酷似弥漫浸润型胃癌的深在性囊性胃炎1例

酷似弥漫浸润型胃癌的深在性囊性胃炎1例,经胃镜、CT、胃肠造影等检查均提示胃癌可能,后经超声内镜深挖活检、手术病理证实为深在性囊性胃炎。     

Multi-center analytical evaluation of a novel automated tacrolimus immunoassay

Background

Tacrolimus (TAC) is a post-transplantation immunosuppressant drug used in patients for whom careful monitoring of TAC concentration is essential. A new semi-automated immunoassay for TAC measurement, the Elecsys Tacrolimus assay, is available and has been assessed in a multi-center evaluation.

Methods

Residual whole blood samples from patients undergoing TAC therapy after organ transplant were used in assay evaluation at five clinical laboratories in Europe. Experiments included imprecision according to CLSI EP5-A2 (within-run and intermediate), functional sensitivity, linearity according to CLSI EP6-A, and recovery from external quality assessment scheme (EQAS) samples. The assay was compared to LC–MS/MS used routinely at each investigational site, and to the Abbott Architect immunoassay.

Results

Linearity from 0.5 to 40 μg/L was observed and functional sensitivity of 0.3 μg/L (CV ≤ 20%) was determined. Within-run imprecision was ≤ 5.1% on cobas e 602 (5.1% at 1.5 μg/L) and ≤ 8.9% (8.9% at 0.8 μg/L) on cobas e 411. The intermediate imprecision for TAC concentrations ≥ 6.8 μg/L was ≤ 6.5%. At lower therapeutic concentrations (to 1.5 μg/L) it was consistently ≤ 10%. Deming regression analysis of method comparison to LC–MS/MS yielded slopes of 1.07 (95%CI: 1.05/1.10) for heart transplant samples, 1.13 (95%CI: 1.09/1.16) for kidney, and 1.05 (95%CI: 1.02/1.08) for lung transplant samples.

Conclusions

The Elecsys Tacrolimus assay has good linearity, functional sensitivity and intermediate imprecision and is comparable to LC–MS/MS methods. The over-all performance of ECLIA demonstrates a modern generation TAC assay that meets the demands of monitoring drug concentrations in current immunosuppressive regimens.     

药品临床试验管理规范的实践与问题

目的：探讨实施临床试验管理规范（ＧＣＰ）过程中所遇到的问题的解决办法。方法：分析执行该规范的现状和存在问题。结果：提出解决问题的几点建议。结论：进一步加强ＧＣＰ的培训工作;起草适合实际情况的知情同意书;加强研究者与申办者、监视员的联系;定期评估实行ＧＣＰ的情况等措施可能是可行的。     

医院药师在药物临床试验中的作用

目的:探讨医院药师在药物临床试验中的作用。方法:分析医院药师在《药物临床试验质量管理规范》的宣传、培训,各项标准操作规程的制订过程中及临床试验各期所发挥的作用。结果与结论:医院药师在药物临床试验中占有举足轻重的地位,而医院药师通过参与药物临床试验也熟悉了科学研究的基本方法,强化了科研意识。     

Bridging non-human primate correlates of protection to reassess the Anthrax Vaccine Adsorbed booster schedule in humans

Anthrax Vaccine Adsorbed (AVA, BioThrax^®) is approved for use in humans as a priming series of 3 intramuscular (i.m.) injections (0, 1, 6 months; 3-IM) with boosters at 12 and 18 months, and annually thereafter for those at continued risk of infection. A reduction in AVA booster frequency would lessen the burden of vaccination, reduce the cumulative frequency of vaccine associated adverse events and potentially expand vaccine coverage by requiring fewer doses per schedule. Because human inhalation anthrax studies are neither feasible nor ethical, AVA efficacy estimates are determined using cross-species bridging of immune correlates of protection (COP) identified in animal models. We have previously reported that the AVA 3-IM priming series provided high levels of protection in non-human primates (NHP) against inhalation anthrax for up to 4 years after the first vaccination. Penalized logistic regressions of those NHP immunological data identified that anti-protective antigen (anti-PA) IgG concentration measured just prior to infectious challenge was the most accurate single COP.In the present analysis, cross-species logistic regression models of this COP were used to predict probability of survival during a 43 month study in humans receiving the current 3-dose priming and 4 boosters (12, 18, 30 and 42 months; 7-IM) and reduced schedules with boosters at months 18 and 42 only (5-IM), or at month 42 only (4-IM). All models predicted high survival probabilities for the reduced schedules from 7 to 43 months. The predicted survival probabilities for the reduced schedules were 86.8% (4-IM) and 95.8% (5-IM) at month 42 when antibody levels were lowest. The data indicated that 4-IM and 5-IM are both viable alternatives to the current AVA pre-exposure prophylaxis schedule.     

Investigator barriers and preferences to conduct clinical drug trials in Finland: a qualitative study

OBJECTIVE: To explore investigator barriers, preferences, and attitudes towards conducting clinical trials in Finland. METHOD: In-depth, semi-structured interviews with 20 clinicians working in the field of cardiovascular medicine were performed. The interviews were audiotaped, transcribed verbatim and analysed qualitatively. Twenty clinicians from all (five) university hospitals in Finland and from three subgroups: 1) with long experience, 2) with limited experience and 3) reluctant to carry out clinical trials, were sampled purposefully. MAIN OUTCOME MEASURES: Barriers and (de)motivating factors in carrying out clinical trials and need for training in Good Clinical Practice (GCP). RESULTS: Overall, the investigators had a positive attitude towards conducting clinical trials. The major barriers seemed to occur at the beginning of the trial: bureaucracy, lack of time and laboriousness. The informants hoped for more specific inhouse rules and flexibility in hospitals. The greatest investigator barriers were insufficient financial incentives, trial-related reasons and administrative affairs/bureaucracy. The smallest barriers were reported in subject recruitment, clinical work, documentation, investigational product logistics and communication with ethics committees. Financial incentives, a possibility to incorporate a personal sub-study or other benefits for personal research and scientific and clinical interest in the trial were reported as the most motivating factors. Carrying out studies in practice and an opportunity to participate in a trial during one's postgraduate specialist education were considered beneficial. Training in GCP, mainly in the course of postgraduate education, and a certificate or equivalent were generally considered necessary, although a voluntary system was preferred. CONCLUSION: The interviews of clinicians provide valuable information about the barriers and preferences related to the practical implementation of clinical trials. If the trial is scientifically/clinically interesting and involves a small administrative burden and sufficient financial compensation, investigators are motivated to participate. The barriers and preferences should be considered in decision-making, to meet the various needs of all parties involved and to produce high-quality GCP-compliant clinical drug research. This would ensure the availability of sufficient conditions to carry out clinical trials also in the future.     

Pharmacodynamic assessment of a novel P2Y12 receptor antagonist in Japanese patients with coronary artery disease undergoing elective percutaneous coronary intervention

Introduction

Numerous reports have shown that prasugrel shows a rapid and consistent antiplatelet effect among European and US patients. Previous studies suggest that prasugrel might be expected to achieve an adequate antiplatelet effect in healthy Asian subjects, even at lower doses than those assessed in the TRITON-TIMI 38 study. In this study, the antiplatelet effect of prasugrel was evaluated in Japanese coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI).

Methods and results

Eighty-four patients were randomized into four treatment groups: prasugrel 10/2.5 mg (loading dose [LD]/maintenance dose [MD]), 15/3.75 mg or 20/5 mg, and clopidogrel 300/75 mg. The LD of each regimen was administered the day before PCI, followed by 28-day MD on aspirin background therapy (81-100 mg). Antiplatelet effects were evaluated by light transmission aggregometry and VASP assay.The mean inhibition of platelet aggregation (IPA) induced by 20 μM of adenosine diphosphate at 4 hours after LD was higher among the prasugrel 10/2.5 mg, 15/3.75 mg and 20/5 mg groups compared with the clopidogrel group (12.3%, 20.9%, 29.8% vs. 8.4%, respectively). The proportion of subjects with an IPA of < 10% on Day 28 was lower among the prasugrel 15/3.75 mg, and 20/5 mg groups than in the clopidogrel group (0%, 6.3% vs. 15.8%, respectively). No “major” or “clinically relevant non-major” bleeding was observed.

Conclusions

Prasugrel 15 mg LD/3.75 mg MD or higher doses was well tolerated and achieved a more rapid, higher and consistent antiplatelet effect than clopidogrel in Japanese CAD patients undergoing PCI.     

药物临床试验GCP管理平台构建

介绍临床试验GCP管理平台的研究与实现,阐明系统总体架构,从系统管理、试验管理、机构资源管理等方面分析系统功能,指出该系统的应用可以对药物临床试验实现全方位、规范化的信息管理。     

Prevention trials in Alzheimer's disease: an EU-US task force report

Despite enormous financial and scientific efforts, still no approved disease-modifying therapies exist for Alzheimer's disease (AD). During the last decade all Phase III clinical trials on disease modifiers in AD have failed. The dementia stage of AD being probably too late in order to allow for successful disease modification has been identified as a possible culprit that could explain the failure of so many clinical trials. In parallel, a major development in the diagnostic research field of AD was achieved by the recent proposal of new diagnostic criteria for AD, which also specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD, thus extending the traditional definition of disease to very early stages that may be a more feasible target for various disease modifying therapeutic interventions. This ongoing paradigm shift in AD definition and diagnosis represents a fundamental basis for redefinition of interventional trials in AD, allowing to specifically focus on preventative measures during very early pathophysiologically confirmed stages of disease. This consensus paper reflects the outcome from a European Union and North American Task Force meeting comprised of experts from academia, industry, private foundations, and regulatory agencies that was convened in Toulouse, France on November 5, 2010 and that focused on prevention trials in AD. This position paper thoroughly analyzes prerequisites for successful preventative trials in AD and concludes with concrete recommendations on biomarkers, statistical tools and other variables important for improved study designs suitable for preventative as well as for early therapeutic interventional trials in AD.