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: 8088842
• 负责人: Stephen R Cole
• 金额: $ 18.18万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8088842
• 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; 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

DESCRIPTION (provided by applicant): 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) PUBLIC HEALTH RELEVANCE: The goal of this work is to quantify effects of sunlight exposure and psychological stress on recurrence of clinical ocular and nonocular herpes simplex virus (HSV) infections using data collected as part of a US National Eye Institute-funded randomized trial. Results from this work 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 to reduce morbidity.

描述（由申请人提供）：该提案的总体目标是量化阳光暴露和心理压力对临床眼和非眼疱疹病毒（HSV）感染的复发的独立影响。该提案的目的是：（1）估计未受保护的阳光暴露对HSV复发风险的总（直接和间接）影响； （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复发呈阳性剂量反应相关性，并且（2）（2）急性心理压力将与HSV的风险增加有关。为了实现这些目标，将重新分析来自探索HSV复发触发器的308名成年人的数据。这一物质在1992年至1996年之间从由疱疹性眼病研究组进行的随机对照试验中招募了参与者，并由美国国家眼科研究所资助，以测试预防HSV复发的预防性抗病毒治疗。在美国74个临床场所之一的一个定期访问中，有308名参与者被观察到。此外，参与者提供了每周的日记，以报告阳光暴露，心理压力和其他变量。先前对此物质收集的数据的分析未适应变化的混杂时间，并且遭受了对阳光暴露的评估不佳。此外，关于HSV复发触发器的现有已发布的报告都没有说明了时间变化的混淆的影响。统计分析的标准方法（例如限制，分层，回归）可能无法估计在存在随时间变化的混杂因素的情况下，变化的暴露/触发因素对HSV复发的总效果。为了改善这一限制，我们将使用边缘结构模型，这些模型可以解散多个时间变化的HSV复发触发器的影响。此外，将创建一个从国家海洋和大气给药中获得的阳光暴露度量，该指标将自我报告的暴露和紫外线（UV）辐射指数（UV）辐射指数组合在一起，以更细微地描述阳光暴露的差异。对于74个地理编码的临床部位，将获得每周平均的UV指数值。该提案的结果将进一步了解HSV复发的决定因素，并为感染HSV感染的个体的有效行为咨询提供其他证据，以及（2）开发环境控制（例如，旨在阻断关键UV波长或UV障碍物阻断眼睛掉落的太阳镜），以降低发病率。 （例如，旨在阻断关键紫外线波长或紫外线障碍物的太阳镜） 公共卫生相关性：这项工作的目的是量化阳光暴露和心理压力对临床眼和非眼疱疹病毒（HSV）复发的影响，使用作为美国国家国家研究所资助的随机试验的一部分收集的数据。这项工作的结果将进一步了解HSV复发的决定因素，并为感染HSV感染的个体的有效行为咨询提供其他证据，以及（2）发展环境控制以降低发病率。