Testing the Reliability and Validity of Pupil Diameter in Opioid-exposed neonates

描述（由申请方提供）：瞳孔直径是阿片类药物在人体中药效学作用最常评估的客观指标之一。阿片类药物的瞳孔效应很容易在成人中进行测量，并且是身体依赖和戒断的存在和程度的高度敏感的测量。瞳孔反应的测量值通常与自我报告和自我评价的效应一起收集沿着，以提供阿片类药物效应的综合特征。在子宫内暴露于阿片类药物的婴儿出生时身体依赖，并且经常患有戒断（即，新生儿戒断综合征（NAS），严重到需要药物治疗。观察员评定量表是唯一可用于评价药物治疗的必要性和有效性的工具 对于临床和研究环境中的NAS以及这些仪器的缺点（例如， 基本的验证、长的培训和管理时间）已经导致对NAS的更敏感、客观的测量的要求。 我们已经制定了一个协议来测量瞳孔直径阿片类药物暴露的新生儿。使用该方案的试点数据（N=10）表明，新生儿学生对阿片类药物的反应与成人相同，并表明瞳孔直径可能是一个更敏感的测量NAS相比，两个额定规模。 因此，下一步是全面测试阿片类药物暴露新生儿瞳孔直径的可靠性和有效性。 两学 旨在实现这一总体目标。第一项研究将在40名阿片类药物暴露的新生儿中正式测试瞳孔摄影方案的可靠性。第二项研究将使用关于阿片类药物瞳孔效应的大量成人文献作为指导，测试新生儿瞳孔变化作为阿片类药物效应指标的有效性。110例阿片类药物暴露新生儿和30例未暴露新生儿将为4项有效性分析提供数据。首先，将检查分娩后前24小时内收集的瞳孔直径测量值，以确定它们是否能区分阿片类药物暴露和未暴露的新生儿，测试判别有效性。第二，在阿片类药物暴露的新生儿中，将检查分娩后前24小时内瞳孔直径变化与新生儿评定的NAS量表评分变化之间的相关性，测试并行有效性。第三，阿片类药物耐受性和 将在需要药物治疗的阿片类药物暴露新生儿（估计n= 35）中检查阿片类药物给药后瞳孔效应的时程，检验结构有效性。第四次也是最后一次分析将通过检测分娩后前24小时内瞳孔直径的变化是否可预测哪些新生儿继续接受药物治疗来检查预测有效性。总之，在阿片类药物暴露的新生儿中建立瞳孔直径的可靠性和有效性，有可能在临床和研究环境中大大改善阿片类药物暴露新生儿的评估和治疗，降低发病率，缩短住院时间，并降低成本。 公共卫生相关性：瞳孔大小是衡量阿片类药物（如海洛因和美沙酮）戒断严重程度以及阿片类药物其他影响的最敏感和最常用的指标之一，并且很容易在成人眼睛的照片中测量。据我们所知，瞳孔的大小从来没有被测量过的婴儿退出阿片类药物后，在子宫内暴露。本研究的主要目的是检验阿片类药物暴露婴儿瞳孔大小测量的可靠性和有效性。这项研究对于改善这种特殊情况下戒断症状的检测和治疗具有重要的潜力。 人口

DESCRIPTION (provided by applicant): Pupil diameter is one of the most frequently assessed objective indices of the pharmacodynamic effects of opioids in humans. The pupillary effects of opioids are easily measured photographically in adults and are a highly sensitive measure of the presence and extent of physical dependence and withdrawal. Measures of pupillary response are often collected along with self-reported and observer-rated effects to provide a comprehensive profile of opioid effects. Infants exposed to opioids in utero are born physically dependent and often suffer from withdrawal (i.e., neonatal abstinence syndrome~ NAS) that is severe enough to require pharmacological treatment. Observer- rated scales are the only tools available to evaluate the need for and effectiveness of pharmacological treatment for NAS in both clinical and research settings and shortcomings of these instruments (e.g., rudimentary validation, long training and administration times) have led to calls for more sensitive, objective measures of NAS. We have developed a protocol to measure pupil diameter in opioid-exposed neonates. Pilot data (N=10) using this protocol indicate neonatal pupils respond to opioids in the same manner as adults and suggest that pupil diameter may be a more sensitive measure of NAS compared to observer-rated scales. Thus, the next step is to fully test the reliability and validity of pupil diameter in opioid-exposed neonates. Two studies are proposed to meet this overarching aim. The first study will formally test the reliability of ou pupil photography protocol in 40 opioid-exposed neonates. The second study will test the validity of pupillary changes in neonates as an index of opioid effects using the extensive adult literature on the pupillary effects of opioids as a guide. One-hundred ten opioid-exposed neonates and 30 non-exposed neonates will provide data for four analyses of validity. First, pupil diameter measurements collected over the first 24 hours after delivery will be examined to see if they discriminate between opioid-exposed and non-exposed neonates, testing discriminant validity. Second, among the opioid-exposed neonates, correlations between changes in pupil diameter and changes in observer-rated NAS scale scores over the first 24 hours after delivery will be examined, testing concurrent validity. Third, opioid tolerance and the time course of pupillary effects after opioid administration will be examined among the opioid-exposed neonates who require pharmacological treatment (estimated n= 35), testing construct validity. The fourth and final analysis will examine predictive validity by testing whether changes in pupil diameter in the first 24 hours after delivery predicts which neonates went on to receive pharmacological treatment. In sum, establishing the reliability and validit of pupil diameter in opioid-exposed neonates has potential to substantially improve assessment and treatment of opioid-exposed neonates in both clinical and research settings, reducing morbidity, shortening hospital stays, and decreasing costs. PUBLIC HEALTH RELEVANCE: Pupil size is one of the most sensitive and commonly used measures of the severity of withdrawal from opiate drugs (like heroin and methadone) as well as other effects of opiate drugs and is easily measured in pictures taken of adult eyes. To our knowledge, pupil size has never been measured in infants withdrawing from opiate drugs after exposure in utero. The primary aim of the proposed studies is to test the reliability and validity f pupil size measured photographically in opiate-exposed infants. The proposed research has significant potential for improving the detection and treatment of withdrawal signs in this special population.