Application of Animal Toxicology Data to Clinical Study of Experimental Drugs

The pharmaceutical industry performs safety studies in animals to underwrite administration of new chemical entities to man. Early clinical evaluation of drugs in volunteers is performed, generally, using highdose acute studies in rodents and 1-month repeat dose studies in one rodent species and one non-rodent species as a basis for risk assessment. Results from the 1-month toxicology studies enable a ceiling for initial clinical doses to be set and give some indication of the major target organs for toxicity. Extrapolation of these results to man helps determine the preliminary safety endpoints, including clinical chemistry parameters, for use in early clinical studies in man.Originally presented at ECCP 93.     

Myelography with a dimeric (iodixanol) and a monomeric (iohexol) contrast medium: a clinical multicentre comparative study

The purpose of this study was to evaluate and compare the radiographic efficacy and safety of iodixanol (Visipaque; 270 and 320 mg I/ml) and iohexol (Omnipaque; 300 mg I/ml) in myelography. The study was randomized, double-blind and comparative including 398 patients from five European university clinics. The radiographic visualisation was evaluated as poor, good or excellent. Adverse events were recorded by interviewing the patients after the myelography, and each patient was given a questionnaire to be returned after 1 week. In cervical myelography with cervical puncture more films with excellent quality was obtained after iodixanol 320 mgI/ml compared with iohexol 300 mgI/ml (p = 0.009). Also in lumbar myelography iodixanol 320 mgI/ml compared favourably with iohexol 300 mgI/ml (p = 0.006). The most frequent adverse event was headache, which occurred in 5–35 % of patients during the first 24 h and in 19–61 % within the first 7 days, depending on the centre. There was no difference in frequency and severity of the adverse effects between the contrast media. Received 13 March 1997; Revision received 29 December 1997; Accepted 5 January 1997     

Safety and efficacy of combined upper blepharoplasties and open Coronal Browlift: A consecutive series of 600 patients

Surgical rejuvenation of the upper face involves the correction of excess and lax forehead, eyelid, and periorbital skin. Improving the appearance by correcting the effects of aging involves a combination of blepharoplasty and open coronal foreheadplasty. Many surgeons and several reports question the safety of both procedures being performed concomitantly. The difficulty arises in precisely balancing the skin excision from the frontal forehead and upper eyelid areas. Over-resection of skin may result in incomplete closure of the eyelid and dry-eye syndrome, while an inadequate resection may produce a poor aesthetic result. There is no large series that documents the safety and effectiveness of these two procedures being performed concomitantly. Furthermore, with the recent and rapid development of complex multiplanar endoscopic facial rejuvenation techniques, the basic open forehead-plasty has become increasingly overlooked as a legitimate, efficacious technique for rejuvenation of the upper face. The technique utilized in this series is presented in detail. The consistently excellent results obtained satisfy the aesthetic goals of patients as well as the goals of surgeons, and suggest a renewed interest in the technique based upon its simplicity and easily reproducible results.     

基于FAERS的地舒单抗安全警戒信号挖掘与评价

基于FAERS数据库挖掘安全警戒信号,分析评估地舒单抗潜在不良反应信号,为其临床使用提供一定参考依据。方法 通过Openvigil 2.1访问 FAERS 数据库,将地舒单抗作为主要药物,检索自该药首次上市时间（2010年5月—2021年9月）的数据,获得与地舒单抗相关的不良事件报告记录。使用报告比值比法（ROR）和贝叶斯置信度递进神经网络法（BCPNN）筛选地舒单抗安全警戒信号,挖掘潜在的不良反应,并通过工具BioPortal对不良事件信号挖掘结果进行系统分类,通过判断信号间置信区间的变化,发现与药物不良事件关联性较大的信号。结果 从FAERS数据库中收集到270503份不良反应事件（ADE）报告,根据ROR法和BCPNN法共得到343个不良事件信号,通过信号间同义合并、剔除与药物无关的信号后,得到316个不良事件信号。地舒单抗的不良事件系统分类主要为肌肉骨骼和结缔组织疾病、医学检查、胃肠道疾病。FAERS数据库的信号挖掘结果发现,高风险且说明书中未收录的安全警戒信号包括颞下颌关节综合征、下颌脓肿、雌激素缺乏症、血液甲状旁腺激素增加,计算高风险信号的置信区间显示颞下关节综合征较有可能发展成为新的不良反应;另外,也发现种植体周围炎为具有临床意义的可疑警戒信号,但有待进一步观察研究。结论 基于FAERS数据库的信号挖掘结果提示临床应规范使用地舒单抗,治疗期间需警惕患者是否出现颞下颌关节综合征、下颌脓肿、雌激素缺乏症、血液甲状旁腺激素增加等不良反应事件,以便尽早发现尽早处理,从而有效降低临床用药风险     

Safety and efficacy of oral nemonoxacin versus levofloxacin in treatment of community-acquired pneumonia: A phase 3, multicenter,randomized, double-blind,double-dummy,active-controlled,non-inferiority trial

Background/Purpose

Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP.

Performance of platinum stimulating electrodes,mapped on the limitvoltage plane

The paper introduces the electrode limit-voltage plane (ELVP)—a useful tool for describing in electrical terms what a polarisable electrode is doing under a particular set of conditions. The ELVP is then used to consider the charge-injection capability of a platinum stimulating electrode.     

阿立哌唑与利培酮治疗精神分裂症的对照研究

目的 比较阿立哌唑与利培酮治疗精神分裂症的疗效.方法 60例符合CCMD-3精神分裂症患者分为两组各30例,分别予阿立哌唑(A组)和利培酮(B组)治疗6周,采用阳性症状与阴性症状量表及不良反应症状量表评定疗效与副反应.结果 两组疗效及不良反应发生率比较差异无显著性意义.结论 阿立哌唑和利培酮对精神分裂症疗效相当,副反应差异亦不显著;但在锥体外系反应,内分泌改变及体重增加方面,阿立哌唑优于利培酮.     

Electronic aspects of spinal-cord stimulation in multiple sclerosis

Patients receiving chronic spinal-cord stimulation in the management of multiple sclerosis have been stimulated at a frequency of 33 Hz, with pulses whose duration has been varied between 0·05 ms and 2·0 ms. Measurements on the stimulating pulses show that the energy requirement was at a minimum when the pulse duration was 0·2 ms. The current and energy requirements of different patients using 0·2 ms pulses vary over a large range but measurement of the current requirement of a particular patient can be a useful observation in predicting his response to treatment: low current requirements are often associated with a good response and high currents with a poor response to treatment. The use of 0·2 ms pulses of the amplitude we have used meets the safety requirements established by other workers and our results indicate that this pulse duration is optimal in terms of safety requirements, as well as energy requirements.     

经颅磁刺激安全性的实验研究

目的 :探讨重复经颅磁刺激的安全性。方法 :选用 3 6只健康Wistar大鼠 ,随机分为对照组 ,低频刺激组和高频刺激组 ,对低频组和高频组分别给予不同频率和强度的经颅磁刺激 ,然后对各组大鼠的行为、组织病理形态学、血清髓鞘碱性蛋白 (MBP)及神经元特异性烯醇化酶 (NSE)含量进行观察。结果 :低频刺激组 (5Hz)和高频刺激组 (2 0Hz)在刺激过程中均未出现异常活动 ,无肢体强直、阵挛等 ,脑组织形态学包括大体观察、普通光镜及电镜改变不明显 ,其血清MBP和NSE含量与正常对照组比较 ,差异无显著性意义 (P >0 0 5 )。结论 :在一定强度和频率内经颅磁刺激是一种比较安全的方法     

文拉法辛与米氮平治疗抑郁症的对照研究

目的 评价文拉法辛与米氮平治疗抑郁症的疗效及安全性.方法 将76例抑郁症患者随机分为两组,分别给予文拉法辛和米氮平治疗,疗程8周.用汉密尔顿抑郁量表(HAMD)评定临床疗效,副反应量表(TESS)评定不良反应.结果 文法拉辛显效率76.3%,有效率92.1%,米氮平组为73.7%,89.5%,两组疗效相仿.在治疗2周末时,文法拉辛组减分多于米氮平,差异有显著性.两组不良反应均轻微.结论 文拉法辛和米氮平抗抑郁疗效肯定,不良反应轻.