Incorporating nonpharmacologic approaches into a comparative effectiveness pharmacologic trial for neonates with neonatal opioid withdrawal syndrome (NOWS)

项目总结/摘要 全国范围内的阿片类药物流行病包括育龄妇女， 出生时患有新生儿阿片类药物戒断综合征（NOWS）的婴儿数量增加。当前 NOWS没有统一接受的治疗策略，主要药物的选择， 治疗和给药/断奶时间表在各中心之间不同。吗啡是目前最常见的 使用药物进行NOWS治疗，然后使用美沙酮。丁丙诺啡是一种很有前途的药物， 在该患者人群中的研究有限。此外，用于诊断NOWS的筛查工具和 启动药物治疗的适当阈值尚未得到最终评价。当历史 根据经验得出的药物治疗和断奶方案已经修改和标准化， 的逗留时间已被观察到。此外，非药物方法似乎在以下方面是成功的： 减轻NOWS的症状。在本申请中，我们提出了一个试点随机的初步数据， 目前我们的托儿所正在进行对照试验。它包括识别有严重症状的婴儿， NOWS通过改良的Finnegan评分，然后将其随机分配至标准吗啡给药/断奶 时间表，或最佳吗啡给药策略。最佳的吗啡剂量策略并不 提供一个预定剂量的吗啡，但只提供一个剂量的吗啡时，撤回 通过非药物手段不能缓解症状。两个研究组均接受了所有优化的 非药物治疗的方法。在最佳吗啡组，我们观察到一个大的 减少吗啡的使用和接受药物治疗的天数。我们推测 最佳吗啡给药策略的使用将药物治疗的使用仅限于 有时非药物干预是不够的。这基本上提供了母亲或 其他护理人员有时间认识和适应婴儿的退缩行为，使他们能够 通过非药物手段消灭它们。最佳吗啡给药策略也防止了 通过允许在需要时使用吗啡，婴儿的戒断症状变得过于严重，但 使婴儿接受延长的预定吗啡治疗疗程，并在以下情况下断奶： 非药物治疗就足够了因此，我们倾向于强调使用 非药理学方法来控制戒断症状，无论药物手臂婴儿是 分配。然而，我们赞成包括一个更新颖的最佳给药策略臂，而不是限制 标准计划给药/断奶组的研究。

PROJECT SUMMARY / ABSTRACT The nationwide opioid epidemic includes women of child birthing age accounting for a dramatically increased number of infants being born with neonatal opioid withdrawal syndrome (NOWS). Currently there is no uniformly accepted treatment strategy for NOWS and the choice of primary medication, criteria for treatment, and dosing/weaning schedules vary between centers. Morphine is by far the most commonly used medication for NOWS treatment, followed by methadone. Buprenorphine is a promising drug but with limited studied in this patient population. Additionally, the screening tools used to diagnose NOWS and the appropriate threshold to initiate drug therapy have not been conclusively evaluated. When historical empirically derived drug treatment and weaning protocols have been modified and standardized, reductions of length of stay have been observed. Additionally, nonpharmalogical methods appear to be successful in reducing the symptoms of NOWS. In this application we present preliminary data of a pilot randomized controlled trial currently in progress in our nursery. It includes identifying infants with severe symptoms of NOWS via modified Finnegan scoring, then randomizing them to a standard morphine dosing/weaning schedule, or to an optimal morphine dosing strategy. The optimal morphine dosing strategy does not provide a scheduled dose of morphine, but only provides a dose of morphine when the withdrawal symptoms cannot be satiated through nonpharmacological means. Both study groups received all optimized nonpharmacological methods available to them. In the optimal morphine arm, we observed a large reduction in the use of morphine and in the duration of days receiving pharmacologic therapy. We speculate that the use of the optimal morphine dosing strategy limited the use of pharmacologic treatment to only times when nonpharmacologic interventions were not sufficient. This essentially provided the mother or other care givers time to recognize and adapt to the infant's withdrawal behaviors, enabling them to extinguish them via nonpharmacological means. The optimal morphine dosing strategy also prevented the infant's withdrawal from becoming too symptomatic by allowing morphine to be used when needed, yet not committing the infant to a prolonged scheduled course of morphine treatment and weaning when nonpharmacological measures could have sufficed. Thus, we favor a clinical trial that emphasizes the use of nonpharmacological methods to control withdrawal symptoms irrespective of the drug arm the infant is assigned. However, we favor including a more novel optimal dosing strategy arm rather than limiting the investigation to standard scheduled dosing/weaning arms.