发展监管科学，促进中药产业传承创新

2008年新药创制重大专项启动实施以来的10多年间,紧密围绕构建国家药物创新技术体系目标,为我国新药研发和公众用药安全提供了重要的保障,获得重大进展。药品监管科学是近十几年发展形成的前沿学科,受到世界科学界和管理界的重视。本文秉着中药监管科学发展与现实存在问题,需要理论创新、药物创新、技术创新、方法创新和应用创新。中药监管科学研究计划是国家推进的9个监管科学行动计划之一。启动以中药临床为导向的中药安全性评价研究,构建中药安全性和质量控制体系。作者认为通过监管科学研究,制定科学规范的中药质量标准和评价指导原则和技术指南,推进中药材、中药饮片和中成药,特别是经典名方制剂品种示范研究,有利于中药产业健康科学发展。在本文中还结合当前的中药监管科学问题,加强药材和饮片的基础研究、中药注射剂质量疗效的再评价研究、经典名方的开发和简化申请的监管科学研究,提出监管科学研究顶层设计建议,制定技术原则与技术指南,有利于药典品种和市场产品的质量和临床有效性再评价。     

Platelet-rich plasma injections for the treatment of refractory Achilles tendinopathy: results at 4 years

Background

Chronic Achilles tendinopathy is responsible for a severe reduction in physical performance and persistent pain. There is currently a number of therapeutic options and the local administration of growth factors is an emerging treatment strategy. In particular, platelet-rich plasma (PRP) is a widely used way to provide a local regenerative stimulus for tendon healing. The aim of this study was to document the mid-term results obtained after treating recalcitrant Achilles tendinopathy with injections of high concentrate, leucocyte-rich PRP.

Materials and methods

Twenty-seven patients (mean age: 44.6 years; 22 men and 5 women) affected by chronic mid-portion Achilles tendinopathy (7 bilateral, for a total of 34 tendons), refractory to previous treatments, were enrolled. Patients were treated with three ultrasound-guided intra-tendinous injections of PRP at 2-week intervals. Patients were prospectively evaluated at baseline, and then at 2, 6, and up to a mean of 54.1 months of follow-up (minimum 30 months), using the following tools: Blanzina, VISA-A, EQ-VAS for general health, and Tegner scores.

Results

The VISA-A score showed a significant improvement: the baseline score of 49.9±18.1 increased to 62.9±19.8 at 2 months (p=0.002), with a further improvement at 6 months (84.3±17.1, p<0.0005), and stable results at 4.5 years (90.0±13.9). The EQ-VAS score also showed a similar positive trend. An evaluation of the activity level confirmed these findings, showing a significant improvement in the Tegner score over time (p=0.017 for the final evaluation). The longer duration of symptoms before treatment was associated with a slower return to sport (p=0.041).

Discussion

PRP injections produced good overall results for the treatment of chronic recalcitrant Achilles tendinopathy with a stable outcome up to a medium-term follow-up. Longer symptom duration was related with a more difficult return to sporting activity.     

贝伐珠单抗联合不同化疗方案治疗进展期结直肠癌54例分析

目的研究贝伐珠单抗(Bev)联合化疗治疗进展期结直肠癌的疗效和安全性。方法对2005年11月至2011年3月北京大学肿瘤医院接受Bev联合化疗治疗进展期结直肠癌54例进行分析。Bev 5 mg/kg静脉输注每2周1次或7.5 mg/kg静脉输注每3周1次,联合以奥沙利铂为基础的化疗,以伊立替康为基础的化疗,或以氟尿嘧啶类为基础的化疗进行治疗。按实体肿瘤疗效评价标准(RECIST)评价疗效,每6周评价1次。按美国癌症研究所常见毒性判定标准(NCI-CTC)3.0版评价不良反应。结果 54例中男26例,女28例;中位年龄50(24～73)岁。初治22例,21例可评价疗效,有效率(RR)为33.3%(7/21),疾病控制率(DCR)为100%(21/21);中位疾病无进展(PFS)时间11.3个月,总生存时间(OS)20.9个月。全部54例中,部分缓解(PR)12例(23.5%),稳定(SD)32例(62.7%),进展(PD)7例(13.5%),3例无法评价疗效;中位PFS 8.4个月,中位OS 15.5个月。主要3～4度不良反应为白细胞减少9例(16.7%),粒细胞减少13例(24.1%),粒细胞减少性发热1例(1.9%);3度恶心、呕吐2例(3.8%),3度腹泻3例(5.7%)。与贝伐珠单抗相关的不良反应为蛋白尿2例(3.8%),血压升高1例,鼻衄2例,痔疮出血2例,但均为1～2度。结论贝伐珠单抗联合化疗治疗进展期结直肠癌对于初治患者疗效较好,且未加重化疗的不良反应。     

Ultrasound-guided versus computed tomography-controlled periradicular injections in the middle and lower cervical spine: a prospective randomized clinical trial

Purpose

We conducted this study to evaluate accuracy, time saving, radiation doses, safety, and pain relief of ultrasound (US)-guided periradicular injections versus computed tomography (CT)-controlled interventions in the cervical spine in a prospective randomized clinical trial.

Methods

Forty adult patients were consecutively enrolled and randomly assigned to either a US or a CT group. US-guided periradicular injections were performed on a standard ultrasound device using a broadband linear array transducer. By basically following the osseous landmarks for level definition in “in-plane techniques”, a spinal needle was advanced as near as possible to the intended, US-depicted nerve root. The respective needle tip positioning was then verified by CT. The control group underwent CT-guided injections, which were performed under standardized procedures using the CT-positioning laser function.

Results

The accuracy of US-guided interventions was 100 %. The mean time to final needle placement in the US group was 02:21 ± 01:43 min:s versus 10:33 ± 02:30 min:s in the CT group. The mean dose-length product radiation dose, including CT confirmation for study purposes only, was 25.1 ± 16.8 mGy cm for the US group and 132.5 ± 78.4 mGy cm for the CT group. Both groups showed the same significant visual analog scale decay (p < 0.05) without “inter-methodic” differences of pain relief (p > 0.05).

Conclusions

US-guided periradicular injections are accurate, result in a significant reduction of procedure expenditure under the avoidance of radiation and show the same therapeutic effect as CT-guided periradicular injections.     

Intra-articular corticosteroid injections in haemophilic arthropathy: are they recommended?

Introduction: Intra-articular (IA) corticosteroid (CS) injections are commonly used in the treatment of osteoarthritis. However, they are rarely utilized in haemophilic arthropathy. In fact, the efficacy of this method in haemophilic arthropathy is frequently discussed and debated in clinical practice.

Aim: To investigate the effectiveness of IA CS injections in patients with painful haemophilic arthropathy.

Methods: A review of the literature on the topic was performed.

Results: In osteoarthritis, reports with a high level of evidence state that the efficacy of IA injections of CS is controversial. In haemophilic arthropathy, some low-level evidence reports seem to indicate that short-term pain alleviation can be achieved.

Conclusions: Considering that pain relief after IA injections of CS is controversial and that the cost of the haematologic treatment required to perform the procedure is high in haemophilic arthropathy, we do not recommend the routine use of CS IS injections in haemophilia. Moreover, point of care (POC) ultrasound (US)-guided injections are not advised, because the injection procedure is so simple that the use of POC-US will unnecessarily prolong the duration of the procedure.     

Suitability of the AUC Ratio as an Indicator of the Pharmacokinetic Advantage in HIPEC

The purpose of this study was to evaluate the area under the concentration-time curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during hyperthermic intraperitoneal perioperative chemotherapy. The impact on the AUC ratio on the variables related to the calculation of systemic drug exposure, instillation time, and peripheral drug distribution was evaluated through simulations as well as through a retrospective analysis of studies published in the literature. Both model simulations and the retrospective analysis showed that the 3 variables evaluated had an impact on the AUC ratio value if the complete systemic exposure was not fully considered. However, when that complete systemic exposure was considered, none of these variables affected the AUC ratio value. AUC ratio is not a characteristic parameter of a drug if the calculated systemic drug exposure is not complete. Thus, AUC ratio is not valid for comparing the pharmacokinetic advantage of 2 drugs, and it should not be employed to prove whether a drug can be used in hyperthermic intraperitoneal perioperative chemotherapy safely with regard to toxicity. As an alternative, the study of the absorption rate constant and the bioavailability are proposed as the true and independent parameters that reflect the amount of drug absorbed.     

精子DNA碎片率对男性生育力评估的预测价值

目的：探讨精子DNA碎片率（DFI）对男性生育力评估方面的预测价值。方法：选择2016年1月-2018年7月于上海市第十人民医院生殖医学中心就诊的460例男性不育患者纳入观察组,同期107例正常生育男性纳入对照组。计算机辅助精液分析系统（CASA）检测精液常规,精子染色质结构分析检测精子DFI。将精液常规结果分为精液正常、少精子、弱精子和少弱精4类。比较观察组和对照组的精液常规构成比和精子DFI;比较不同年龄（＜30岁,30～39岁,≥40岁）患者精子DFI水平的变化趋势及不同水平精子DFI（≤15%,15%～30%,≥30%）患者的体外受精（IVF）/胞浆内单精子注射（ICSI）的生殖结局。结果：观察组中精液正常、少精子、弱精子、少弱精所占比列分别为22.17%、13.26%、52.62%和11.95%,对照组分别为60.96%、34.59%、1.75%和2.70%。与对照组相比,观察组精液正常比例下降,少精子、弱精子和少弱精比例增加,差异有统计学意义（P＜0.05）。与对照组相比,观察组精子DFI≤15%所占比例下降,DFI≥30%比例增加,差异有统计学意义（P＜0.05）。随着年龄增加,精子DFI≤15%患者所占比例下降,精子DFI（15%～30%）与精子DFI≥30%患者所占比例增加,3组间精子DFI的分布比例差异有统计学意义（P＜0.05）。精子DFI≥30%来源的IVF或ICSI胚胎,其早期流产率显著升高（31%和25%,均P＜0.05）,但受精率、卵裂率、生化妊娠率、临床妊娠率、着床率等指标差异均无统计学意义（P＞0.05）。结论：不育男性的精子DNA碎片率更高,并且随年龄的增加而增加。DFI≥30%的精子受精的胚胎早期流产率较高,影响辅助生殖技术的妊娠结局,因此DFI对不育男性的生育力评估有实用参考价值。     

某院2014-2016年中药注射剂使用情况专项点评分析

目的：专项点评某三甲医院中药注射剂的使用情况,促进临床合理使用中药注射剂。方法：利用医院HIS系统,调阅2014年2月-2016年10月期间住院患者的病历,每月抽取1个病区住院患者病历,对使用中药注射剂情况进行统计分析,计算各科室的使用率、合理使用率,并对不合理情况进行分析,在每月全院医师大会上进行反馈。结果：经过专项点评发现内科干部病房、心内1科、心内2科中药注射剂使用率最高占100%,小儿科合理率100%;外科中骨科中药注射剂使用率最高占96%,妇产科、眼科未使用中药注射剂。不合理使用情况主要包括用药无指征,用法用量不适宜,溶媒选择不合理,联合用药不适宜;以活血化瘀类中药注射剂使用最多。结论：中药注射剂的使用存在一些问题,需要进一步干预规范。