加强质量体系建设,提高技术监督水平

本文对药品检验机构建立和完善质量体系的重要性，质量体系的内涵，建立和完善质量体系应注意的主要问题进行了分析并提出了建议。     

眼刺激试验替代方法研究进展

由于动物眼刺激试验 (Draizetest)本身存在的问题和“3R”运动的兴起 ,各国广泛开展了动物眼刺激试验替代方法的研究和验证试验。各种替代方法作用机制不一 ,优缺点各异 ,故需要一组互补性体外试验来对化学物质的眼刺激性进行评价     

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Predictive testing for Huntington's disease: I. Predictors of uptake in South Wales

In Wales, predictive testing for Huntington's disease (HD) has not been offered proactively to families and uptake of testing is low in comparison to other centres. Little is known of those not requesting testing, particularly those not in direct contact with the genetics service. This study examined differences between a cohort of 22 test applicants and a random group of 32 'non-requesters', drawn from the South Wales HD register. Respondents were interviewed by means of a semi-structured schedule in their own homes. The study groups differed significantly on a number of variables including: knowledge of the availability of testing; perceived attitudes of family members and significant others to testing; length of knowledge and perceived stressfulness of being at risk; and perceived ability to cope with an unfavourable result. Overall, knowledge of testing procedures was poor and at-risk individuals' understanding of genetic terminology was at odds with scientific distinctions. Discussion focuses on the organisational and psychological factors associated with lack of knowledge of the availability of testing and the interpretation of reported coping capacities.     

Quantitative MRI of the brain in children with sickle cell disease reveals abnormalities unseen by conventional MRI

Conventional MRI (cMRI) has shown that brain abnormalities without clinical stroke can manifest in patients with sickle cell disease (SCD). We used quantitative MRI (qMRI) and psychometric testing to determine whether brain abnormalities can also be present in patients with SCD who appear normal on cMRI. Patients 4 years of age and older with no clinical evidence of stroke were stratified by cMRI as normal (n = 17) or abnormal (n = 13). Spin-lattice relaxation time (T1) of gray and white matter structures was measured by the precise and accurate inversion recovery (PAIR) qMRI method. Patient cognitive ability was assessed with a standard psychometric instrument (WISC-III or WISC-R). In all 30 patients with SCD, qMRI T1 was lower than in 24 age- and race-matched controls, in cortical gray matter (P < .0006) and caudate (P < .0009), as well as in the ratio of gray-to-white matter T1 (P < .008). In the 17 patients who were shown to be normal by cMRI, qMRI T1 was still lower than in controls, in both cortical gray matter (P < .02) and caudate (P < .004). Histograms of voxel T1 show that the proportion of voxels with T1 values intermediate between gray and white matter (ie, consistent with encephalomalacia) was 9% higher than controls in patients shown to be normal by cMRI (P < .05) and 15% higher than controls in patients shown to be abnormal by cMRI (P < .0005). The full scale intelligence quotient (FSIQ) of all patients with SCD was 75, compared to the FSIQ of 88 in a historical control group of patient siblings (P < .001). The FSIQ of patients shown to be normal by cMRI was 79, significantly lower than the FSIQ of patient siblings (P < .04). The FSIQ of 71 in patients shown to be abnormal by cMRI was significantly lower than both the patient siblings (P < .005) and the patients shown to be normal by cMRI (P < .04). Patients shown to be abnormal by cMRI scored lower than patients shown to be normal by cMRI, specifically on the subtests of vocabulary (P = .003) and information (P = .03). Cognitive impairment is thus significant, even in patients with SCD who were shown to be normal by cMRI, suggesting that cMRI may be insensitive to subtle neurologic damage that can be detected by qMRI. Because cognitive impairment can occur in children normal by cMRI, our findings imply that prophylactic therapy may be needed earlier in the course of SCD to mitigate neurologic damage.     

Clinical importance,statistical significance and the assessment of economic and quality-of-life outcomes

The assessment of economic and quality-of-life outcomes of health care interventions is moving into a new era, with such assessments increasingly being made within the context of controlled clinical trials. Traditionally the measurement of many variables in economic evaluations, particularly costs, has been deterministic. In the context of clinical trials the measurement of variables is stochastic, with the standard principles of statistical inference being applied to analyse differences between treatments in terms of effectiveness. Economists participating in clinical research are therefore being called upon to specify the sample size for the economic component of the evaluation and to undertake statistical tests for differences in cost or cost-effectiveness. This paper discusses the current methodological issues surrounding stochastic measurement in clinical trials, discusses the additional issues raised by the assessment of economic and quality-of-life outcomes and specifies the challenges facing economists if they are to answer the questions now being posed about economic analysis by statisticians and clinical researchers. It is concluded that application of the standard principles of statistical inference to economic data is not straightforward and will require value judgements to be made about statistical significance and economic importance, which may differ from those already made in purely clinical studies.     

Day 4 is better than day 3 for a single patch test reading

Readings were performed on day (D)2, D3 and D4 after application of patch tests in NN patients. 90 patch lest reactions in 49 patients were interpreted as allergic und of past or present relevance. A single D2 reading detected 58 of the allergic reactions, with 32 false-negatives and 23 false-positives. A single D3 reading detected 77 allergic reactions, with 13 false-negatives and 17 False-positives. A single D4 reading detected 85 allergic reactions, with 5 false-negatives und 4 false-positives. Therefore, if only a single reading is feasible, it is better performed on D4 than on D3.     

胚胎种植前遗传学检测助孕妊娠结局的影响因素研究

背景 育龄期女性胚胎着床失败及流产的最常见原因是胚胎异常,但移植经胚胎种植前遗传学检测(PGT)筛选后的正常胚胎后,仍出现种植失败或流产的原因目前并没有形成统一的结论。目的 分析PGT助孕后种植失败及流产的影响因素。方法 回顾性分析2018年12月至2021年2月在安徽医科大学第一附属医院生殖中心行PGT助孕的329例患者的临床资料,根据患者是否临床妊娠分为临床妊娠组(n=218)和种植失败组(n=111),并将临床妊娠组患者根据妊娠结局分为活产亚组(n=175)和流产亚组(n=43)。比较临床妊娠组和种植失败组,活产亚组和流产亚组的一般情况、促排卵及体外胚胎发育情况。采用多因素Logistic回归分析探讨PGT患者种植失败及流产的影响因素。绘制受试者工作特征(ROC)曲线分析多因素Logistic回归分析筛选出的影响因素对PGT患者发生种植失败及流产的预测价值。结果 多因素Logistic回归分析显示,既往流产次数≥2次〔OR=4.032 0,95%CI(2.423 0,6.710 0)〕、高密度脂蛋白胆固醇(HDL-C)水平低〔OR=3.890 0,95%CI(1.455 0,10...