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

测试阿片类药物暴露新生儿瞳孔直径的可靠性和有效性

• 批准号: 8545754
• 负责人: Sarah H Heil
• 金额: $ 40.14万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545754
• 关键词: Adult; Caliber; Clinical; Clinical Research; Data; Detection; Development; Digital Photography; Dose; Effectiveness; Eye; Family; Health Care Costs; Heroin; Hour; Human; Infant; Length of Stay; Literature; Measurement; Measures; Methadone; Methods; Morbidity - disease rate; Neonatal; Neonatal Abstinence Syndrome; Opiate Addiction; Opiates; Opioid; Outcome Measure; Patient Self-Report; Perinatal Exposure; Pharmaceutical Preparations; Pharmacodynamics; Pharmacological Treatment; Pharmacotherapy; Photography; Physical Dependence; Postpartum Women; Protocols documentation; Pupil; Relative (related person); Research; Risk; Severities; Substance-Related Disorders; Sum; Testing; Therapeutic Intervention; Time; Training; Validation; Validity and Reliability; Vulnerable Populations; Weaning; Withdrawal; cost; improved; in utero; indexing; innovation; instrument; meetings; named group; neonate; opioid withdrawal; pregnant; response; therapy development; tool

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.

描述（由申请人提供）：学生直径是阿片类药物对人类药效动力学作用最常评估的客观指标之一。阿片类药物的瞳孔作用在成人中很容易通过照相进行测量，并且是对物理依赖性和戒断的存在和程度的高度敏感的衡量。通常收集瞳孔反应的度量以及自我报告和观察者评级的效果，以提供阿片类药物影响的全面特征。在子宫内暴露于阿片类药物的婴儿天生在身体上依赖，并且经常患有戒断（即新生儿戒酒综合征〜NAS），这足以需要药理治疗。观察者量表是评估药理治疗需求和有效性的唯一工具 对于NAS，在临床和研究环境中以及这些工具的缺点（例如，基本验证，长期培训和管理时间）导致呼吁对NAS进行更敏感，客观的测量。 我们已经开发了一项方案来测量阿片类药物暴露的新生儿中的学生直径。使用此方案的试点数据（n = 10）表明，新生儿学生对阿片类药物的反应与成年人相同，并表明与观察者评级量表相比，学生直径可能是NAS的更敏感的NAS量度。 因此，下一步是充分测试阿片类药物暴露的新生儿学生直径的可靠性和有效性。 两项研究 建议实现这一总体目标。第一项研究将正式测试40种阿片类药物新生儿中OU瞳孔摄影方案的可靠性。第二项研究将使用广泛的成人文献对阿片类药物作为指导的瞳孔作用，以作为阿片类药物作用的瞳孔变化作为阿片类药物作用的指标。一百十个暴露于阿片类药物的新生儿和30个不暴露的新生儿将提供四个有效性分析的数据。首先，将检查分娩后24小时内收集的学生直径测量值，以查看它们是否区分阿片类药物暴露和不暴露的新生儿，以测试歧视有效性。其次，在暴露于阿片类药物的新生儿中，将检查瞳孔直径变化与观察者评级的NAS量表分数在交付后的前24小时之间的相关性，从而测试并发的有效性。第三，阿片类药物耐受性和 在需要药理治疗的阿片类药物新生儿（估计n = 35），测试构建体有效性的情况下，将检查阿片类药物给药后瞳孔影响的时间过程。第四个也是最终分析将通过测试分娩后的最初24小时内学生直径的变化来检查预测有效性，预测哪些新生儿继续接受药理治疗。总而言之，在接触阿片类药物的新生儿中建立学生直径的可靠性和验证有可能大大改善对临床和研究环境中阿片类药物暴露的新生儿的评估和治疗，从而降低发病率，缩短医院的住院和降低成本。