both trials on events that occurred in the hospital during the scheduled treatment period (4 weeks in CAST, 2 weeks in IST), with 10 characteristics used to define 28 subgroups. This represents 99% of the worldwide evidence from randomized trials. RESULTS: There was a highly significant reduction of 7 per 1000 (SD 1) in recurrent ischemic stroke (320 [1.6%] aspirin versus 457 [2. 3%] control, 2P<0.000001) and a less clearly significant reduction of 4 (SD 2) per 1000 in death without further stroke (5.0% versus 5. 4%, 2P=0.05). Against these benefits, there was an increase of 2 (SD 1) per 1000 in hemorrhagic stroke or hemorrhagic transformation of the original infarct (1.0% versus 0.8%, 2P=0.07) and no apparent effect on further stroke of unknown cause (0.9% versus 0.9%). In total, therefore, there was a net decrease of 9 (SD 3) per 1000 in the overall risk of further stroke or death in hospital (8.2% versus 9.1%, 2P=0.001). For the reduction of one third in recurrent ischemic stroke, subgroup-specific analyses found no significant heterogeneity of the proportional benefit of aspirin (chi(2)(18)=20. 9, NS), even though the overall treatment effect (chi(2)(1)=24.8, 2P<0.000001) was sufficiently large for such subgroup analyses to be statistically informative. The absolute risk among control patients was similar in all 28 subgroups, so the absolute reduction of approximately 7 per 1000 in recurrent ischemic stroke does not differ substantially with respect to age, sex, level of consciousness, atrial fibrillation, CT findings, blood pressure, stroke subtype, or concomitant heparin use. There was no good evidence that the apparent decrease of approximately 4 per 1000 in death without further stroke was reversed in any subgroup or that in any subgroup the increase in hemorrhagic stroke was much larger than the overall average of approximately 2 per 1000. Finally, there was no significant heterogeneity between the reductions in the composite outcome of any further stroke or death (chi(2)(18)=16.5, NS). Among the 9000 patients (22%) randomized without a prior CT scan, aspirin appeared to be of net benefit with no unusual excess of hemorrhagic stroke; moreover, even among the 800 (2%) who had inadvertently been randomized after a hemorrhagic stroke, there was no evidence of net hazard (further stroke or death, 63 aspirin versus 67 control). CONCLUSIONS: Early aspirin is of benefit for a wide range of patients, and its prompt use should be routinely considered for all patients with suspected acute ischemic stroke, mainly to reduce the risk of early recurrence.     

A randomised control trial of physical activity in a perceived environment on self-esteem and mood in UK adolescents

This study assessed whether exercising whilst viewing natural or built scenes affected self-esteem (SE) and mood in adolescents. Twenty-five adolescents participated in three exercise tests on consecutive days. A graded exercise test established the work rate equivalent to 50% heart rate reserve for use in subsequent constant load tests (CLTs). Participants undertook two 15-min CLTs in random order viewing scenes of either natural or built environments. Participants completed Rosenberg’s SE scale and the adolescent profile of mood states questionnaire pre- and post-exercise. There was a significant main effect for SE (F(1) = 6.10; P < 0.05) and mood (F(6) = 5.29; P < 0.001) due to exercise, but no effect of viewing different environmental scenes (P > 0.05). Short bouts of moderate physical activity can have a positive impact on SE and mood in adolescents. Future research should incorporate field studies to examine the psychological effects of contact with real environments.