The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results.

From 1979-85, 2435 patients with a transient ischaemic attack or minor ischaemic stroke were randomly allocated to receive long term "blind" treatment with aspirin 600 mg twice daily (n = 815), aspirin 300 mg once daily (n = 806) or placebo (n = 814). No patient was lost to follow up. The "intention to treat" comparison included all the serious vascular events and deaths which occurred before the end of the follow up period on 30 September 1986. There was no difference in efficacy between the 300 mg and 1200 mg daily doses of aspirin, but the lower dose was undoubtedly less gastrotoxic. Also, there was no definite difference in the response of males and females to aspirin. The odds of suffering a major stroke, myocardial infarction or vascular death were 15% less in the combined aspirin groups compared with the placebo group (95% confidence interval 29% reduction to 3% increase in odds) which is compatible with the continuing overview of all the similar trials of antiplatelet drugs where the relative reduction in odds was 25%. There was no statistically significant reduction in the likelihood of either disabling major stroke and vascular death or vascular death occurring.     

Current oral antiplatelet agents to prevent atherothrombosis

Aspirin inhibits platelet activation by irreversibly inhibiting platelet cyclooxygenase and thromboxane production, and reduces the odds of serious vascular events (stroke, myocardial infarction or vascular death) by about one quarter in a range of patients with symptomatic atherosclerosis at high risk of a subsequent event. The adenosine diphosphate (ADP) receptor antagonists clopidogrel and ticlopidine are significantly more effective than aspirin in high-risk vascular patients, further reducing the odds of serious vascular events by about 10% (95% CI 2-19%) over the benefit provided by aspirin. The ADP receptor antagonists are also associated with a significant 30% reduction in the odds of gastrointestinal haemorrhage (odds ratio 0.71, 95% CI 0.59-0.86). Ticlopidine increases the odds of skin rash and of diarrhoea by more than twofold compared with aspirin, whereas clopidogrel is associated with a one-third increase in the odds of rash and of diarrhoea. Only ticlopidine increases the odds of neutropenia compared with aspirin. There is no clear evidence as yet for the benefit of dipyridamole or an oral GP IIb/IIIa receptor antagonist as single antiplatelet agents in atherothrombotic patients. Amongst high vascular risk patients, the combination of low-dose aspirin and high-dose dipyridamole is associated with about a 10% (95% CI 0-20%) reduction in the odds of a serious vascular event. Most of this reduction is due to a 23% reduction in non-fatal stroke. The size of this estimate continues to be investigated in an ongoing study of patients with transient ischaemic attack and stroke. The combined use of aspirin and ticlopidine is markedly superior to heparin, warfarin and aspirin for reducing thrombotic complications after coronary artery stenting. Clopidogrel plus aspirin has been shown to be safer than aspirin and ticlopidine in coronary stenting, and is now under long-term evaluation in unstable angina, and other conditions in which patients are at high risk of atherothrombotic events.     

Antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke: a critical review

For patients with ischemic stroke or transient ischemic attack caused by atherothromboembolism, immediate and long-term aspirin reduces the relative risk of recurrent stroke, MI, and death attributable to vascular causes. Oral anticoagulation is not more effective than aspirin. Long-term clopidogrel reduces the relative risk of stroke, MI, or vascular death by about 9% (0.3% to 16.5%) compared with aspirin. Any long-term benefits of clopidogrel combined with aspirin, compared with aspirin or clopidogrel alone, appear to be offset by increased major bleeding. The combination of aspirin and extended-release dipyridamole reduces the relative odds of stroke, MI, or vascular death by about 18% (odds ratio 0.82, 0.74 to 0.91) compared with aspirin alone without causing more bleeding. Cilostazole reduces the risk of stroke, MI, or vascular death by 39% compared to placebo. A large clinical trial comparing clopidogrel with the combination of aspirin and dipyridamole, in >20 000 patients with recent (<120 days) atherothrombotic ischemic stroke, is expected to report in 2008. Emerging antiplatelet therapies presently being evaluated for secondary prevention of atherothromboembolism include other P(2)Y(12) ADP receptor antagonists (prasugrel, cangrelor, AZD 6140), thromboxane receptor antagonists (eg, S18886 - terutroban), and thrombin receptor (PAR-1) antagonists (eg, SCH530348).     

Antiplatelet therapy is effective in the prevention of stroke or death in women: subgroup analysis of the European stroke prevention study (ESPS)

Previous stroke prevention studies have suggested that the efficacy of antiplatelet therapy may be less in women than in men. This however, could be due to the small number of women in these trials and the low incidence of cases among female subjects. The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of dipyridamole 75 mg t.i.d and acetylsalicylic acid 330 mg t.i.d. to placebo in the secondary prevention of stroke or death after one or more recent attacks of TIA (transient ischemic attack), RIND (reversible ischemic neurological deficit) or stroke of atherothrombotic origin. From the 2500 patients recruited, 1307 patients were from a single center, Kuopio, East Finland. Forty-five percent of the patients were women. The number of end-point events (stroke or death from any cause) in women was one-third lower than that in men. End-point reduction in the treatment group was about 50% in women and about 40% in men, significantly lower than in the placebo group in both sexes. Thus, in the relatively randomly selected patient population from one Finnish center, a combination of dipyridamole and acetylsalicylic acid is as effective in women as in men in the prevention of stroke or death. It is unclear, however, whether this beneficial effect in both sexes is due to aspirin only or to the combination therapy of aspirin and dipyridamole.     

Thrombolysis in acute ischemic stroke: does it work?

BACKGROUND: This article is presented to provoke further discussion regarding the use of thrombolytic drugs to treat acute ischemic stroke. SUMMARY OF REVIEW: Overview analysis of the six randomized trials of thrombolysis in acute ischemic stroke available in the world literature shows a 20% increase in the odds of death and a 30% reduction in the odds of death or deterioration (both with wide confidence intervals, neither result significant) after thrombolytic treatment for acute ischemic stroke. Exclusion of the two trials conducted without the benefit of computed tomographic scanning shows a 37% reduction in the odds of death (95% confidence interval, 74% reduction to 40% excess) and a significant reduction of 56% in the odds of death or deterioration after thrombolytic treatment (95% confidence interval, 20-76% reduction; 2p = 0.007). Analysis of all published studies (randomized and nonrandomized) shows that there does not appear to be an excess risk of hemorrhagic transformation of the cerebral infarct or of severe edema formation. CONCLUSIONS: We believe the present evidence is sufficiently encouraging to warrant proper testing of thrombolysis in sufficiently large and well-designed randomized clinical trials to influence clinical practice.     

Adding aspirin to clopidogrel after TIA and ischemic stroke: benefits do not match risks

Antiplatelet therapy is effective for reducing the risk of recurrent stroke and other serious vascular events in patients with recent TIA and ischemic stroke. Effective antiplatelet agents include aspirin, ticlopidine, clopidogrel, dipyridamole, and the combination of aspirin and dipyridamole. The combination of aspirin and clopidogrel is more effective than aspirin in patients with acute coronary syndrome but is more hazardous than clopidogrel alone in patients with recent TIA and ischemic stroke. Further trials are needed to determine whether the combination of aspirin and clopidogrel may have a role immediately after TIA and ischemic stroke in patients with symptomatic large artery atherothromboembolism and continued for approximately 3 months before switching to less hazardous antiplatelet regimens.     

Association between atrial septal aneurysm and patent foramen ovale in young patients with recent stroke and normal carotid arteries

BACKGROUND: Atrial septal aneurysm (ASA) has been considered a potential source of cardiogenic embolism for many years. The ASA Multicenter Italian (ASA-MI) Study evaluated the prevalence and characteristics of ASA in patients with stroke and normal carotid arteries compared with control patients without stroke. The purpose of the present study was to evaluate the frequency of ASA and the association with patent foramen ovale (PFO) in the subgroup of younger patients (aged less than 55 years) included in the ASA-MI Study. METHODS: The ASA-MI Study included 606 patients, enrolled between November 1990 and December 1996: 245 patients with a previous cerebral embolic attack and normal carotid study and a control group of 316 patients. They all underwent transthoracic and transesophageal echocardiography. The subgroup of younger patients aged less than 55 years included 90 patients (61 men and 29 women of mean age 49 +/- 5 years) (group AY). This group was evaluated and compared with an age- and sex-matched control population (61 men; of mean age 48 +/- 6 years) (group BY). RESULTS: The prevalence of ASA was 48.8% (95% confidence interval 40-61) in group AY and 22.2% in the group BY (95% confidence interval 18-33) (chi(2) = 5.968; p = 0.01). Morphological features were similar in the 2 groups of patients. ASA involved the entire septum in 52% of patients of group AY, and in 47.2% of group BY. The prevalence of PFO was 58.8% (95% confidence interval 43-62) in group AY and 28.8% in group BY (95% confidence interval 17-35) (chi(2) = 5.811; p = 0.01). A strong association was found between ASA and PFO. Of the 90 younger patients with stroke, 39 of 44 (88.6%) with ASA also had PFO, compared with 14 of 46 (30.4%) without ASA (chi(2) = 7.370; p = 0.007). CONCLUSION: We found that ASA and PFO were independent predictive factors for stroke in younger patients with stroke and normal carotid arteries and that the association between ASA and PFO bore an increased odds risk.     

Increased platelet aggregates in patients with transient ischemic attacks.

In order to evaluate the pathogenetic importance of platelet aggregates in cerebrovascular disease, a platelet count ratio method was used to study 66 patients with transient ischemic attacks (TIAs). Thirty normal subjects and 22 patients without thromboembolic disorders were also included as controls. The mean platelet aggregate ratio of the TIA group was 0.75 +/- 0.03 SEM which was significantly lower than that of normal subjects (0.90 +/- 0.02) or patients controls (0.88 +/- 0.01) (P less than 0.01). Seventeen patients with TIA were then treated with aspirin (1,200 mg) and dipyridamole (200 mg) daily. The platelet aggregate ratios were normalized in 13 patients. Of four patients who did not respond to this regimen, one did respond to sulfinpyrazone. When sulfinpyrazone was discontinued, recurrence of symptoms was preceded by an increase in platelet aggregates. These findings suggest that platelet aggregates may play an important role in the pathogenesis of cerebrovascular insufficiency. The determination of platelet aggregates appears useful in selecting patients for antiplatelet therapy.     

抗血小板药物治疗腔隙性梗死效果的Meta分析

目的评价抗血小板药物对腔隙性梗死患者二级预防的治疗效果。方法以stroke,lacunar infarction,platelet aggregation inhibitors,antiplatelet,randomized controlled trial等英文词汇计算机检索1980年1月1日-2016年11月20日美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、Cochrane在线图书馆等数据库收录的关于腔隙性梗死患者抗血小板治疗的随机对照临床试验,采用Jadad量表、Cochrane系统评价手册和Rev Man 5.3统计软件进行文献质量评价和Meta分析,R软件Gemtc程序包和JAGS软件进行网状Meta分析。结果共获得4068篇英文文献,经剔除重复和不符合纳入标准者,最终纳入12项质量较高(Jadad评分≥4分)的临床试验共24 969例腔隙性梗死患者。Meta分析显示:与安慰剂相比,抗血小板药物单抗治疗可以显著降低缺血性卒中复发率(RR=0.480,95%CI:0.300~0.780;P=0.003)和所有脑卒中复发率(RR=0.780,95%CI:0.630~0.970;P=0.030);而抗血小板药物单抗与双抗治疗效果差异无统计学意义(缺血性卒中复发率:RR=0.900,95%CI:0.760~1.050,P=0.170;所有脑卒中复发率:RR=0.910,95%CI:0.820~1.010,P=0.070)。网状Meta分析(包括阿司匹林、安慰剂、西洛他唑和噻氯匹定4种干预措施)显示:仅西洛他唑治疗后所有脑卒中复发率低于阿司匹林(OR=0.341,95%Cr I:0.011~0.673)和安慰剂(OR=0.615,95%Cr I:0.191~1.042)。结论抗血小板药物单抗治疗可以显著降低腔隙性梗死患者缺血性卒中和所有脑卒中复发风险,且与双抗治疗效果无明显差异;西洛他唑较阿司匹林能够更显著降低腔隙性梗死患者所有脑卒中复发风险。     

Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease? A systematic review of the evidence from randomized trials

BACKGROUND AND PURPOSE: Aspirin is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. We aimed to establish how the thienopyridines (ticlopidine and clopidogrel) compare with aspirin in terms of effectiveness and safety. METHODS: We did a systematic review of all unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin for patients at high risk of vascular disease. The primary outcome was vascular events (stroke, myocardial infarction, or vascular death). Adverse outcomes were intracranial and extracranial hemorrhage, upper and lower gastrointestinal disturbances, neutropenia, thrombocytopenia, and skin rash. RESULTS: In 4 trials among 22 656 patients (including 9840 presenting with a transient ischemic attack/ischemic stroke), the thienopyridines reduced the odds of a vascular event by 9% (odds ratio 0.91, 95% CI 0.84 to 0. 98; 2P=0.01), preventing 11 (95% CI 2 to 19) events per 1000 patients treated for approximately 2 years. The thienopyridines produced significantly less gastrointestinal hemorrhage and upper gastrointestinal upset (indigestion/nausea/vomiting) than did aspirin. Both thienopyridines increased the odds of skin rash and of diarrhea (ticlopidine by approximately 2-fold and clopidogrel by approximately one third). Only ticlopidine increased the odds of neutropenia. CONCLUSIONS: The thienopyridines appear modestly more effective than aspirin in preventing serious vascular events in high-risk patients. Clopidogrel appears to be safer than ticlopidine and as safe as aspirin, making it an appropriate, but more expensive, alternative antiplatelet drug for patients unable to tolerate aspirin. However, there is insufficient information to determine which particular types of patients would benefit most, and which least, from clopidogrel instead of aspirin.     

Comparison of Antiplatelet Therapies for Prevention of Patent Foramen Ovale-Associated Stroke

AimsThe REDUCE study demonstrated a reduction in the risk of recurrent stroke with patent foramen ovale closure and antiplatelet therapy compared to antiplatelet therapy alone. The clinicians were allowed to choose among aspirin, clopidogrel, or aspirin/dipyridamole with the expectation that all antiplatelet therapies would have similar efficacy in this population. We tested that presumption by comparing recurrent stroke rates among antiplatelet agents within the control arm of the trial.MethodsWe evaluated patients in REDUCE study who were randomized to the medical arm. The primary endpoint for this analysis was freedom from clinical ischemic stroke through at least 2 years of follow-up, to a maximum of 5 years. In the primary analysis, antiplatelet treatment was defined as the agent during the week prior to a recurrent stroke or last known contact.ResultsOf 223 patients in the medical treatment arm, the initial agent was aspirin 52%, clopidogrel 30%, and aspirin/dipyridamole 12%. Patients treated with aspirin were similar to those treated with alternatives, but were more likely to be enrolled in the United States. The last reported agent was aspirin alone in 55%, clopidogrel alone in 31%, aspirin/dipyridamole in 7%, and other/nothing/missing in 7%. Recurrent stroke rates were similar for all 3 antiplatelet regimens in unadjusted and adjusted analyses, with no overall difference among agents (P= .17).ConclusionsAmong patients with patent foramen ovale-associated stroke who were managed medically, there were no differences among antiplatelet agents in the risk of recurrent stroke, though confidence intervals were wide.     

Low molecular weight heparin versus aspirin for acute ischemic stroke: A systematic review

Aspirin is the standard treatment for acute ischemic stroke, although heparins are widely prescribed. We performed a systematic review of randomized controlled trials to compare the safety and efficacy of low molecular weight heparins (LMWH) with aspirin in acute ischemic stroke. Two completed randomized controlled trials involving 1,933 patients were identified; 1 trial only included patients with presumed cardioembolic stroke. As compared with aspirin, treatment with heparin was associated with a significant reduction in symptomatic venous thromboembolism (odds ratio [OR] - 0.29, 95% confidence interval [CI] - 0.12-0.66) and an increase in major extracranial hemorrhage (OR - 2.57, 95% CI - 1.01-6.52). Nonsignificant increases in end-of-treatment case fatality (OR - 1.35, 95% CI - 0.87-2.08) and symptomatic intracranial haemorrhage (OR - 1.82, 95% CI - 0.68-4.87) were seen; symptomatic intracranial haemorrhage was significantly raised (OR - 4.26, 95% CI - 1.04-17.4) with heparin in patients treated within 24 hours of stroke onset. Stroke recurrence (OR - 1.24, 95% CI - 0.79-1.94) and deterioration (OR - 1.13, 95% CI - 0.85-1.50) during treatment and end-of-trial death (OR - 1.00, 95% CI - 0.77-1.30) or dependency and case fatality (OR - 1.03, 95% CI - 0.85-1.25) did not differ between the 2 treatments. No benefit of LMWH over aspirin was seen in patients with presumed cardioembolic stroke. Low molecular weight heparin should not replace aspirin in the routine management of patients with ischemic stroke, including those with presumed cardioembolic stroke. Copyright © 2002 by National Stroke Association     

A pilot study of resistance to aspirin in stroke patients

Aspirin resistance has been shown to be a significant risk factor for recurrent cardiovascular ischaemic events. However, there are a lack of data correlating aspirin resistance and risk of cerebrovascular ischaemic events. This pilot study aimed to determine the prevalence of aspirin resistance in an Australian stroke population and to correlate aspirin resistance with an increased risk of ischaemic stroke. Fifty patients treated with aspirin for 2 years were tested for aspirin resistance using the Ultegra Rapid Platelet Function Assay (Accumetrics, San Diego, CA, USA) on admission to Royal Melbourne Hospital for ischaemic stroke. The 2-year history of ischaemic stroke and transient ischaemic attack (TIA) were assessed. Prevalence of aspirin resistance among our patients was 30%. Univariate analysis suggested a non-significant trend towards increased rate of previous ischaemic stroke or TIA and aspirin resistance (odds ratio, OR=3.88; 95% confidence interval 0.54-29.87; p=0.18). This study shows that aspirin resistance is prevalent within the Australian ischaemic stroke population.     

Telomere length predicts poststroke mortality, dementia, and cognitive decline

OBJECTIVE: Long-term cognitive development is variable among stroke survivors, with a high proportion developing dementia. Early identification of those at risk is highly desirable to target interventions for secondary prevention. Telomere length in peripheral blood mononuclear cells was tested as prognostic risk marker. METHODS: A cohort of 195 nondemented stroke survivors was followed prospectively from 3 months after stroke for 2 years for cognitive assessment and diagnosis of dementia and for 5 years for survival. Telomere lengths in peripheral blood mononuclear cells were measured at 3 months after stroke by in-gel hybridization. Hazard ratios for survival in relation to telomere length and odds ratios for dementia were estimated using multivariate techniques, and changes in Mini-Mental State Examination scores between baseline and 2 years were related to telomere length using multivariate linear regression. RESULTS: Longer telomeres at baseline were associated with reduced risk for death (hazard ratio for linear trend per 1,000 bp = 0.52; 95% confidence interval, 0.28-0.98; p = 0.04, adjusted for age) and dementia (odds ratio for linear trend per 1,000 bp = 0.19; 95% confidence interval, 0.07-0.54; p = 0.002) and less reduction in Mini-Mental State Examination score (p = 0.04, adjusted for baseline score). INTERPRETATION: Telomere length is a prognostic marker for poststroke cognitive decline, dementia, and death.     

Aspirin for the primary prevention of stroke and other major vascular events: meta-analysis and hypotheses

BACKGROUND: Aspirin therapy reduces stroke by about 25% for persons with atherosclerotic vascular disease, but the effect in those without clinically apparent vascular disease is distinctly different. OBJECTIVE: To define the effect of aspirin use on stroke and other major vascular events when given for primary prevention to persons without clinically recognized vascular disease. DATA SOURCES AND EXTRACTION: Systematic review of randomized clinical trials and large prospective observational cohort studies examining the relation between aspirin use and stroke in persons at low intrinsic risk. Studies were identified by a computerized search of the English-language literature. DATA SYNTHESIS: Five randomized trials of primary prevention included 52 251 participants randomized to aspirin doses ranging from 75 to 650 mg/d; the mean overall stroke rate was 0.3% per year during an average follow-up of 4.6 years. Meta-analysis revealed no significant effect on stroke (relative risk = 1.08; 95% confidence interval, 0.95-1.24) contrasting with a decrease in myocardial infarction (relative risk = 0.74; 95% confidence interval, 0.68-0.82). The lack of reduction of stroke by aspirin for primary prevention was incompatible with its protective effect against stroke in patients with manifest vascular disease (P = .001). Intracranial hemorrhage was increased by the regular use of aspirin (relative risk = 1.35; P = .03), similarly for both primary and secondary prevention. In 4 large observational studies, self-selected use of aspirin was consistently associated with higher rates of stroke. CONCLUSIONS: The effect of aspirin therapy on stroke differs between individuals based on the presence or absence of overt vascular disease, in contrast with the consistent reduction in myocardial infarction by aspirin therapy observed in all populations. We hypothesize that the effect of aspirin therapy on stroke for persons with major risk factors for vascular disease may be intermediate between a substantial decrease for those with manifest vascular disease and a possible small increase for healthy persons due to accentuated intracranial hemorrhage. When aspirin is given for primary prevention of vascular events, available data support using 75 to 81 mg/d.     

Extended-release epidural morphine (DepoDur): review and safety analysis

Extended-release epidural morphine (EREM) provides effective postoperative analgesia for 48 h following injection. It is administered as a single bolus into the lumbar epidural space, and is indicated for lower abdominal and lower extremity surgery associated with moderate-to-severe pain. While its efficacy has been well documented in randomized controlled trials, the safety and clinically appropriate dosing are less well defined. A meta-analysis approach was used to assess the adverse effects of EREM (n = 801) in comparison with intravenous opioids and standard epidural morphine. EREM 15 mg or greater was associated with a trend towards a higher incidence of hypoventilation (odds ratio: 0.48; 95% confidence interval [CI]: 0.21-1.09; p = 0.081; number-needed-to-treat [NNT] = 14) compared with placebo. The incidence of pruritus was significantly higher for all EREM doses compared with both placebo (p = 0.004) and standard epidural morphine (p = 0.03). Vomiting was also increased with EREM 15 mg or greater compared with placebo (odds ratio: 0.40; 95% CI: 0.18-0.89; p = 0.02; NNT = 5). A multimodal analgesic regime is recommended to permit the use of lower EREM doses, thus reducing the risk for adverse effects including respiratory depression. Prophylactic time-contingent antiemetics are also recommended when EREM is used.     

Cilostazol combined with aspirin prevents early neurological deterioration in patients with acute ischemic stroke: a pilot study

Recent randomized trials have shown that cilostazol is superior to aspirin for secondary stroke prevention. We hypothesized that combining cilostazol with aspirin is more effective than aspirin alone in patients with acute ischemic stroke. This randomized study compared the effects of oral aspirin alone to aspirin plus cilostazol in patients with non-cardioembolic ischemic stroke within 48 h of stroke onset. NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were checked before and after 14 days and 6 months of drug administration. The primary and secondary endpoints were neurological deterioration or stroke recurrence (NIHSS score ≥ 1) within 14 days and 6 months, respectively. For statistical analysis, on-treatment analysis was conducted. Seventy-six patients were enrolled in the study. The primary endpoint was significantly higher in the aspirin group than in the aspirin plus cilostazol group (28% vs. 6%, relative risk (RR): 0.21, 95% confidence intervals (CI): 0.05-0.87, p=0.013). Among the patients who did not reach these endpoints, the mean improvement in the NIHSS score at day 14 tended to be better (-1.8 ± 1.2 vs. -1.2 ± 1.0, p=0.078) and the frequency of the favorable functional status of mRS 0-1 at month 6 was significantly higher (RR: 1.48, 95% CI: 1.07-2.06, p=0.0048) in the aspirin plus cilostazol group than in the aspirin group. Patients treated with aspirin plus cilostazol during the acute phase of stroke had less neurological deterioration and more favorable functional status than those treated with aspirin alone.     

Mutation screening and association analysis of the parkin gene in Parkinson's disease patients from South-West China

Various deletions and point mutations in the Parkin gene have been strongly associated with Parkinson's disease (PD) and parkinsonism, especially when the onset occurs at a young age. In this study, we screened 25 "early-onset" (<49 years at onset) and 91 later-onset PD patients from a Han Chinese population from South-West China for deletions and mutations in the Parkin gene. We found no deletions or point mutations in exons 1-12 of the Parkin gene using direct sequence analysis and only detected the common Ser167Asn polymorphism. We analysed Ser167Asn in 116 patients with sporadic PD and 124 controls, matched for age and gender. There were significant differences in allele and genotype frequency between PD patients, with the 167Asn allele more common in cases than controls (46.6 vs. 35.1%; chi(2) = 6.54, p = 0.011, odds ratio = 1.61, 95% confidence interval, CI, 1.10-2.37), as was the 167Asn genotype (17.3 vs. 11.3%; p = 0.04). The frequency of the 167Ser genotype was significantly lower in PD patients than in controls when compared with that of the other two genotypes combined (chi(2) = 7.84, p = 0.005, odds ratio = 0.46, 95% CI 0.25 - 0.82). No significant differences in the frequencies of the allele and genotypes were found between patients classified into two groups according to symptoms at onset (chi(2) = 0.191, p = 0.66, odds ratio = 1.12, 95% CI 0.65-1.95; chi(2) = 0.24, p = 0.887) or age of onset (p = 0.787). In summary, homozygous deletion mutations and point mutations in exons 1-12 of the Parkin gene were not detected in this Han Chinese population, although we cannot exclude compound heterozygous deletions. In addition, our study suggests that the variant 167Asn increases the risk of developing PD.     

Aspirin and stroke prevention

According to meta-analyses aspirin provides a relative reduction in the rate of major vascular events of 19% in patients with arterial disease in general, whereas for patients with ischaemic cerebrovascular disease this reduction is only 13%. The discrepancy may well result from pathophysiological differences and not from a play of chance. There is no proven difference in efficacy according to dose. The evidence for this equivalence is most compelling in the range between 75 and 1300 mg daily, but still fairly convincing for doses between 30 and 50 mg. In contrast, side effects are clearly more frequent as the dose is higher. Other antiplatelet agents (sulfinpyrazone, ticlopidine, clopidogrel, dipyridamole, orally administered IIb/IIIa inhibitors) have no clear advantages over aspirin and in some cases definite disadvantages; the combination of aspirin and dipyridamole may be more efficacious than aspirin alone, but the evidence hinges on a single trial. If recurrent TIAs occur under treatment with aspirin, the rational response is not to change to a different antiplatelet agent, but to review the diagnosis and consider causes other than artery-to-artery embolism. Platelet aggregation can probably still occur despite complete acetylation of platelets, via pathways other than COX-1 inhibition, but in vitro aggregation tests are an unreliable measure.     

Selective Mutism and Social Anxiety Disorder: All in the Family?

OBJECTIVE: To examine the history of lifetime psychiatric disorders in the parents of children with selective mutism (SM) compared to parents of children in a control group. METHOD: Seventy parent dyads (n = 140) of children with lifetime SM and 31 parent dyads (n = 62) of children without SM were interviewed with the Structured Clinical Interview for DSM-IV (IV and II) anxiety disorders, mood disorders, avoidant personality disorder, and schizoid personality disorder modules via telephone. Interviewers were blind to proband status. The NEO Personality Inventory was also administered. RESULTS: Lifetime generalized social phobia was present in 37.0% of SM parents compared to 14.1% of control parents (chi2 = 10.98; p < .001; odds ratio 3.6, 95% confidence interval 1.6-7.9). Avoidant personality disorder was present in 17.5% of the SM parents compared to 4.7% of control parents (chi2 = 6.18; p < .05; odds ratio 4.3, 95% confidence interval 1.3-14.9). The proportion of parents with other psychiatric disorders was not different between groups. SM parents had higher neuroticism and lower openness scores on the NEO Personality Inventory than control parents. CONCLUSIONS: These results support earlier uncontrolled findings of a familial relationship between generalized social phobia and SM.