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Background and PurposeThere have been few communitybased studies of long-term prognosis after acute stroke. This study aims to provide precise estimates of the absolute and relative risks of stroke recurrence in an unselected cohort of patients with a first-ever stroke.Methods Six hundred seventy-five patients were registered in a community-based stroke register (the Oxfordshire Community Stroke Project) and prospectively followed for up to 6.5 years. Their relative risk of recurrent stroke was calculated using age-and sex-specific incidence rates for first stroke in Oxfordshire.Results One hundred eighty recurrent episodes of stroke were identified, of which 135 were first recurrences. Given survival, the actuarial risk of suffering a recurrence was 30% (95% confidence interval, 20% to 39%) by 5 years, about nine

The age and sex specific incidence rates for cerebral infarction, primary intracerebral haemorrhage and subarachnoid haemorrhage in a population of approximately 105,000 are presented. Over four years 675 patients with a first-ever stroke were registered with the Oxfordshire Community Stroke Project. The pathological diagnosis was confirmed by computerised tomography (CT) scan, necropsy or lumbar puncture (cases of subarachnoid haemorrhage only) in 78% ofcases and a further 17% were diagnosed according to the Guy's Hospital Stroke Diagnostic Score. The proportion of all first-ever strokes by pathological type was: cerebral infarction 81% (95% confidence interval 78-84), primary intracerebral haemorrhage 10% (8-12), subarachnoid haemorrhage 5% (3-7) and uncertain type 5% (3-7). These proportions are similar to other communitybased studies. The overall 30 day case fatality rate was 19% (16)(17)(18)(19)(20)(21)(22), that for cerebral infarction being 10% (7-13), primary intracerebral haemorrhage 50% (38-62) and subarachnoid haemorrhage 46% (29-63). One year post stroke 23% (19)(20)(21)(22)(23)(24)(25)(26)(27) with cerebral infarction were dead and 65% (60-70) of survivors were functionally independent. The figures for primary intracerebral haemorrhage were 62% (43-81) dead and 68% (50-86) of survivors functionally independent and for subarachnoid haemorrhage were 48% (24-72) dead and 76% (56-96) of survivors functionally independent. There are important differences between these rates and those from other sources possibly due to more complete case ascertainment in our study. Nevertheless, the generally more optimistic early prognosis in our study, particularly for cases of cerebral infarction, has important implications for the planning of clinical trials and for the expected impact that any treatment might have on the general population.

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In a prospective, community-based study of 675 consecutive patients with a first-ever stroke, of whom over 90% had computed tomography (CT) The age-adjusted relative risk of death for patients who had been functionally dependent pre-stroke was not significantly greater (1-8, 95% confidence interval 0 to 4 3). There was a significant trend for CFR to increase with age (Chi square for trend = 4 0, p < 0 05). This relationship was found in those patients who had been functionally independent prestroke (Chi square for trend = 7 9, p < 0 005) but not in those who had been dependent pre-stroke (Chi square for trend = 0.5, NS). The pattern of increasing CFR with increasing age amongst those who had been independent prestroke was seen particularly in patients with cerebral infarction (Chi square for trend = 8-6, p < 0-005). The age-adjusted relative risk of death for patients with cerebral infarction who had been functionally dependent pre-stroke was 2-2 (95% confidence interval 1-2 to 4-1). Fifty three percent of all deaths within 30 days of stroke were due to the direct neurological sequelae of the stroke. Patients with primary intracerebral or subarachnoid haemorrhages were significantly more likely to die in this way than those with cerebral infarction (relative risk 4-1; 95% confidence interval 3-4-4 9) and 56% of such deaths occurred within 72 hours of onset. In patients with cerebral infarction, 51% of deaths were due to complications of immobility (for example, pneumonia, pulmonary embolism) and these were more likely to occur after the first week. These findings have implications for clinical practice and the planning of clinical trials.There is some evidence that the case fatality rate (CFR) in the first few weeks after a stroke has declined in recent years.' It is not clear whether this reduction has been caused by changes in management but it has been noted that the decline was most evident between five and 21 days post stroke.2 This suggests that it is deaths from the complications of immobility rather than those due to the direct neurological damage that have been reduced. Detailed information concerning the timing and cause of death in unbiased groups of patients where the pathological type of stroke is known accurately is scarce. New therapies such as fibrinolysis may have a significant effect on survival and therefore death should obviously be included as a major endpoint in future stroke treatment trials. We have already reported the value of accurate epidemiological data in planning a trial of secondary stroke prevention3 and now wish to report data which might be used to plan trials of treatment to prevent death after an acute stroke. We have analysed the frequency, causes and timing of early death in patients who were registered with a large, prospective, community-based study of first-ever stroke.4 Over 90% of patients had a CT scan or necropsy and this allowed accurate correlations to be made with the pathological type of stroke. MethodsThe detailed methodology of the Oxfordshire Communi...

Sixty-six patients with primary intracerebral haemorrhage were identified in a prospective, community-based register of 675 consecutive patients with first-ever in a lifetime stroke. No patient was lost to follow-up (up to 6 years). The 30-day case fatality rate was 52%. For patients surviving 30 days the average annual mortality rate was 8% per year for the next 5 years. The main cause of early death (≤30 days) was the neurological sequelae of the original stroke (73%, whilst late deaths (> 30 days) were due to either complications of immobility (45%) or vascular disease (55%). Twenty one percent of all patients were independent at 6 months (52% of survivors). The main predictors for death within 30 days were age, reduced conscious level, abnormal proprioception and rupture of blood into the ventricles or subarachnoid space. In addition, the size of the initial haemorrhage was predictive for death at any stage of follow-up, and the degree of limb weakness was predictive of death or dependency at 6 months. Nine patients had 14 recurrent strokes (including 4 definite haemorrhages and 4 definite cerebral infarctions). Five of the recurrences were fatal. The actuarial risk of recurrence in 30-day survivors was 7% per year (14 per 100 patient-years) and the actuarial risk of death or recurrence in 30-day survivors was 11% per year. Seven patients (11%) had at least one seizure during follow-up, the risk of first seizure being 8 per 100 patient-years overall. Patients with primary intracerebral haemorrhage have a high early case fatality but survivors have a similar outcome to patients with cerebral infarction.

The impact of COVID-19 varies markedly, not only between individual patients but also between different populations. We hypothesised that differences in human leukocyte antigen (HLA) genes might influence this variation. Using next generation sequencing, we analysed the class I and class II classical HLA genes of 147 individuals of European descent experiencing variable clinical outcomes following COVID-19 infection. Forty-nine of these patients were admitted to hospital with severe respiratory disease. They had no significant pre-existing comorbidities. We compared the results to those obtained from a group of 69 asymptomatic hospital workers who evidence of COVID exposure based on blood antibody testing. Allele frequencies in both the severe and asymptomatic groups were compared to local and national healthy controls with adjustments made for age and sex. With the inclusion of hospital staff who had reported localised symptoms only (limited to loss of smell/taste, n = 13) or systemic symptoms not requiring hospital treatment (n = 16), we carried out ordinal logistic regression modelling to determine the relative influence of age, BMI, sex and the presence of specific HLA genes on symptomatology. We found a significant difference in the allele frequency of HLA-DRB1*04:01 in the severe patient compared to the asymptomatic staff group (5.1% vs. 16.7%, P = .003 after adjustment for age and sex). There was a significantly lower frequency of the haplotype DQA1*01:01-DQB1*05:01-DRB1*01:01 in the asymptomatic group compared to the background population (P = .007). Ordinal logistic regression modelling confirmed the significant influence of DRB1*04:01 on the clinical severity of COVID-19 observed in the cohorts. These alleles are found in greater frequencies in the North Western European population. This regional study provides evidence that HLA genotype influences clinical outcome in COVID-19 infection. Validation studies must take account of the complex genetic architecture of the immune system across different geographies and ethnicities.