Pregnancy and the mechanical prosthetic valve: dilemmas about the choice of antithrombotic prophylaxis

Two pregnant women aged 32 and 34, both of whom had mechanical prosthetic mitral valves, for which they were using low molecular weight heparin. One developed orthopnoea and dyspnoea at 36 weeks amenorrhoea, and the other suffered an acute myocardial infarction at 18 weeks. Both had valvular thrombosis. Following effective treatment, both women delivered at term and one week later after an uncomplicated course, were discharged home from hospital. Clinicians caring for pregnantwomen with mechanical prosthetic valves are faced with a dilemma when trying to provide optimal treatment. Inadequate anticoagulant therapy can result in thrombosis of the mechanical prosthetic valve while, on the other hand, anticoagulant therapy is associated with foetal and maternal bleeding and teratogenic effects. Pregnant women with mechanical prosthetic valves should be thoroughly counselled before or shortly after the confirmation of pregnancy regarding the risks associated with available anticoagulant options, allowing them to make an informed decision concerning the best management plan. This is an algorithm for optimal care of these patients.     

下肢深静脉血栓形成患者抗凝蛋白缺陷的临床研究

目的探讨中国人群下肢深静脉血栓形成(LDVT)患者抗凝蛋白缺陷的发生率。方法检测100例LDVT患者和100例健康成人的抗凝血酶(AT)、蛋白S(PS)、蛋白C(PC)活性及活化蛋白C抵抗性(APCR)。结果与正常对照组相比,LDVT组AT、PS、PC活性明显降低,APCR阳性率明显升高,差异有高度统计学意义(P<0.01);本组100例LDVT患者抗凝蛋白缺陷的总发生率为25%(25100),以PS缺陷的发生率最高,为13%(13100),其次是PC,为8%(8100),AT缺陷占5%(5100),APCR缺陷的发生率最小,为4%(4100)。结论先天性或获得性抗凝蛋白缺陷是中国人群LDVT发病和复发的重要机制之一,因此有必要对LDVT病人进行抗凝蛋白水平的筛选。     

The incidence of endocarditis caused by a prosthetic valve and its risk factors

To study the incidence and risk factors of prosthetic valve endocarditis (PVE) we followed 99.5% of 912 patients who had valve replacement from January 1, 1981 through December 31, 1985, for 1 to 6 (mean 3) years. PVE occurred in 27 patients (2.96% or 0.98% per patient-year). The incidence of PVE in the aortic position (3.9%) was significantly higher than in the mitral position (1.5%): p less than 0.25. PVE developed in 19 out of 329 patients with bioprostheses (5.8%) and in 8 out of 583 patients with mechanical valves (1.4%): p less than 0.005. Actuarially at 5 years follow-up 90.7% of the bioprosthetic group and 98.4% of the mechanical valve group was free of PVE (p less than 0.01). Bioprosthetic valve replacement in infective endocarditis further increased the risk of PVE compared to valve replacement by mechanical prostheses. In conclusion: in order of importance antecedent endocarditis, bioprostheses, male sex and aortic position are risk factors in the development of PVE. In patients requiring operation for infective endocarditis, mechanical valves are recommended. As the outcome of PVE is still very grave, authors stress the importance of prophylaxis, early diagnosis and timely operation.     

超高效液相色谱法测定血浆华法林浓度及临床应用

目的建立超高效液相色谱法(ultra performance liquid chromatography,UPLC)测定血浆华法林浓度,探讨心脏换瓣术后患者华法林血药浓度与国际标准化比率(international normalized ratio,INR)测值的关系,以寻求更安全可靠的监测指标,指导临床抗凝治疗的合理用药。 方法利用6-甲氧基萘乙酸作为内标,建立一种超高效液相色谱法,测定血浆中的华法林浓度。同时对79例样本的INR、华法林剂量和血浆华法林浓度进行相关性分析。 结果华法林和内标的保留时间分别是2.2和1.1 min,血浆中华法林的平均提取回收率为96.0%,华法林浓度在15.6~4000 ng/ml具有良好的线性(R²=0.9996),方法回收率为98.5%~99.9%,最低检测限为5.0 ng/ml。日内和日间精密度分别低于1.34%和2.69%。79例患者INR和华法林剂量相关性为r²=0.006(P=0.481),INR和血浆华法林浓度为r²=0.006(P=0.497),华法林剂量和血浆浓度相关性为r²=0.298(P=0.001)。 结论该方法是一种简便、快速、准确、灵敏的定量测定人体血浆中华法林浓度的UPLC方法,华法林血药浓度测定对于心脏瓣膜置换手术后患者的抗凝治疗具有指导意义。     

Systemic thrombolysis in acute obstruction of an artificial valve

Prosthetic valve thrombosis is a characteristic, but fortunately not frequent complication of surgical valve replacement. Its occurrence may lead to haemodynamic catastrophe. Three cases involving prosthetic valve thrombosis are presented. Two patients suffered from thrombosis after tricuspid valve replacement (St. Jude Medical), while the third occurred after mitral valve replacement (Sorin). In the acute phase, systemic thrombolysis was initiated (2 MU Streptokinase during 22-28 hours). The obstruction of one of the tricuspid valves and the mitral valve was eliminated. Lysis of the other tricuspid valve was not complete, but it helped the patient to survive the acute phase until reoperation. Embolization occurred in the inferior extremity after thrombolysis of the mitral prosthetic valve, but it was cured. Two-dimensional and Doppler echocardiography (conventional and colour-coded) played an important role in the diagnosis of the obstruction and in the follow-up of the effectivity of thrombolysis. Systemic thrombolysis may be a lifesaving procedure in acute prosthetic valve thrombosis. In spite of the potentially dangerous complications, it has to be attempted.     

华法林对围产期心肌病抗凝治疗的临床观察

目的通过对比接受华法林治疗3个月与6个月时的临床效果,以探讨华法林对围产期心肌病患者的影响。方法选择2010年12月-2012年12月住院的42例围产期心肌病患者作为研究对象．按照入院顺序将上述患者随机分为两组．两组患者均予以抗心力衰竭治疗,20例（A组）使用华法林治疗3个月,22例（B组）使用华法林治疗6个月,调整华法林剂量将国际标准化比值维持在2．0～3．0,观察比较两组血浆D-二聚体、深静脉血栓和出血率。结果两组治疗后D-二聚体水平显著下降,B组的下降效果明显好于A组,随访发现B组的深静脉血栓形成率明显低于A组,两组出血率比较不存在显著性差异。结论华法林对围产期心肌病抗凝效果明显。持续治疗时间可能是影响抗凝效果的重要因素。     

Economic Evaluation of the Combined Use of Warfarin and Low-dose Aspirin Versus Warfarin Alone in Mechanical Valve Prostheses

Background

The use of combined therapy of antiplatelet and anticoagulant versus anticoagulant alone to reduce instances of thromboembolic events in patients with heart valve prostheses is an established standard of care in many countries but not in Egypt. A previous Markov model cost-effectiveness study on Egyptian patients aged 50–60 years demonstrated that the combined therapy reduces the overall treatment cost. However, due to the lack of actual real-world data on cost-effectiveness and the limitation of the Markov model study to 50- to 60-year-old patients, the Egyptian medical community is still questioning whether the added benefit is worth the cost.

Objective

To assess, from the perspective of the Egyptian health sector, the cost-effectiveness of the combined use of warfarin and low-dose aspirin (75 mg) versus that of warfarin alone in patients with mechanical heart valve prostheses who began therapy between the age of 15 and 50 years.

Methods

An economic evaluation was conducted alongside a randomized, controlled trial to assess the cost-effectiveness of the combined therapy in patients with mechanical valve prostheses. A total of 316 patients aged between 15 and 50 years were included in the study and randomly assigned to a group treated with both warfarin and aspirin or a group treated with warfarin alone.

Results

The patients in the combined therapy group exhibited a significantly longer duration of protection against the first event. Fewer primary events were observed in the patients treated with warfarin plus aspirin than in those treated with warfarin alone (1.4 %/year, vs. 4.8 %/year), and a higher mean quality-adjusted life-years (QALYs) value over 4 years was obtained for the group treated with warfarin plus aspirin (difference 0.058; 95 % CI 0.013–0.118), although this difference did not reach a conventional level of statistical significance. The total costs over a 4-year period were lower with the combined therapy (difference ?US$244; 95 % CI ?US$483.1 to ?US$3.8), which yielded an incremental cost-effectiveness ratio of ?US$4206 per QALY gained. Thus, the combined therapy was dominant. All costs were reported in US dollars (USD) for the financial year 2014.

Conclusions

The results of this analysis indicate that from the perspective of the Egyptian health sector, the addition of aspirin to the typical warfarin therapy is more effective and less costly for patients with mechanical valve prostheses than treatment with warfarin alone. This combined strategy could be adopted to prevent the complications of mechanical valve prostheses. Our study adds to the body of evidence supporting the option of warfarin-plus-aspirin therapy for patients with mechanical valve prostheses.

     

Two years experience with the Pericarbon stentless valve in Hungary

OBJECTIVE: In 1999 stentless heart valves were introduced for treatment of the aortic valve disease in elderly patients at the Department of Cardiac Surgery of the University of Debrecen. PATIENTS, METHODS: Between December 1999 and November 2001 63 patients underwent aortic valve replacement with Sorin Pericarbon stentless valve. The mean gradient was 80 +/- 11 mmHg, the left ventricular wall thickness was 15.5 +/- 0.7 mm and the ejection fraction was 54 +/- 8% preoperatively. 4 patients were in NYHA II, 47 in NYHA III and 12 in NYHA IV functional class. 42 patients had isolated aortic valve replacement, the remaining 21 patients underwent combined surgical procedure. The aortic x-clamp and perfusion times were 125 +/- 27 and 153 +/- 48 minutes respectively. Nine 21 mm, twenty-three 23 mm, seventeen 25 mm, twelve 27 mm and two 29 mm valves were implanted. RESULTS: The hospital mortality was 6% (four patients). Transient atrial fibrillation was the most frequent postoperative complication. 77% of the patients had uneventful recovery and left hospital one week after surgery. Transthoracic echocardiography was performed at all patients before discharge and in December 2001. The mean follow up time was 9.7 +/- 5.8 months. 86% of the patients were in NYHA I functional class at the time of the follow up. The mean and peak transvalvular gradients were 9.4 +/- 4.1 mmHg and 16.1 +/- 6.8 mmHg respectively. The left ventricular wall thickness has decreased significantly (12.5 +/- 1.1 mm). CONCLUSION: The Sorin Pericarbon stentless valve is an easily implantable valve replacement device. Due to the excellent hemodynamic properties and the unnecessary anticoagulation it could be safely used in elderly patients.     

机械瓣置换术后永久性起搏器植入率及危险因素分析

目的:分析机械瓣置换术后永久性起搏器植入率及其危险因素。方法:选取本院2010年1月~2019年1月收治的852例行机械瓣置换术进行治疗的患者作为研究对象,开展回顾性分析研究,统计机械瓣置换术后永久性起搏器植入率,然后将永久性起搏器植入患者作为研究组,将其非永久性起搏器植入患者作为对照组,分析永久性起搏器植入危险因素。结果:852例机械瓣置换术患者中共有31例患者植入永久性起搏器,永久性起搏器置入率为3.64%,包括6例患者近期植入,3例患者中期植入和22例患者远期植入。研究组患者的年龄以及房颤患者比例分别为(54.25±8.42)岁和48.39%(15/31),分别高于对照组患者的(46.23±7.69)岁和17.30%(142/821)(P<0.05)。结论:机械瓣置换术后永久性起搏器植入率目前处于较低的水平,远期植入率显著高于中期和近期植入率,年龄和房颤是机械瓣置换术后永久性起搏器植入的危险因素。     

Haplogroup analysis of vitamin-K epoxide reductase (VKORC1) gene: novel element in the optimization of anticoagulant therapy

Warfarin and acenocoumarols are the most commonly prescribed anticoagulants that is difficult to use because of the wide intra- and interpatient variation in the dose requirements, the narrow therapeutic range and the risk of serious bleeding. Vitamin K epoxide reductase (VKORC1) is the site of inhibition by coumarins. Mutations in the VKORC1 gene affect the sensitivity of the epoxy reductase enzyme for warfarin. The three main haplotypes of VKORC1 gene, *2, *3, *4, explain most of the genetic variability in warfarin dose among Caucasians. In the current paper we focus on this subject in view of our experience gained during molecular genetic tests for the main VKORC1 haplotypes in Hungarian patients with anticoagulant therapy and unusual clinical response. A total of 28 selected cases were characterized for VKORC1 G-1639A, G9041A and C6009T alleles. Genotyping has been carried out by molecular biology techniques, including PCR-RFLP assay and direct sequencing. In patients undergoing anticoagulant therapy we could identify VKORC1 *1*2, *2*2, *2*3, *1*4, *2*4 and *3*4 haplotypes. Patients with A haplotype group (14% of the studied patients) require much lower warfarin doses than other patients (2.7+/-0.2 mg/day). In our patients we found some with B haplotype group (25%) who require high warfarin dose (6.2+/-0.3 mg/day). There were also subjects bearing the A/B haplotype group (61%) with intermediate warfarin dose (4.9+/-0.2 mg/day), estimated by the haplotype analyses of the VKORC1 gene. Results presented here underline the need of VKORC1 haplotyping in anticoagulated patients with unusual clinical anticoagulant response, and the examination can have further therapeutic consequences.     

深静脉血栓患者血浆蛋白Z水平的研究

目的研究深静脉血栓(DVT)患者的血浆蛋白Z(PZ)水平,探讨DVT和PZ的相关性。方法采用酶联免疫吸附检测(ELISA)法测定68例DVT患者和55名健康人的蛋白Z水平;采用发色法测定蛋白C(PC),抗凝血酶(AT);采用凝固法测定蛋白S(PS)活性。结果DVT组PZ、PC、PS、AT水平分别为:PZ(1.31±0.60)mg/L,PC(123±25)%,PS(54±23)%,AT(114±17)%;健康对照组PZ、PC、PS、AT水平分别为:PZ(1.11±0.51)mg/L,PC(135±26)%,PS(68±17)%,AT(130±8)%。两组PZ水平无显著性差异(P>0.05);两组PC,PS,AT活性有显著性差异(P<0.05)。DVT组男性和女性PZ水平分别为(1.34±0.61)mg/L和(1.27±0.60)mg/L,健康对照组男性和女性PZ水平分别为(1.09±0.55)mg/L和(1.12±0.49)mg/L,不同性别之间PZ水平无显著性差异(P>0.05)。结论DVT患者和健康人的PC,PS和AT水平有显著性差异,DVT和PC,PS和AT水平具有相关性。DVT患者和健康人的PZ水平无显...     

Perioperative management of patients on oral anticoagulants: a decision analysis.

BACKGROUND: To better inform clinicians on the optimal management of patients on oral anticoagulation who need to undergo surgery or invasive procedures, the authors performed a decision analysis examining whether a perioperative aggressive or minimalist strategy results in greater quality-adjusted survival. METHODS: A decision analysis model was created comparing withholding warfarin (minimalist strategy) to withholding warfarin and administering treatment-dose subcutaneous low-molecular-weight heparin (LMWH) or intravenous heparin perioperatively (aggressive strategy). The base-case analysis examined a hypothetical 60-year-old hypertensive individual with mechanical aortic valve replacement undergoing major abdominal surgery. A probabilistic sensitivity analysis was performed using a Monte Carlo simulation with quality-adjusted life expectancy (QALE) as the outcome. Secondary analyses examined patients with a mechanical mitral valve and atrial fibrillation. Sensitivity analyses were performed for each variable. RESULTS: Under the base-case scenario, the minimalist strategy was preferred for 78% of trials in the Monte Carlo simulation, with a mean benefit of 0.003 years (95% confidence interval, -0.005 years to 0.011 years). Sensitivity analyses based on point estimates indicate that the aggressive strategy is preferred when the annual stroke rate is >5.6% or the increase in postoperative major bleeding induced by heparin is <2.0%; however, the benefit is small over the range of plausible values. CONCLUSIONS: For most patients with a mechanical aortic valve or atrial fibrillation undergoing major surgery, a minimalist strategy of simply withholding oral anticoagulation provides similar QALE as an aggressive strategy of administering perioperative subcutaneous LMWH or intravenous heparin. The aggressive therapy provides greater QALE for patients at higher risk of stroke (e.g., mechanical mitral valves), although the benefit is small.     

机械瓣膜置换术后华法林对妊娠与分娩过程的影响

目的:探讨心脏瓣膜置换术后产妇适合的抗凝方案以及华法林对妊娠和分娩过程的影响。方法:回顾性分析该院1998年1月~2004年12月的23例机械瓣膜置换术后妊娠、分娩的病例资料。21例于12周前换用肝素,有2例始终服用华法林,其中17例足月分娩,均37周左右住院,术前3 d华法林改用肝素钠,监测APTT值,术后24 h恢复华法林。结果:6例为早中期流产或死胎而中止,其中3例为3个月前流产。17例分娩均行剖宫产,新生儿体重2 600~3 500 g,有4例出现不同形式的胎儿畸形,2例一直服用华法林未换肝素钠者,其胎儿为正常儿。所有孕妇分娩后心功能均维持在Ⅰ~Ⅱ级,术中出血量为(247±139)m l,无严重出血及栓塞等并发症而导致的死亡病例。结论:妊娠期间口服华法林能有效防止血栓形成,且不会增加分娩时母婴出血,但可能对胎儿畸形和流产有一定的影响。     

心脏机械换瓣术后妊娠妇女孕期处理效果的临床观察

目的:探讨心脏机械瓣膜置换术后妊娠妇女孕期终止妊娠的方式、孕期抗凝以及母婴并发症。方法:对32例次有记录换瓣术后妇女妊娠期的处理进行回顾性分析。结果:32例次妊娠中,14例次非意愿性妊娠,2例人流后放置曼月乐环效果好;整个孕期均常规应用华发林抗凝,无1例孕产妇发生瓣膜血栓和栓子栓塞并发症,胎儿发生流产3例,死胎1例,畸形2例。15例次晚期妊娠,11例择期剖宫产,其中1例发生产后大出血,1例急诊剖宫产出现产后大出血,3例阴道分娩中1例产后大出血;1例孕妇中孕引产过程中发生心衰,同时产后大出血。结论:换瓣术后生育年龄妇女急需有效控制生育,曼月乐环可能满足她们的需要;孕期单一、小剂量华发林抗凝对孕产妇比较安全;终止妊娠方式宜选择择期剖宫产。     

Long-term anticoagulant treatment after acute myocardial infarction. The Warfarin Re-Infarction Study.

High levels of fibrinogen and clotting factor VII are associated with an increased risk for subsequent death and cardiovascular disease in apparently healthy individuals. Furthermore, pathoanatomic studies and coronary angiography have confirmed a relationship between coronary thrombus formation and acute Q-wave infarction. Effective antithrombotic agents may prevent or limit thrombus formation and events related to thrombosis. The Warfarin Re-Infarction Study (WARIS) studied the effect of warfarin in survivors of acute myocardial infarction. Patients aged 75 years or less were randomized in a double-blind, placebo-controlled study to test whether long-term treatment with warfarin reduces the risk of death, reinfarction, and thromboembolic morbidity. A total of 1918 patients were screened for participation; 1214 were recruited. The mean follow-up was 37 months. Analyzed on an intention-to-treat basis, 123 (20%) in the placebo group died, versus 94 (15%) in the warfarin group, a risk reduction of 24% (P = 0.026). Considering patients on treatment or within 28 days after discontinuing the test medication, 92 in the placebo group died, as compared with 60 of the warfarin-treated patients, a risk reduction of 35% (P = 0.005). Relapsing myocardial infarction (fatal and nonfatal) was reduced by 43% (P = 0.0001). The incidence of cerebrovascular attacks was lower in the warfarin group (16 patients) than the placebo group (41 patients), a highly significant reduction of 61% (P = 0.0003). Serious bleeding occurred in 11 patients taking warfarin, an incidence of 0.6% per year. In conclusion, long-term anticoagulant therapy may be recommended after acute myocardial infarction.     

Ximelagatran: direct thrombin inhibitor

Warfarin sodium is an effective oral anticoagulant drug. However, warfarin has a narrow therapeutic window with significant risks of hemorrhage at therapeutic concentrations. Dosing is difficult and requires frequent monitoring. New oral anticoagulant agents are required to improve current anticoagulant therapy. Furthermore, while warfarin is effective in venous disease, it does not provide more than 60% risk reduction compared with placebo in venous thrombosis prophylaxis and considerably lower risk reduction in terms of arterial thrombosis. Ximelagatran is an oral pro-drug of melagatran, a synthetic small peptidomimetic with direct thrombin inhibitory actions and anticoagulant activity. As an oral agent, ximelagatran has a number of desirable properties including a rapid onset of action, fixed dosing, stable absorption, apparent low potential for medication interactions, and no requirement for monitoring of drug levels or dose adjustment. It has a short plasma elimination half-life of about 4 hours in cases of unexpected hemorrhage or need for reversal. Its main toxicity relates to the development of abnormal liver biochemistry and/or liver dysfunction with "long-term" use of the drug. This usually occurs within the first 6 months of commencing therapy, with a small percentage of patients developing jaundice. The biochemical abnormality usually resolves despite continuation of the drug. The cause of this toxicity remains unknown. Clinical studies to date have shown that ximelagatran is noninferior to warfarin in stroke prevention in patients with nonvalvular atrial fibrillation, noninferior to standard therapy as acute and extended therapy of deep vein thrombosis (DVT), and superior to warfarin for the prevention of venous thromboembolism post-major orthopedic surgery. It has also been shown to be more effective than aspirin alone for prevention of recurrent major cardiovascular events in patients with recent myocardial infarction.     

The incidence of PICC line-associated thrombosis with and without the use of prophylactic anticoagulants

BACKGROUND: Indications for peripherally inserted central catheters (PICC) for long-term venous access have grown during the last several years. There are various complications associated with PICC lines, a common one being venous thrombosis. This study's purpose was to determine the incidence of venous thrombosis associated with PICCs with and without prophylactic anticoagulants. METHODS: In this observational, prospective, cohort study, patients with PICC lines were evaluated using Doppler ultrasound for the presence of PICC-associated venous thrombosis at 5-7 days and again at 12-14 days after line placement. When present, clinical signs and symptoms of thrombosis were documented. Fifty-six patients were evaluated for the type of anticoagulation used, if any, and other clinical parameters such as smoking, ambulation, and previous surgery. The incidence of thrombus was then calculated for the entire population as well as for specific patient subgroups. RESULTS: Patient age was 55.7 +/- 2.6 (mean +/- SEM) years, and BMI was 28.2 +/- 1.2 (n = 56). There were 38 (67.9%) nonambulatory subjects, 15 (26.8%) smokers, 4 (7.1%) coagulopathic subjects, 2 (3.6%) patients receiving estrogen-containing medications, 25 (44.6%) who had undergone surgery within the past 6 months, and 5 (8.9%) cancer patients. There were 21/56 patients (37.5%) with thrombus. Patients who received anticoagulation had a 22.9% (8/35) incidence of thrombosis, which was significantly less (P < .05) than for those who received no anticoagulant (13/21, 61.9%). CONCLUSION: The use of anticoagulants for prophylaxis in patients with a PICC line was associated with a decreased rate of associated venous thrombosis.     

Comparison of hospital length of stay between hospitalized non-valvular atrial fibrillation patients treated with either apixaban or warfarin

Background. Hospital length of stay (LOS) is an important cost driver for hospitals and payers alike. Hospitalized non-valvular atrial fibrillation (NVAF) patients treated with apixaban may have shorter LOS than those treated with warfarin because of the absence of need for INR monitoring in apixaban. Thus, this study compared hospital LOS between hospitalized NVAF patients treated with either apixaban or warfarin. Methods. This was a retrospective, observational cohort study based on a large US database including diagnosis, procedure, and drug administration information from >600 acute-care hospitals. Patients selected for study were aged ≥18 years and had a hospitalization record with an ICD-9-CM diagnosis code for atrial fibrillation (AF) in any position from 1 January 2013 to 28 February 2014 (index hospitalization). Patients with diagnoses indicative of rheumatic mitral valvular heart disease or a valve replacement procedure during index hospitalization were excluded. Patients were required to have been treated with either apixaban or warfarin, and not treated with rivaroxaban or dabigatran, during index hospitalization. Apixaban patients were propensity score (PS) matched to warfarin patients at a 1:1 ratio, using patient demographic/clinical and hospital characteristics. The study outcome was hospital LOS, calculated as discharge date minus admission date; a sensitivity analysis calculated hospital LOS as discharge date minus first anticoagulant administration date. Sub-analyses were conducted among patients with a primary diagnosis of AF. Results. The study included 832 apixaban patients matched to 832 warfarin patients. Mean [standard deviation (SD)] and median hospital LOS were significantly (p < 0.001) shorter in apixaban patients (4.5 [4.2] and 3 days) than in warfarin patients (5.4 [5.0] and 4). Results were consistent in the sensitivity and sub-analyses. Conclusions. Among NVAF patients, apixaban treatment was associated with shorter hospital LOS when compared with warfarin treatment. These findings may have important clinical and economic implications for hospitals, payers, and patients.     

Assessment of healthcare professionals' knowledge about warfarin-vitamin K drug-nutrient interactions

OBJECTIVE: Dietary vitamin K can interact with oral anticoagulant drugs and interfere with their therapeutic safety and efficacy. Therefore, knowledge about drug-nutrient interactions involving vitamin K possessed by physicians, pharmacists, dietitians and nurses practicing anticoagulant therapy was assessed. METHODS: Healthcare practitioners were surveyed using a 30-question, 98-item questionnaire on the most common and/or important food interactions with warfarin, drug interactions with warfarin and general drug-nutrient interactions involving vitamin K. The study sample included 160 randomly selected healthcare providers (40 physicians, pharmacists, dietitians and nurses) from 10 hospitals with 200 to 1000 beds from six Massachusetts regions. Random selection was conducted from a pool of selected healthcare providers practicing anticoagulant therapy who counsel patients receiving warfarin. RESULTS: All surveys were completed within three months of the start of the study, and all participants provided usable data for statistical analysis. The mean scores (+/- SD) on the overall test were 72.5+/-9.0 for pharmacists, 62.51+/-10.6 for physicians, 56.9+/-8.8 for dietitians and 50.2+/-9.3 for nurses, with 100 being a perfect score. Pharmacists scored significantly higher in the area of drug interactions (75.9+/-11.3, p<0.05). Dietitians scored higher in the area of food interactions (73.0+/-10.3). No significant differences between physicians and pharmacists were evident on general drug-nutrient interactions. While over 87% of the healthcare professionals correctly identified some common foods containing large amounts of vitamin K, such as broccoli and spinach, fewer than 25% were able to identify others such as pea soup, coleslaw and dill pickles. CONCLUSIONS: Although the healthcare professionals surveyed in this study appear to have demonstrated some proficiency in their respective areas of expertise, they exhibited less knowledge in others. Therefore, additional training and integration of knowledge and expertise about drug-nutrient interactions among healthcare professionals are essential to provide appropriate patient counseling and optimal therapeutic outcomes.     

氯诺昔康术后镇痛对二尖瓣置换患者内皮素-1的影响与脑保护

目的 观察术后患者静脉自控镇痛(PCIA)对二尖瓣置换患者血浆内皮素-1(ET-1)水平的影响.方法 将120例ASA分级Ⅱ～Ⅲ级择期行二尖瓣置换手术患者按随机数字表法分为四组,每组各30例,术后接受不同镇痛方法 :L组PCLA氯诺昔康16μg/(kg·h),F组PCIA芬太尼0.2μg/(kg·h),T组PCIA曲马多0.2 mg/(kg·h),D组未行PCIA.记录术后8、12、24和48 h的静息疼痛视觉模拟评分(VAS)和Ramsay镇静评分.于术前及术后8、12、24 h采血检测血浆ET-1水平.结果术后8、12h,L、F及T组VAS均显著低于D组(P<0.05).L组和D组术后各时间点Ramsay镇静评分显著低于F组和T组(P<0.05).L、F及T组患者术后8、12及24h的血浆ET-1水平显著低于D组(P<0.05).L组和D组患者术后嗜睡、恶心、呕吐发生率[L组:3.3%(1/30)、3.3%(1/30)、0;D组:均为0]低于F组和T组[F组:13.3%(4/13)、13.3%(4/13)、10.0%(3/30);T组:10.0%(3/30)、26.7%(8/30)、16.7%(5/30)](P<0.05).结论 氯诺昔康、芬太尼及曲马多行PCIA均有利于抑制二尖瓣置换术后应激导致的血浆ET-1水平增高,氯诺昔康PCIA更适合于二尖瓣置换术后镇痛.