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）：本提案的总体目标是量化阳光照射和心理应激对临床眼部和非眼部单纯疱疹病毒（HSV）感染复发的独立影响。本建议的目的是：(1)估计无保护的阳光照射对HSV复发风险的总（即直接和间接）影响；(2)评估心理应激对HSV复发风险的总影响。我们假设：(1)无保护的阳光照射将与HSV复发呈现正剂量反应相关；(2)急性心理应激将与HSV复发风险增加相关。为了实现这些目标，将重新分析308名成人的数据，这些数据参加了一项旨在探索HSV复发诱因的子研究。这项亚研究在1992年至1996年间招募了一项随机对照试验的参与者，该试验由疱疹性眼病研究组管理，由美国国家眼科研究所资助，以测试预防性抗病毒治疗预防HSV复发的效果。308名参与者在美国74个临床地点之一的定期就诊；此外，参与者提供了关于阳光照射、心理压力和其他变量的每周日记。在此子研究中收集的数据的先前分析没有调整时变混淆，并且对阳光照射的评估不佳。此外，现有发表的关于HSV复发诱因的报告中，没有一个考虑到时变混杂的影响。标准的统计分析方法（如限制、分层、回归）可能无法在存在随时间变化的混杂因素的情况下估计时变暴露/触发因素对HSV复发的总影响。为了改善这一限制，我们将使用边际结构模型来解开HSV复发的多个时变触发因素的影响。此外，还将创建一个阳光照射度量标准，该度量标准结合了从国家海洋和大气管理局获得的自我报告暴露和紫外线（UV）辐射指数，以更精细地描绘阳光照射的差异。我们会为74个地理编码的临床地点，分别取得每周平均的紫外线指数。这一建议的结果将进一步了解HSV复发的决定因素，并为以下方面提供额外的证据：(1)对HSV感染者进行有效的行为咨询；(2)开发环境控制（例如，设计用于阻挡关键紫外线波长的太阳镜或阻挡紫外线的眼药水）以降低发病率。（例如，阻挡关键紫外线波长的太阳镜或阻挡紫外线的眼药水）