噻托溴铵治疗慢性阻塞性肺病的进展

噻托溴铵（tiotropium bromide）是一个新型的治疗慢性阻塞性肺病（COPD）的吸入型支气管扩张药物,通过与M3受体结合阻滞乙酰胆碱的作用从而缓解支气管平滑肌的痉挛,吸入一次疗效持续24h以上.临床试验结果表明该药对中重度COPD具有良好疗效,在改善呼吸困难、生活质量、减少住院次数方面优于沙美特罗,噻托溴铵qd对支气管的舒张作用明显好于溴化异丙托品qid和沙美特罗bid,且能改善通气功能和肺容积,耐受性和安全性较好.主要不良反应为口干.     

噻托溴铵与异丙托溴铵在慢性阻塞性肺疾病治疗中的成本-效果评价分析

目的:开展对噻托溴铵与异丙托溴铵在临床治疗慢性阻塞性肺疾病(COPD)患者的药物经济学研究,为临床用药决策提供依据。方法:采用回顾性研究筛选某院COPD患者,建立马尔可夫(Markov)模型对接受噻托溴铵与异丙托溴铵的患者进行模拟,并参考相关随机对照试验研究成果以及中外公开发表的文献。结果:5年噻托溴铵组和异丙托溴铵组的效果值质量调整生命年(QALYs)分别为3.90和3.87,噻托溴胺组成本为5 792.55元,比对照组减少1 262.9元,增量成本-效果比为119 977.67元/QALY。结论:在治疗COPD过程中,5年内噻托溴铵组和异丙托溴铵组治疗方案疗效相当,但噻托溴铵组的成本更低,治疗更具有成本-效果性。     

UPLIFT Study: the effects of long-term therapy with inhaled tiotropium in chronic obstructive pulmonary disease

Background: In chronic obstructive pulmonary disease (COPD), inhaled tiotropium bromide, a long-acting anticholinergic, has been shown to exert a sustained bronchodilator effect and to be superior to ipratropium bromide, a short-acting formulation of the same pharmacological class. Objective: To discuss the effects of long-term therapy with tiotropium in COPD. Methods/results: Analysis of efficacy and safety data on tiotropium from a 4-year randomized placebo controlled study performed in moderate to very severe COPD patients. Tiotropium was found to reduce significantly COPD-related morbidity, to improve health-related quality of life (HRQoL) irrespective of disease severity and to slow significantly lung function decline in patients not using inhaled corticosteroids or other long-acting bronchodilators. The safety profile – and in particular cardiovascular safety – of tiotropium was good. Conclusions: Tiotropium bromide, alone or in combination with other inhaled therapies, can maintain an adequate control of COPD on a long-term basis.     

Olodaterol + tiotropium bromide for the treatment of chronic obstructive pulmonary disease

A solid scientific rationale and an increasing body of clinical evidence for combining a β₂-agonist with an antimuscarinic agent in COPD fully support the opinion that patients not controlled by a single bronchodilator should be given two bronchodilators with different mechanisms of action. Tiotropium is an established choice for the management of patients with stable COPD, and olodaterol is a new effective and safe once-daily long-acting β2-agonist. The parallel bronchodilating modes of action of olodaterol and tiotropium make them an attractive combination in COPD. The large ongoing TOviTO Phase III trial program is documenting the efficacy and safety of olodaterol/tiotropium fixed dose combination delivered via the Respimat Soft Mist Inhaler as maintenance therapy in patients with moderate to very severe COPD. However, we must still know whether this fixed-dose combination will affect exacerbations and hospitalizations, and ultimately death, and also the precise estimates of its relative cardiovascular safety.     

免疫接种的安全性及不良事件

免疫接种是预防和控制传染病的重要手段之一,随着免疫接种覆盖率的提高,疑似免疫接种不良事件（AEFI）也日益增多。中国疾病预防控制中心将AEFI分为7类,包括疫苗本身的不良反应（一般反应和异常反应）、疫苗质量、实施差错、非疫苗引起的偶合反应、心因性反应和不明原因的反应。本文概述了乙型肝炎疫苗、卡介苗、口服脊髓灰质炎疫苗、麻疹/麻疹-腮腺炎-风疹疫苗、百白破疫苗、乙型脑炎疫苗、B型流感嗜血杆菌偶联疫苗、狂犬病疫苗和甲型H1N1流感疫苗等9种疫苗不良事件的发生情况,以及AEFI的监测和管理措施,旨在为增强免疫接种的安全性提供参考。     

布地奈德联合噻托溴铵治疗支气管哮喘的临床研究

目的 观察布地奈德联合噻托溴铵对支气管哮喘的肺功能影响.方法 将92例患者依据随机数字的方法分为对照组46例与试验组46例.对照组在常规治疗基础上使用布地奈德混悬液:布地奈德混悬液,2 mL,bid,吸入.试验组在常规治疗基础上使用布地奈德混悬液+噻托溴铵粉雾剂:噻托溴铵粉雾剂,18μg,qd,吸入.布地奈德混悬液使用...     

Pharmacokinetics and tissue distribution of the anticholinergics tiotropium and ipratropium in the rat and dog.

Ipratropium, a current treatment for chronic obstructive pulmonary disease (COPD) and tiotropium, a longer acting anticholinergic bronchodilator currently being developed for COPD are structurally related to atropine. In this study, the intravenous (i.v.), oral (p.o.) and intratracheal (i.tr.) single dose pharmacokinetics (PK) of tiotropium and ipratropium were determined in rat and dog. In rats, concentration-time profiles of tiotropium and ipratropium after single i.v. bolus administration of 7-8 mg kg(-1) are similar. Both drugs are highly cleared (Cl between 87 and 150 ml min(-1) kg(-1)) and extensively distributed into tissues (volume of distribution V(ss) between 3 and 15 l kg(-1)). In dogs, this holds also true for both drugs (Cl between 34 and 42 ml min(-1) kg(-1), V(ss) between 2 and 10 l kg(-1)), although different dose regimen were applied (i.v. bolus of 0.08 mg kg(-1) vs. infusion of 0.1 mg kg(-1) h(-1) for 3 h). Tiotropium plasma concentrations increased linearly in rats over a wide dose range following single i.v. administration. Both ipratropium and tiotropium showed a comparable terminal elimination half-life in rat urine (21-24 h) after single i.v. administration, which was much longer than the corresponding half-life in plasma (6-8 h). Whole body autoradiography in rats revealed a broad and rapid tissue distribution of [(14)C]tiotropium radioactivity after single i.v. administration. A comparable distribution pattern has also been reported earlier for ipratropium.     

噻托溴铵治疗慢性阻塞性肺疾病作用机制的研究进展

慢性阻塞性肺疾病(COPD)是呼吸系统疾病中常见的疾病,可引起呼吸衰竭、肺源性心脏病、心力衰竭等严重疾病。噻托溴铵作为长效的抗胆碱制剂,现为临床治疗慢性阻塞性肺炎的常用药物,其可通过扩张支气管、抑制炎症因子和抑制气道重塑的作用机制,进而有效缓解支气管痉挛、呼吸困难和降低炎症反应。主要对噻托溴铵治疗慢性阻塞性肺疾病的作用机制进行综述。     

噻托溴铵对慢性阻塞性肺疾病患者肺功能的影响

目的 评价噻托溴铵治疗慢性阻塞性肺疾病(COPD)的疗效和安全性.方法 采用随机、双盲、平行对照方法,对轻、中度稳定期COPD患者吸入噻托溴铵(20例)与异丙托溴铵(20例)治疗4周,通过检测肺功能,观察其临床疗效.结果 用药后,噻托溴铵组患者第1秒用力呼气容积(FEV1)和用力肺活量(FVC)均显著增加(P<0.01);4周时,FEV1的增加较异丙托溴铵组差异有统计学意义(P<0.05);两组应急药物应用情况及药物不良反应发生率差异无统计学意义(P<0.05).结论 噻托溴铵是治疗COPD患者有效和安全的支气管扩张药物,疗效显著而且安全可靠.     

乙酰半胱氨酸泡腾片合用噻托溴铵吸入剂对50例COPD合并肺气肿的临床疗效研究

目的：观察和评估乙酰半胱氨酸泡腾片合用噻托溴铵吸入剂对COPD合并肺气肿患者的肺功能和临床症状的影响。方法：随机选取我院2013年2月—2014年12月收治的COPD合并肺气肿患者共100例,按治疗方式分为观察组和对照组,观察组用乙酰半胱氨酸泡腾片联合噻托溴铵吸入剂治疗,对照组单纯口服乙酰半胱氨酸泡腾片治疗。对两组患者CRP及IL-18水平,肺功能指标以及临床症状评分,SGRQ的症状分,活动分,影响分的分值等指标进行对比分析。结果：观察组患者CRP及IL-18水平,临床症状评分, SGRQ的症状分,活动分,影响分的分值明显低于对照组(P<0.01);观察组肺功能指标明显优于对照组(P<0.01)。结论：采用乙酰半胱氨酸泡腾片合用噻托溴铵吸入剂临床疗效显著,具有一定的抗炎作用,可以明显降低COPD合并肺气肿患者的CRP及IL-18水平,有效改善患者的肺功能和临床症状,提高患者的生活质量。     

噻托溴铵联合沙美特罗/氟替卡松对老年支气管哮喘患者肺通气功能的改善

目的：探讨联合吸入噻托溴铵和沙美特罗/氟替卡松对老年支气管哮喘患者肺通气功能的影响。方法：将本院呼吸内科100例确诊为支气管哮喘的患者随机分为吸入噻托溴铵和沙美特罗/氟替卡松治疗组43例,沙美特罗/氟替卡松组29例,噻托溴铵组28例。治疗6个月后,观察治疗疗效、治疗前后肺功能变化及治疗后肺功能改善率。结果：联合吸入噻托溴铵和沙美特罗/氟替卡松组的总有效率为88.4%,明显高于噻托溴铵组的67.9%和沙美特罗/氟替卡松组的72.4%,差异具有统计学意义,P〈0.05。同时联合吸入噻托溴铵和沙美特罗/氟替卡松组的肺功能改善率高于其他两组,改善更显著,差异具有统计学意义。结论：噻托溴铵联合沙美特罗/氟替卡松能明显改善支气管哮喘患者肺通气功能,疗效显著。     

国产噻托溴铵对稳定期慢性阻塞性肺疾病患者的影响

目的:研究吸入国产噻托溴铵治疗稳定期慢性阻塞性肺疾病(COPD)的疗效和安全性。方法:将60例稳定期COPD患者分成两组,治疗组给予吸入国产噻托溴铵,对照组给予常规治疗,比较两组治疗前后肺功能、6 min步行距离、临床症状积分和急性加重次数,并观察不良反应。结果:治疗组肺功能明显好转,6 min步行距离、临床症状明显改善(P<0.05),急性加重次数减少,无严重不良反应发生。结论:国产噻托溴铵对于轻中度COPD稳定期患者疗效显著且安全可靠。     

Safety and tolerability profile of new antiepileptic drug treatment in children with epilepsy

Introduction: Treatment of pediatric epilepsy requires a careful evaluation of the safety and tolerability profile of antiepileptic drugs (AEDs) to avoid or minimize as much as possible adverse events (AEs) on various organs, hematological parameters, and growth, pubertal, motor, cognitive and behavioral development.

Areas covered: Treatment-emergent AEs (TEAEs) reported in the literature 2000–2018 regarding second- and third-generation AEDs used in the pediatric age, with exclusion of the neonatal period that exhibits specific peculiarities, have been described on the basis of their frequency, severity/tolerability, and particular association with a given AED.

Expert opinion: Somnolence/sedation and behavioral changes, like irritability and nervousness, are among the most commonly observed TEAEs associated with almost all AEDs. Lamotrigine, Gabapentin, Oxcarbazepine, and Levetiracetam appear to be the best-tolerated AEDs with a ≤2% withdrawal rate, while Tiagabine and Everolimus are discontinued in up to >20% of the patients because of intolerable TEAEs. For some AEDs, literature data are scanty to draw a high-level evidence on their safety and tolerability profile. The reasons are: insufficient population size, short duration of treatments, or lack of controlled trials. A future goal is that of identifying clearer, easier, and more homogeneous methodological strategies to facilitate AED testing in pediatric populations.     

Safety review in 10,008 users of lansoprazole in daily practice

Purpose —Soon after the introduction of the proton pump inhibitor, lansoprazole, a 4‐year observational follow‐up study was started to evaluate the safety of this drug in naturally‐occurring groups of patients in The Netherlands. Results of this study were compared with clinical trial data and the limited published data from observational studies. Methods — prospective, observational study in which patients with a new episode of lansoprazole use were followed during the medication period for a maximum of 2 years. All (adverse) events during use were documented by the prescriber, irrespective of possible association with lansoprazole therapy. Results — total of 805 general practitioners (GPs) and 266 specialists provided a total of 10,008 lansoprazole users with a broad range of diagnoses. Of all patients, 17.4% reported one or more adverse events. The profile and frequency of reported adverse events was consistent with results from clinical trials and other observational studies. The most frequently reported adverse events were diarrhoea, headache, nausea, skin disorders, dizziness and generalized abdominal pain/cramps. There was no new evidence of rare adverse events. Furthermore, no lansoprazole‐related unlabelled adverse events of clinical significance were recorded. Conclusions — Although the patterns of use of lansoprazole in daily practice deviated to some extent from the diagnoses in the information leaflet, lansoprazole was found to have a highly acceptable safety profile in this large naturally‐occurring group of users. Reporting rates were higher soon after introduction of lansoprazole before falling to a lower stable level. Copyright © 2000 John Wiley & Sons, Ltd.     

噻托溴铵联合沙美特罗/氟替卡松吸入治疗慢性阻塞性肺疾病疗效观察

目的探讨噻托溴铵联合沙美特罗/氟替卡松吸入治疗对慢性阻塞性肺疾病（COPD）的疗效。方法 76例COPD随机分为两组,对照组吸入沙美特罗/氟替卡松,观察组吸入沙美特罗/氟替卡松和噻托溴铵,其他治疗一致。3个月后比较两组治疗前后症状、FEV1（第1秒呼气量）/预计值和FEV1/FVC（用力肺活量）及血气变化。结果两组各有36例完成治疗。治疗前两组之间各项指标无显著差异,治疗后两组自觉症状改善明显,FEV1/预计值和FEV1/FVC差异明显（P〈0.01）,PaO2显著升高（P〈0.01）,PaCO2降低（P〈0.05）。结论噻托溴铵联合沙美特罗/氟替卡松吸入是治疗COPD的安全有效方法。     

Safety of human papillomavirus vaccines: a review

Introduction: Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere.

Areas covered: Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed.

Expert opinion: Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence.     

噻托溴铵治疗慢性阻塞性肺病病人的临床疗效及安全性

目的:评价国产噻托溴铵干粉剂对轻、中度慢性阻塞性肺疾病(COPD)稳定期病人的临床疗效和安全性。方法:采用随机、双盲平行对照试验。60例轻、中度COPD病人分为2组,噻托溴铵组男性23例,女性7例,年龄(62±s 6)a,予噻托溴铵干粉剂吸入,18μg,每日1次;对照组男性19例,女性11例,年龄(62±7)a,予安慰剂吸入,每日1粒,总观察时间均为13 wk,包括1 wk的洗脱期。结果:治疗后噻托溴铵组的临床控制率为37%,总有效率为63%,无1例出现COPD病情恶化;对照组临床控制率为11%,总有效率为33%,有4例出现病情恶化,2组疗效比较有显著差异(P＜0．05)。治疗后噻托溴铵组第1秒用力呼气量增加了(214±201)mL,用力肺活量增加了(206±314)mL,而对照组仅增加(5±207)mL和(25±307)mL(P＜0．01)。2组不良反应发生率无显著差异。结论:国产噻托溴铵对于轻、中度COPD稳定期病人疗效显著且安全可靠。