Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 patients with coronary artery disease

To determine whether pre-hospitalization use of aspirin is associated with all-cause mortality in coronavirus disease 2019 (COVID-19) patients with coronary artery disease (CAD). We recruited 183 adult patients with CAD diagnosed with COVID-19, including 52 taking low-dose aspirin (mean [SD] age, 69.7 [1.1] years; 59.6% men) and 131 without using aspirin (mean [SD] age, 71.8 [0.9] years; 51.9% men), who were admitted in the Tongji hospital in Wuhan, China from January 10, 2020 to March 30, 2020. There was no difference on in-hospital mortality between aspirin group and non-aspirin group (21.2% vs. 22.1%, P = .885). Similarly, for critically severe COVID-19 patients, the mortality in aspirin group was close to that in non-aspirin group (44% vs. 45.9%, P = .872). Moreover, the percentage of patients with CAD taking low-dose aspirin did not differ between those survivors and non-survivors (28.7% vs. 27.5%, P = .885). Meanwhile, the usage of aspirin was not correlated with all-cause mortality in multivariate analysis (OR = 0.944, 95% CI: 0.411-2.172, P = .893). Collectively, our study suggested that the pre-hospitalization use of low-dose aspirin was not associated with the clinical outcome of patients with CAD hospitalized with COVID-19 infections.     

United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results

From 1979 to 1985, 2435 patients thought to have had a transient ischaemic attack or minor ischaemic stroke were allocated at random to receive long term blind treatment with either aspirin 600 mg twice daily (n=815), aspirin 300 mg once daily (806), or placebo (814). Treatment continued with about 85% compliance until September 1986 (mean four years). The odds of suffering one or more of four categories of event—namely, non-fatal myocardial infarction, non-fatal major stroke, vascular death, or non-vascular death—were 18% less in the two groups allocated to receive aspirin than in the group allocated to receive placebo (2p=0·01). The more relevant but less frequent composite event of disabling stroke or vascular death was reduced by only 7%; this reduction was not significantly different from zero, but nor was it significantly different from a 25% reduction. There was no definite difference between responses to the 300 mg and 1200 mg daily doses, except that the lower dose was significantly less gastrotoxic.     

A randomised controlled trial of triple antiplatelet therapy (aspirin, clopidogrel and dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility

Background

Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention. Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment in the secondary prevention of ischaemic stroke.

Methodology/Principal Findings

A randomised, parallel group, observer-blinded phase II trial compared the combination of aspirin, clopidogrel and dipyridamole with aspirin alone. Adult patients with ischaemic stroke or transient ischaemic attack (TIA) within 5 years were included. The primary outcome was tolerability to treatment assessed as the number of patients completing randomised treatment. Recruitment was halted prematurely after publication of the ESPRIT trial (which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone). 17 patients were enrolled: male 12 (71%), mean age 62 (SD 13) years, lacunar stroke syndrome 12 (71%), median stroke/TIA onset to randomisation 8 months. Treatment was discontinued in 4 of 9 (44%) patients receiving triple therapy vs. none of 8 taking aspirin (p = 0.08). One recurrent stroke occurred in a patient in the triple group who was noncompliant of all antiplatelet medications. The number of patients with adverse events and bleeding complications, and their severity, were significantly greater in the triple therapy group (p<0.01).

Conclusions/Significance

Long term triple antiplatelet therapy was asociated with a significant increase in adverse events and bleeding rates, and their severity, and a trend to increased discontinuations. However, the patients had a low risk of recurrence and future trials should focus on short term therapy in high risk patients characterised by a very recent event or failure of dual antiplatelet therapy.

Trial Registration

Controlled-Trials.com ISRCTN83673558     

Controversies and future perspectives of antiplatelet therapy in secondary stroke prevention

Antiplatelet agents are a cornerstone in the treatment of acute arterial thrombotic events and in the prevention of thrombus formation. However, existing antiplatelet agents (mainly aspirin, the combination of aspirin and dipyridamole and clopidogrel) reduce the risk of vascular events only by about one quarter compared with placebo. As a consequence, more efficacious antiplatelet therapies with a reduced bleeding risk are needed. We give an overview of several new antiplatelet agents that are currently investigated in secondary stroke prevention: adenosine 5′-diphosphonate receptor antagonists, cilostazol, sarpogrelate, terutroban and SCH 530348. There are unique features in secondary stroke prevention that have to be taken into account: ischaemic stroke is a heterogeneous disease caused by multiple aetiologies and the blood–brain barrier is disturbed after stroke which may result in a higher intracerebral bleeding risk. Several small randomized trials indicated that the combination of aspirin and clopidogrel might be superior to antiplatelet monotherapy in the acute and early post-ischaemic phase. There is an ongoing debate about antiplatelet resistance. Decreasing response to aspirin is correlated independently with an increased risk of cardiovascular events. However, there is still no evidence from randomized trials linking aspirin resistance and recurrent ischaemic events. Similarly, randomized trials have not demonstrated a clinical significantly decreased antiplatelet effect by the concomitant use of clopidogrel and proton pump inhibitors. Nevertheless, a routine use of this drug combination is not recommended.     

Pretreatment with statins improves early outcome in patients with first-ever ischaemic stroke: a pleiotropic effect of statins or a beneficial effect of hypercholesterolemia?

Background

Data from different studies suggest a favourable association between pretreatment with statins or hypercholesterolemia and outcome after ischaemic stroke. We examined whether there were differences in in-hospital mortality according to the presence or absence of statin therapy in a large population of first-ever ischaemic stroke patients and assessed the influence of statins upon early death and spontaneous neurological recovery.

Methods

In 2,082 consecutive patients with first-ever ischaemic stroke collected from a prospective hospital-based stroke registry during a period of 19 years (1986-2004), statin use or hypercholesterolemia before stroke was documented in 381 patients. On the other hand, favourable outcome defined as grades 0-2 in the modified Rankin scale was recorded in 382 patients.

Results

Early outcome was better in the presence of statin therapy or hypercholesterolemia (cholesterol levels were not measured) with significant differences between the groups with and without pretreatment with statins in in-hospital mortality (6% vs 13.3%, P = 0.001) and symptom-free (22% vs 17.5%, P = 0.025) and severe functional limitation (6.6% vs 11.5%, P = 0.002) at hospital discharge, as well as lower rates of infectious respiratory complications during hospitalization. In the logistic regression model, statin therapy was the only variable inversely associated with in-hospital death (odds ratio 0.57) and directly associated with favourable outcome (odds ratio 1.32).

Conclusions

Use of statins or hypercholesterolemia before first-ever ischaemic stroke was associated with better early outcome with a reduced mortality during hospitalization and neurological disability at hospital discharge. However, statin therapy may increase the risk of intracerebral haemorrhage, particularly in the setting of thrombolysis.

     

Cyclooxygenase-mediated prostaglandin F2alpha is decreased in an elderly population treated with low-dose aspirin

Low-dose aspirin (acetylsalicylic acid) is used as prophylaxis against cardiovascular diseases. The effect of aspirin on inflammation and oxidative stress, processes known to be involved in cardiovascular diseases, are not fully known. The cyclooxygenase(COX)-mediated inflammatory indicator prostaglandin F2alpha (PGF2alpha) (15-keto-dihydro-PGF2alpha), cytokine-mediated inflammatory indicators (interleukin-6, high-sensitivity C-reactive protein, serum amyloid A protein), and oxidative stress indicators (8-iso-PGF2alpha, tocopherols) were quantified in men with daily 75 mg of aspirin (n=175) and control men (n=464), all of age 77, in a cross-sectional study. Men treated with aspirin had decreased levels of urinary 15-keto-dihydro-PGF2alpha than controls (P<0.01), independent of possible cardiovascular risk factors. Aspirin-treated men had increased levels of alpha-tocopherol than controls (P<0.05). This is the first study to indicate that low-dose aspirin treatment is associated with decreased levels of PGF2alpha. This observation suggests a possible COX-mediated anti-inflammatory effect of low-dose aspirin, which should be further confirmed by intervention studies.     

Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients

ObjectiveTo determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events.DesignCollaborative meta-analyses (systematic overviews).ResultsOverall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000.ConclusionsAspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.

What is already known on this topic

Antiplatelet therapy is effective for short term treatment of patients with suspected acute myocardial infarction and unstable anginaLong term treatment is beneficial for patients who have had a myocardial infarction, stroke, or transient ischaemic attackDaily aspirin doses of 75-325 mg are effective

What this study adds

Antiplatelet therapy protects against vascular events among patients with stable angina, intermittent claudication, and (if oral anticoagulants are unsuitable) atrial fibrillationAntiplatelet therapy can be started promptly during acute presumed ischaemic stroke and continued long termDaily aspirin doses of 75-150 mg seem to be as effective as higher doses for long term treatments (and clopidrogel is an appropriate alternative for patients with a contraindication to aspirin)Short term addition of a glycoprotein IIb/IIIa antagonist to aspirin prevents vascular events in patients having percutaneous coronary intervention and those with unstable angina but causes increased bleeding     

Low-dose aspirin and incidence of lung carcinoma in patients with chronic obstructive pulmonary disease in Hong Kong: A cohort study

BackgroundEvidence suggests that chronic obstructive pulmonary disease (COPD) is associated with a higher risk of lung carcinoma. Using a territory-wide clinical electronic medical records system, we investigated the association between low-dose aspirin use (≤160 mg) among patients with COPD and incidence of lung carcinoma and the corresponding risk of bleeding.Methods and findingsThis is a retrospective cohort study conducted utilizing Clinical Data Analysis Reporting System (CDARS), a territory-wide database developed by the Hong Kong Hospital Authority. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between aspirin nonusers (35,049 patients) with new aspirin users (7,679 patients) among all eligible COPD patients from 2005 to 2018 attending any public hospitals. The median age of the cohort was 75.7 years (SD = 11.5), and 80.3% were male. Competing risk regression with Cox proportional hazards model were performed to estimate the subdistribution hazard ratio (SHR) of lung carcinoma with low-dose aspirin and the associated bleeding events. Of all eligible patients, 1,779 (4.2%, 1,526 and 253 among nonusers and users) were diagnosed with lung carcinoma over a median follow-up period of 2.6 years (interquartile range [IQR]: 1.4 to 4.8). Aspirin use was associated with a 25% lower risk of lung carcinoma (SHR = 0.75, 95% confidence interval [CI] 0.65 to 0.87, p = <0.001) and 26% decrease in lung carcinoma–related mortality (SHR = 0.74, 95% CI 0.64 to 0.86, p = <0.001). Subgroup analysis revealed that aspirin was beneficial for patients aged above or below 75 years, but was also beneficial among populations who were male, nondiabetic, and nonhypertensive. Aspirin use was not associated with an increased risk of upper gastrointestinal bleeding (UGIB) (SHR = 1.19, 95% CI 0.94 to 1.53, p = 0.16), but was associated with an increased risk of hemoptysis (SHR = 1.96, 95% CI 1.73 to 2.23, p < 0.001). The main limitations of the study were (i) that one group of patients may be more likely to seek additional medical attention, although this was partially mitigated by the use of propensity score analysis; and (ii) the observational nature of the study renders it unable to establish causality between aspirin use and lung carcinoma incidence.ConclusionsIn this study, we observed that low-dose aspirin use was associated with a lower risk of lung carcinoma and lung carcinoma–related mortality among COPD patients. While aspirin was not associated with an increased risk of UGIB, the risk of hemoptysis was elevated.

In a cohort study, Si-Yeung Yu and colleagues investigate the association between low-dose aspirin and incidence of lung carcinoma in patients with chronic obstructive pulmonary disease in Hong Kong.     

Antiplatelet therapy in secondary stroke prevention – state of the art

Our objective is to provide the reader with an overview as well as an update on current antiplatelet therapy for secondary stroke prevention. Relevant journals were hand-searched by the authors to compile a broad but by far not comprehensive summary of innovative and clinically relevant studies. Aspirin, clopidogrel and the combination of dipyridamole plus aspirin are the cornerstone therapy in secondary prevention after non-cardio-embolic stroke or transient ischaemic attack. A head-to-head comparison showed no difference in the prevention of recurrent stroke between dipyridamole plus aspirin and clopidogrel. More potent antiplatelet drugs or the combination of aspirin and clopidogrel prevent more ischaemic events, but also lead to more bleeding complications. For secondary stroke prevention in patients with atrial fibrillation, oral anticoagulation is more effective than aspirin or the combination of aspirin and clopidogrel.     

Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study

BackgroundPreclinical evidence from breast cancer cell lines and animal models suggest that aspirin could have anti-cancer properties. In a large breast cancer patient cohort, we investigated whether post-diagnostic low-dose aspirin use was associated with a reduction in the risk of breast cancer-specific mortality.MethodsWe identified 15,140 newly diagnosed breast cancer patients within the Scottish Cancer Registry. Linkages to the Scottish Prescribing Information System provided data on dispensed medications and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% CIs for breast cancer-specific and all-cause mortality by post-diagnostic low-dose aspirin use. HRs were adjusted for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of statins. Secondary analysis investigated the association between pre-diagnostic low-dose aspirin use and breast cancer-specific and all-cause mortality.ResultsPost-diagnostic users of low-dose aspirin appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.44, 95% CI 1.26, 1.65) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.92, 95% CI 0.75, 1.14). Findings were similar in analysis by increasing duration of use and in analysis of pre-diagnostic low-dose aspirin use.ConclusionIn this large nationwide study of breast cancer patients, we found little evidence of an association between post-diagnostic low-dose aspirin use and cancer-specific mortality.     

Immediate and one-year outcome of patients presenting with Acute Coronary Syndrome complicated by stroke: Findings from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2)

ABSTRACT: BACKGROUND: Stroke is a potential complication of acute coronary syndrome (ACS). The aim of this study was to identify the prevalence, risk factors predisposing to stroke, in-hospital and 1-year mortality among patients presenting with ACS in the Middle East. METHODS: For a period of 9 months in 2008 to 2009, 7,930 consecutive ACS patients were enrolled from 65 hospitals in 6 Middle East countries. RESULTS: The prevalence of in-hospital stroke following ACS was 0.70%. Most cases were ST segment elevation MI-related (STEMI) and ischemic stroke in nature. Patients with in-hospital stroke were 5 years older than patients without stroke and were more likely to have hypertension (66% vs. 47.6%, P = 0.001). There were no differences between the two groups in regards to gender, other cardiovascular risk factors, or prior cardiovascular disease. Patients with stroke were more likely to present with atypical symptoms, advanced Killip class and less likely to be treated with evidence-based therapies. Independent predictors of stroke were hypertension, advanced killip class, ACS type --STEMI and cardiogenic shock. Stroke was associated with increased risk of in-hospital (39.3% vs. 4.3%) and one-year mortality (52% vs. 12.3%). CONCLUSION: There is low incidence of in-hospital stroke in Middle-Eastern patients presenting with ACS but with very high in-hospital and one-year mortality rates. Stroke patients were less likely to be appropriately treated with evidence-based therapy. Future work should be focused on reducing the risk and improving the outcome of this devastating complication.     

Trends in the Use of Guideline-Recommended Medications and In-Hospital Mortality of Patients with Acute Myocardial Infarction in a Chinese Population

ObjectiveCurrent practice guidelines recommend the routine use of several cardiac medications early in the course of acute myocardial infarction (AMI). Our objective was to analyze temporal trends in medication use and in-hospital mortality of AMI patients in a Chinese population.MethodsThis is a retrospective observational study using electronic medical records from the hospital information system (HIS) of 14 Chinese hospitals. We identified 5599 patients with AMI between 2005 and 2011. Factors associated with medication use and in-hospital mortality were explored by using hierarchical logistic regression.ResultsThe use of several guideline-recommended medications all increased during the study period: statins (57.7%–90.1%), clopidogrel (61.8%–92.3%), β-Blockers (45.4%–65.1%), ACEI/ARB (46.7%–58.7%), aspirin (81.9%–92.9%), and the combinations thereof increased from 24.9% to 42.8% (P<0.001 for all). Multivariate analyses showed statistically significant increases in all these medications. The in-hospital mortality decreased from 15.9% to 5.7% from 2005 to 2011 (P<0.001). After multivariate adjustment, admission year was still a significant factor (OR = 0.87, 95% CI 0.79–0.96, P = 0.007), the use of aspirin (OR = 0.64, 95% CI 0.46–0.87), clopidogrel (OR = 0.44, 95% CI 0.31–0.61), ACEI/ARB (OR = 0.73, 95% CI 0.56–0.94) and statins (OR = 0.54, 95% CI 0.40–0.73) were associated with a decrease in in-hospital mortality. Patients with older age, cancer and renal insufficiency had higher in-hospital mortality, while they were generally less likely to receive all these medications.ConclusionUse of guideline-recommended medications early in the course of AMI increased between 2005 and 2011 in a Chinese population. During this same time, there was a decrease in in-hospital mortality.     

Randomised trial of prophylactic daily aspirin in British male doctors

A six year randomised trial was conducted among 5139 apparently healthy male doctors to see whether 500 mg aspirin daily would reduce the incidence of and mortality from stroke, myocardial infarction, or other vascular conditions. Though total mortality was 10% lower in the treated than control group, this difference was not statistically significant and chiefly involved diseases other than stroke or myocardial infarction. Likewise, there was no significant difference in the incidence of non-fatal myocardial infarction or stroke—indeed, disabling strokes were somewhat commoner among those allocated aspirin. The lower confidence limit for the effect of aspirin on non-fatal stroke or myocardial infarction, however, was a substantial 25% reduction. Migraine and certain types of musculoskeletal pain were reported significantly less often in the treated than control group, but as the control group was not given a placebo the relevance of these findings was difficult to assess. There was no apparent reduction in the incidence of cataract in the treated group.The lack of any apparent reduction in disabling stroke or vascular death contrasts with the established value of antiplatelet treatment after occlusive vascular disease.     

Influence of transoesophageal echocardiography on therapy and prognosis in young patients with TIA or ischaemic stroke

Objective. To determine the influence of transoesophageal echocardiography (TEE) on therapy and prognosis in patients with cryptogenic transient ischaemic attack (TIA) or ischaemic stroke under the age of 50 years. Methods and results. We evaluated all patients aged 50 and under who were referred to our university hospital for cryptogenic TIA or ischaemic stroke during the period 1 January 1996 to 31 December 2004. All patients underwent both transthoracic echocardiography (TTE) and TEE. Patients with known pre-existent heart disease, such as atrial fibrillation, were excluded. Eighty-three patients with TIA (22) and ischaemic stroke (61) were enrolled. Mean age was 39±8 years (range 18 to 50). In 30% of the patients TEE detected one or more potential cardioembolic source, compared with 10% for TTE (p=0.003). Standard treatment (aspirin 38 mg daily) was changed in 7% of the patients due to the TEE findings. Complete followup was obtained in 93% with an average of 5±3 years. Twelve recurrences occurred; two out of six patients (33%) with therapy change and ten out of 71 (14%) of the patients without therapy change had a recurrent TIA or ischaemic Stroke. Conclusion. In patients with cryptogenic TIA or ischaemic stroke, TEE is superior to TTE in the detection of a potential cardiac source of embolism. However, findings obtained by TEE only influence the already initiated treatment in a small percentage of patients. The recurrence rate both in the group with and without therapy change is high. (Neth Heart J 2009;17:373–7.)     

Is hyperglycaemia an independent predictor of poor outcome after acute stroke? Results of a long-term follow up study.

OBJECTIVE: To determine whether raised plasma glucose concentration independently influences outcome after acute stroke or is a stress response reflecting increased stroke severity. DESIGN: Long-term follow up study of patients admitted to an acute stroke unit. SETTING: Western Infirmary, Glasgow. SUBJECTS: 811 patients with acute stroke confirmed by computed tomography. Analysis was restricted to the 750 non-diabetic patients. MAIN OUTCOME MEASURES: Survival time and placement three months after stroke. RESULTS: 645 patients (86%) had ischaemic stroke and 105 patients (14%) haemorrhagic stroke. Cox''s proportional hazards modelling with stratification according to Oxfordshire Community Stroke Project categories identified increased age (relative hazard 1.36 per decade; 95% confidence interval 1.21 to 1.53), haemorrhagic stroke (relative hazard 1.67; 1.22 to 2.28), time to resolution of symptoms > 72 hours (relative hazard 2.15; 1.15 to 4.05), and hyperglycaemia (relative hazard 1.87; 1.43 to 2.45) as predictors of mortality. The effect of glucose concentration on survival was greatest in the first month. CONCLUSIONS: Plasma glucose concentration above 8 mmol/l after acute stroke predicts a poor prognosis after correcting for age, stroke severity, and stroke subtype. Raised plasma glucose concentration is therefore unlikely to be solely a stress response and should arguably be treated actively. A randomised trial is warranted.     

丁苯酞联合低剂量阿替普酶治疗急性脑梗死的疗效及对患者神经内分泌因子的影响

目的:探讨丁苯酞联合低剂量阿替普酶治疗急性脑梗死的疗效及对患者神经内分泌因子的影响。方法:按照随机数表法将105例患者分为对照组(n=52)和研究组(n=53)。对照组患者采用低剂量阿替普酶治疗,研究组患者在对照组基础上加用丁苯酞治疗。评价并比较两组临床疗效,比较两组治疗前后美国国立卫生研究院卒中量表(NIHSS)评分和血清S-100蛋白(S100B)、神经元特异性烯醇化酶(NSE)、髓鞘碱性蛋白(MBP)水平,比较两组治疗14 d内的颅内出血发生率和病死率。结果:研究组的临床总有效率为94.34%(50/53),明显高于对照组的76.92%(40/52),且差异具有统计学意义(x2=6.502,P=0.011)。与治疗前相比,两组治疗后NIHSS评分均明显降低,且研究组治疗后的NIHSS评分明显低于对照组,差异有统计学意义(P<0.05)。与治疗前相比,两组治疗后血清S100B、NSE及MBP水平均明显降低(P<0.05),且研究组治疗后血清S100B、NSE及MBP水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗14 d内,研究组的颅内出血发生率和死亡率均明显低于对照组,差异有统计学意义(P<0.05)。结论:丁苯酞联合低剂量阿替普酶治疗急性脑梗死的疗效显著,能够明显改善神经功能,降低神经内分泌因子水平,且安全性较好。     

阿斯匹林治疗急性缺血性脑卒中临床疗效随机双盲对照研究

目的 探讨阿斯匹林抗血小板治疗急性缺血性脑卒中,对降低死亡率,改善致残率的临床疗效。方法 采取随机、双盲、安慰剂对照,对发病48h内的急性缺血性脑卒中患者,均经头颅CT检查排除出血性脑卒中。入选患者在常规治疗的基础上,口服阿斯匹林,每天160mg或安慰剂4周。结果 服阿斯匹林的患者（阿斯匹林组）和服安慰剂的患者（安慰剂组）相比较,两组对降低死亡率,减轻致残率的结果差异无统计学意义（P＞0．05）。结论 在常规治疗急性缺血性脑卒中的基础上,加服阿斯匹林160mg对降低病死率和出院时的致残率效果不明显。     

Light, electron microscopic and immunohistochemical study of the effect of low-dose aspirin during the proestrus phase on rat endometrium in the preimplantation period

OBJECTIVE: To evaluate structural alterations in rat endometrium at preimplantation following treatment with aspirin beginning from proestrus by light microscopy, electron microscopy and immunohistochemical techniques. STUDY DESIGN: Twenty rats were divided into control (n = 10) and experimental (n = 10) groups. Experimental rats were treated with low-dose aspirin daily (2 mg/kg/day) during estrus, beginning from the proestrus phase, mated at end of cycle and treated with aspirin. Untreated pregnant rats were the control group. Rats in both groups were sacrificed at the 84th pregnancy hour; the uterus was rapidly removed and dissected free of surrounding adipose tissue. Uteri specimens from nonpregnant rats were transferred into fixative solution and processed for light, electron microscopic and immunohistochemical study. RESULTS: Light and electron microscopy of endometrium from control rats conformed to mid-diestrus phase; endometrial histology of the aspirin-treated group conformed to late diestrus phase. The endometrial layer was significantly thicker in the aspirin-treated group compared to the untreated control group (p <0.001). No significant difference was found in vessel number between groups. Staining with alphaV integrin was more dense in the aspirin-treated group. CONCLUSION: Based on histologic findings, we suggest low-dose aspirin has positive effects on preparing endometrium before implantation.     

Variation in Risk-Standardized Mortality of Stroke among Hospitals in Japan

Despite recent advances in care, stroke remains a life-threatening disease. Little is known about current hospital mortality with stroke and how it varies by hospital in a national clinical setting in Japan. Using the Diagnosis Procedure Combination database (a national inpatient database in Japan), we identified patients aged ≥20 years who were admitted to the hospital with a primary diagnosis of stroke within 3 days of stroke onset from April 2012 to March 2013. We constructed a multivariable logistic regression model to predict in-hospital death for each patient with patient-level factors, including age, sex, type of stroke, Japan Coma Scale, and modified Rankin Scale. We defined risk-standardized mortality ratio as the ratio of the actual number of in-hospital deaths to the expected number of such deaths for each hospital. A hospital-level multivariable linear regression was modeled to analyze the association between risk-standardized mortality ratio and hospital-level factors. We performed a patient-level Cox regression analysis to examine the association of in-hospital death with both patient-level and hospital-level factors. Of 176,753 eligible patients from 894 hospitals, overall in-hospital mortality was 10.8%. The risk-standardized mortality ratio for stroke varied widely among the hospitals; the proportions of hospitals with risk-standardized mortality ratio categories of ≤0.50, 0.51–1.00, 1.01–1.50, 1.51–2.00, and >2.00 were 3.9%, 47.9%, 41.4%, 5.2%, and 1.5%, respectively. Academic status, presence of a stroke care unit, higher hospital volume and availability of endovascular therapy had a significantly lower risk-standardized mortality ratio; distance from the patient’s residence to the hospital was not associated with the risk-standardized mortality ratio. Our results suggest that stroke-ready hospitals play an important role in improving stroke mortality in Japan.