Oral anti-coagulants use in Chinese hospitalized patients with atrial fibrillation

Background:Oral anti-coagulants(OAC)are the intervention for the prevention of stroke,which consistently improve clinical outcomes and survival among patients with atrial fibrillation(AF).The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods:Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation(CCC-AF)registry,guideline-recommended OAC use in eligible patients was assessed.Results:A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019,of whom 38,203 were at a high risk of stroke,9717 were at a moderate risk,and 4610 were at a low risk.On admission,only 20.0%(6075/30,420)of patients with a diagnosed AF and a high risk of stroke were taking OAC.The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population(adjusted odds ratio:0.54,95%confidence interval:0.43-0.68;P<0.001).At discharge,the prescription rate of OAC was 45.2%(16,757/37,087)in eligible patients with high stroke risk and 60.7%(2778/4578)in eligible patients with low stroke risk.OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time(all P<0.001).Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies,including catheter ablation(adjusted odds ratio[OR]11.63,95%confidence interval[CI]10.04-13.47;P<0.001),electronic cardioversion(adjusted OR 2.41,95%CI 1.65-3.51;P<0.001),and anti-arrhythmic drug use(adjusted OR 1.45,95%CI 1.38-1.53;P<0.001).Conclusions:In hospitals participated in the CCC-AF project,>70%of AF patients were at a high risk of stroke.Although poor performance on guideline-recommended OAC use was found in this study,over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov,NCT02309398.

Multicenter experience with photoselective vaporization of the prostate on men taking novel oral anticoagulants

Objective:Photoselective vaporization of the prostate(PVP)is a widely performed surgical procedure for benign prostatic obstruction.This approach has become particular favoured for men on anti-platelet and anticoagulation agents such as clopidogrel and warfarin but there is minimal published experience in the setting of novel oral anticoagulants(NOACs).This study was to examine the perioperative outcomes in men on NOACs undergoing PVP,with particular reference to perioperative morbidity.Methods:A retrospective analysis of PVP datasets was undertaken from three centres in Sydney(Australia),Toulouse(France)and Boston(USA).Subjects who had been treated whilst on NOACs without discontinuation or bridging were identified.Perioperative outcomes and treatment parameters were examined and morbidity recorded according to Clavien-Dindo(CD)classification.Results:There were a total of 20 subjects who had undergone PVP whilst NOACs had been continued during the perioperative period.The mean age was 776.5 years.The mean prostate volume,energy utilization and vaporisation time was 9456 mL,301211 kJ,and 3521 min respectively.The mean postoperative duration of catheterization and duration of hospitalization was 2.22.4 days and 2.42.4 days respectively.There was a single episode of urinary tract infection and four subjects required re-catheterisation for non-hematuric retentions.Conclusions:This study supports the safety of men on NOACs undergoing PVP.Whilst this study represents the largest experience of PVP in these men,larger studies are necessary to confirm the safety of PVP in this group of men undergoing BPH-related surgery.

Role of novel oral anticoagulants in the management and prevention of venous thromboembolism

Venous thromboembolism(VTE) encompasses deep vein thrombosis and pulmonary embolism and is a major health burden, both medically and economically. Anticoagulation is the primary treatment and can be divided into three stages: initial, long term and extended treatment. Initial anticoagulation is given to reduce the risk of complications including fatal pulmonary embolism, while long term and extended treatment are aimed at prevention of recurrent VTE. Until recently, initial anticoagulation has only been achievable with administration of parental agents such as unfractionated or low molecular weight heparin, while vitamin K antagonists such as warfarin, have been the mainstay of long term and extended treatment. Factor-Xa inhibitors and direct thrombin inhibitors are oral anticoagulants that are being increasingly utilized as an alternative form of anticoagulation. This article aims to review the current guidelines in the management of VTE, the recent literature regarding novel anticoagulants in VTE, suggested treatment regimes and limitations.

Liver injury from direct oral anticoagulants

BACKGROUND Drug-induced liver injury(DILI)can be caused by any prescribed drug and is a significant reason for the withdrawal of newly launched drugs.Direct-acting oral anticoagulants(DOACs)are non-vitamin K-based antagonists recently introduced and increasingly used for various clinical conditions.A meta-analysis of 29 randomised controlled trials and 152116 patients reported no increased risk of DILI with DOACs.However,it is challenging to predict the risk factors for DILI in individual patients with exclusion of patients with pre-existing liver disease from these studies.AIM To determine the risk factors and outcomes of patients who developed DILI secondary to DOACs by systematic review and meta-summary of recent case reports and series.METHODS A systematic search was conducted on multiple databases including PubMed,Science Direct,Reference Citation Analysis,and Google Scholar.The search terms included“Acute Liver Failure”OR“Acute-On-Chronic Liver Failure”OR“Acute Chemical and Drug Induced Liver Injury”OR“Chronic Chemical and Drug Induced Liver Injury”AND“Factor Xa Inhibitors”OR“Dabigatran”OR“Rivaroxaban”OR“apixaban”OR“betrixaban”OR“edoxaban”OR“Otamixaban”.The results were filtered for literature published in English and on adult patients.Only case reports and case studies reporting cases of DILI secondary to DOACs were included.Data on demographics,comorbidities,medication history,laboratory investigations,imaging,histology,management,and outcomes were extracted.RESULTS A total of 15 studies(13 case reports and 2 case series)were included in the analysis,comprising 27 patients who developed DILI secondary to DOACs.Rivaroxaban was the most commonly implicated DOAC(n=20,74.1%).The mean time to onset of DILI was 40.6 d.The most common symptoms were jaundice(n=15,55.6%),malaise(n=9,33.3%),and vomiting(n=9,33.3%).Laboratory investigations showed elevated liver enzymes and bilirubin levels.Imaging studies and liver biopsies revealed features of acute hepatitis and cholestatic injury.Most patients had a favourable outcome,and only 1 patient(3.7%)died due to liver failure.CONCLUSION DOACs are increasingly used for various clinical conditions,and DILI secondary to DOACs is a rare but potentially serious complication.Prompt identification and cessation of the offending drug are crucial for the management of DILI.Most patients with DILI secondary to DOACs have a favourable outcome,but a small proportion may progress to liver failure and death.Further research,including post-marketing population-based studies,is needed to better understand the incidence and risk factors for DILI secondary to DOACs.

新型口服抗凝药对急性心肌梗死后心力衰竭合并室壁瘤附壁血栓消退影响的研究

目的:探讨新型口服抗凝药(novel oral anticoagulants,NOAC)用于治疗急性心肌梗死(acute myocardial infarction,AMI)后心力衰竭合并室壁瘤内附壁血栓的疗效。方法:入选2019年6月至2023年5月,首都医科大学附属北京安贞医院心内科门诊和病房患者中AMI后发生心力衰竭合并室壁瘤内附壁血栓患者118例,分别给予NOAC(NOAC组,65例)或维生素K受体拮抗剂(VKA组,53例)治疗,3个月后复查经胸超声心动图,如血栓尚未完全溶解,则在首次给药6个月后再次复查超声心动图。结果:NOAC组中,使用利伐沙班治疗者为46例,使用达比加群治疗者为19例,治疗3个月后血栓完全溶解率为70.8%。所有VKA组患者均使用华法林治疗,3个月后血栓完全溶解率为67.9%,与NOAC组相比差异无统计学意义(P>0.05)。治疗6个月后,NOAC组的血栓完全溶解率为90.8%,VKA组的血栓完全溶解率为84.9%,两组血栓溶解率对比差异无统计学意义(P>0.05)。结论:NOAC可考虑作为AMI后心力衰竭合并室壁瘤内附壁血栓消退的治疗药物,且无须监测INR,使用方便,安全性好。

新型口服抗凝剂治疗癌症患者静脉血栓栓塞有效性及安全性的Meta分析

目的系统评价癌症相关静脉血栓栓塞(VTE)患者使用新型口服抗凝剂(NOAC)的有效性和安全性。方法检索PubMed、Cochrane Library、Embase、Web of Science、中国知网、万方数据库,检索时限为各数据库建库起至2023年8月,收集低分子肝素(LMWH,对照组)对比NOAC(试验组)治疗癌症相关VTE患者疗效的随机对照试验(RCT),对纳入临床研究进行资料提取后,采用RevMan 5.0统计软件进行Meta分析。结果共计纳入7项RCT,合计3790例癌症相关VTE患者。与对照组相比,试验组患者的VTE复发率(RR=0.65,95%CI为0.51~0.82,P=0.0004)显著降低,而其大出血发生率略高于对照组,但差异无统计学意义(RR=1.13,95%CI为0.83~1.53,P=0.45)。试验组患者的临床相关非主要大出血(RR=1.69,95%CI为1.34~2.13,P<0.00001)、消化道出血(RR=1.96,95%CI为1.15~3.34,P=0.01)发生率均较对照组显著升高。两组患者颅内出血发生率、全因死亡率、致死性肺栓塞发生率比较,差异均无统计学意义(P>0.05)。结论对于癌症相关VTE患者,NOAC在预防VTE复发方面优于LMWH,在大出血、颅内出血、全因死亡、致死性肺栓塞方面不劣于LMWH。

吞咽困难患者新型口服抗肿瘤药物的替代给药方法

目的为吞咽困难的患者提供新型口服抗肿瘤药物的替代给药方法。方法根据“新型抗肿瘤药物临床应用指导原则(2022年版)”药品目录确定检索范围,通过查阅说明书,检索PubMed、Micromedex、UpToDate等数据库获得药品临时液体制剂的制备、稳定性、储存和相关临床信息。结果70种口服抗肿瘤药物被纳入文献检索,其中33种药物有相关的文献或数据支持替代给药方法,8种在说明书中有替代给药的相关信息,其他药物的证据水平各不相同。结论大部分药物临时液体制剂的证据水平较低,医疗团队在使用说明书以外的用法时应充分考虑利弊,谨慎使用。

新型口服抗凝药治疗肿瘤相关静脉血栓栓塞症网状Meta分析

目的 系统评价不同新型口服抗凝药(NOACs)治疗肿瘤相关静脉血栓栓塞症(CAVTE)的有效性和安全性。方法 采用计算机检索中国知网(CNKI)、中国生物医学文献数据库(CBM)、万方(WanFang)、维普(VIP)及PubMed,The Cochrane Library,Embase数据库中与NOACs治疗CAVTE相关的随机对照试验(RCT),检索时限为各数据库自建库起至2023年2月28日,采用Cochrane系统评价工具评价纳入文献的质量,采用RevMan 5.3软件进行风险评估,采用Stata 16.0软件进行网状Meta分析。结果 纳入10篇文献,涉及12项RCT,共5 080例患者及5种干预措施。网状Meta分析结果显示,在有效性指标中,考虑全因死亡率和深静脉血栓复发率的最优选择均为利伐沙班,考虑静脉血栓复发率和肺栓塞复发率的最优选择均为阿哌沙班;在安全性指标中,考虑大出血率、临床相关非大出血率和临床相关出血率的最优选择均为利伐沙班。结论 临床选择NOACs治疗CAVTE时,应综合考虑其有效性与安全性,利伐沙班可作为首选药物。

利伐沙班、达比加群酯在冠心病合并房颤患者冠脉支架植入术后应用的疗效对比

目的:观察冠心病合并房颤患者冠脉支架植入术后应用利伐沙班、达比加群酯的效果。方法:选取2021年6月—2023年6月景德镇市第二人民医院收治的80例行冠脉支架植入术治疗的冠心病合并房颤患者,随机分为两组,各40例。两组术后均予以氯吡格雷,在此基础上,A组给予利伐沙班,B组给予达比加群酯。比较两组治疗前后凝血功能[纤维蛋白原(FIB)、凝血酶原时间(PT)、血小板计数(PLT)与D-二聚体(D-D)]、炎症因子[超敏C反应蛋白(hs-CRP)]、出血事件、心脑血管不良事件、不良反应发生率及住院时间。结果:治疗前,两组FIB、PT、PLT、D-D及hs-CRP比较,差异均无统计学意义(P>0.05);治疗后,两组FIB、PT、PLT、D-D及hs-CRP均低于治疗前,差异均有统计学意义(P<0.05),但两组间比较,差异均无统计学意义(P>0.05)。两组出血事件、心脑血管不良事件、药物不良反应总发生率及住院时间比较,差异均无统计学意义(P>0.05)。结论:冠心病合并房颤患者冠脉支架植入术后应用利伐沙班或者达比加群酯均可有效改善机体凝血功能及炎症状态,效果及安全性相当。

论“徐芾东渡”故事与张炜的长篇小说创作

张炜主张中国当代文学创作应该向民间口头文学汲取营养,徐芾东渡故事这一民间口头文学资源在他的长篇小说中得到了独特运用。从小说发生学的意义上来看,徐芾东渡故事是张炜小说的叙事动力,是张炜小说主人公的精神支柱和研究对象,是小说情节往前推进的依据。徐芾东渡故事在张炜小说中的存在既笼罩全篇,又具体融入故事情节之中,它的存在形态主要有三种:一是直接由叙述者叙述,二是在古歌中呈现,三是在其他人物的“作品”中呈现。因与现实的密切关联,徐芾东渡故事的运用使得张炜小说主题的表达具有强烈的隐喻性质。中国口头文学元素赋予张炜小说创作鲜明个性特征,充分体现出民间口头文学传统对中国当代小说创作的重要意义。

Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs direct oral anticoagulants

AIM To verify the validity of the endoscopy guidelines for patients taking warfarin or direct oral anticoagulants(DOAC).METHODS We collected data from 218 patients receiving oral anticoagulants(73 DOAC users, 145 warfarin users) and 218 patients not receiving any antithrombotics(age-and sexmatched controls) who underwent polypectomy.(1) We evaluated post-polypectomy bleeding(PPB) risk in patients receiving warfarin or DOAC compared with controls;(2) we assessed the risks of PPB and thromboembolism between three AC management methods: Discontinuing AC with heparin bridge(HPB)(endoscopy guideline recommendation), continuing AC, and discontinuing AC without HPB.RESULTS PPB rate was significantly higher in warfarin users and DOAC users compared with controls(13.7% and 13.7% vs 0.9%, P < 0.001), but was not significantly different between rivaroxaban(13.2%), dabigatran(11.1%), and apixaban(13.3%) users. Two thromboembolic events occurred in warfarin users, but none in DOAC users. Compared with the continuing anticoagulant group, the discontinuing anticoagulant with HPB group(guideline recommendation) had a higher PPB rate(10.8% vs 19.6%, P = 0.087). These findings were significantly evident in warfarin but not DOAC users. One thrombotic event occurred in the discontinuing anticoagulant with HPB group and the discontinuing anticoagulant without HPB group; none occurred in the continuing anticoagulant group.CONCLUSION PPB risk was similar between patients taking warfarin and DOAC. Thromboembolism was observed in warfarin users only. The guideline recommendations for HPB should be re-considered.

Compliance and adherence to oral anticoagulation therapy in elderly patients with atrial fibrillation in the era of direct oral anticoagulants

Thromboembolic complications represent a substantial problem in patients with atrial fibrillation （AF）. The prevalence of AF burden and associated arterial and venous thrombosis progressively increases with age. At the same time, representative national data regarding stroke incidence in AF patients aged 80 and older are limited.

Efficacy and safety of novel anticoagulants in the elderly

Atrial fibrillation and venous thromboembolism （VTE） are common disorders associated with maleficent thrombotic events, particularly in the elderly patients. Polypharmacy, co-morbidities, and altered pharmacokinetics, often present in these patients, render the use of antico-agulants quite challenging. Novel oral anticoagulants （NOACs） have recently emerged as alternatives to Vitamin K Antagonists （VKAs） and are gradually increasing their popularity mainly because of their fewer drug and food interactions and ease of use. Their effectiveness and safety has been weU-established in the general population but the balance between benefit and harm in the elderly is still unclear. Routine use in these patients is uncommon. Accumulating data have shown that the benefit of NOACs is consistent among all age groups, featuring equal or greater efficacy in preventing thrombotic events. Excess bleedings were lower with NOACs in comparison to VKAs, but bleeding patterns were disparate among them and head to head comparison is not available. The present review highlights on the efficacy and safety of novel anticoagulants in the elderly population.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants post-kidney transplantation

BACKGROUND Novel oral anticoagulants(NOACs)were developed as alternatives to vitamin K antagonists,primarily warfarin,as they do not require routine monitoring and have limited drug-drug and drug-food interactions.However,the efficacy and safety of these agents in kidney transplantation are not well studied.AIM To assess the profile and safety of NOACs for patients who had kidney transplantation,and to provide recommendations and guidelines on therapeutic strategies in these patients.METHODS This was a retrospective study carried out among adult patients who were actively on the following NOACs(apixaban,rivaroxaban or dabigatran)in our renal transplantation program from December 2015 to December 2016.The patients were identified primarily through electronic medical record system(patient data linkage).Data on the clinical and laboratory profile of the patients were retrieved and analyzed with SPSS 22.0.RESULTS Complete data on 42 renal transplant patients were retrieved:59.5%males,90.5%were whites and 66.7%were older than 60 years old.The mean duration since renal transplantation of the patients was 8.8±7.4 years.The most common risk factors for the development of end-stage renal disease in the subjects were hypertension(19.0%),polycystic kidney disease(19.0%),followed by diabetic nephropathy(16.7%)and chronic glomerulonephritis(16.7%).The main indications for NOACs use in the cohort were atrial fibrillation in 25 patients(59.5%)and venous thromboembolism in 10 patients(23.8%).Overall,29 patients(69%)were treated with apixaban,10 patients(23.8%)with rivaroxaban and 3 patients(7.14%)with dabigatran.No(0%)thromboembolic events were observed during the one-year period,but 3(7.1%)bleeding events occurred in the cohort consisting of 1 patient treated with rivaroxaban 15 mg daily and 2 patients who received apixaban 2.5 mg twice daily.There were no significant changes in serum tacrolimus level three days after the initiation of NOACs among patients treated with tacrolimus(pre-and post-NOACs tacrolimus levels were 7.2516 and 7.8867 ng/m L,P=0.55,respectively).Also,after one-year of treatment with NOACs there were no significant changes in the pre-and post-NOACs serum creatinine level(P=0.772)and estimated glomerular filtration rates(P=0.232).CONCLUSION No thromboembolic events or significant changes in renal profile were observed in our cohort of kidney transplant recipients who were treated with NOACs for at least a year.However,a few bleeding events were observed.This calls for further well-planned randomized controlled trials to assess the efficacy and safety of NOACs among renal transplant recipients.

国内上市新型口服抗凝药预防非瓣膜性房颤卒中药物经济学研究系统评价

目的系统评价国内上市新型口服抗凝药(NOAC)预防非瓣膜性房颤(NVAF)卒中的经济性。方法计算机检索PubMed,Embase,The Cochrane Library数据库,以及中国知网(CNKI)、万方(WanFang)数据库、维普(VIP)数据库,收集使用国内上市的NOAC(利伐沙班、阿哌沙班、达比加群)和华法林预防NVAF卒中的经济学评价研究,检索时限为各数据库自建库起至2021年11月30日。由2名研究者根据标准独立筛选文献,并分别采用卫生经济评估报告综合标准(CHEERS)评估纳入文献的质量;描述性方法总结纳入文献的基本特征,归纳其经济学评价结果。结果共纳入10项研究,均为中国环境下的成本-效果或成本-效用研究、并经质量评价均有一定参考价值(得分>75%)。2014年至2019年的7项研究结果均显示,NOAC与华法林比较无成本-效果优势,而2021年的2项研究结果则显示NOAC比华法林更具有成本-效果优势。其中1项对比研究结果显示达比加群的成本-效果优于利伐沙班,更具有经济学优势。结论NOAC预防NVAF卒中可能比华法林更具有成本-效果优势。

BOPPPS结合超星学习通在口腔护理教学中的应用

目的:探讨BOPPPS教学法结合超星学习通在口腔护理教学的应用效果。方法:以2018级口腔护理专业学生为研究对象,分为对照组和试验组,分别采用学习通线上直播和BOPPPS结合超星学习通教学法,课程结束后对两组进行问卷调查和理论考试综合评估。结果:试验组对教学法更为满意(P<0.05),且试验组理论成绩均优于对照组(P<0.05)。结论:BOPPPS结合超星学习通教学法可提高口腔护理学的教学质量及其对教学方法的满意度。

新型口服抗凝药在心房颤动合并冠心病抗栓治疗中有效性及安全性的研究进展

心房颤动合并冠心病(冠状动脉粥样硬化性心脏病)抗栓治疗的选择一直是一个难题。在抗血小板的同时也需要抗凝治疗,选择抗栓治疗方案时,兼顾降低出血风险的同时又能取得最大的临床疗效是心房颤动合并冠心病抗栓治疗方案的关键。华法林作为心房颤动传统的抗凝药物,由于其自身的局限性,推动了新型口服抗凝药(NOAC)的兴起,在抗栓治疗中选择口服抗凝药有了新的选择和认识。然而NOAC在心房颤动合并冠心病患者中的临床疗效及安全性仍有一些争议。本文就NOAC应用于心房颤动合并冠心病患者抗栓治疗中的有效性及安全性作一综述。

再论明代公案小说的叙事策略及其成因——科举歧视、说唱与小说理念对叙事的影响

学界常感叹公案小说不如西方侦探小说那么引人入胜。但此类比较未能很好地结合中国文化环境,也忽略了“引人入胜”叙事方式的某些内在机制。法医学知识和细密的故事时间是破案严谨的基石。明代科举和教育体系歧视仵作,强化了文人与法医学知识的割裂。限制计时仪器的发展,因此故事时间较为模糊。说唱常渲染作案经过以强化善恶对立,史传文化按时序叙述,导致隐藏作案经过的方式散见却未成主流。拟话本的题目与入话会提前叙述后文,设置反转和悬念时易顾此失彼。虚构看似相关实则无关的线索,可强化悬念,也使重要的线索与反转更难被觉察,结局更出人意料。但明小说作者视“奇”与“通俗”为手段而非核心,所以很少虚构假线索。悬念、推理和反转多散见却未实现精致的融合。此外,中国独创的密室情节值得更多关注。

5-氨基酮戊酸光动力疗法治疗口腔潜在恶性疾患中药物因素影响的分析

目的探讨药物因素对5-氨基酮戊酸(ALA)光动力疗法治疗口腔潜在恶性疾患疗效的影响,以期提高临床疗效及推动临床合理用药。方法检索Pubmed、ISI Web of Knowledge数据库、中国知网、维普以及万方数据库中关于ALA光动力疗法治疗口腔潜在恶性疾患的临床研究,并进行文献分析。结果检索到ALA光动力疗法治疗口腔潜在恶性疾患的临床研究病例共690例,平均完全缓解率为65.94%;16.8%氨基酮戊酸甲酯乳膏组、局部外用组、每周1次组及预激活时间2~4 h组优于其他亚组,平均完全缓解率分别为100%、66.91%、78.28%及77.54%。结论药物因素对5-氨基酮戊酸光动力疗法治疗口腔潜在恶性疾患疗效有直接影响,从药物改良的角度开发新的口腔ALA制剂是提高疗效的重要途径。

新型口服抗凝药在经皮左心耳封堵术后应用的研究进展

心房颤动包括瓣膜性心房颤动与非瓣膜性心房颤动,具有发病率高、预后差等特点,严重威胁人类生命健康。经皮左心耳封堵术(PLAAC)已经广泛应用于治疗存在高出血风险或有口服抗凝药物禁忌证的非瓣膜性心房颤动患者,虽然PLAAC用于治疗难以耐受抗凝治疗风险的患者有一定的风险,但其仍然是治疗心房颤动患者的重要举措。器械相关血栓、缺血性脑卒中为PLAAC术后常见的并发症,临床上常采用华法林、维生素K拮抗剂等抗凝药物治疗,但这些药物的实际使用效果往往是次优的。目前,各指南推荐PLAAC术后以抗凝治疗为主的方案,抗凝治疗尤其是新型口服抗凝药(NOACs)在PLAAC术后应用的安全性与有效性仍需要进一步研究。本文归纳并探讨NOACs在PLAAC术后的应用研究。