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1.
Stroke ; 52(10): 3243-3248, 2021 10.
Article in English | MEDLINE | ID: mdl-34233466

ABSTRACT

Background and Purpose: The PROGRESS trial (Perindopril Protection Against Recurrent Stroke Study) conducted in the early 1990s showed that blood pressure (BP) lowering therapy reduced the risks of recurrent stroke by about 50% after spontaneous intracerebral hemorrhage (ICH). However, the ICH subgroup was a minority, and trial cohorts are invariably selective. Therefore, it is unclear whether the impact of BP control on risk of recurrent stroke in ICH observed in PROGRESS would be as great in real-world practice. Methods: We compared BP control (mean BP during study follow-up) and risks of recurrent stroke after first-ever primary ICH in 2 colocated population-based studies before and after the PROGRESS trial (1995­2001) in Oxfordshire: Oxfordshire Community Stroke Project (OCSP; 1981­1986) and OXVASC (Oxford Vascular Study; 2002­2018). Results: Two hundred seventy-seven patients (753 patient-years of follow-up) with first-ever primary ICH were ascertained in OXVASC and OCSP. Baseline systolic BP was comparable between the 2 studies (mean/SD=183.8/36.5 in OXVASC versus 178.1/38.2 in OCSP, P=0.30) but among one hundred thirty-seven 90-day survivors, mean BP during follow-up was substantially lower in OXVASC versus OCSP (135.2/16.4 versus 157.3/17.8, P<0.0001). Risks of recurrent stroke (per 100 patient-years) decreased from 10.3 (95% CI, 4.7­19.5) in OCSP to 3.1 (1.8­4.8) in OXVASC (P=0.006), predominantly driven by a reduction at younger ages (5-year risk at age <75 years: 35.4% versus 6.9%, P=0.001; hazard ratio, 0.14 [0.04­0.54]). Conclusions: Risks of recurrent stroke after primary ICH have fallen significantly in Oxfordshire over the past 4 decades, coinciding with substantial improvements in BP control during follow-up.


Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure , Hypertension/drug therapy , Intracranial Hemorrhage, Hypertensive/complications , Stroke/prevention & control , Adult , Age Factors , Aged , Aged, 80 and over , England/epidemiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Perindopril/therapeutic use , Recurrence , Risk , Risk Factors , Survival Analysis
3.
Neurology ; 83(7): 582-9, 2014 Aug 12.
Article in English | MEDLINE | ID: mdl-24994841

ABSTRACT

OBJECTIVE: There have been few comparative studies of microsurgical excision vs conservative management of cerebral cavernous malformations (CCM) and none of them has reliably demonstrated a statistically and clinically significant difference. METHODS: We conducted a prospective, population-based study to identify and independently validate definite CCM diagnoses first made in 1999-2003 in Scottish adult residents. We used multiple sources of prospective follow-up to assess adults' dependence and to identify and independently validate outcome events. We used univariate and multivariable survival analyses to test the influence of CCM excision on outcome, adjusted for prognostic factors and baseline imbalances. RESULTS: Of 134 adults, 25 underwent CCM excision; these adults were younger (34 vs 43 years at diagnosis, p = 0.004) and more likely to present with symptomatic intracranial hemorrhage or focal neurologic deficit than adults managed conservatively (48% vs 26%; odds ratio 2.7, 95% confidence interval [CI] 1.1-6.5). During 5 years of follow-up, CCM excision was associated with a deterioration to an Oxford Handicap Scale score 2-6 sustained over at least 2 successive years (adjusted hazard ratio [HR] 2.2, 95% CI 1.1-4.3) and the occurrence of symptomatic intracranial hemorrhage or new focal neurologic deficit (adjusted HR 3.6, 95% CI 1.3-10.0). CONCLUSIONS: CCM excision was associated with worse outcomes over 5 years compared to conservative management. Long-term follow-up will determine whether this difference is sustained over patients' lifetimes. Meanwhile, a randomized controlled trial appears justified. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CCM excision worsens short-term disability scores and increases the risk of symptomatic intracranial hemorrhage and new focal neurologic deficits.


Subject(s)
Hemangioma, Cavernous, Central Nervous System/surgery , Hemangioma, Cavernous, Central Nervous System/therapy , Microsurgery/adverse effects , Adult , Age Factors , Disability Evaluation , Female , Follow-Up Studies , Hemangioma, Cavernous, Central Nervous System/complications , Humans , Intracranial Hemorrhages/complications , Intracranial Hemorrhages/surgery , Intracranial Hemorrhages/therapy , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Prospective Studies , Scotland , Survival Analysis , Time Factors , Treatment Outcome
4.
JAMA ; 311(16): 1661-9, 2014.
Article in English | MEDLINE | ID: mdl-24756516

ABSTRACT

IMPORTANCE: Whether conservative management is superior to interventional treatment for unruptured brain arteriovenous malformations (bAVMs) is uncertain because of the shortage of long-term comparative data. OBJECTIVE: To compare the long-term outcomes of conservative management vs intervention for unruptured bAVM. DESIGN, SETTING, AND POPULATION: Population-based inception cohort study of 204 residents of Scotland aged 16 years or older who were first diagnosed as having an unruptured bAVM during 1999-2003 or 2006-2010 and followed up prospectively for 12 years. EXPOSURES: Conservative management (no intervention) vs intervention (any endovascular embolization, neurosurgical excision, or stereotactic radiosurgery alone or in combination). MAIN OUTCOMES AND MEASURES: Cox regression analyses, with multivariable adjustment for prognostic factors and baseline imbalances if hazards were proportional, to compare rates of the primary outcome (death or sustained morbidity of any cause by Oxford Handicap Scale [OHS] score ≥2 for ≥2 successive years [0 = no symptoms and 6 = death]) and the secondary outcome (nonfatal symptomatic stroke or death due to bAVM, associated arterial aneurysm, or intervention). RESULTS: Of 204 patients, 103 underwent intervention. Those who underwent intervention were younger, more likely to have presented with seizure, and less likely to have large bAVMs than patients managed conservatively. During a median follow-up of 6.9 years (94% completeness), the rate of progression to the primary outcome was lower with conservative management during the first 4 years of follow-up (36 vs 39 events; 9.5 vs 9.8 per 100 person-years; adjusted hazard ratio, 0.59; 95% CI, 0.35-0.99), but rates were similar thereafter. The rate of the secondary outcome was lower with conservative management during 12 years of follow-up (14 vs 38 events; 1.6 vs 3.3 per 100 person-years; adjusted hazard ratio, 0.37; 95% CI, 0.19-0.72). CONCLUSIONS AND RELEVANCE: Among patients aged 16 years or older diagnosed as having unruptured bAVM, use of conservative management compared with intervention was associated with better clinical outcomes for up to 12 years. Longer follow-up is required to understand whether this association persists.


Subject(s)
Embolization, Therapeutic , Intracranial Arteriovenous Malformations/surgery , Radiosurgery , Watchful Waiting , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Neurosurgical Procedures/methods , Scotland , Survival Analysis , Treatment Outcome
6.
Neurology ; 79(6): 500-7, 2012 Aug 07.
Article in English | MEDLINE | ID: mdl-22764257

ABSTRACT

OBJECTIVES: To compare the risk of epileptic seizures in adults during conservative management or following invasive treatment for a brain arteriovenous malformation (AVM). METHODS: We used annual general practitioner follow-up, patient questionnaires, and medical records surveillance to quantify the 5-year risk of seizures and the chances of achieving 2-year seizure freedom for adults undergoing AVM treatment compared to adults managed conservatively in a prospective, population-based observational study of adults in Scotland, newly diagnosed with an AVM in 1999-2003. RESULTS: We identified 229 adults with a new diagnosis of an AVM, of whom two-thirds received AVM treatment (154/229; 67%) during 1,862 person-years of follow-up (median completeness of follow-up 97%). There was no significant difference in the proportions with a first or recurrent seizure over 5 years following AVM treatment, compared to the first 5 years following clinical presentation in conservatively managed adults, in analyses stratified by mode of presentation (intracerebral hemorrhage, 35% vs 26%, p = 0.5; seizure, 67% vs 72%, p = 0.6; incidental, 21% vs 10%, p = 0.4). For patients with epilepsy, the chances of achieving 2-year seizure freedom during 5-year follow-up were similar following AVM treatment (n = 39; 52%, 95% confidence interval [CI] 36% to 68%) or conservative management (n = 21; 57%, 95% CI 35% to 79%; p = 0.7). CONCLUSIONS: In this observational study, there was no difference in the 5-year risk of seizures with AVM treatment or conservative management, irrespective of whether the AVM had presented with hemorrhage or epileptic seizures.


Subject(s)
Arteriovenous Fistula/therapy , Intracranial Arteriovenous Malformations/therapy , Seizures/epidemiology , Seizures/etiology , Adult , Arteriovenous Fistula/complications , Embolization, Therapeutic/adverse effects , Female , Humans , Intracranial Arteriovenous Malformations/complications , Male , Middle Aged , Neurosurgical Procedures/adverse effects , Radiosurgery/adverse effects , Risk Factors
8.
Lancet Neurol ; 11(3): 217-24, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22297119

ABSTRACT

BACKGROUND: Cerebral cavernous malformations (CCMs) are prone to bleeding but the risk of intracranial haemorrhage and focal neurological deficits, and the factors that might predict their occurrence, are unclear. We aimed to quantify these risks and investigate whether they are affected by sex and CCM location. METHODS: We undertook a population-based study using multiple overlapping sources of case ascertainment (including a Scotland-wide collaboration of neurologists, neurosurgeons, stroke physicians, radiologists, and pathologists, as well as searches of registers of hospital discharges and death certificates) to identify definite CCM diagnoses first made in Scottish residents between 1999 and 2003, which study neuroradiologists independently validated. We used multiple sources of prospective follow-up both to identify outcome events (which were assessed by use of brain imaging, by investigators masked to potential predictive factors) and to assess adults' dependence. The primary outcome was a composite of intracranial haemorrhage or focal neurological deficits (not including epileptic seizure) that were definitely or possibly related to CCM. FINDINGS: 139 adults had at least one definite CCM and 134 were alive at initial presentation. During 1177 person-years of follow-up (completeness 97%), for intracranial haemorrhage alone the 5-year risk of a first haemorrhage was lower than the risk of recurrent haemorrhage (2·4%, 95% CI 0·0-5·7 vs 29·5%, 4·1-55·0; p<0·0001). For the primary outcome, the 5-year risk of a first event was lower than the risk of recurrence (9·3%, 3·1-15·4 vs 42·4%, 26·8-58·0; p<0·0001). The annual risk of recurrence of the primary outcome declined from 19·8% (95% CI 6·1-33·4) in year 1 to 5·0% (0·0-14·8) in year 5 and was higher for women than men (p=0·01) but not for adults with brainstem CCMs versus CCMs in other locations (p=0·17). INTERPRETATION: The risk of recurrent intracranial haemorrhage or focal neurological deficit from a CCM is greater than the risk of a first event, is greater for women than for men, and declines over 5 years. This information can be used in clinical practice, but further work is needed to quantify risks precisely in the long term and to understand why women are at greater risk of recurrence than men. FUNDING: UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.


Subject(s)
Central Nervous System Vascular Malformations/complications , Intracranial Hemorrhages/etiology , Adult , Central Nervous System Vascular Malformations/epidemiology , Female , Follow-Up Studies , Humans , Intracranial Hemorrhages/epidemiology , Male , Middle Aged , Prospective Studies , Recurrence , Risk , Scotland/epidemiology , Sex Factors
10.
Br J Neurosurg ; 25(1): 109-10, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21323405

ABSTRACT

We present a case of a 48-year-old man who was initially thought to have had a brainstem stroke and was clinically 'locked-in'. Upon investigation, a petrous apex dural atriovenous fistula was identified causing profound brainstem venous hypertension. Surgical clipping lead to complete neurological recovery.


Subject(s)
Brain Stem Infarctions/diagnosis , Brain Stem/blood supply , Central Nervous System Vascular Malformations/diagnosis , Quadriplegia/diagnosis , Brain Stem/surgery , Central Nervous System Vascular Malformations/complications , Central Nervous System Vascular Malformations/surgery , Cerebral Angiography , Diagnosis, Differential , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Quadriplegia/surgery , Treatment Outcome
11.
Lancet ; 377(9759): 31-41, 2011 Jan 01.
Article in English | MEDLINE | ID: mdl-21144578

ABSTRACT

BACKGROUND: Treatment with daily aspirin for 5 years or longer reduces subsequent risk of colorectal cancer. Several lines of evidence suggest that aspirin might also reduce risk of other cancers, particularly of the gastrointestinal tract, but proof in man is lacking. We studied deaths due to cancer during and after randomised trials of daily aspirin versus control done originally for prevention of vascular events. METHODS: We used individual patient data from all randomised trials of daily aspirin versus no aspirin with mean duration of scheduled trial treatment of 4 years or longer to determine the effect of allocation to aspirin on risk of cancer death in relation to scheduled duration of trial treatment for gastrointestinal and non-gastrointestinal cancers. In three large UK trials, long-term post-trial follow-up of individual patients was obtained from death certificates and cancer registries. RESULTS: In eight eligible trials (25 570 patients, 674 cancer deaths), allocation to aspirin reduced death due to cancer (pooled odds ratio [OR] 0·79, 95% CI 0·68-0·92, p=0·003). On analysis of individual patient data, which were available from seven trials (23 535 patients, 657 cancer deaths), benefit was apparent only after 5 years' follow-up (all cancers, hazard ratio [HR] 0·66, 0·50-0·87; gastrointestinal cancers, 0·46, 0·27-0·77; both p=0·003). The 20-year risk of cancer death (1634 deaths in 12 659 patients in three trials) remained lower in the aspirin groups than in the control groups (all solid cancers, HR 0·80, 0·72-0·88, p<0·0001; gastrointestinal cancers, 0·65, 0·54-0·78, p<0·0001), and benefit increased (interaction p=0·01) with scheduled duration of trial treatment (≥7·5 years: all solid cancers, 0·69, 0·54-0·88, p=0·003; gastrointestinal cancers, 0·41, 0·26-0·66, p=0·0001). The latent period before an effect on deaths was about 5 years for oesophageal, pancreatic, brain, and lung cancer, but was more delayed for stomach, colorectal, and prostate cancer. For lung and oesophageal cancer, benefit was confined to adenocarcinomas, and the overall effect on 20-year risk of cancer death was greatest for adenocarcinomas (HR 0·66, 0·56-0·77, p<0·0001). Benefit was unrelated to aspirin dose (75 mg upwards), sex, or smoking, but increased with age-the absolute reduction in 20-year risk of cancer death reaching 7·08% (2·42-11·74) at age 65 years and older. INTERPRETATION: Daily aspirin reduced deaths due to several common cancers during and after the trials. Benefit increased with duration of treatment and was consistent across the different study populations. These findings have implications for guidelines on use of aspirin and for understanding of carcinogenesis and its susceptibility to drug intervention. FUNDING: None.


Subject(s)
Aspirin/administration & dosage , Cyclooxygenase 2 Inhibitors/administration & dosage , Neoplasms/prevention & control , Drug Administration Schedule , Humans , Randomized Controlled Trials as Topic , Survival Analysis
12.
Lancet ; 376(9754): 1741-50, 2010 Nov 20.
Article in English | MEDLINE | ID: mdl-20970847

ABSTRACT

BACKGROUND: High-dose aspirin (≥500 mg daily) reduces long-term incidence of colorectal cancer, but adverse effects might limit its potential for long-term prevention. The long-term effectiveness of lower doses (75-300 mg daily) is unknown. We assessed the effects of aspirin on incidence and mortality due to colorectal cancer in relation to dose, duration of treatment, and site of tumour. METHODS: We followed up four randomised trials of aspirin versus control in primary (Thrombosis Prevention Trial, British Doctors Aspirin Trial) and secondary (Swedish Aspirin Low Dose Trial, UK-TIA Aspirin Trial) prevention of vascular events and one trial of different doses of aspirin (Dutch TIA Aspirin Trial) and established the effect of aspirin on risk of colorectal cancer over 20 years during and after the trials by analysis of pooled individual patient data. RESULTS: In the four trials of aspirin versus control (mean duration of scheduled treatment 6·0 years), 391 (2·8%) of 14 033 patients had colorectal cancer during a median follow-up of 18·3 years. Allocation to aspirin reduced the 20-year risk of colon cancer (incidence hazard ratio [HR] 0·76, 0·60-0·96, p=0·02; mortality HR 0·65, 0·48-0·88, p=0·005), but not rectal cancer (0·90, 0·63-1·30, p=0·58; 0·80, 0·50-1·28, p=0·35). Where subsite data were available, aspirin reduced risk of cancer of the proximal colon (0·45, 0·28-0·74, p=0·001; 0·34, 0·18-0·66, p=0·001), but not the distal colon (1·10, 0·73-1·64, p=0·66; 1·21, 0·66-2·24, p=0·54; for incidence difference p=0·04, for mortality difference p=0·01). However, benefit increased with scheduled duration of treatment, such that allocation to aspirin of 5 years or longer reduced risk of proximal colon cancer by about 70% (0·35, 0·20-0·63; 0·24, 0·11-0·52; both p<0·0001) and also reduced risk of rectal cancer (0·58, 0·36-0·92, p=0·02; 0·47, 0·26-0·87, p=0·01). There was no increase in benefit at doses of aspirin greater than 75 mg daily, with an absolute reduction of 1·76% (0·61-2·91; p=0·001) in 20-year risk of any fatal colorectal cancer after 5-years scheduled treatment with 75-300 mg daily. However, risk of fatal colorectal cancer was higher on 30 mg versus 283 mg daily on long-term follow-up of the Dutch TIA trial (odds ratio 2·02, 0·70-6·05, p=0·15). INTERPRETATION: Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer. Benefit was greatest for cancers of the proximal colon, which are not otherwise prevented effectively by screening with sigmoidoscopy or colonoscopy. FUNDING: None.


Subject(s)
Aspirin/administration & dosage , Colorectal Neoplasms/prevention & control , Aspirin/adverse effects , Cardiovascular Diseases/prevention & control , Colonic Neoplasms/prevention & control , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/mortality , Follow-Up Studies , Humans , Incidence , Randomized Controlled Trials as Topic , Thrombosis/prevention & control
13.
Stroke ; 40(6): 1980-5, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19390075

ABSTRACT

BACKGROUND AND PURPOSE: Reported risks of hemorrhage from intracranial developmental venous anomalies (DVAs) vary, so we investigated this in a systematic review and population-based study. METHODS: We systematically reviewed the literature (Ovid Medline and Embase to November 7, 2007) and selected studies of >or=20 participants with >or=1 DVA(s) that described their clinical presentation and/or their clinical course over a specified follow-up period. We also identified every adult first diagnosed with a DVA in Scotland from 1999 to 2003 and followed them in a prospective, population-based study. RESULTS: Of 2068 articles detected by the literature search, 15 met our inclusion criteria and described clinical presentation, 8 of which also described the clinical course of DVAs. In the 15 studies of 714 people first presenting with a DVA, 61% were incidental findings, the mode of presentation was unclear in 23%, 6% presented with nonhemorrhagic focal neurological deficit, 6% had caused symptomatic hemorrhage, 4% were associated with epileptic seizure, and <1% were associated with infarction. In studies of the clinical course of 422 people with a DVA, the hemorrhage rate after first presentation ranged from 0% to 1.28% per year. In the population-based study of 93 adults with DVAs, 98% were incidental, 1% presented with symptomatic hemorrhage, and 1% presented with an infarct, but there were no symptomatic hemorrhages or infarcts in 492 person-years of follow-up (0% per person-year; 95% CI, 0% to 0.7%). CONCLUSIONS: Intracranial DVAs have a benign presentation and clinical course.


Subject(s)
Intracranial Arteriovenous Malformations/therapy , Adult , Aged , Aged, 80 and over , Cerebral Hemorrhage/etiology , Cerebral Hemorrhage/therapy , Cerebral Infarction/etiology , Cerebral Infarction/therapy , Cognition Disorders/etiology , Cognition Disorders/therapy , Female , Follow-Up Studies , Humans , Intracranial Arteriovenous Malformations/epidemiology , Magnetic Resonance Imaging , Male , Middle Aged , Population , Prospective Studies , Scotland/epidemiology , Seizures/etiology , Seizures/therapy , Treatment Outcome , Young Adult
14.
Stroke ; 40(2): 355-62, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19095967

ABSTRACT

BACKGROUND AND PURPOSE: The burden of stroke is increasing in Sub-Saharan Africa (SSA) as the population undergoes epidemiological and demographic transition. Little is known about the nature (risk factors, stroke type and subtype, and causes) of stroke in SSA and whether it differs from stroke in high-income populations. We aimed to compare the nature of stroke between black and white populations in South Africa. METHODS: We used overlapping sources to ascertain consecutive first-ever-in-a-lifetime stroke patients admitted to Johannesburg Hospital over 23 months. We assessed each patient's demographic details, risk factors, CT confirmed pathological stroke type, ischemic stroke subtype and stroke severity, and compared the nature of stroke between black and white stroke patients. RESULTS: 524 patients with presumed stroke were referred. Of these, 432 were first-ever strokes; 308 patients were black and 76 white. Black patients were significantly younger (mean age 51) than white patients (61). Stroke severity was similar (median NIH stroke score 10; 95% CI 8 to 11). More black than white patients had cerebral hemorrhage (27% versus 15%), lacunar stroke (28% versus 22%) and total anterior circulation infarcts (28% versus 22%). Large vessel atherosclerosis (none detected) and ischemic heart disease were very uncommon (1%) as a cause of stroke in black patients. Hypertension (70% versus 68%) and diabetes (14 versus 15%) were as common in black and white stroke patients, but mean cholesterol levels were lower (4.6 mmol/L; 95% CI 4.3 to 4.9 versus 5.3 mmol/L; 4.8 to 5.7) and cigarette smoking less frequent in black patients (23 versus 54%). CONCLUSIONS: Although this was a hospital-based study, the difference in the nature of stroke between black and white stroke patients likely reflects the profile of stroke risk factors. There is an opportunity to prevent an otherwise inevitable increase in atherosclerotic stroke (and IHD) by targeting dietary and smoking habits in the black South African population.


Subject(s)
Stroke/epidemiology , Aged , Black People , Blood Pressure/physiology , Brain Ischemia/complications , Cerebral Hemorrhage/complications , Ethnicity , Female , Humans , Hypertension/epidemiology , Intracranial Embolism/complications , Male , Middle Aged , Neurologic Examination , Registries , Risk Factors , South Africa/epidemiology , Stroke/etiology , Stroke/pathology , Surveys and Questionnaires , Tomography, X-Ray Computed , White People
15.
Cerebrovasc Dis ; 26(5): 517-24, 2008.
Article in English | MEDLINE | ID: mdl-18810239

ABSTRACT

BACKGROUND: Several studies have shown serum urate to be an independent risk factor for vascular disease, but others have not, although a stronger association in women than in men has been a consistent finding. Studies of stroke patients have shown possible associations between urate level and stroke severity, but there have been no large cohort studies of the effect of urate on the long-term risk of future vascular events in patients with a transient ischaemic attack (TIA) or stroke. We studied this relationship in 2 independent cohorts. METHODS: Individual data on 15,483 patient-years of follow-up from the UK-TIA trial (13,182 patient-years) and the Oxford TIA study (2,301 patient-years) were analyzed. Hazard ratios (per unit increase of baseline urate in mg/dl) for the risks of stroke and acute coronary events (ACE) were obtained from Cox models stratified by study, with and without adjustment for potential confounders. Potential interactions between urate and baseline characteristics were also assessed. RESULTS: Linear associations between urate and risk of ACE were found in both studies: pooled age- and sex-adjusted hazard ratio = 1.17, 95% CI 1.06-1.30, per unit increase of urate (p = 0.003). Sex, body mass index and previous myocardial infarction or angina were effect modifiers, but only the effect of sex remained after adjustment for other risk factors (p = 0.002), with a 5th:1st quintile hazard ratio of 4.23 (1.97-9.07, p < 0.0001) in women and 1.09 (0.70-1.71, p = 0.69) in men. These findings were consistent across the 2 studies. No associations were found between urate level and either risk or severity of stroke. CONCLUSIONS: High urate levels were independent predictors of long-term risk of ACE in women who had a TIA or stroke, but not in men, in 2 independent studies. Urate levels could be useful in identifying women at high risk of coronary events in routine practice.


Subject(s)
Coronary Disease/etiology , Ischemic Attack, Transient/blood , Stroke/blood , Uric Acid/blood , Acute Disease , Aged , Aspirin/therapeutic use , Biomarkers/blood , Coronary Disease/blood , Coronary Disease/prevention & control , Female , Humans , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/drug therapy , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Predictive Value of Tests , Proportional Hazards Models , Prospective Studies , Risk Assessment , Risk Factors , Sex Factors , Stroke/complications , Stroke/drug therapy , Time Factors , United Kingdom , Up-Regulation
16.
Lancet Neurol ; 7(3): 223-30, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18243054

ABSTRACT

BACKGROUND: The decision about whether to treat an unruptured brain arteriovenous malformation (AVM) depends on a comparison of the estimated lifetime risk of intracranial haemorrhage with the risks of interventional treatment. We aimed to test whether outcome differs between adults who had interventional AVM treatment and those who did not. METHODS: All adults in Scotland who were first diagnosed with an unruptured AVM during 1999-2003 (n=114) entered our prospective, population-based study. We compared the baseline characteristics and 3-year outcome of adults who received interventional treatment for their AVM (n=63) with those who did not (n=51). FINDINGS: At presentation, adults who were treated were younger (mean 40 vs 55 years of age, 95% CI for difference 9-20; p<0.0001), more likely to present with a seizure (odds ratio 2.4, 95% CI 1.1-5.0), and had fewer comorbidities (median 3 vs 4, p=0.03) than those who were not treated. Despite these baseline imbalances, treated and untreated groups did not differ in progression to Oxford Handicap Scale (OHS) scores of 2-6 (log-rank p=0.12) or 3-6 (log-rank p=0.98) in survival analyses. In a multivariable Cox proportional hazards analysis, the risk of poor outcome (OHS 2-6) was greater in patients who had interventional treatment than in those who did not (hazard ratio 2.5, 95% CI 1.1-6.0) and was greater in patients with a larger AVM nidus (hazard ratio 1.3, 95% CI 1.1-1.7). The treated and untreated groups did not differ in time to an OHS score of 2 or more that was sustained until the end of the third year of follow-up, or in the spectrum of dependence as measured by the OHS at 1, 2, and 3 years of follow-up. INTERPRETATION: Greater AVM size and interventional treatment were associated with worse short-term functional outcome for unruptured AVMs, but the longer-term effects of intervention are unclear.


Subject(s)
Intracranial Arteriovenous Malformations/epidemiology , Intracranial Arteriovenous Malformations/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Community Health Planning , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Scotland/epidemiology , Severity of Illness Index , Survival Analysis , Time Factors
17.
Cerebrovasc Dis ; 24(4): 391-9, 2007.
Article in English | MEDLINE | ID: mdl-17804910

ABSTRACT

Here I have reviewed how good luck, bad luck and barriers determined my research directions in stroke over the last 30 or so years. Good luck should be exploited, and very often barriers can be not just overcome but put to good use as well. It is crucial for the young researcher to find mentors as good as I have had, and to move around to gain a broad experience, and for the experienced researchers to bring on the younger generation as I have tried to do.


Subject(s)
Biomedical Research/history , Ischemic Attack, Transient/history , Stroke/history , Aspirin/therapeutic use , Endarterectomy, Carotid , Europe , Fibrinolytic Agents/therapeutic use , History, 20th Century , History, 21st Century , Humans , Ischemic Attack, Transient/drug therapy , Ischemic Attack, Transient/epidemiology , Ischemic Attack, Transient/surgery , Registries , Stroke/drug therapy , Stroke/epidemiology , Stroke/surgery , Treatment Outcome
19.
Lancet Neurol ; 6(3): 269-78, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17303533

ABSTRACT

Sub-Saharan Africa is undergoing epidemiological transition. Stroke and other vascular diseases increasingly contribute to the burden of disease. There are no systematic reviews of stroke mortality, prevalence, incidence, and case fatality. We combined a thorough search and critical assessment of the published research. Stroke mortality is as high, perhaps higher, than in high-income regions and increases with age in sub-Saharan Africa as in high-income countries, but the absolute number of stroke deaths remains low. There are no adequate community-based stroke incidence studies. Hospital-based incidence is lower than in high-income regions, but higher in young people, possibly due to hospital admission bias. There are no community-based data on case fatality, but hospital-based case fatality is higher than elsewhere. The prevalence of stroke is lower than in high-income regions, but disabling stroke is as prevalent. As the region develops economically, the incidence of stroke and other vascular diseases will increase unless interventions are implemented. Only community-based incidence studies will accurately reveal the burden of stroke.


Subject(s)
Stroke/epidemiology , Africa South of the Sahara/epidemiology , Autopsy , Black People , Female , Hospital Mortality , Humans , Male , Population Surveillance , Risk Factors , Stroke/mortality , Vital Statistics
20.
Stroke ; 38(1): 62-8, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17138946

ABSTRACT

BACKGROUND AND PURPOSE: The burden of stroke in sub-Saharan Africa is already high and likely to increase, but few patients with stroke have access to brain imaging. Distinguishing pathologic stroke types is relevant both for clinical management and epidemiologic studies. We assessed the accuracy of two stroke scores in distinguishing stroke types in a population known to have a high prevalence of intracranial hemorrhage but low prevalence of atherosclerosis and compared them with the clinicians' assessment of stroke type with computed tomography brain scanning as the "gold standard." METHODS: We assessed the stroke scores and the clinicians' blind assessment of pathologic stroke type in consecutive black patients with stroke included in the Johannesburg Hospital Stroke Register over 23 months. We calculated the accuracy of the scores and clinicians compared with computed tomography brain scan (sensitivity, specificity, positive predictive value, likelihood ratio, kappa statistic). RESULTS: Two hundred twenty-two patients were scanned and assessed within 15 days. Sixty-two (28%) had cerebral hemorrhage and nine (4%) subarachnoid hemorrhage. Neither the Siriraj (sub-Saharan Africa) nor Guy's Hospital score was accurate or offered much advantage over clinician assessment (sensitivity 0.60 and 0.34, specificity 0.88 and 0.95 for intracranial hemorrhage in the Siriraj Stroke Score and Guy's Hospital Stroke Score, respectively; sensitivity 0.70 and 0.71, specificity 0.84 and 0.74, respectively, for ischemic stroke). Although the scores were more accurate when we used new cutoff points, they then failed to diagnose over 80% of stroke types. CONCLUSIONS: The Siriraj Stroke Score and Guy's Hospital Stroke Score are not sufficiently accurate for use in either epidemiologic studies or to guide clinical management in sub-Saharan Africa at present.


Subject(s)
Brain Ischemia/diagnosis , Cerebral Hemorrhage/diagnosis , Diagnostic Errors/statistics & numerical data , Stroke/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Brain Ischemia/epidemiology , Brain Ischemia/physiopathology , Cerebral Hemorrhage/epidemiology , Cerebral Hemorrhage/physiopathology , Diagnosis, Differential , Diagnostic Errors/trends , Diagnostic Tests, Routine/standards , Diagnostic Tests, Routine/statistics & numerical data , Female , Humans , Male , Middle Aged , Neurologic Examination/standards , Neurologic Examination/statistics & numerical data , Observer Variation , Predictive Value of Tests , Quality Assurance, Health Care , South Africa/epidemiology , Stroke/epidemiology , Stroke/physiopathology , Subarachnoid Hemorrhage/diagnosis , Subarachnoid Hemorrhage/epidemiology , Subarachnoid Hemorrhage/physiopathology , Tomography, X-Ray Computed/standards , Tomography, X-Ray Computed/statistics & numerical data
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