Innovation in Chemistry,Manufacturing, and Controls—A Regulatory Perspective From Industry

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics.     

Increased hand washing reduces influenza virus surface contamination in Bangkok households, 2009–2010

Within a hand‐washing clinical trial, we evaluated factors associated with fomite contamination in households with an influenza‐infected child. Influenza virus RNA contamination was higher in households with low absolute humidity and in control households, suggesting that hand washing reduces surface contamination.     

Urinary phthalate metabolites and metabolic syndrome in U.S. adolescents: Cross-sectional results from the National Health and Nutrition Examination Survey (2003–2014) data

Objective

There is limited research on the association between phthalates and metabolic syndrome (MetS). Among adolescents, phthalate exposure, which can occur from multiple sources, has been linked to several risk factors for MetS. The objective was to investigate the association between urinary phthalate metabolite concentrations (i.e., mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), mono-(3-carboxylpropyl) phthalate (MCPP), and di(2-ethylhexyl phthalate (DEHP)) and MetS in adolescents aged 12–19 years using the National Health and Nutrition Examination Survey (NHANES) data (2003–2014). A secondary aim was to assess if observed associations varied by a measure of socioeconomic status, economic adversity, which was defined using parental income and educational attainment as well as household food security.

Using conceptual work products of health care to design health IT

This paper introduces a new, model-based design method for interactive health information technology (IT) systems. This method extends workflow models with models of conceptual work products. When the health care work being modeled is substantially cognitive, tacit, and complex in nature, graphical workflow models can become too complex to be useful to designers. Conceptual models complement and simplify workflows by providing an explicit specification for the information product they must produce. We illustrate how conceptual work products can be modeled using standard software modeling language, which allows them to provide fundamental requirements for what the workflow must accomplish and the information that a new system should provide. Developers can use these specifications to envision how health IT could enable an effective cognitive strategy as a workflow with precise information requirements. We illustrate the new method with a study conducted in an outpatient multiple sclerosis (MS) clinic. This study shows specifically how the different phases of the method can be carried out, how the method allows for iteration across phases, and how the method generated a health IT design for case management of MS that is efficient and easy to use.     

False-positive Aspergillus galactomannan immunoassays associated with intravenous human immunoglobulin administration

ObjectivesEvidence of false-positive galactomannan enzyme immunoassay (GM-EIA) results associated with intravenous immunoglobulin (IVIG) administration is scarce. Here, we aimed to determine the false-positive rate of GM-EIA after IVIG administration and to identify the related factors.MethodsStandard GM-EIA was performed using diluted and pure human IVIG samples with and without heat treatment. We also included adult patients who had at least one GM-EIA result within 1 week of IVIG administration for analysis. Those who had prior invasive aspergillosis within 1 year before IVIG therapy were excluded. The clinical characteristics and galactomannan index (GMI) kinetics between patients with false-positive and true-positive GMI were compared.ResultsAll diluted and pure IVIG samples tested positive for GM. Heat treatment resulted in the considerable elevation of GMI. Of 48 patients with positive GM-EIA results within 1 week of IVIG administration, 22 (45.8%) were considered to have false-positive antigenaemia (false-positive group, FPG). After the completion of IVIG administration, a decline in GMI was observed in all FPG patients but in only 18 out of 26 patients (69.2%) with true-positive results (true-positive group, TPG). By 7, 14, and 18 days of IVIG administration, GMI reverted to negative values in 7/15 (46.7%), 18/20 (90%) and 22/22 (100%) FPG patients, respectively, and 6/24 (25%), 14/24 (58.3%), and 16/26 (61.5%) of TPG patients, respectively. The TPG was more likely to have two or more consecutively positive GMIs after IVIG administration than the FPG (adjusted odds ratio, 9.01; 95% confidence interval, 1.99–40.9).ConclusionsIVIG treatment may produce false-positive GM-EIA results. A positive GMI among patients receiving human IVIG should be interpreted with caution.     

反向点杂交法测定浙江省4620例男性HPV感染者的流行病学特征

目的调查浙江省男性人乳头瘤病毒(human papilloma virus，HPV)感染的亚型分布及流行病学特点，为男性HPV感染早期筛查、预防、诊断提供依据。 方法回顾性汇总分析2014年1月至2016年12月期间，浙江省17~74岁的4620名男性尖锐湿疣皮损拭子或组织标本；4620例样本中，其中120份因细胞量不足判定采样失败，剩余4500例样本按不同年龄分为6组(17~20岁组268名、21~30岁组1958名、31~40岁组1156名、41~50岁组667名、51~60岁组355名、>60岁组96名)。用聚合酶链反应(polymerase chain reaction, PCR)和反向点杂交法测定23种HPV基因型，并分析其HPV阳性率分布、HPV阳性率差异和高低危型HPV感染特征。 结果4500例样本中有2799例HPV阳性，总阳性率为62.2%，其中：以6型和11型阳性率最高，分别为15.58%(436/2799例)和10.00%(280/2799例)。高危型阳性率最高的为52型，占4.72% (132/2799例)。在2799例HPV DNA阳性者中，有1266例为单一感染；混合感染1533例，占44.26%，单纯低危型最高为三重感染，单纯高危型最高为四重感染，而高低危混合感染达七重，其中七重感染占2.25%(63/2799例)。高低危混合感染数高于单纯高危型和单纯低危型，两者比较有统计学差异(χ²分别为28.1、82.8，P均<0.05)。HPV阳性结果以21~40岁青壮年为主，占总人数的69.2% (3114/4500)。而HPV阳性率以17~20岁组(75.0%)和51~60岁组(79.7%)最高，与其他年龄段[21~30岁(60.7%)、31~40岁(59.1%)、41~50岁(59.6%)和>60岁(46.4%)组]相比χ²分别为20.48、22.51、18.86、26.02和46.03、48.89、40.99、41.84，P均<0.05。 结论浙江地区男性HPV感染者主要以6、11型为主，高发于青壮年，HPV混合感染比例较高，高低危混合感染较常见。     

公立医院人力资源配置竞争力及问题研究

人力资源配置实际上是用人的艺术,强调人才是一类重要的资源,根据人才的不同能力在不同岗位上进行分配,最大程度发挥人才的价值。当前因为经济水平的不断提升,新医疗体制改革越来越深入,公立医院需要承受非常大的压力。在人力资源配置上,公立医院具有一定竞争力,但同时也存在一些问题,医院必须保持较高的竞争意识,保证人力资源的合理配置,才可以确保医院始终具备良好的竞争力,保证可持续的发展。     

Aberrancies in Antigen-presenting Cells and T Cells in Autoimmune Thyroid Disease. A Role in Faulty Tolerance Induction

Various thyrocyte, monocyte, macrophage, DC and T cell abnormalities exist in the animal models of spontaneously developing autoimmune thyroiditis and in patients with autoimmune thyroid disease. An aberrant interaction between such abnormal thyrocytes, abnormal professional antigen-presenting cells (APC) and abnormal T cells forms the basis for the atypical autoimmune reaction targeting thyroid antigens. In the atypical interaction more than one gene and various environmental factors are involved. The genetic and environmental factors must act together to induce full-blown disease.

Although there is a general blueprint for the development of destructive autoimmune thyroiditis, thyrocyte and immune cell abnormalities differ between the various animal models and the various forms of autoimmune thyroid disease (either associated with type 1 diabetes, associated with bipolar disorder or not associated). This tells us that there are different etio-pathogenic forms of destructive autoimmune thyroiditis. Whether such heterogeneity is also the case for the etio-pathogenesis of Graves' disease remains unknown. Animal models of spontaneously developing Graves' disease would be helpful in unraveling this question.

If indeed there are various etio-pathogenic routes in different patients that lead to destructive autoimmune thyroiditis, then tailor-made therapeutic approaches need to be carried out in attempts to correct the underlying immune abnormalities in individual patients or to prevent the development of destructive autoimmune thyroiditis in individuals at risk. While in some forms of destructive autoimmune thyroiditis (f.i. those associated with bipolar disorder) immune suppression should be the first choice of intervention, other forms (f.i. those associated with type 1 diabetes) may benefit from immune stimulation in certain pre-stages of the disease (to restore f.i. the faulty APC function characteristic of this condition). Obviously a more precise determination of the spectrum of cell-mediated immune abnormalities is required in individual cases of destructive autoimmune thyroiditis, before therapies that aim at correcting the immune abnormalities can be tested successfully.