Structural models to untangle triggers of ocular/nonocular herpesvirus recurrence

描述(由申请人提供)：这项建议的总体目标是量化阳光暴露和心理压力对临床眼和非眼单纯疱疹病毒(HSV)感染复发的独立影响。这项建议的目的是：(1)估计无保护阳光暴晒对HSV复发风险的总体(即直接和间接)影响；以及(2)估计心理应激对HSV复发风险的总体影响。我们假设：(1)无保护措施的阳光暴露与HSV复发呈正向剂量-反应关系，(2)急性心理应激与HSV复发风险增加有关。为了实现这些目标，来自308名成年人的数据将被重新分析，该研究是为了探索HSV复发的触发因素而成立的。这项附属研究在1992至1996年间从一项由疱疹眼病研究小组管理、由美国国家眼科研究所资助的随机对照试验中招募参与者，以测试预防HSV复发的预防性抗病毒疗法。308名参与者在美国74个临床站点中的一个定期安排的访问中被看到；此外，参与者每周都会提供关于阳光暴露、心理压力和其他变量的日记。在这项子研究中收集的数据之前的分析没有根据时间变化的混淆进行调整，并且遭受了对阳光暴露的糟糕评估。此外，现有发表的关于HSV复发触发因素的报告中，没有一篇考虑到时变混杂的影响。在存在随时间变化的混杂因素的情况下，统计分析的标准方法(如限制、分层、回归)可能无法估计随时间变化的暴露/触发因素对HSV复发的总体影响。为了改善这一局限性，我们将使用边际结构模型，该模型分离了HSV复发的多个时变触发因素的影响。此外，还将创建一个阳光暴露量指标，将自我报告的暴露量和从美国国家海洋和大气管理局获得的紫外线(UV)辐射指数结合起来，以更精细地描绘阳光暴露量的差异。将获得74个地理编码的临床站点的每周平均紫外线指数值。这项建议的结果将进一步了解HSV复发的决定因素，并为(1)为HSV感染者提供有效的行为咨询，以及(2)开发环境控制措施(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)以减少发病率提供额外证据。(例如，设计用来阻挡关键紫外线波长的太阳镜或阻挡紫外线的眼药水) 公共卫生相关性：这项工作的目标是利用作为美国国家眼科研究所资助的随机试验的一部分收集的数据，量化阳光暴露和心理压力对临床眼部和非眼部单纯疱疹病毒(HSV)感染复发的影响。这项工作的结果将进一步了解HSV复发的决定因素，并为(1)对HSV感染者进行有效的行为咨询和(2)发展环境控制以减少发病率提供额外的证据。

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.