Evaluation of ibuprofen (Motrin). A new antirheumatic agent.

Ibuprofen is a new, mild analgesic agent that may be useful in the symptomatic treatment of rheumatoid arthritis and osteoarthritis. Results of clinical studies have shown that its beneficial effects in these conditions are comparable, but not superior, to those of aspirin. However, at recommended doses it has less anti-inflammatory effect than aspirin. Its usefulness as an analgesic in the treatment of other types of pain and as an antipyretic has not yet been established. Ibuprofen causes fewer adverse effects on the gastrointestinal system, including occult bleeding, than aspirin. Serious adverse reactions have not been reported. Thus, ibuprofen may be acceptable for use in patients who cannot tolerate aspirin or other antirheumatic drugs.     

The real cost of aspirin

Aspirin is a widely used drug and perceived by most physicians to be inexpensive. High rates of concurrent gastroprotective agents are reported from a study of cardiology outpatients. Aspirin takers are more likely to also be taking a proton pump inhibitor, H(2) antagonist, or antacid than non-aspirin takers. They are more than 10 times as likely to be experiencing upper gastrointestinal symptoms. Although aspirin is inexpensive, it is emphasised that the overall cost implications for therapy can be significant and it is suggested that it may be more appropriate to consider the use of alternative antiplatelet agents in patients who tolerate aspirin poorly.     

肠溶阿司匹林引起上消化道出血的危险因素分析

目的探讨肠溶阿司匹林引起上消化道出血的临床特点。方法选择2012年1月-2014年1月我院门诊或住院服用肠溶阿司匹林的患者565例,比较不同服药时间、服药剂量及是否加用胃黏膜保护剂、质子泵抑制剂（PPI）、H2受体拮抗剂对上消化道出血发生率的影响。结果随着肠溶阿司匹林服用时间延长、服药剂量加大,上消化道出血发生率增加（P〈0．05）;联用胃黏膜保护剂、PPI或H2受体拮抗剂可以减少上消化道出血发生率（P〈0．05）,PPI组和H2受体拮抗剂组效果优于胃黏膜保护剂组（P〈0．05）。结论建议小剂量服用肠溶阿司匹林,需要长期服用的患者建议联合应用PPI或H2受体拮抗剂。     

Aspirin for lower limb arthroplasty thromboprophylaxis: review of international guidelines

Introduction

Aspirin is one of the pharmacological agents used for thromboprophylaxis.

Materials and methods

National thromboprophylaxis guidelines, peer-reviewed studies and data from national joint register of England and Wales were analysed for evidence regarding the efficacy of aspirin versus other agents in thromboprophylaxis and the recommendations of guidelines.

Results

Two of five guidelines reviewed recommend the use of aspirin for thromboprophylaxis. Aspirin is used as thromboprophylactic agent in approximately 25% of patients undergoing total hip and total knee arthroplasty in year 2006 in England and Wales. There is no difference in mortality in these patients compared to patients on other pharmacological agents.

Conclusion

There is conflicting evidence and differences in interpretation of the data from the literature. If specific outcome measures and complications such as symptomatic DVT, PE and bleeding were logged in arthroplasty registers, the resulting data would be useful in individualised decision-making.     

Prospective study of acute gastrointestinal bleeding attributable to anti-inflammatory drug ingestion in the Yorkshire region of the United Kingdom

Objective: To assess the general use of all non-steroidal anti-inflammatory drugs (NSAID) and their relation to upper gastrointestinal bleeding in view of National Institute for Clinical Excellence guidelines published in July 2001 in the UK. Methods: Cross sectional study on all patients who were referred for endoscopy for suspected upper gastrointestinal bleeding in six hospitals in Yorkshire region of the UK. Results: One hundred and sixty three patients presented for endoscopy for suspected upper gastrointestinal bleeding, 43 patients were taking at least one ulcerogenic drug, and 120 were not. The mean age difference between these two groups was eight years (p<0.01). The absolute difference between the proportion of patients with peptic ulcer disease/erosion (PUD) in NSAID with/without aspirin group and no ulcerogenic drug group was 31% (p = 0.02). The difference between the proportion of PUD in cyclo-oxygenase 2 with/without aspirin group and no ulcerogenic drug group was 30% (p = 0.1). The overall 30 days mortality rate was 14.1%. Conclusions: Elderly patients are being inappropriately prescribed conventional NSAIDs. NSAIDs with or without aspirin use are still associated with a significant risk of upper gastrointestinal bleeding in the era of cyclo-oxygenase 2 selective agents. Substitution with cyclo-oxygenase 2 selective NSAIDs is not without risk of upper gastrointestinal bleeding.     

肠溶阿司匹林在冠心病治疗中致上消化道出血的相关因素分析

目的探讨肠溶阿司匹林在冠心病治疗中致上消化道出血的发生情况及其相关影响因素。方法对福建省立医院心内科的1086例服用肠溶阿司匹林的冠心病患者进行回顾性分析,内容包括:性别、年龄、服药时间和剂量、既往消化道病史、吸烟史及联用胃保护剂等情况。结果年龄≥70岁、服药时间≥3个月、服药剂量为300mg/d、有消化道病史是肠溶阿司匹林致冠心病患者上消化道出血的危险因素(P<0.05);联用胃保护剂后,出血发生率明显减少(P<0.05)。结论肠溶阿司匹林致上消化道出血的发生率与患者的年龄、服药剂量、服药时间、消化道病史有关。及时辅以胃保护剂治疗,可有效减少肠溶阿司匹林致上消化道出血的发生。     

Polycystic ovary syndrome (PCOS), insulin resistance and insulin-like growth factors (IGfs)/IGF-binding proteins (IGFBPs)

Polycystic ovary syndrome (PCOS) is the most frequent androgen disorder of ovarian function. Hyperinsulinemia with insulin resistance is believed to be a key link in the enigmatic generation of the symptoms of PCOS such as anovulatory infertility and hyperandrogenism. Regression of these symptoms may be achieved by reducing the hyperinsulinemia. A growing body of evidence suggests that PCOS patients with hyperinsulinemia have a higher risk to develop diabetes mellitus, hypertension and cardiovascular disease as compared to age-matched women. Although oral contraceptives, progestins, antiandrogens, and ovulation induction agents remain standard therapies, weight loss should also be vigorously encouraged to ameliorate the metabolic consequences of PCOS. In addition, insulin-sensitizing agents are now being shown to be useful alone or combined with standard therapies to alleviate hyperinsulinemia in PCOS. Finally and most importantly, early identification of patients at risk and prompt initiation of therapies, followed by long-term surveillance and management, may promote the patient's long-term health.     

小剂量阿司匹林致上消化道出血患者83例临床分析

目的分析长期服用小剂量阿司匹林患者上消化道出血的临床特点及影响因素,以指导临床诊治。方法 2008年1月～2011年12月惠州市中心人民医院消化内科收治的每天服用100mg阿司匹林患者上消化道出血83例进行回顾分析。结果小剂量阿司匹林致上消化道出血以老年人多见,主要表现为黑便,内镜下表现以胃粘膜病变为主,常伴幽门螺杆菌感染。结论长期服用阿司匹林患者中,年龄大于60岁者上消化道出血发病率明显上升;幽门螺杆菌感染并长期服用小剂量阿司匹林患者可能增加上消化道出血风险。     

尼美舒利和肠溶阿司匹林治疗牙科手术后疼痛的疗效对比

目的 比较研究所尼美舒利（ＮＩＭ）和肠溶阿司匹林（ＡＳＰ）治疗牙科手术后疼痛的疗效和安全性。方法 试验设计为随机单盲对照。试验组１２０例病例,于手术后疼痛时一次口服ＮＩＭ２００ｍｇ,过２４ｈ再口服２００ｍｇ;对照组６０例病例,于手术后疼痛时一次口服ＡＳＰ６００ｍｇ,过２４ｈ再口服６００ｍｇ。结果 ＮＩＭ总有效率为９１．６７％,ＡＳＰ总有效率为８６．６７％。两药均能改善患者的症状和体征。经安全性评价     

阿斯匹林对胃癌细胞株SGC-7901的细胞毒作用及体外增效作用

目的：观察阿斯匹林（ASA）对胃癌细胞株SGC－7901的细胞毒作用以及联用其它抗肿瘤药的增效作用。方法：应用流式细胞仪（FCM）测定细胞周期,噻唑蓝（MTT）法测定药物细胞的抑制率。结果：MTT显示体外ASA对SGC－7901有细胞毒作用,与ASA的浓度和作用时间有显著的相关性。同时可使SGC－7901细胞周期中S期及G2／M期比例升高,G1期比例下降,呈一定的剂量效应关系。低浓度ASA与5－氟脲噻啶（5－Fu)、阿霉素（DOX）和丝列霉素（MMC）合用,可增强它们对SGC－7901的杀伤作用,与各药物有相加或协同作用。结论：ASA体外对SGC－7901有细胞毒作用,可明显阻断SGC－7901细胞在S期和G2／M期;增强上述药物对SGC－7901的杀伤作用。鉴于所试药物对细胞周期的影响不同,提示ASA的体外增效作用可能与此相关。     

Antiplatelets in secondary stroke prevention: should clopidogrel be the first choice?

Antiplatelet therapy has proven efficacy in the secondary prevention of recurrent non-cardioembolic ischaemic stroke. Recent evidence suggests clopidogrel is as effective as combined therapy with aspirin and extended-release dipyridamole for the prevention of recurrent stroke. As cerebrovascular and ischaemic heart disease are closely related, it would be sensible to use a drug shown to prevent vascular events in both territories. Clopidogrel meets these criteria, is superior to aspirin monotherapy, and has fewer side effects compared with extended-release dipyridamole. While there is no direct evidence supporting the use of clopidogrel in transient ischaemic attacks, it is likely that clopidogrel is effective because transient ischaemic attacks and stroke are part of the same disease spectrum. Clopidogrel could thus be useful as first line secondary prevention therapy in all non-cardioembolic stroke subtypes and transient ischaemic attacks, to prevent recurrent ischaemic events in all vascular territories.     

Gastrointestinal and Cardiovascular Risk of Nonsteroidal Anti-inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) confer a gastrointestinal (GI) side effect profile and concerns regarding adverse cardiovascular effects have emerged associated with considerable morbidity and mortality. NSAIDs are highly effective in treating pain and inflammation, but it is well recognized that these agents are associated with substantial gastrointestinal toxicity. Cyclo-oxygenase-2 inhibitors may also reduce the risk for gastrointestinal events, although they may increase cardiovascular adverse events. The selection of an appropriate analgesic or anti-inflammatory agent with or without gastroprotective therapy should be individualized.     

氯吡格雷与质子泵抑制剂相互作用的探讨

阿司匹林与氯吡格雷双联抗血小板被广泛用于急性冠状动脉综合征及经皮冠状动脉介入治疗术后的患者。质子泵抑制剂(PPI)被推荐降低抗血小板药物引起的胃肠道损害,但研究发现PPI影响氯吡格雷的临床药效。提示临床医师应合理选择使用与氯吡格雷相互作用的PPI,或应用不影响CYP2C19途径的H2受体拮抗剂,或在服用氯吡格雷4 h后再服用PPI,积极防控血栓事件的同时降低消化道出血风险。     

非甾体类抗炎药与消化道肿瘤的化学预防

近年来,流行病学及实验室研究表明,长期使用阿斯匹林或其它非甾体类抗类药（NSAIDs),可降低结,直肠癌,食管癌,胃癌,胰腺癌等消化道肿瘤的发病危险性。提示NSAIDs可能对消化道肿瘤具有一定的化学预防作用。同时,这一保护作用也很有可能在肿瘤的前期病变过程中发挥有着的阻断,逆转或预防作用,NSAIDs化学预防作用的可能机制：（1）抑制前列腺素（PG）合成和细胞环氧化酶（COX）活性;（2）诱导胃肠道来源的上皮细胞凋亡。（3）引起PG和COX调节通路的障碍。目前,NSAIDs的化学预防作用已经成为肿瘤二级预防领域的研究热点并已基本肯定了它在消化道肿瘤预防中的作用。NSAIDs,尤其是特异性环氧化酶2－抑制剂,有望成为肿瘤以及癌前病变新的化学预防的药物。     

Role of the parietal cell in gastric damage induced by aspirin and related drugs: implications for safer therapy.

The proton-secreting parietal cell is shown, from recent evidence, to be the principal focus for the actions of aspirin (and related drugs) in damaging the gastric mucosa. It is suggested that the selective damage to the parietal cells is due to the ph gradient favouring a high rate of aspirin uptake and subsequent entrapment of drug anions inside these cells. This concept may serve as a useful basis for developing procedures to minimize the gastric damage by aspirin and related acidic drugs.     

ERCC1、ERCC2的多态性对常见消化系统肿瘤的影响

机体DNA修复系统如核苷酸切除修复在维持基因组功能整体性、修复致癌因素所致的损伤及抗癌过程中有着重要作用。一些核酸修复基因,如切除修复交叉互补基因1(ERCC1)及人类着色性干皮病基因D(XPD/ERCC2)的水平下降,可能会成为某种或某几种肿瘤的易感因素;但如果此种基因的水平较高,修复损伤的能力提高,对化疗药物所致基因损伤的修复能力也就增强了,那么可能对化疗药物产生耐药现象。以上两种基因的单核苷酸多态与以DDP、5-FU为基础的化疗方案的疗效存在一定关系,而消化道肿瘤又多应用铂剂及5-FU治疗,故本文对ERCC1、XPD/ERCC2与几种常见消化道肿瘤的发生及其化疗疗效的关系予以综述。     

Advances in antiplatelet therapy for acute coronary syndromes

Admissions to emergency care centres with acute coronary syndromes remain one of the principal burdens on healthcare systems in the Western world. Early pharmacological treatment in these patients is crucial, lessening the impact on both morbidity and mortality, with the cornerstone of management being antiplatelet agents. While aspirin and clopidogrel have been the drugs of choice for nearly a decade, an array of newer, more potent antiplatelet agents are now available or in late stage development. Data are rapidly gathering suggesting these agents have superior anti-ischaemic properties, improving patient outcomes, but that for some agents increased vigilance and appropriate patient selection may be necessary to guard against bleeding complications. In this review, the authors aim to deliver an overview of the changing field of antiplatelet therapy and provide information about the relative risks and benefits of these newer agents, many of which will be entering widespread clinical use imminently.     

长期服用阿司匹林预防缺血性脑卒中的有效性及安全性分析

目的探讨长期服用阿司匹林对缺血性脑卒中的有效性及安全性。方法纳入2015年1月至2016年5月在重庆市陆军特色医学中心体检中心的老年人群,入组时纳入2 381人,随访丢失263人,5年随访结束时共2 118人被纳入基线分析,平均年龄71.7岁,51.1%是男性。根据阿司匹林的服用情况进行分组,其中阿司匹林组被定义为根据处方记录入组时服用阿司匹林者,非阿司匹林组被定义为入组后观察期间未服用阿司匹林者。研究中观察的主要结果为缺血性脑卒中,包括缺血性脑梗死和短暂性脑缺血(TIA);次要结果为心绞痛、心肌梗死、心血管死亡和全因死亡。安全性结果包括胃肠道出血、颅内出血和其他部位的出血,采用Cox比例风险模型估计阿司匹林与缺血性脑卒中的关系。结果阿司匹林组共1 015人,非阿司匹林组1 103人。5年随访结束时,阿司匹林组381人、非阿司匹林组491人发生缺血性脑卒中。主要结果和次要结果(心绞痛、心肌梗死)在2组间差异有统计学意义(P < 0.05),心血管死亡与全因死亡差异无统计学意义(P>0.05)。阿司匹林组胃肠道出血(4.2% VS 2.4%)和胃肠道不良反应(16.1% VS 8.3%)高于非阿司匹林组(P < 0.05)。阿司匹林组与非阿司匹林组比较,服用阿司匹林 < 13个月、13~24个月、25~36个月和37~48个月缺血性脑卒中的风险显著降低(P < 0.05),而服用阿司匹林49~60个月缺血性脑卒中发生率差异无统计学意义(P>0.05)。结论长期服用阿司匹林降低缺血性脑卒中的发生有效性逐渐降低,并增加胃肠道出血的风险。     

Direct thrombin inhibitors: novel antithrombotics on the horizon in the thromboprophylactic management of atrial fibrillation

Antithrombotic agents have verified efficacy in reducing the thromboembolic risk associated with atrial fibrillation. This article focuses on the emergence of a new oral direct thrombin inhibitor, ximelagatran, into the arena of atrial fibrillation thromboprophylaxis. This review does not cover atrial fibrillation in the context of valvular heart disease. The efficacy of aspirin and warfarin will be discussed briefly.     

Consensus guidelines for warfarin therapy. Recommendations from the Australasian Society of Thrombosis and Haemostasis

The anticoagulant effect of warfarin should be kept at an international normalised ratio (INR) of about 2.5 (desirable range, 2.0-3.0), although a higher level may be better in a few clinical conditions. The risk of bleeding increases exponentially with INR and becomes clinically unacceptable once the INR exceeds 5.0. Warfarin therapy should be continued for around six weeks for symptomatic calf vein thrombosis, and for 3-6 months after proximal deep vein thrombosis (DVT) that occurs after surgery or limited medical illness. Therapy for six months or longer could be considered for DVT occurring without an obvious precipitating factor, proven recurrent venous thromboembolism (VTE), or if there are continuing risk factors. Oral anticoagulants prevent ischaemic stroke in atrial fibrillation (AF). Maximum efficacy requires an INR > 2.0, but some benefit remains at an INR of 1.5-1.9. Patients aged over 75 years are at greatest risk of intracranial bleeding during warfarin therapy for AF, and the target INR may be reduced to 2.0-2.5, or perhaps as low as 1.5-2.0, in such patients. Warfarin should be withheld if it is more likely to cause major bleeding than to protect from stroke (e.g., in young people with isolated AF where the annual baseline risk of stroke is < 1%). In patients with AF, aspirin is less effective than warfarin (much less effective after such patients have had a stroke or transient cerebral ischaemia). In people with prosthetic heart valves, an INR of 2.5-3.5 is probably sufficient for bileaflet or tilting disc valves, but a higher target INR is necessary for caged ball or caged disc valves. The addition of aspirin (100 mg/day) further decreases the risk of embolism but increases the risk of gastrointestinal bleeding.