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)

摘要 这项建议的总体目标是量化阳光暴露和心理健康的独立影响。 强调眼部和非眼部单纯疱疹病毒(HSV)感染的临床复发。这样做的目的是 建议是：(1)估计无保护日光照射对以下疾病风险的总体(即直接和间接)影响 (2)估计心理应激对HSV复发风险的总体影响。我们 假设：(1)无保护措施的日光照射与单纯疱疹病毒感染呈正相关。 (2)急性心理应激会增加HSV复发的风险。至 为了实现这些目标，来自308名成年人的数据参加了一项旨在探索HSV触发因素的子研究 将重新分析重复出现的情况。这项子研究在1992至1996年间从一项随机的 由疱疹眼病研究小组管理并由美国国家眼科中心资助的对照试验 研究机构测试预防HSV复发的预防性抗病毒疗法。308名参与者被看到 定期访问美国74个临床站点之一；此外，参与者每周提供 关于日光照射、心理压力和其他变量的日记。数据的先验分析 在这项子研究中收集的数据没有针对时变混淆进行调整，并且遭受了较差的评估 日光照射。此外，现有已发表的关于HSV复发诱因的报告中，没有一篇报道 说明了时变混杂的影响。统计分析的标准方法(例如，限制， 分层、回归)可能无法估计时变暴露/触发因素对HSV的总体影响 在存在随时间变化的混杂因素的情况下反复出现。为了改善这一限制，我们将使用边际 结构模型，解开了HSV复发的多个时变触发因素的影响。此外，还有一个 将自我报告的曝光量和所获得的紫外线(UV)辐射指数相结合的日照曝光量指标 来自国家海洋和大气管理局的数据将被创建，以更精细地描绘差异 在阳光下暴晒。将获得74个地理编码的临床诊所的每周平均紫外线指数值 网站。这一建议的结果将进一步了解单纯疱疹病毒复发和 为(1)对单纯疱疹病毒感染者进行有效的行为咨询和(2)提供更多的证据 开发环境控制措施(例如，设计用于阻挡关键紫外线波长或紫外线的太阳镜 阻塞眼药水)，以减少发病率。(例如，设计用于阻挡关键紫外线波长或紫外线的太阳镜 阻塞眼药水)