羟基磷灰石涂层与骨组织界面生物相容性与毒理学研究

依据卫生部新近制定的《生物材料和制品的生物学评价标准》(简称《标准》),确定五项评价项目,按照标准的生物学试验方法,对目前临床应用的羟基磷灰石制品进行系统研究。结果表明：国产羟基磷灰石制品除有轻微细胞毒性外,其致敏性、溶血性、致突变性和组织相容性均符合《标准》要求,临床应用安全。     

人工气管组分材料胶原蛋白/羟基磷灰石体外细胞毒理学研究

细胞毒性和细胞相容性是生物材料应用于临床所遇到的首要问题。将胶原蛋白作为载体与羟基磷灰石混合制成人工气管的组分材料，通过体外实验研究其细咆毒性和细胞相容性，为临床应用作前期准备。采用体外细胞培养法、MTT比色法评价胶原蛋白和羟基磷灰石复合材料对培养细胞L-929的细胞形态、生长和增殖的影响，同时采用溶血试验评价该复合材料是否对红细咆的功能和代谢产生不良反应。结果显示，胶原蛋白和羟基磷灰石复合材料对体外培养的细胞形态不构成损害，对其生长和增殖无明显抑制作用，细胞毒性为0级；溶血率为1．85％，低于5％的国家标准，在体外不引起溶血反应。实验表明，胶原蛋白和羟基磷灰石复合材料具有良好的细胞相容性，属无毒级生物材料，其作为人工气管组分材料应用于临床具有可行性和安全性。     

The Use of Electronic Data Capture Tools in Clinical Trials: Web-Survey of 259 Canadian Trials

Background

Electronic data capture (EDC) tools provide automated support for data collection, reporting, query resolution, randomization, and validation, among other features, for clinical trials. There is a trend toward greater adoption of EDC tools in clinical trials, but there is also uncertainty about how many trials are actually using this technology in practice. A systematic review of EDC adoption surveys conducted up to 2007 concluded that only 20% of trials are using EDC systems, but previous surveys had weaknesses.

Objectives

Our primary objective was to estimate the proportion of phase II/III/IV Canadian clinical trials that used an EDC system in 2006 and 2007. The secondary objectives were to investigate the factors that can have an impact on adoption and to develop a scale to assess the extent of sophistication of EDC systems.

Methods

We conducted a Web survey to estimate the proportion of trials that were using an EDC system. The survey was sent to the Canadian site coordinators for 331 trials. We also developed and validated a scale using Guttman scaling to assess the extent of sophistication of EDC systems. Trials using EDC were compared by the level of sophistication of their systems.

Results

We had a 78.2% response rate (259/331) for the survey. It is estimated that 41% (95% CI 37.5%-44%) of clinical trials were using an EDC system. Trials funded by academic institutions, government, and foundations were less likely to use an EDC system compared to those sponsored by industry. Also, larger trials tended to be more likely to adopt EDC. The EDC sophistication scale had six levels and a coefficient of reproducibility of 0.901 (P< .001) and a coefficient of scalability of 0.79. There was no difference in sophistication based on the funding source, but pediatric trials were likely to use a more sophisticated EDC system.

Conclusion

The adoption of EDC systems in clinical trials in Canada is higher than the literature indicated: a large proportion of clinical trials in Canada use some form of automated data capture system. To inform future adoption, research should gather stronger evidence on the costs and benefits of using different EDC systems.     

Imaging Infrastructure for Research. Part 2. Data Management Practices

In part one of this series, best practices were described for acquiring and handling data at study sites and importing them into an image repository or database. Here, we present a similar treatment on data management practices for imaging-based studies.     

Differences Between Clinical Trials of Medical Devices and Drugs

How to design clinical trials for medical devices is a problem plaguing the industry today. As there are many differences in clinical trials of medical devices and drugs. This paper describes the differences of the two points from the perspectivs of defi- nition of medical devices and drugs, scope, phasing, subjects and design of clinical trials in details, aiming to help the related personnel make scientific decisions while conduct- ing clinical trial design for medical devices.     

Product Regulation and the Clinical Translation of Stem Cell Research

The recent approval by the United States Food and Drug Administration of a clinical trial involving a product derived from human embryonic stem cells, along with recent concerns about unproven stem cell therapies being offered to patients, highlight the importance of regulation at the critical stage of beginning human trials of novel therapies. The regulations governing therapeutic products (drugs and related products) are one part of the broader legal framework, but will play an increasingly prominent role as we move into clinical translation. The classification of products as drugs or biologics, on one hand, or minimally manipulated cell and tissue products for homologous use, on the other, will determine the requirements that will apply, including whether use in clinical trials requires approval. Product regulation works alongside other parts of the legal and policy framework, notably research ethics review and legal responsibilities of medical professionals, that play important though limited roles. Three key developments and challenges currently facing product regulation and related areas will affect stem cell research in this phase: regulatory reform, fragmentation, and capacity.     

痛立舒口服液动物毒理学研究

目的：研究痛立舒口服液小白鼠急性毒性和大白鼠60天长期毒性试验。方法：采用小白鼠最大耐受量测定法和长期毒性试验进行研究。结果：痛立舒口服液对小鼠灌胃给药的LD50＞189g(生药)kg。大鼠长期毒性试验对动物一般行为活动、体重增长、外周血象、肝肾功能及病理组织学检查等与对照组比较未见明显差异(P＞0.05)。     

Clinical pharmacology and clinical trials in Japan

Clinical pharmacology is the pursuit of rational therapeutics by following the scientific principles of medicine and pharmacology. In Japan the roles for clinical pharmacology and clinical pharmacologists have been evolving since the discipline appeared in the 1950s. Clinical pharmacology and clinical trials for drug development depend on each other, and clinical pharmacologists play an important role in drug development in Japan. As the discipline becomes more important and complicated, many issues regarding drug therapeutics and clinical trials in Japan have been raised, and several points of view have been expressed. The following suggestions have been made to improve clinical pharmacology in Japan: (a) Medical education in the field of clinical pharmacology must be improved by creating or improving clinical pharmacology programs in medical schools. (b) The appropriate infrastructure for clinical trials must be established so that the physicians' workload is reduced, and patients' participation in clinical trials becomes much easier. (c) Scientific and ethical standards of the pharmaceutical industry must be improved, and the effort should be made to produce drugs with new mechanisms of action or with significant expected benefits. (d) The regulatory agency must provide stronger support, encompassing all the various points of view of academic institutes and the pharmaceutical industry. In light of the enthusiasm demonstrated by the government, physicians, and pharmaceutical industry in Japan for continued progress in clinical pharmacology, it seems likely that all its challenges will be overcome in the near future. Hence, despite the various problems discussed here the future seems promising for the continued development of clinical pharmacology.Abbreviations GCP Good clinical practice - JSCPT Japanese Society of Clinical Pharmacology and Therapeutics     

Easy-to-Read Informed Consent Form for Hematopoietic Cell Transplantation Clinical Trials: Results from the Blood and Marrow Transplant Clinical Trials Network 1205 Study

Because of the complexity of hematopoietic cell transplant trial treatments, informed consent forms are often long and difficult to read. We evaluated a 2-column easy-to-read informed consent (ETRIC) form that incorporates elements of health literacy and readability in participants and centers participating in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) clinical trials. In a randomized study 198 adult patients from 25 centers potentially eligible to participate in 4 BMT CTN interventional trials were randomized to the ETRIC form or a standard consent form for that trial. Both forms were written at no more than an eighth-grade reading level. The primary endpoint was objective comprehension score on the Quality of Informed Consent, part A (QuIC-A) instrument. In a parallel evaluation study, 2 moderators conducted semistructured interviews of 49 investigators, research staff, and institutional review board (IRB) members at 9 BMT CTN trial sites. The mean QuIC-A scores were comparable in 152 patients (77%) assessable for the primary endpoint (ETRIC form, 80.5; standard form, 81.8; P?=?.37). In regression analysis there was no significant association between the consent type and QuIC-A score. In the evaluation study dominant themes identified on qualitative analyses included general comfort and willingness to use the ETRIC template and that its formatting and layout enhancements would offer additional value to research participants, investigators, and IRBs. IRB language preferences and requirements, length, and prior experience with alternative consent formats were perceived as barriers. Among patients considering participation in BMT CTN clinical trials, the formatting enhancements of the ETRIC form did not alter comprehension of the trial. Despite local challenges to implementation, trial sites generally viewed the ETRIC form favorably and expressed willingness to use it over standard consent form.     

Blood and Marrow Transplant Clinical Trials Network Report on the Development of Novel Endpoints and Selection of Promising Approaches for Graft-versus-Host Disease Prevention Trials

Graft-versus-host disease (GVHD) is a common complication after hematopoietic cell transplantation (HCT) and associated with significant morbidity and mortality. Preventing GVHD without chronic therapy or increasing relapse is a desired goal. Here we report a benchmark analysis to evaluate the performance of 6 GVHD prevention strategies tested at single institutions compared with a large multicenter outcomes database as a control. Each intervention was compared with the control for the incidence of acute and chronic GVHD and overall survival and against novel composite endpoints: acute and chronic GVHD, relapse-free survival (GRFS), and chronic GVHD, relapse-free survival (CRFS). Modeling GRFS and CRFS using the benchmark analysis further informed the design of 2 clinical trials testing GVHD prophylaxis interventions. This study demonstrates the potential benefit of using an outcomes database to select promising interventions for multicenter clinical trials and proposes novel composite endpoints for use in GVHD prevention trials.     

非甾体抗炎药的胃肠副作用临床分析

目的 研究非甾体抗炎药的临床胃肠副作用,为临床的良好应用提供参考依据。方法 选取2015年1月~2017年12月在我院采用非甾体抗炎药治疗的846例患者临床资料为研究对象,总结临床患者出现的胃肠副作用表现。结果 846例患者中101例发生胃肠道症状,占11.94%;5例发生胃肠道出血,占0.59%。消化道症状包括上腹不适、腹胀、腹痛、烧心、纳差、嗳气、反酸、恶心、呕吐、腹泻、便秘等;非甾体抗炎药单独使用胃肠副作用发生率低于2种非甾体抗炎药联合应用或非甾体抗炎药联用皮质激素者,差异有统计学意义（P＜0.05）;临床通过改用非甾体抗炎药或对症治疗,患者消化道症状均得到缓解,且患者可坚持用药,消化道出血患者也恢复正常,无胃肠副作用而导致的死亡。结论 临床应科学合理的控制非甾体抗炎药使用,不仅可减少严重并发症,而且可降低患者经济负担,并应尽量避免非甾体抗炎药的联合应用。     

国产支架型人工血管的实验研究与临床应用

目的研究和开发国产支架型人工血管经腔内治疗动脉疾病.方法1993年6月至1999年8月,用北京地区杂种狗24条,分别制作了腹主动脉瘤(8条)、降胸主动脉瘤(6条)、升主动脉瘤(4条)、主动脉弓瘤(4条)和动静脉瘘(2条)模型,用自制的支架型人工血管置入.置于腹主动脉的支架是编织式镍钛合金记忆金属,长3cm,直径8cm;胸主动脉支架是联体不锈钢“Z“型支架,长3cm,直径2cm.覆膜均为国产超薄涤纶人工血管.临床应用20例,男17例,女3例.主动脉夹层11例,肾下腹主动脉瘤7例和创伤性动静脉瘘2例.结果17条狗术后存活,分别于2、4、8周获取标本,支架型人工血管通畅良好,无血栓形成.临床病例中,有1例腹主动脉瘤并发肾功能不全,于术后20天血液透析中死于心肌梗塞,其余病人均被成功治疗.随访2个月至5年,除1例夹层动脉瘤术后3个月支架移位外,所有病人恢复良好.结论自制的支架型人工血管费用低,操作简便,应用前景可观.     

Gender and Ethnicity of Enrolled Participants in U.S. Food and Drug Administration (FDA) Clinical Trials for Approved Ophthalmological New Molecular Entities

Purpose

The purpose of this review is to describe the demographics (age, gender, race and iris color) of subjects enrolled in clinical trials supportive of approved New Molecular Entities (NMEs) in ophthalmology over the last 10 years (2006–2016).

Immunochemical Approaches to the Detection of Sulfathiazole in Animal Tissues

A series of ELISAs based on anti-sulfathiazole (STZ) monoclonal antibodies (MAbs) were developed that can detect STZ below the tolerance level in tissues. The IC⁵⁰ values (concentrations of STZ inhibiting 50% of binding in a competitive ELISA) for each MAb ranged from 6 to 21 ng ml^?1 of STZ. Immunoassays based upon two MAbs, STZ-23 and SDM44, were evaluated for their assay performance using swine liver samples spiked with STZ. Swine liver tissue was analyzed without a complex sample preparation step, with only a simple dilution of swine liver extract being necessary. A good correlation between immunoassay results and spike levels in swine liver (R² >0.98) was obtained, demonstrating that the immunoassays are capable of quantifying STZ in swine liver. The cross-reactivities of other sulfonamide drugs and STZ metabolites in these immunoassays were also examined.     

纤维蛋白胶的实验研究及临床应用

本文讨论了纤维蛋白胶的配方、工具和使用方法,并报告了6例临床经验。纤维蛋白原浓度需>40mg/ml,凝血酶浓度>500U/ml能立即凝固,<50U/ml,凝固时间>60秒。可根据不同目的选用不同的工具和配方。抑肽酶并非必要成份。通过6例初步临应用总结使用时的方法及注意事项。     

风险防范式护理在儿科安全管理中的应用及效果观察

目的 探讨风险防范式护理在儿科安全管理当中的应用效果。方法 选取2016年4月~2017年9月在我院儿科就诊的140例患儿作为对象,将其随机分为研究组与对照组,每组70例。对照组给予常规护理措施干预,研究组在常规护理基础上给予风险防范式护理干预,对两组满意度,抑郁、焦虑评分,不良事件进行对比。结果 研究组患者对治疗性、心理、生活、健康教育等满意度评分,高于对照组,差异有统计意义（P＜0.05）。研究组患者抑郁、焦虑评分、不良事件发生率低于对照组,差异有统计学意义（P＜0.05）。结论 在儿科安全管理当中采取风险防范式护理干预,能够有效提高临床治疗效果,降低不良事故发生率,提高患者对护理满意度。