An information criterion for marginal structural models

Marginal structural models were developed as a semiparametric alternative to the G‐computation formula to estimate causal effects of exposures. In practice, these models are often specified using parametric regression models. As such, the usual conventions regarding regression model specification apply. This paper outlines strategies for marginal structural model specification and considerations for the functional form of the exposure metric in the final structural model. We propose a quasi‐likelihood information criterion adapted from use in generalized estimating equations. We evaluate the properties of our proposed information criterion using a limited simulation study. We illustrate our approach using two empirical examples. In the first example, we use data from a randomized breastfeeding promotion trial to estimate the effect of breastfeeding duration on infant weight at 1 year. In the second example, we use data from two prospective cohorts studies to estimate the effect of highly active antiretroviral therapy on CD4 count in an observational cohort of HIV‐infected men and women. The marginal structural model specified should reflect the scientific question being addressed but can also assist in exploration of other plausible and closely related questions. In marginal structural models, as in any regression setting, correct inference depends on correct model specification. Our proposed information criterion provides a formal method for comparing model fit for different specifications. Copyright © 2012 John Wiley & Sons, Ltd.     

免气腹腹腔镜胃癌根治术的手术操作规范(2021版)

腹腔镜技术在胃癌治疗中已得到广泛应用,大量前瞻性研究也证实了其手术安全性.腹腔镜下操作空间多依靠CO2气腹构建,对高龄或心肺基础较差的患者可能增加围手术期并发症的发生风险,因此,自20世纪90年代起以悬吊技术为代表的免气腹技术可在一定程度上替代传统气腹,扩大了腹腔镜胃癌手术的适应证.目前大量免气腹装置的研发推动了此技术...     

微波消解/电感耦合等离子体质谱法测定西洋参重金属及有害元素含量

目的:分析不同产地不同商品规格西洋参中重金属及有害元素的含量,评价西洋参的药用安全性,为其行业标准的制定提供试验依据。方法:采用微波消解/电感耦合等离子体质谱(ICP-MS)法测定了22个不同产地不同规格西洋参中Pb、Cd、Cu、As、Hg的含量,用SPSS16.0软件进行统计分析;并以中国药典2010年版一部限量标准为依据,判断西洋参中重金属及有害元素含量超标情况。结果:建立了不同产地西洋参样品重金属及有害元素分布特征图谱;西洋参中Pb、Cd、Cu、As、Hg的含量均低于中国药典的限量标准;方差分析表明长度对西洋参中Pb、Cd的含量具有显著性影响,单枝质量对Pb、Cd、Cu、As、Hg的含量影响差异不显著。结论:西洋参具有较高的药用安全性,从药用安全性角度为西洋参商品规格标准的修订提供了参考。     

大蒜质量标准中商榷内容的研究

目的:参照美国药典、欧盟药典和英国药典对2010版中国药典收载的大蒜薄层鉴别和含量测定等进行研究。方法:采用微波灭酶法处理样品,对大蒜药材进行薄层色谱鉴别;采用阳离子交换色谱柱,以磷酸盐缓冲溶液为流动相,流速0.5 mL.min-1,检测波长214 nm,测定大蒜药材中蒜氨酸含量。结果:不同产地大蒜药材的薄层色谱在与蒜氨酸和精氨酸对照品斑点Rf值相同的位置上,均检出相同的斑点。建立的蒜氨酸含量测定HPLC法,经方法学实验表明,蒜氨酸浓度在31.2～374.4μg.mL-1范围内呈良好线性关系(r=0.9999);低、中、高浓度平均回收率(n=9)分别为102.8%(RSD=4.0%),101.8%(RSD=3.0%),111.0%(RSD=3.8%)。结论:本研究建立了大蒜药材的薄层色谱鉴别和高效液相色谱含量测定方法,可用于大蒜药材的定性与定量分析,建议作为大蒜质量标准进一步研究的参考。     

中医药学语言系统的语义网络框架：一个面向中医药领域的规范化顶层本体

中医药学语言系统（TCMLS）旨在实现规范化、一体化的中医药术语体系,以支持中医药文献与数据资源的合理组织和有效检索。“Health informatics—Semantic network framework of traditional Chinese medicine language system[ISO／DTS17938]”（健康信息学-中医药学语言系统的语义网络框架）是国际标准化组织（ISO）于近期完成、正在审核的技术规范草案。它作为一个面向中医药领域的规范化顶层本体,为中医药学语言系统中的所有概念提供了一体化的概念框架,对于中医药学语言系统的规范化和国际化具有重要意义。     

衡阳市医院制剂风险调查与对策探讨

目的： 提高我市医院制剂风险防范和控制水平，提高制剂的安全性和可靠性。方法： 通过生产现场调查，对4家医院制剂室的制药用水进行抽样检验，结合查阅相关文献，分析我市医院制剂的潜在风险及产生原因，针对性地提出相应的管理措施。结果： 实现医院制剂室的规范化管理，制定完善的管理制度，建立可靠的标准操作规程，从制剂生产控制、环境管理、人员管理、设备管理等方面，切实做到每项工作都有章可循。结论： 医疗机构制剂室应顺应形势需求，加大投入力度，加强《医疗机构制剂配制质量管理规范》培训，认真执行标准，建立良好的质量运行体系，确保患者用药安全有效。     

简述我所进口药品注册检验的电子化管理

随着进口药品注册检验的数量逐年增长,使得如何对进口药品注册检验进行行之有效的管理成为一个值得深入研究和探索的问题,通过采用Lotus Notes系统开发出的进口药品管理系统软件可方便的对进口药品注册检验进行管理。     

New levothyroxine formulation meeting 95–105% specification over the whole shelf-life: results from two pharmacokinetic trials

Objective: Small levothyroxine (L-T4) dose changes can lead to significant clinical effects. To ensure thyroid hormone levels are safely maintained, authorities are increasingly adopting stricter potency specifications for L-T4, the most stringent of these being 95–105% of the labeled dose over the whole shelf-life. Levothyroxine sodium (Euthyrox, Eutirox, Lévothyrox) has been reformulated, and two studies performed, to ensure bioequivalence to the currently marketed formulation and dosage form proportionality of the new formulation.

Methods: The bioequivalence study was an open-label, randomized, single-dose, two-period, two-sequence crossover comparing the highest dosage strengths of the currently marketed and the new L-T4 formulation at a total dose of 600?μg. The dosage form proportionality study was an open-label, randomized, three-period, six-sequence crossover, comparing 50?μg, 100?μg, and 200?μg L-T4 tablets, at a total dose of 600?μg. Blood samples were taken at predefined time intervals. Primary outcomes were area under the curve (AUC) and maximum concentration (C_max) of thyroxine (T4) in plasma.

Results: In the bioequivalence study, comparing the T4 profiles for the new and current formulation of L-T4, the geometric least square mean ratio of the baseline-adjusted AUC_0–72,adj was 99.3% (90% confidence interval [CI]: 95.6–103.2) and the C_max,adj was 101.7% (90% CI: 98.8–104.6). Bioequivalence was established if the 90% CI lay within the predefined 0.9–1.11 limits. In the dosage form proportionality study, pairwise comparisons ranged from 99.3% to 104.8%, and all 95% CIs were within the predefined CI range (0.8–1.25): the three dose strengths were dosage form proportional.

Conclusions: The new formulation of L-T4 meets the most stringent potency specification guidelines, and has been demonstrated to be bioequivalent to the current formulation and to show dosage form proportionality. The new formulation will enable patients to receive a dose fine tuned to their medical needs, contributing to improved safety in the use of L-T4.     

A comparison of existing methods for multiple imputation in individual participant data meta‐analysis

Multiple imputation is a popular method for addressing missing data, but its implementation is difficult when data have a multilevel structure and one or more variables are systematically missing. This systematic missing data pattern may commonly occur in meta‐analysis of individual participant data, where some variables are never observed in some studies, but are present in other hierarchical data settings. In these cases, valid imputation must account for both relationships between variables and correlation within studies. Proposed methods for multilevel imputation include specifying a full joint model and multiple imputation with chained equations (MICE). While MICE is attractive for its ease of implementation, there is little existing work describing conditions under which this is a valid alternative to specifying the full joint model. We present results showing that for multilevel normal models, MICE is rarely exactly equivalent to joint model imputation. Through a simulation study and an example using data from a traumatic brain injury study, we found that in spite of theoretical differences, MICE imputations often produce results similar to those obtained using the joint model. We also assess the influence of prior distributions in MICE imputation methods and find that when missingness is high, prior choices in MICE models tend to affect estimation of across‐study variability more than compatibility of conditional likelihoods. Copyright © 2017 John Wiley & Sons, Ltd.