Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study

ABSTRACT

Objectives: Limited evidence has suggested that cefoperazone-sulbactam causes coagulation disorders and bleeding.

Methods: The authors conducted a retrospective study to compare patients receiving cefoperazone-sulbactam versus those treated with cefoperazone-tazobactam or ceftazidime. Propensity-score matching was used to explore whether treatment with cefoperazone-sulbactam increased the risk of prothrombin time (PT) prolongation, coagulation disorders, and bleeding, or decreased platelets (PLT).

Results: The cohort included 23,242 patients. Among patients receiving cefoperazone-sulbactam, the risk of PT prolongation, coagulation disorders, decreased PLT, and bleeding was 5.3%, 9.2%, 15.7%, and 4.2%, respectively. Propensity-score matching analyses suggested that cefoperazone-sulbactam increased the risk of PT prolongation (aOR 2.26, 95% CI 1.61–3.18), coagulation disorders (aOR 1.81, 95% CI 1.43–2.30), and decreased PLT (aOR 1.46, 95% CI 1.25–1.72), but not increase bleeding (aOR 1.05, 95% CI 0.79–1.40) compared with ceftazidime. Patients receiving cefoperazone-sulbactam had higher risk of PT prolongation (aOR 1.53, 95% CI 1.11–2.10), coagulation disorders (aOR 1.53, 95% CI 1.21–1.95), but not decreased PLT (aOR 0.93, 95% CI 0.81–1.07) or bleeding (aOR 1.11, 95% CI 0.87–1.42), compared with those receiving cefoperazone-tazobactam.

Conclusion: Cefoperazone-sulbactam may be associated with a higher risk of PT prolongation and coagulation disorders compared with cefoperazone-tazobactam and ceftazidime.     

妇宝胶囊止血机制的实验研究

目的:通过观察妇宝胶囊对动物出凝血时间、血液凝固系统的影响,探讨妇宝胶囊的止血机制。方法:采用毛细玻璃管法测定小鼠凝血时间(CT),用断尾法测定出血时间(BT);用ACL-200型血液凝集仪测定大鼠凝血酶原时间(PT)和部分凝血活酶时间(APTT)。结果:妇宝胶囊能明显缩短小鼠CT、BT,缩短大鼠PT和APTT。结论:妇宝胶囊的止血机制主要通过促进内源性和外源性凝血系统,抑制纤维蛋白溶解系统达到目的。     

Prothrombin times and activated partial thromboplastin times in toxicology: a comparison of different blood withdrawal sites for wistar rats

The prothrombin time (PT) and the activated partial thromboplastin time (APTT) for untreated male Wistar rats were determined on the Sysmex CA-5000 Instrument for blood taken from the orbital sinus, tail vein, vena cava and aorta. Boxplot and statistical analysis was performed. Only orbital sinus puncture yields unpredictable and unacceptable variation/prolongation of clotting times.     

Post-conference session: Experience with patient self-management of oral anticoagulation

Long-term oral anticoagulation requires careful patient monitoring in order to optimize results and to limit hemorrhagic or thromboembolic complications of treatment. For this reason, any improvement in anticoagulant control and management can be expected to have far-reaching consequences in extending longevity and decreasing complications in anticoagulated patients after heart valve surgery. Because one attractive means of improving anticoagulant management is to give patients a share of the responsibility, a program was designed to encourage patients to take an active role in monitoring their own prothrombin time (PT) and managing their own oral anticoagulation. During the period from August 1986 to February 1992, 600 patients requiring long-term anticoagulation, mainly after heart valve replacement, were trained to measure their own PT at the Cardiac Rehabilitation Center (Herz-Krauslauf-Klinik, Bad Berleburg, Germany) and to manage their own therapy: 216 patients could be followed with regard to their self-determined prothrombin times. The results were within the target range in 83.1% of the PT determinations (n=12,306 measurements) taken by the patients themselves. Neither major bleeding nor thromboembolic complications were observed in 205 patient-years of self-monitoring of PT and self-management of oral anticoagulation.     

Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

17 alpha-Alkylated androgens are highly effective in preventing attacks in HAE patients. These drugs, however, seem to be implicated in the development of cholestatic jaundice, peliosis hepatis, and liver tumors. In order to assess the risk-benefit balance of the long-term therapy with androgen derivatives, a follow-up investigation was performed in 13 HAE patients. The results of this study indicate that long-term treatment (15 to 47 mo) with low doses of danazol or stanozolol does not induce significant hepatic damage detectable by laboratory tests or liver biopsy. However, the limited number of patients, although in a rather long period of observation, still suggests a careful control and the use of minimal effective doses.     

Influences of different adenosine receptor subtypes on catalepsy in mice

The effects of adenosine A₁ and A₂ receptors on catalepsy were studied in mice. The adenosine agonists 5-N-ethylcarboxamide-adenosine (NECA), N⁶-phenylisopropyladenosine (PIA) and N⁶-cyclohexyladenosine (CHA) induced dose dependent catalepsy. The A₁ adenosine antagonist 8-phenyltheophylline (8-PT) potentiated catalepsy induced by NECA, R-PIA and CHA. However, theophylline did not potentiate but inhibited the responses induced by NECA, R-PIA and CHA. Neither 8-PT nor theophylline alone has any effect on catalepsy in mice. It is concluded that catalepsy induced by the adenosine agonists may be due to A₂ receptor stimulation and that the A₁ antagonism may potentiate the response.     

脑卒中失语康复综合治疗的临床研究

目的 :观察传统医学与现代康复医学结合治疗脑卒中的失语的临床疗效。方法将 6 0患者随机分成 ,治疗组 30例和对照组 30例 ,治疗 2 0日后疗效评定。结果与结论治疗组综合疗效高于对照组 (P<0 .0 5 )。     

国际敏感指数在血浆凝血酶原时间测定中的应用

目的 :分析在测定 PT- INR实验过程中建立实验室敏感指数 (L ocal ISI)值的方法和必要性。方法 :在 CA- 15 0 0全自动凝血仪上使用 INR定标血浆建立 INR标准曲线 ,并做回归分析 ,计算出 L ocal ISI值 ,并利用 Dade- behring公司产品 Thromborel S凝血活酶试剂 ISI值和 L ocal ISI值分别测定 4 3例正常对照组和 2 0例长期口服抗凝药物治疗患者的凝血酶原时间 PT- INR,对两组结果进行统计处理。结果 :经校正本实验所用 Dade- behring公司产品 Throm borel S凝血活酶试剂 L ocal ISI值为 1.10 ,高于厂家提供的 ISI值。两组受试者利用 L ocal ISI值和 ISI值测定所得 PT- INR值差异有极显著性 (P<0 .0 1) L ocal ISI值组明显高于 ISI值组。结论 :直接利用试剂厂家标定的 ISI值进行 PT- INR值测定可能造成误差 ,仍应用 PT- INR定标血浆仪器上进行校正。利用实验室敏感指数 (L ocal ISI)值测定 PT- INR具有可信性 ,可应用于口服抗凝药物治疗监测     

Oral Anticoagulation in Patients With Liver Disease

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are “auto-anticoagulated” and thus protected from thrombotic events. Warfarin and non–vitamin K–antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population.