Structural models to untangle triggers of ocular/nonocular herpesvirus recurrence

解开眼/非眼疱疹病毒复发触发因素的结构模型

• 批准号: 8312498
• 负责人: Stephen R Cole
• 金额: $ 18.17万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8312498
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Acute; Acyclovir; Adult; Affect; Age; Antiviral Therapy; Area; Aspirin; Behavioral; Blindness; Cardiovascular system; Clinical; Code; Collection; Complex; Cornea; Counseling; Data; Data Analyses; Development; Dose; Enrollment; Etiology; Exhibits; Eye Infections; Eye diseases; Eyedrops; Face; Feedback; Funding; Future; Genital system; Goals; Herpesviridae; Herpesvirus 1; Herpetic Keratitis; Human Herpesvirus 2; Incidence; Individual; Lesion; Methods; Metric; Morbidity - disease rate; National Eye Institute; Observational Study; Oral; Outcome; Participant; Patient Self-Report; Population; Prevention; Probability; Psychological Stress; Publishing; Randomized; Randomized Controlled Trials; Recruitment Activity; Recurrence; Reporting; Risk; Schedule; Simplexvirus; Site; Statistical Methods; Stratification; Structural Models; Sun Exposure; Testing; Time; Ultraviolet Rays; Virus Activation; Virus Diseases; Visit; Weather; Weight; Work; abstracting; antiretroviral therapy; base; burden of illness; clinical research site; cohort; cost effective; design; diaries; genital herpes; improved; indexing; innovation; mortality; prophylactic; prospective; randomized trial; response; sunglasses; ultraviolet

Abstract The overall goal of this proposal is to quantify independent effects of sunlight exposure and psychological stress on recurrence of clinical ocular and nonocular herpes simplex virus (HSV) infections. The aims of this proposal are to: (1) estimate the total (i.e. direct and indirect) effect of unprotected sunlight exposure on risk of HSV recurrence; and (2) estimate the total effect of psychological stress on risk of HSV recurrence. We hypothesize that: (1) unprotected sunlight exposure will exhibit a positive dose-response association with HSV recurrence and that (2) acute psychological stress will be associated with increased risk HSV recurrence. To accomplish these aims, data from 308 adults enrolled in a substudy formed to explore the triggers for HSV recurrence will be reanalyzed. This substudy recruited participants between 1992 and 1996 from a randomized control trial administered by the Herpetic Eye Disease Study group and funded by the US National Eye Institute to test prophylactic antiviral therapy for prevention of HSV recurrence. The 308 participants were seen at regularly scheduled visits at one of 74 clinical sites in the US; additionally, participants provided weekly diaries reporting on sunlight exposure, psychological stress, and other variables. Prior analyses of data collected in this substudy did not adjust for time varying confounding, and suffered from poor assessment of sunlight exposure. Moreover, none of the existing published reports on triggers of HSV recurrence have accounted for the effects of time varying confounding. Standard methods for statistical analysis (e.g. restriction, stratification, regression) may fail to estimate the total effect of time varying exposures/triggers on HSV recurrence in the presence of confounders that vary in time. To ameliorate this limitation, we will use marginal structural models which disentangle the effects of multiple time varying triggers of HSV recurrence. Also, a sunlight exposure metric that combines self-reported exposure and ultraviolet (UV) radiation index as obtained from the National Oceanic and Atmospheric Administration will be created to more finely delineate differences in sunlight exposure. Weekly averaged UV index values will be obtained for each of the 74 geo-coded clinical sites. Results from this proposal will further the understanding of the determinants of HSV recurrence and provide additional evidence for (1) effective behavioral counseling for individuals infected with HSV and (2) development of environmental controls (e.g., sunglasses designed to block critical UV wavelengths or UV blocking eye drops) to reduce morbidity. (e.g., sunglasses designed to block critical UV wavelengths or UV blocking eye drops)

抽象的 该提案的总体目标是量化阳光暴露和心理的独立影响 对临床眼和非眼疱疹病毒（HSV）感染复发的压力。这个目的 提案是：（1）估计未受保护的阳光暴露对风险的总（即直接和间接）影响 HSV复发； （2）估计心理压力对HSV复发风险的总影响。我们 假设：（1）未受保护的阳光暴露将与HSV表现出阳性剂量反应关联 复发，（2）急性心理压力将与HSV复发的增加有关。到 实现这些目标，来自308名成年人的数据，这些成年人被录入了用于探索HSV触发因素的物质 复发将被重新分析。这种物质在1992年至1996年之间从随机分析中招募了参与者 由疱疹性眼病研究小组管理并由美国全国眼资助的对照试验 测试预防预防HSV复发的预防性抗病毒疗法的研究所。看到308名参与者 在美国的74个临床场所之一定期访问；此外，参与者每周提供 关于阳光暴露，心理压力和其他变量报告的日记。事先分析数据 在这种物质中收集的时间没有调整为变化的时间，并且患有不良评估 阳光暴露。此外，没有关于HSV复发触发器的现有已发表的报告 计算时间变化的混杂的影响。统计分析的标准方法（例如限制， 分层，回归）可能无法估计时间变化的暴露/触发因素对HSV的总效果 在及时变化的混杂因素面前复发。为了改善这一限制，我们将使用边际 结构模型可以解散多个时间变化的HSV复发触发器的影响。另外， 阳光暴露度量指标将自我报告的暴露和紫外线（UV）辐射指数结合在一起 将创建来自国家海洋和大气管理部门，以更细微地描述差异 在阳光暴露中。对于74个地理编码的临床中的每一个，将获得每周平均的UV指数值 站点。该提案的结果将进一步了解HSV复发的决定因素和 为（1）为感染HSV和（2）的个人提供有效的行为咨询的其他证据 环境控制的开发（例如，旨在阻断关键紫外线或紫外线的太阳镜 阻塞眼滴）以降低发病率。 （例如，旨在阻止关键紫外线波长或紫外线的太阳镜 阻塞眼滴）