NEJM:新生儿阿片戒断综合征的处理 (ESC-NOW研究)

2023-05-02 MedSci原创 MedSci原创 发表于上海

尽管临床医生传统上使用 Finnegan 新生儿戒断评分工具来评估新生儿阿片类药物戒断的严重程度,但一种更新的基于功能的方法——吃、睡、安抚护理方法——

母亲有物质使用障碍的婴儿有发生物质戒断的风险,通常称为新生儿戒断综合征(neonatal abstinence syndrome, NAS)。NAS是一系列复杂多变且尚未完全理解的新生儿神经行为调节障碍表现。虽然戒断综合征最常与阿片类物质暴露有关,但也有其他物质与戒断综合征有关,包括尼古丁。此外,诸如香烟、苯二氮卓类药物及选择性5-羟色胺再摄取抑制剂(selective serotonin reuptake inhibitor, SSRI)等其他物质,可加重阿片类物质诱发性NAS的严重程度。

尽管临床医生传统上使用 Finnegan 新生儿戒断评分工具来评估新生儿阿片类药物戒断的严重程度,但一种更新的基于功能的方法——吃、睡、安抚护理方法——的使用正在增加。 当这种新方法在不同地点广泛应用时,它是否可以安全地缩短婴儿在医学上准备好出院的时间尚不清楚。

2014 年,Grossman 及其同事提出了用于评估阿片类药物戒断婴儿的“饮食、睡眠、安抚”方法。最近,“饮食、睡眠、安抚”方法及其相关护理工具的使用越来越多。Eat, Sleep, Console Care Tool 依赖于基于功能的戒断严重程度评估,该评估侧重于婴儿进食、睡眠和安抚的能力,以及使用非药物干预措施(例如,低刺激环境 、皮肤接触、集中护理和母乳喂养)作为第一线治疗,并增强家庭和护理人员照顾婴儿的能力。 与使用 Finnegan 工具的护理相比,这种方法得到了一些全州和地区质量改进计划的好评,因此在美国和国际上被采用和实施到临床实践中。 

尽管这些举措的结果看起来很有希望,这种方法在没有强有力的证据支持其有效性、安全性或在不同人群和不同护理环境中的普遍性的情况下迅速传播,这引起了人们的担忧。这些担忧包括 药物治疗不足和受影响婴儿过早出院的可能性,这可能会使他们面临再次入院、非意外伤害和死亡的风险增加。

推进新生儿阿片类药物戒断临床试验 (ACT NOW) 协作,是美国国立卫生研究院帮助长期戒除成瘾 (HEAL) 计划的一部分,旨在推进高质量证据,为标准护理方法提供信息作为这项合作的一部分,我们进行了一项随机对照试验——新生儿阿片类药物戒断的饮食、睡眠、安抚 (ESC-NOW)——以评估饮食、睡眠的安全性、有效性和普遍性 , 安抚方法与通常使用 Finnegan 工具的护理方法相比。

这项多中心、阶梯楔形、整群随机对照试验是根据良好临床实践指南在 ACT NOW 协作组织的美国 26 个地点进行的。 阿肯色大学医学科学学院担任中央机构审查委员会,与所有试验地点签订信赖协议。 经中央机构审查委员会批准并根据联邦法规 (45 CFR 46.116),在放弃知情同意的情况下进行了试验的住院和初始随访部分。

为了提高普遍性,我们选择了地理上多样化的地点,其中包括学术中心和社区医院。 这些地点在接受治疗的阿片类药物戒断婴儿数量、接受药物治疗的婴儿比例、医院内的护理地点(包括开放式新生儿重症监护病房)以及 对阿片类药物戒断婴儿可用的非药物干预措施。

在整个试验过程中,我们招募了以下婴儿:妊娠 36 周或以上、在试验地点出生或在出生后 60 小时内转移到试验地点、有产前阿片类药物暴露证据以及正在接受阿片类药物治疗的婴儿 阿片类药物戒断。 

在第一个试验期间,所有阿片类药物戒断的婴儿都根据每个地点的常规护理做法进行治疗,包括使用 Finnegan 工具。 然后,按照随机分配的顺序,每个站点进入 3 个月的过渡期,其中包括站点的培训和实施活动(图 1)。 婴儿在此期间没有登记。 实施后,阿片类药物戒断婴儿按照“吃、睡、控制台”方法进行护理,包括使用相关护理工具。

在常规护理期间,根据每个地点的常规做法,将非药物干预纳入为阿片类药物戒断婴儿提供的护理中。 在实施吃、睡、控制台方法后,每个站点的护理人员根据每个婴儿的需要并在可用站点资源的基础上尽可能地应用非药物干预。

在整个试验过程中,研究中心保持当地药物治疗的做法,包括阿片类药物类型、给药方法和辅助药物的使用。 仅在必要时对局部治疗算法进行了修改,以允许它们与 Eat、Sleep、Console Care Tool 一起使用,并且不包括添加基于症状的剂量。 临床团队根据他们通常的现场实践让婴儿出院,而不考虑出院医疗准备的试验标准。

主要终点是从出生到婴儿在医学上可以出院的时间。 医疗准备的标准被前瞻性地定义为年龄至少 96 小时,至少 48 小时没有接受阿片类药物,至少 24 小时没有呼吸支持和 100% 经口进食,以及至少 24 小时 从最大热量密度开始。 美国儿科学会 2012 年发布的标准为出院医疗准备的定义提供了依据。 24

关键的次要结果包括接受药物治疗和住院时间。 安全结果包括院内综合安全措施(癫痫发作或意外创伤 [例如,由跌倒引起] 或呼吸功能不全 [记录的呼吸暂停或需要正压通气或补充氧气] 归因于阿片类药物治疗),综合安全措施 到 3 个月大(任何急性或紧急护理就诊、急诊科就诊或再入院),以及出院时和 3 个月大(非意外创伤或死亡)的综合关键安全结果。 出院后的结果在 3 个月大时通过审查电子病历(包括链接的病历)和媒体审查通过搜索公共记录(例如,新闻报道、讣告和登记)进行前瞻性评估。

结果

从 2020 年 9 月到 2022 年 3 月,在接受筛查的 1874 名婴儿中,有 1305 名入组(702 名在常规护理期间,603 名在饮食、睡眠、安抚期间)(图 2)。 表 1 提供了母亲和婴儿的特征。除西班牙裔母亲的比例和居住在大都市地区的比例外,各组的特征在基线时是平衡的。 所有调整后的模型都考虑了这些因素的差异,这些差异反映了站点转换的时间(例如,具有较大西班牙裔人口的站点稍后转换)。 纳入试验的婴儿主要代表美国阿片类药物戒断者,但非西班牙裔黑人和西班牙裔婴儿的人数略多(表 S1)。 26 个地点中的每一个都在随机分配的时间过渡到吃、睡、控制台方法,并在整个试验期间根据地点分配照顾婴儿。 由于与 2019 年冠状病毒病 (Covid-19) 相关的特定地点限制,一个地点需要重新随机化。

主要终点显示,1305 名婴儿中有 837 名 (64%) 满足出院医疗准备的试验定义。 婴儿不符合试验定义的最常见原因是 96 小时前出院(211 名婴儿)和服用阿片类药物后不到 48 小时出院(231 名婴儿)(图 2)。

表 2。主要、次要和安全结果。

在符合主要结果标准的 837 名婴儿中,饮食、睡眠、安抚组从出生到出院的医疗准备时间平均比常规护理组短(8.2 天对 14.9 天;调整后的平均 差异,6.7 天;95% 置信区间 [CI],4.7 至 8.8),比率为 0.55(95% CI,0.46 至 0.65;P<0.001)(表 2)。 在试验期间,新方法的效果随着时间的推移是一致的,尽管不同地点的治疗效果存在异质性。 有关根据研究中心和试验期的分层模型结果的详细信息,请参见补充附录。

对于主要敏感性分析,由于在达到试验的医疗准备定义之前出院而进行数据删失的婴儿比例在两组中相似(常规护理组为 37% [702 人中的 262 人],常规护理组为 34% [206 人] 603] 在吃、睡、控制台组中)(表 S5)。 在一项涉及 89% 婴儿(1305 名中的 1164 名)的事后分析中,使用修改后的医疗准备定义,调整后的平均组间差异为 6.4 天(95% CI,4.7 至 8.0).

安全措施的描述性总结。

饮食、睡眠、控制台组的平均住院时间为 7.8 天,常规护理组为 14.0 天(平均差异为 6.2 天;95% CI,4.6 至 7.7;率比,0.56;95% CI, 0.49 至 0.64)(表 2)。 接受阿片类药物治疗的婴儿比例在常规护理组为 52.0%,在饮食、睡眠、安抚组为 19.5%(绝对差异,32.5 个百分点;相对风险,0.38;95% CI,0.30 至 0.47)。 对 3 个月大婴儿安全性的综合衡量表明,饮食、睡眠、安抚组的婴儿出现不良后果的风险与常规护理组相似(分别为 16.1% 和 15.8%;相对风险 ,1.02;95% CI,0.71 至 1.47)。 出院时和 3 个月大时的复合关键安全性结果在两组中也相似(表 3)。

讨论

该试验的局限性包括阶梯楔形设计的暴露性质及其易受处理污染和时间趋势的影响。 试验期间已知的时间趋势包括 Covid-19 大流行期间探视政策的变化和新生儿提前出院、护士人手短缺以及对出院前监测婴儿阿片类药物戒断情况的建议26 的更新。 通过限制对特定干预材料的访问,直到站点接近其过渡期,解决了污染的可能性。 所选择的主要结局限制了新生儿提前出院的潜在影响。 我们推测探视限制和护士短缺将使“吃、睡、安抚”方法的实施和使用更具挑战性,并且这些变化会削弱治疗效果。 出院后安全结果仅限于 3 个月大,并依赖于来自登记医院的电子病历、可用时的关联病历和媒体审查。 尽管这种方法可能无法获得所有结果,但它有助于评估所有试验患者的短期安全性。 计划的长期随访包括对所有 2 岁时入组婴儿的关键安全结果进行重新评估。

该试验观察到的治疗效果大于假设,支持饮食、睡眠、安抚方法在不同地点和不同人群中的普遍性,包括那些以前没有在文献中出现过的人群。 尽管预期治疗效果存在异质性,但鉴于已知各医院之间存在差异,因此有必要进一步研究潜在的影响因素(例如,人口的地点差异、护理地点以及将非药物干预作为常规护理的一部分) 进一步告知使用这种护理方法。

在这项多中心、随机、对照试验中,吃、睡、安抚方法大大缩短了阿片类药物戒断婴儿在医学上准备好出院的时间,没有短期伤害的证据。 长期随访对于进一步了解这种方法的安全性至关重要。

原始出处

Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal, NEJM,April 30, 2023
DOI: 10.1056/NEJMoa2214470

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    打卡

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=2133569, encodeId=9383213356948, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=34f08675510, createdName=ms6000001806643324, createdTime=Sat May 13 18:13:33 CST 2023, time=2023-05-13, status=1, ipAttribution=福建省), GetPortalCommentsPageByObjectIdResponse(id=2131439, encodeId=6c1e2131439ac, content=受教了, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:04:14 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2131438, encodeId=65be21314382c, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:03:41 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2130182, encodeId=1d2a213018241, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:25:21 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2130180, encodeId=f9d02130180b8, content=**类药物临床使用管理的研究还是十分重要的, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:23:42 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2129682, encodeId=36772129682ad, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5bf26472850, createdName=ms2000000147841561, createdTime=Tue May 02 11:11:29 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129669, encodeId=b00b212966957, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Tue May 02 09:58:26 CST 2023, time=2023-05-02, status=1, ipAttribution=贵州省), GetPortalCommentsPageByObjectIdResponse(id=2129655, encodeId=c493212965558, content=母亲有物质使用障碍的婴儿有发生物质戒断的风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d3d3015017, createdName=jshbyywk2008, createdTime=Tue May 02 06:21:25 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129651, encodeId=d97921296514c, content=不错,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4dfa6526517, createdName=仁术2023, createdTime=Tue May 02 06:03:17 CST 2023, time=2023-05-02, status=1, ipAttribution=)]
    2023-05-10 ms1000000281102309 来自甘肃省

    受教了

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2133569, encodeId=9383213356948, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=34f08675510, createdName=ms6000001806643324, createdTime=Sat May 13 18:13:33 CST 2023, time=2023-05-13, status=1, ipAttribution=福建省), GetPortalCommentsPageByObjectIdResponse(id=2131439, encodeId=6c1e2131439ac, content=受教了, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:04:14 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2131438, encodeId=65be21314382c, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:03:41 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2130182, encodeId=1d2a213018241, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:25:21 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2130180, encodeId=f9d02130180b8, content=**类药物临床使用管理的研究还是十分重要的, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:23:42 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2129682, encodeId=36772129682ad, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5bf26472850, createdName=ms2000000147841561, createdTime=Tue May 02 11:11:29 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129669, encodeId=b00b212966957, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Tue May 02 09:58:26 CST 2023, time=2023-05-02, status=1, ipAttribution=贵州省), GetPortalCommentsPageByObjectIdResponse(id=2129655, encodeId=c493212965558, content=母亲有物质使用障碍的婴儿有发生物质戒断的风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d3d3015017, createdName=jshbyywk2008, createdTime=Tue May 02 06:21:25 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129651, encodeId=d97921296514c, content=不错,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4dfa6526517, createdName=仁术2023, createdTime=Tue May 02 06:03:17 CST 2023, time=2023-05-02, status=1, ipAttribution=)]
    2023-05-10 ms1000000281102309 来自甘肃省

    学习了

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2133569, encodeId=9383213356948, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=34f08675510, createdName=ms6000001806643324, createdTime=Sat May 13 18:13:33 CST 2023, time=2023-05-13, status=1, ipAttribution=福建省), GetPortalCommentsPageByObjectIdResponse(id=2131439, encodeId=6c1e2131439ac, content=受教了, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:04:14 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2131438, encodeId=65be21314382c, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:03:41 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2130182, encodeId=1d2a213018241, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:25:21 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2130180, encodeId=f9d02130180b8, content=**类药物临床使用管理的研究还是十分重要的, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:23:42 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2129682, encodeId=36772129682ad, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5bf26472850, createdName=ms2000000147841561, createdTime=Tue May 02 11:11:29 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129669, encodeId=b00b212966957, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Tue May 02 09:58:26 CST 2023, time=2023-05-02, status=1, ipAttribution=贵州省), GetPortalCommentsPageByObjectIdResponse(id=2129655, encodeId=c493212965558, content=母亲有物质使用障碍的婴儿有发生物质戒断的风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d3d3015017, createdName=jshbyywk2008, createdTime=Tue May 02 06:21:25 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129651, encodeId=d97921296514c, content=不错,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4dfa6526517, createdName=仁术2023, createdTime=Tue May 02 06:03:17 CST 2023, time=2023-05-02, status=1, ipAttribution=)]
    2023-05-05 没脑子3 来自云南省

    打卡

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2133569, encodeId=9383213356948, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=34f08675510, createdName=ms6000001806643324, createdTime=Sat May 13 18:13:33 CST 2023, time=2023-05-13, status=1, ipAttribution=福建省), GetPortalCommentsPageByObjectIdResponse(id=2131439, encodeId=6c1e2131439ac, content=受教了, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:04:14 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2131438, encodeId=65be21314382c, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:03:41 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2130182, encodeId=1d2a213018241, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:25:21 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2130180, encodeId=f9d02130180b8, content=**类药物临床使用管理的研究还是十分重要的, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:23:42 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2129682, encodeId=36772129682ad, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5bf26472850, createdName=ms2000000147841561, createdTime=Tue May 02 11:11:29 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129669, encodeId=b00b212966957, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Tue May 02 09:58:26 CST 2023, time=2023-05-02, status=1, ipAttribution=贵州省), GetPortalCommentsPageByObjectIdResponse(id=2129655, encodeId=c493212965558, content=母亲有物质使用障碍的婴儿有发生物质戒断的风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d3d3015017, createdName=jshbyywk2008, createdTime=Tue May 02 06:21:25 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129651, encodeId=d97921296514c, content=不错,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4dfa6526517, createdName=仁术2023, createdTime=Tue May 02 06:03:17 CST 2023, time=2023-05-02, status=1, ipAttribution=)]
    2023-05-05 没脑子3 来自云南省

    **类药物临床使用管理的研究还是十分重要的

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2133569, encodeId=9383213356948, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=34f08675510, createdName=ms6000001806643324, createdTime=Sat May 13 18:13:33 CST 2023, time=2023-05-13, status=1, ipAttribution=福建省), GetPortalCommentsPageByObjectIdResponse(id=2131439, encodeId=6c1e2131439ac, content=受教了, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:04:14 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2131438, encodeId=65be21314382c, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:03:41 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2130182, encodeId=1d2a213018241, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:25:21 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2130180, encodeId=f9d02130180b8, content=**类药物临床使用管理的研究还是十分重要的, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:23:42 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2129682, encodeId=36772129682ad, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5bf26472850, createdName=ms2000000147841561, createdTime=Tue May 02 11:11:29 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129669, encodeId=b00b212966957, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Tue May 02 09:58:26 CST 2023, time=2023-05-02, status=1, ipAttribution=贵州省), GetPortalCommentsPageByObjectIdResponse(id=2129655, encodeId=c493212965558, content=母亲有物质使用障碍的婴儿有发生物质戒断的风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d3d3015017, createdName=jshbyywk2008, createdTime=Tue May 02 06:21:25 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129651, encodeId=d97921296514c, content=不错,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4dfa6526517, createdName=仁术2023, createdTime=Tue May 02 06:03:17 CST 2023, time=2023-05-02, status=1, ipAttribution=)]
    2023-05-02 ms2000000147841561 来自河北省

    打卡

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=2133569, encodeId=9383213356948, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=34f08675510, createdName=ms6000001806643324, createdTime=Sat May 13 18:13:33 CST 2023, time=2023-05-13, status=1, ipAttribution=福建省), GetPortalCommentsPageByObjectIdResponse(id=2131439, encodeId=6c1e2131439ac, content=受教了, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:04:14 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2131438, encodeId=65be21314382c, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07bc8551869, createdName=ms1000000281102309, createdTime=Wed May 10 19:03:41 CST 2023, time=2023-05-10, status=1, ipAttribution=甘肃省), GetPortalCommentsPageByObjectIdResponse(id=2130182, encodeId=1d2a213018241, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:25:21 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2130180, encodeId=f9d02130180b8, content=**类药物临床使用管理的研究还是十分重要的, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eecc8372843, createdName=没脑子3, createdTime=Fri May 05 08:23:42 CST 2023, time=2023-05-05, status=1, ipAttribution=云南省), GetPortalCommentsPageByObjectIdResponse(id=2129682, encodeId=36772129682ad, content=打卡, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5bf26472850, createdName=ms2000000147841561, createdTime=Tue May 02 11:11:29 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129669, encodeId=b00b212966957, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Tue May 02 09:58:26 CST 2023, time=2023-05-02, status=1, ipAttribution=贵州省), GetPortalCommentsPageByObjectIdResponse(id=2129655, encodeId=c493212965558, content=母亲有物质使用障碍的婴儿有发生物质戒断的风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d3d3015017, createdName=jshbyywk2008, createdTime=Tue May 02 06:21:25 CST 2023, time=2023-05-02, status=1, ipAttribution=河北省), GetPortalCommentsPageByObjectIdResponse(id=2129651, encodeId=d97921296514c, content=不错,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4dfa6526517, createdName=仁术2023, createdTime=Tue May 02 06:03:17 CST 2023, time=2023-05-02, status=1, ipAttribution=)]
    2023-05-02 屋顶瞄爱赏月 来自贵州省

    签到学习

    0

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    2023-05-02 jshbyywk2008 来自河北省

    母亲有物质使用障碍的婴儿有发生物质戒断的风险

    0

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    2023-05-02 仁术2023

    不错,学习了。

    0

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