Drug Prices and Value of Oncology Drugs in Italy

ObjectiveThe main objective of this study was to evaluate the potential role of efficacy data and other information available at the time of price and reimbursement (P&R) decision-making process within the definition of oncology treatment costs in Italy.MethodsThe study included all P&R dossiers submitted to the Italian Medicines Agency between July 2015 and December 2017. It prospectively collected the data of the P&R process starting from dossier submission up to the Italian Health Service reimbursement decision. The cost of treatment per patient was estimated using both the list price (“gross cost”) and the confidential net price (“net cost”) of drug packages and applied to the median duration of treatment. A 2-sample stage Heckman decomposition model was used to evaluate the potential role of efficacy data and other information available at the time of P&R decision making on the gross and net cost.ResultsA total of 37 oncology drugs related to 58 therapeutic indications were analyzed. The multivariate model showed that the variation of progression-free survival is the only variable predictor statistically associated with treatment cost, but this effect was observed only when confidential net prices were used (P=.026).ConclusionsConsidering the perspective of a developed country having a public healthcare service with a central reimbursement negotiation is determined a relevant reduction in the treatment cost purchased by public payers. This is a useful approach to guarantee the affordability of innovative oncology drugs and to contain public expenditures on healthcare. Furthermore, the negotiation of confidential discounts and agreement clauses in managed entry agreements seemed to reward oncology drugs displaying an added therapeutic benefit.     

益气活血药对低氧性肺动脉高压大鼠神经肽Y、降钙素基因相关肽的影响

目的：探讨由黄芪、川芎组方的益气活血药对低氧性肺动脉高压大鼠神经肽Y（NPY）、 降钙素基因相关肽（CGRP）的影响。方法：采用常压低氧21天复制大鼠肺动脉高压模型,应用放射免疫技术测定大鼠血浆、肺组织中NPY、CGRP的含量变化。结果：益气活血药可降低肺动脉压,改善心功能及血液流变学。益气活血药中剂量组血浆及肺组织中NPY含量与缺氧组比较明显降低;而CGRP含量较缺氧组有所回升,肺组织中CGRP含量与缺氧组比较则趋于下降。结论：益气活血药可防止低氧性肺动脉高压的形成,也提示益气活血药的降压作用可能通过影响NPY、CGRP的含量来调节肺血管舒缩,从而降低肺动脉压。     

蒙药毛勒日—达布斯—4汤中微量元素及氨基酸含量的测定

目的：测定蒙药毛勒日-达布斯-4汤中微量元素和氨基酸的含量。方法：用原子吸收分光光度计,测定蒙药毛勒日-达布斯-4汤中几种重要的微量元素含量;用氨基酸自动分析仪测定氨基酸的含量。结果与结论：蒙药毛勒日-达布斯-4汤中含有较高的Mn、Fe、Zn和Mg;含有17种氨基酸,包括7种人体必需氨基酸,氨基酸总量为4.615%（mg/g）。     

益气止血药对脾不统血证模型动物前列腺素的作用

采用复合因素的脾不统血证大鼠模型 ,以 6 酮 前列腺素F1α(6 酮 PGF1α)和血栓素B2(TXB2 )作为观测指标 ,对益气止血药对脾不统血证模型大鼠血浆和子宫前列腺素的影响进行了研究。结果 :大剂量组益气止血药能降低脾不统血证模型血浆和子宫的 6 酮 PGF1α及子宫 6 酮 PGF1α/TXB2 比值。说明 6 酮 PGF1α及 6 酮 PGF1α/TXB2 比值升高可能是脾不统血证的重要机理之一。     

慢性乙型肝炎患者TNF-α和IL-6的变化及双利肝对其影响

目的探讨TNF-α、IL-6在慢性乙肝不同阶段的作用及双利肝对于两种细胞因子的影响.方法 55 例慢性乙肝患者在治疗前测定血清TNF-α、IL-6水平及肝功能.在一般保肝治疗基础上口服双利肝,在治疗前后测定血清TNF-α、IL-6水平及肝功能.结果随着肝功能损害加重,TNF-α、IL-6水平显著升高(P＜0.01,P＜0.05),经过双利肝治疗,患者转氨酶、胆红素、TNF-α水平明显下降(P＜0.01),IL-6水平略有上升但无显著性差异(P＞0.05).结论慢性乙肝病程中,TNF-α与肝细胞坏死程度有关,可作为病情轻重的判别指示.IL-6与肝脏损伤过程有关.双利肝可明显降低慢性乙肝患者TNF-α水平,有效地改善肝功能.     

温阳活血方对大鼠阿霉素肾病模型的影响

目的：探讨不同治法治疗原发性肾病综合征高脂血症的疗效差异。方法：用阿霉素（ADR）诱导一种类似人类微小病变肾病模型,然后用中药温阳方、活血方及温阳活血方对模型进行治疗,并设空白、病理及强的松组对照。结果：温阳活血方组尿蛋白、血脂、脂蛋白及肾脏病理损害明显改善;温阳方及活血方组血脂、脂蛋白部分指标及肾脏病理损害有所改善。结论：温阳活血方对ADR肾病的治疗作用较全面,其疗效优于温阳法和活血法。     

15种理气中药体外对人血小板聚集的影响

目的观察15种理气中药对体外肾上腺素诱导的人血小板聚集的影响.方法试管内人血小板加中药孵育前后,比浊法测定血小板聚集.结果11种理气药具有抗血小板聚集作用(P＜0.05～0.001),其中枳实的抑制作用较阳性对照阿司匹林明显(P＜0.01),青皮、陈皮与阿司匹林无差异(P＜0.05).柿蒂、甘松、檀香、沉香对血小板聚集无明显作用(P＞0.05).结论多数理气药(11/15)在体外具有抗人血小板聚集作用,枳实、青皮、陈皮3种作用强于或与阿司匹林相当.     

Risk of Gastrointestinal Bleeding With Extended Use of Nonsteroidal Anti-Inflammatory Drug Analgesia After Joint Arthroplasty

BackgroundChronic nonsteroidal anti-inflammatory drug (NSAID) use is associated with gastrointestinal bleeding via inhibition of endogenous mucosal protection and platelet aggregation. This study aimed to determine whether extended NSAIDs after joint arthroplasty is associated with increased risk of gastrointestinal bleeding.MethodsThis was a retrospective study examining 28,794 adults who underwent joint arthroplasty by one of 50 surgeons from 2016 to 2018. Episodes of gastrointestinal bleeding within 90 days postoperatively were identified prospectively. Postoperative medications were reported directly by patients with electronic questionnaires. The primary analysis was performed using binary logistic regression.ResultsA total of 74 (0.26%) episodes of gastrointestinal bleeding occurred within 90 days (median 8 days) postoperatively. Of 5086 patients with complete data included in the primary analysis, 59.6% had used NSAIDs with median duration of 2 weeks (interquartile range, 0-6 weeks). Patients with gastrointestinal bleeding were significantly older (71.3 vs 67.0 years), required longer hospitalizations (2.1 vs 1.5 days), and more commonly had a history of peptic ulcers (10.8% vs 0.9%). However, there was no positive association between NSAID use and gastrointestinal bleeding. In fact, the odds of gastrointestinal bleeding were lower in patients taking NSAIDs. Gastrointestinal bleeding was associated with anticoagulants, antiplatelet agents, and, to a lesser extent, aspirin.ConclusionNSAIDs were not associated with gastrointestinal bleeding and may be prescribed safely for a majority of patients after joint arthroplasty. The greatest odds of gastrointestinal bleeding occurred in patients with peptic ulcer disease and those who received antiplatelet and anticoagulation agents. Increasing age and bilateral surgery were also associated with gastrointestinal bleeding.Level of EvidenceLevel III.     

桂枝芍药知母汤联合西药治疗急性痛风性关节炎的疗效和安全性Meta分析

目的：系统评价桂枝芍药知母汤联合西药治疗急性痛风性关节炎的安全性和疗效。方法：计算机检索PubMeb、The Cochrane Library、EMBASE、Web of Science、国家知识基础设施数据库（CNKI）、中国学术期刊数据库（CSPD）、中文科技期刊数据库（CCD）和中国生物医学文献数据库（CBM）,搜索桂枝芍药知母汤联用西药与单用西药治疗急性痛风性关节炎的疗效与安全性临床随机对照试验,并用改良后的Jadad量表对纳入的文献质量进行初步评价,利用Revman5.3软件进行Meta分析。结果：共纳入7篇文献,共498例患者。Meta分析结果显示：中西药联用观察组患者总有效率明显高于西药对照组,差异有统计学意义（RR=1.20,95%CI为1.12～1.28,P<0.000 01）;中西药联用观察组在降低BUA（MD=-61.35,95%CI为-93.17～-29.53）,CRP（MD=-1.83,95%CI为-2.56～-1.11）,ESR（MD=-3.93,95%CI为-6.60～-1.26）,关节肿胀积分（SMD=-2.89,95%CI为-3.36～-2.43）和关节疼痛积分（SMD=-3.11,95%CI为-3.87～-2.35）的效果明显优于西药对照组,差异有统计学意义（P<0.05）;中西药联用干预的观察组不良反应发生率明显低于西药对照组（P<0.05）。结论：桂枝芍药知母汤联合西药治疗急性痛风性关节炎的疗效和安全性明显优于单用西药,但受纳入研究质量和数量的限制,仍需更多高质量的临床随机对照试验来证实上述结论。