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标题: 张文宏谈新冠治疗的黄金72小时 [打印本页]
作者: 老福    时间: 2023-1-6 05:54
标题: 张文宏谈新冠治疗的黄金72小时
本帖最后由 老福 于 2023-1-6 05:57 编辑

近日，国家传染病医学中心主任、复旦大学附属华山医院感染科主任张文宏在对闵行区社区医生的一次培训会中，对中国目前的新冠治疗方式及医疗挤兑现象提出了自己的看法和建议。凤凰网《肿瘤情报局》整理张文宏讲话要点及全文，以飨读者。
链接：https://i.ifeng.com/c/8MKZqXn4nbc

（注：下面是其中的一段，谈前72小时的诊疗方案和营养问题）

张文宏：我不管你国产进口的抗病毒药，只要能救中国人民的，使得老人不死的，我管你进口国产的，只要救得活的，我都要

所以拜托大家，我们市里通过社区，我们把72小时黄金时间用到，你们把抗病毒药物用起来，然后再加激素。如果到区中心医院去吊针的，第一件事情就要看你的氧饱和度怎么样。氧饱和度一看是好的，93以上的这些病人，你到区中心医院吊针什么好吊？那个地方一塌糊涂，全世界最堵的地方就是他那里，人山人海挤在一起，整个闵行区病毒载量最高的就是闵安区中心医院的急诊间。你现在把病人和家属扔到急诊里让他们去吊水，您觉得有意思吗？毫无意义。

你应该是把氧饱和度在93以上的病人，你给他吊水开好，应该是怎么开医嘱啊？我告诉你，应该是，第一告诉他现在全世界最好的小分子药物，（我不管你国产进口的，只要能救中国人民的，使得老人不死的，我管你进口国产的，只要救得活的，我都要。）抗病毒药现在只有社区有，所以要社区开这个药，他们有我们这里现在全没有。

第二，你吊水我让你把医嘱带过去。全上海条件最好就的莘庄社区服务中心，这里的吊水的输液的地方，你赶快过去输什么液，我上面有给他写。如果没有细菌感染，补液里面加5毫克地米（地塞米松），然后再加一个Paxlovid，让他们自己到这里来拿。在莘庄这里吊水吊多少？不要吊太多！这些轻症病人你开这么多补液干什么？补液多全部到肺里去了！补液要开少，开到100毫升，5毫克地米，吊好了吸氧。然后再坐一个小时，他会感觉到开始爽起来了。一个地米5毫克，你知道的吊下来一个小时后，他就体温开始退了，然后氧饱和开始改善了，晚上回去开始有胃口了。

然后你接着去开：你今天晚上回去胃口不太好，要吃粥。你说张医生不是说不吃粥吗，怎么又吃粥了？要吃菜粥，菜里有维生素，要放点盐，要补充盐分。然后再给他说一下炖蛋。蛋白质也有了，再来点酱油，补充一些电解质对吧？然后你看吃点菜粥，如果消化还好，再放点肉糜对吧？那就更好了，肉糜菜粥对吧？艇仔粥也是可以的。再加一个炖蛋。这一顿晚上吃饭，血氧饱和度就涨了。

你说还要来吗，还要吊水吗？不要吊水了。第二天在区中心医院，在我们莘庄社区医院，明天你就吃药。一个是小分子药物吃继续吃。第二个，你把静脉的地米，直接改成口服的地米。用多少你根据他的情况。情况很好的、饱和度很好的，不要吃这么多地米，2-3片就可以了，0.75毫克2-3片，是吧？如果重一点的4片，3天就改善了，改为2片。再过两三天再很好改为1片两三天，就结束。

你在他莘庄的中心医院挤在急诊间吊抗菌素，不是越吊越重？你不说我都知道是越吊越重的。所以我为什么激动你知道吧，我就感觉到是吧，我就感觉到大家没有在用正确的救治方案，该活的病人都没活下来。

所以像这样的一个治疗方案，就是社区服务服务中心的医生——我们今天看到很多技术骨干院长在这里——我的意思是说今年也是社区服务中心的最关键的一战。通过这一个战役，我们疏解大量闵行区的老人这一波疫情的重大攻击，而且让死亡率显著低于其他区域。

接下去，死亡的高峰已经来了。大家都在社区，要到你这里开死亡证明的，我讲的没错吧是吧？能不能大家不开死亡证明了？你说是过段时间再开，不是这个意思！不要死了就不用开了嘛！能不能不要死呢？只要这一步做到了，我就认为我们奠定了社区卫生中心的江湖地位。江湖地位是自己打出来的，不是求出来的。这些江湖地位是没有用的，我们江湖地位就是这一次，我们第五人民医院我们自己搞定了，把你拦住了，大量的病人让你们活下来，兄弟们你是不是要感谢我？下次再收个病人你是不是应该收？所以我的意思是说，我们通过这一次战争，这次战争是什么？我手里有药，抗病毒药，再加激素的合理使用，再加营养的提升。如果家里有吸氧的也可以，没有吸氧的就在社区服务中心这里吸氧。

这样我就完成了4个方面。第一个方面，病人刚来的时候让他吸氧，氧疗，第二个，抗病毒药物送上去。第三，糖皮质激素用上去。第四回家营养给我加上去。就这4步法：氧疗、抗病毒药物、抗炎治疗，糖皮质激素的合理应用，再加一个营养治疗。而不是你前面走的抗生素，咳嗽药水，然后退烧药，这些都不是针对核心的。今天跟你讲的是针对这一次新冠的核心的病例环节去做的。你说用点中药可以，用点中药当然是可以的。但中药我不太懂，所以我没有跟你讲怎么用。中药的话你肯定比我懂？那么我们就加第五种，所以我们叫“4加x”。

有些社区服务中心它有小分子肝素，小分子肝素就特别好。有些社区服务中心、养老院里面有小分子肝素，都用起来啊，怎么可以让这批老人这时候同年同月同日死？我们绝不允许同年同月同日死，关系再好也不许死，都得活着。这样的话我们做到了我们社区卫生中心的江湖地位。

这一次的将由社区卫生中心以及他们所主管的下面的养老院和护理院做主体，承担72小时黄金救治。 如果这次救治能挽救大量生命，只要闵行区死亡率大幅度下来，其他的区都是上去的，剪刀差就是证明闵行区这边的公共卫生力量是强大无比。我们的社区卫生中心的医生证明了自己的力量，我们在这里就有江湖地位的。你说张老师江湖地位没什么用，我们要什么江湖地位，我说江湖地位也要的，我们要证明社区服务中心在我们整个医疗体系里面是非常重要的。

你一旦奠定江湖地位了，我就和领导讲两件事情，第一件事情就是我说这边的社区服务中心水平非常高，这个方法要向全国推广，我们应该请国家级的央媒来这里宣传我们基层卫生中心的伟大意义。第二件事情，我在这里跟大家讲就有点庸俗了，我会和领导提应该重奖。这一个战役打下来，功劳大的人应该重奖。你说闵中心的和第五人民医院是不是重奖的，我说闵中心的第五人民医院就算了，让他们院长自己看着办，因为他们长期以来的资源要比我们社区多。但是社区这一次的伟大力量，我一定会传达到。只要做到除了上海市发的奖金以外，闵行区必须发奖金。怎么可以不发奖金？这句我一定会提的。

但是今天社区力量如果完成这么伟大的贡献，我是觉得一个是央媒报道，我会反复给他们说的，因为只有这样做的好，下一步的疫情我们才完得成。第二件我觉得是奖金，因为这是一次了不起的贡献。我们也就这样两个礼拜奠定了自己的江湖地位。第二个奖金我是一定会去申请的。我就觉得这个事情没有谁比这个更伟大的一件事情，会挽救无数的人，我就跟你说无数的人！我这句话绝不虚言。你把这一个合理的治疗方案，你只要推下去，我们一定会看到效果。

作者: 面朝大海    时间: 2023-1-6 10:37
很实在，就是张医生本人
作者: 老票    时间: 2023-1-6 10:55
本帖最后由 老票 于 2023-1-7 14:04 编辑
面朝大海 发表于 2023-1-6 10:37
很实在，就是张医生本人


当然是他本人咯，一口瑞安+上海混杂味的普通话，语速还快，辨识度极高的
作者: landlord    时间: 2023-1-7 08:55
这话说的条理很清楚嘛。搞不懂为啥这么多人骂他
作者: 伯威    时间: 2023-1-7 14:00
老票 发表于 2023-1-6 10:55
当然是他本人咯，一口宁波+上海混杂味的普通话，语速还快，辨识度极高的 ...

明明是温州腔。
作者: 老票    时间: 2023-1-7 14:05
伯威 发表于 2023-1-7 14:00
明明是温州腔。

是我说错了，马上改    ............
作者: 老科学的家    时间: 2023-1-8 06:53
landlord 发表于 2023-1-7 08:55
这话说的条理很清楚嘛。搞不懂为啥这么多人骂他

老张这人啊，有表演型人格，大嘴巴，不严谨的地方挺多。而且他崇美崇洋。

但我还是肯定他。当很多人不说人话的时候，他一直说人话。难能可贵。
作者: 伯威    时间: 2023-1-8 11:54
老科学的家 发表于 2023-1-8 06:53
老张这人啊，有表演型人格，大嘴巴，不严谨的地方挺多。而且他崇美崇洋。

但我还是肯定他。当很多人不说 ...

是的。有时想想自己骨子里还是崇洋的，理工科的宿命。当然崇的是科学文化，对懂王睡王还是坚决斗争的。
作者: Flux    时间: 2023-1-8 13:01



呵呵
作者: 易水    时间: 2023-1-8 19:57
本帖最后由 易水 于 2023-1-8 20:10 编辑
landlord 发表于 2023-1-7 08:55
这话说的条理很清楚嘛。搞不懂为啥这么多人骂他


为什么这么多人骂他？

很多是因为他说只有5%的人发烧。

我骂他就是因为他条理清楚，条理越清楚他越有欺骗性——不管内行外行，都看不出逻辑漏洞。因为他完全没有逻辑上的漏洞，只有直截了当的事实错误（或者是谎言）。

比如之前说只有5%发烧，小感冒，为什么要封控，老百姓要生活啊。一点逻辑问题没有，只有那个5%不成立。

这一篇里面的一些事实错误：
1. 从头到尾都避免谈论这些小分子抗病毒药物的适用人群，oversimplify 这些药物的应用条件。事实上，paxlovid 的条件 是65岁以上，有基础病，肝肾本身没有问题，容易变成重症，但是还能承受药物副作用的人群，因为老年人吃的药物本来就多，还有一个Liverpool COVID-19 Drug Interaction Checker 要满足。培训社区医务人员，怎么可以不说这些呢？而说清楚这些专业问题，外行就会头晕，就可能没有那么“清楚”了。阿兹夫定没有那么清楚的用药禁忌，副作用也是很多。

2. 激素的应用。作为医学院的药理老师，每个学期都要讲糖皮质激素临床应用和副作用，看见张医生说糖皮质激素可以用于轻症转重症的预防，真是吓了一跳。这是一个经典抗炎药物，副作用非常大，抗炎抗免疫，会彻底撤掉身体的抵抗力，所以不建议用于普通的病毒感染，只用于严重的炎症反应或者防止严重的炎症后遗症。新冠对于大部分人都是“小感冒”，真的要在这个阶段用激素吗？用激素之后，可以肯定的是，必须配着抗病毒药使用，因为你自己已经没有抵抗力了。为了谨慎起见，我还查了一下相关文献，避免在这段时间内又出现了什么我不知道的科学发展。
guideline-激素
上面这个链接，是国外治疗新冠的指南中，对于糖皮质激素的描述，并没有颠覆性的变化，还是要求用于必须吸氧的住院病人，并且明确说了对无须住院的病人不但没有好处，还有害处。

There are no data to support the use of systemic corticosteroids in nonhospitalized patients with COVID-19.

In contrast, in hospitalized patients with COVID-19 who do not require supplemental oxygen, the use of systemic corticosteroids has not shown any benefits and may cause harm.3,4



因为他说话是那么的接地气，条理是那么的清晰，普通的医生和闲杂人等根本无法匹敌。这一篇，可以肯定流毒更广。因为是否放开是由专家和政府决定的，他改变不了那么多。而放开之后用什么药，怎么用，病人本来就会参与意见。可以想象得有多少人拿着这份“医嘱”，要求社区医生这么用药。

作者: 易水    时间: 2023-1-8 20:08
易水 发表于 2023-1-8 19:57
为什么这么多人骂他？

很多是因为他说只有5%的人发烧。

很可能是有史以来间接害死病人最多的医生，药王庙立个跪像吧。
作者: 北京阿新    时间: 2023-1-8 23:25
易水 发表于 2023-1-8 19:57
为什么这么多人骂他？

很多是因为他说只有5%的人发烧。

黄金72小时怎么算呢？肯定不能等抗原检测，只能靠核酸检测才能尽早发现
网红这是助推核酸经济 - 现在可没有免费核酸检测了
作者: 老票    时间: 2023-1-9 00:01
北京阿新 发表于 2023-1-8 23:25
黄金72小时怎么算呢？肯定不能等抗原检测，只能靠核酸检测才能尽早发现
网红这是助推核酸经济 - 现在可没 ...

从今天开始，上海取消所有免费核酸，以后单管收费16元RMB。  抗原倒是很多人家里都有，去年3月那一次发了很多，存量够用挺久的。   不过因为抗原检测可能有一定滞后性（核酸阳性后1-2天抗原才阳的案例在我身边就有不少），所以一旦抗原阳就默认是感染已经超过24小时了。   

核酸结果需要等待至少6-8小时，这是免费时段，收费后不知道会快还是慢。 抗原不到10分钟就可以，而且是自己随时可测。  最近几个月，抗原会很大程度上承担第一道检测。  票太和我就是这样确认已经阳性了的...没有再去复查核酸，证据链已经充足...


黄金72小时不仅仅是指病人自身的指数诸如血氧、血压、脉搏、呼吸频率等观察监护，现在也有期待社区医院预诊、处置、分流来减轻大医院压力的意思。


目前按照多个民间智库的模型推算，上海感染高峰确定已过，但重症和死亡高峰仍在峰值。 截止到今天，推算死亡率是千分之0.2（分母是感染者，这数字肯定还会上升），比吴尊友之前预测的千分之0.9-1.6略低，也侧面证明了吴的推算相对更靠谱一些。  



虽然一直努力在整点吃喝聊聊过去，也深刻理解国家战略转型的迫不得已，更自豪自己曾是三年来战斗的一分子，但心情还是悲凉的...... 这一年的元旦到春节，注定会在多年后被回忆起来。


也不应该被忘记...


作者: 黑洞的颜色    时间: 2023-1-9 00:28
易水 发表于 2023-1-8 20:08
很可能是有史以来间接害死病人最多的医生，药王庙立个跪像吧。

专家撒谎，最为致命。
这也是为什么要有职务犯罪！
作者: 雨楼    时间: 2023-1-9 00:38
易水 发表于 2023-1-8 06:57
为什么这么多人骂他？

很多是因为他说只有5%的人发烧。

无论是土鳖还是其他政府，说什么的时候老百姓要留个心眼。远的不说，疫情初期国外戴不戴口罩。。。鼓吹连花的老贼。。
作者: 老福    时间: 2023-1-9 01:54
本帖最后由 老福 于 2023-1-9 02:03 编辑
易水 发表于 2023-1-8 19:57
为什么这么多人骂他？

很多是因为他说只有5%的人发烧。


张文宏有点大嘴巴，讲话风格确实不太讨搞科研的同学喜欢。但是呢，给社区医生普及治疗方案，就有点像TG动员群众搞运动，总有简单化的嫌疑，最后总不免冤假错案。所以我不会在这方面挑毛病。

至于治疗方案本身，我没有能力评论。但也看到其他专业人士讲到推荐小分子抗病毒药物。激素使用方面，张文宏自己解释了如此建议的原因，同时也确实存在争议。
在临床救治方面，香港大学医学院教授金冬雁建议：第一，向60岁以上感染者和60岁以下的基础病感染者，尽早提供Paxlovid；第二，无法提供Paxlovid的情况下，应向他们提供Molnupiravir或阿兹夫定；第三，推行规范治疗，遏止农村及基层医疗单位中对抗生素和激素的滥用；第四，推行网络会诊诊疗。
https://i.ifeng.com/c/8MPpCsr4pLI
作者: 老福    时间: 2023-1-9 07:30
黑洞的颜色 发表于 2023-1-9 06:59
有一个5%就够了。
又来了个”有争议”的激素使用方案。怎么这么巧啊

这5%的事，坛里前两天讨论过，建议您去逐条看一下。有争议归有争议，从科学上讲并非不可能。

一线临床治疗方案出现争议很正常，我不奇怪。至于生病看医生，其实有赌博的成分，一方面要信赖自己的医生不能靠互联网给自己和家人看病，另一方面如果真有疑虑无法释怀，干脆换医生，不能强迫医生按网上方案治病。
作者: hsb    时间: 2023-1-9 08:33
老票 发表于 2023-1-9 00:01
从今天开始，上海取消所有免费核酸，以后单管收费16元RMB。  抗原倒是很多人家里都有，去年3月那一次发了 ...
  1. 截止到今天，推算死亡率是千分之0.2
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国内是“应阳尽阳”，和国外不同，如此之分母，那么这个死亡数。。。。。。
作者: 老福    时间: 2023-1-9 10:00
本帖最后由 老福 于 2023-1-9 10:06 编辑
易水 发表于 2023-1-8 19:57
为什么这么多人骂他？

很多是因为他说只有5%的人发烧。


看到另一篇讨论新冠治疗方案的，其中涉及到激素的使用问题。（原文：新冠到底该怎么治？村医和专家展开了一场“大论战” https://k.sina.com.cn/article_1887344341_707e96d502001c1d9.html#/）

下文说的村医四件套，指在一些私人诊所和乡村医生处，“抗病毒+抗生素+激素+退烧药”的“四件套”成为新冠治疗的主流方式。引文也明确指出基于循证医学，对于有进展为重型和危重型高危因素的患者，如果早期小剂量、短程使用激素，能减少重症肺炎的发生几率，降低死亡风险。这一方案也被写进了上海市新冠病毒基层诊治规范中，但具体使用人群和用量均有讲究。

一个不被大城市医生认可的治疗方案，为何患者却普遍反映“疗效显著”？对此，复旦大学附属中山医院感染病科主任胡必杰告诉“医学界”，“四件套”的治疗方案的确覆盖了很多患者，但真正起作用的可能只是其中一、两种药。

　　“例如，大部分新冠患者使用糖皮质激素有效，少部分有细菌感染或继发细菌感染的患者使用抗生素有效，再加上还有退烧药，所以见效迅速。”在胡必杰看来，这一治疗组合被称为“赤脚医生常用方法”，但从科学用药的角度看，并不合适。

　　以糖皮质激素类药物为例，它被广泛应用于抗炎、抗毒、抗休克、免疫抑制等用途，在新冠肺炎的治疗中，主要是用来抑制体内的过度炎症反应。胡必杰介绍，新冠肺炎是一种自限性疾病，当人体内病毒载量过多，机体免疫系统会被激活，从而去攻击病毒。

　　然而，若炎症细胞因子产生过多，这套免疫调节机制“失控”，就会在攻击病毒的同时，也杀害自身的组织器官，造成过度炎症反应，甚至会造成人体的衰竭和死亡，而糖皮质激素类药物的作用恰好是通过抑制免疫，从而避免过度炎症反应，就能有效地缓解症状。

　　但问题在于，免疫被抑制住了，一系列麻烦会接踵而来。“免疫被抑制，病毒数量就会增加，不利于清除病原体，如果是细菌感染时使用激素，还有可能会加重肺部感染和产生一系列毒副作用。”胡必杰反对不分青红皂白就用激素的治疗方式。

　　但面对新冠病毒这一全新的病原体，胡必杰同时指出，激素确实可以在临床治疗中发挥作用。基于循证医学，对于有进展为重型和危重型高危因素的患者，如果早期小剂量、短程使用激素，能减少重症肺炎的发生几率，降低死亡风险。这一方案也被写进了上海市新冠病毒基层诊治规范中，但具体使用人群和用量均有讲究。

　　胡必杰介绍，目前正规医院在治疗新冠患者时，会要求医生准确衡量激素的使用条件，也有一些年轻医生识别不出或是不敢轻易使用激素，所以治疗效果看上去没有村医显著，但其实是在最大限度地避免药物滥用，减少毒副作用的发生概率。

　　早在非典时期，为了抢救生命，激素类药物曾被大量用于紧急治疗，激素的副作用也曾导致部分患者出现股骨头坏死和肺部继发真菌感染等多种并发症。胡必杰认为，虽然当下使用激素的情况比较普遍，但不太可能再发生类似“非典后遗症”那种情况了。

　　“治疗SARS时存在认识不足等问题，临床上存在激素使用剂量太大、时间太长的情况。现在大家达成共识，只需要短期、小剂量使用激素，就能把过度炎症反应控制住，据我所知，基层乡村医生是优先考虑病人的感受，如果能做到短期、小剂量使用，副作用也会减少很多。”胡必杰说。

　　如果没有明确的细菌感染，他也不主张大面积使用抗生素。《柳叶刀》杂志2022年初发布了一项迄今对抗生素耐药性全球影响最全面的分析，该研究估计，2019年抗生素耐药菌感染直接导致127万人死亡，间接导致495万人死亡。

　　“如果病原体诊断不清，盲目使用抗生素，除了增加医疗费用外，还会增加患者肝肾毒性反应，并且诱导耐药等，所以合理使用抗生素的前提，就是要强调精准诊断。”胡必杰表示，“四件套”过于简单化，而实际临床诊疗要复杂得多，他建议乡村医生调整一下治疗方案，提高治疗的精准性。
作者: nukearchie    时间: 2023-1-9 11:32
老福 发表于 2023-1-9 10:00
看到另一篇讨论新冠治疗方案的，其中涉及到激素的使用问题。（原文：新冠到底该怎么治？村医和专家展开了 ...

很多用激素退烧的，很快觉得没事回家了，但是那是症状被撤销了，症状是怎么来的？是免疫系统战斗来的，用激素关闭免疫系统，症状可不是没有了？ 那回家以后呢，我认识的医生很多说使用激素退烧回家以后，很多病人特别是老年体弱或者剧烈运动之后就一觉不醒了。拿着还算COVID死亡吗？可以不算了吧？您不是好了退烧了回家了吗？所以村医可以这么干，正规大医院不敢。那么您觉得张网红作为医学博士给这样的建议/定论，从好了说从坏了说可以怎么解释。
作者: 老福    时间: 2023-1-9 11:37
nukearchie 发表于 2023-1-9 11:32
很多用激素退烧的，很快觉得没事回家了，但是那是症状被撤销了，症状是怎么来的？是免疫系统战斗来的，用 ...

我不是医生，无法给你答案。不过，提醒一下，你回复的引文不是张文宏说的，是复旦大学附属中山医院感染病科主任胡必杰说的。文章来自观察者网。
作者: nukearchie    时间: 2023-1-9 15:21
老福 发表于 2023-1-9 11:37
我不是医生，无法给你答案。不过，提醒一下，你回复的引文不是张文宏说的，是复旦大学附属中山医院感染病 ...

推荐用一大堆激素好像张先生明明白白写在上文里吧？
作者: 易水    时间: 2023-1-9 16:29
老福 发表于 2023-1-9 01:54
张文宏有点大嘴巴，讲话风格确实不太讨搞科研的同学喜欢。但是呢，给社区医生普及治疗方案，就有点像TG动 ...

社区医生是有执业医师证的专业人士。同时，因为没有用过这些药物，的确需要培训。他们最不需要的就是这种哗众取宠，过度简化的“培训”。这是对他们专业素质的侮辱。

临床应用药物，搞清楚适应症和禁忌症是极为重要的，怎么能这么简化呢。此处我不否认p药有效，应在合适的情况下使用。能救一命也是好的。
作者: 易水    时间: 2023-1-9 16:58
老福 发表于 2023-1-9 10:00
看到另一篇讨论新冠治疗方案的，其中涉及到激素的使用问题。（原文：新冠到底该怎么治？村医和专家展开了 ...

https://www.thelancet.com/journals/landig/article/PIIS2589-7500(22)00018-8/fulltext#seccestitle150

看一下这一篇。我不会贴图。
作者: indy    时间: 2023-1-9 19:19
易水 发表于 2023-1-9 03:58
https://www.thelancet.com/journals/landig/article/PIIS2589-7500(22)00018-8/fulltext#seccestitle150 ...

太长，晚一点到电脑上分两部分贴出来


https://www.thelancet.com/journa ... text#seccestitle150
作者: hsb    时间: 2023-1-9 19:22
张文宏医生现在受到中央力挺，怼他的被禁、或自己删文等等。
作者: 老福    时间: 2023-1-9 21:03
易水 发表于 2023-1-9 16:29
社区医生是有执业医师证的专业人士。同时，因为没有用过这些药物，的确需要培训。他们最不需要的就是这种 ...

上海中山医院感染科胡主任说过激素疗法写入了上海基层治疗方案，相信在培训中人手一册，其中禁忌副作用肯定清清楚楚，所以我不担心张文宏在培训中的讲法会有大的副作用。正如你所说，社区医生也受过基本的医学教育，是专业人士。

把张文宏的内部培训讲话发布到公众平台，在缺乏医学知识的群体里，是有可能造成一定的误解，但这并非张文宏所为，也就没有相应的责任。
作者: 老福    时间: 2023-1-9 21:09
nukearchie 发表于 2023-1-9 15:21
推荐用一大堆激素好像张先生明明白白写在上文里吧？

能不能明示张医生哪一句说大量使用激素的，他只说了吊水5毫克地米，第一次以后口服剂量类似。这个推荐是大剂量吗?
作者: 易水    时间: 2023-1-9 21:34
老福 发表于 2023-1-9 21:09
能不能明示张医生哪一句说大量使用激素的，他只说了吊水5毫克地米，第一次以后口服剂量类似。这个推荐是 ...

5mg地米，相当于133mg氢化可的松，比常用的大剂量冲击疗法略低，但高于一般剂量。
作者: indy    时间: 2023-1-9 22:10
indy 发表于 2023-1-9 06:19
太长，晚一点到电脑上分两部分贴出来

(PART I)

SummaryBackgroundDexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.
MethodsWe did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260.
FindingsBetween June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p<0·0001, for >80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021.
InterpretationImplementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered.
FundingUK National Institute for Health Research and UK Medical Research Council.

• View related content for this article




IntroductionDuring the COVID-19 pandemic, several large-scale trials have attempted to identify life-saving therapies. Currently, the most robust recommendations are for corticosteroids.1

Dexamethasone is a readily available, commonly used, and cheap intervention2
that decreased all-cause 28-day mortality in adult patients (aged ≥18 years) admitted to hospital with COVID-19 by an absolute risk reduction of 2·8% in the open-label Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial.3
Greater benefit was found in patients on higher levels of respiratory support and, importantly, there was possibility of harm in those not receiving oxygen therapy.3
On June 16, 2020, when preliminary results from RECOVERY were published,4
UK clinical guidelines were updated to recommend low-dose oral or intravenous corticosteroids—dexamethasone, prednisolone, methylprednisolone, or hydrocortisone—to patients with COVID-19 requiring supplementary oxygen.5

On Sept 2, 2020, the Rapid Evidence Appraisal for COVID-19 (REACT) meta-analysis of critically ill patients with COVID-19 showed lower mortality associated with administration of corticosteroids than with standard care (summary odds ratio 0·66).6
The next day, the UK National Institute for Health and Care Excellence (NICE) and WHO published guidelines recommending oral or intravenous administration of 6 mg dexamethasone for up to 10 days to patients with severe or critical COVID-19, defined by oxygen saturation (SpO2) of less than 90%, a respiratory rate of more than 30 breaths per min, sepsis, septic shock, acute respiratory distress syndrome, mechanical ventilation, vasopressor therapy, or signs of severe respiratory distress.7
Months later, on April 8, 2021, NICE updated their guideline to recommend corticosteroids for all patients requiring supplementary oxygen, noting “the need for clear and unambiguous terminology”.8

[color=var(--theme-font-color,#fff)][backcolor=var(--theme-journal,#ec1c24)][size=0.9375][size=1.125]Research in context[size=1.125]Evidence before this studyWe searched PubMed for primary research articles documenting changes in rates of corticosteroid administration in COVID-19 over time, published between June 16, 2020, and July 8, 2021, with no language restrictions and using the search terms (“SARS-CoV-2” OR “COVID-19”) AND (“corticosteroids” OR “steroids” OR “dexamethasone”). Of the 1985 studies identified, most focused on the relationship between corticosteroids and outcome, led by the RECOVERY trial. We found no studies that documented changes in corticosteroid administration over time or those that identified differential administration between patient groups. Understanding the implementation of corticosteroids and identifying groups of patients who are systematically less likely to be prescribed steroids are essential to ensure that this cheap and effective medication is available to all eligible patients.[size=1.125]Added value of this studyAlthough randomised controlled trials have convincingly shown the mortality benefit of corticosteroids for patients on supplemental oxygen, no studies have previously looked at whether this evidence has translated into clinical practice. We have shown that the majority of patients on oxygen in UK hospitals have been prescribed corticosteroids. However, we found that corticosteroid administration was significantly lower for patients older than 70 years, and this low uptake could not be explained by other factors associated with lower rates of steroid administration, such as dementia, clinical frailty, and treatment escalation decisions.[size=1.125]Implications of all the available evidenceThe quick implementation of one of the only mortality-reducing therapies for COVID-19 has been very successful in the UK. However, the potential inequities in administration that we have found are extremely important for individual, local, and global health-care communities to evaluate their practices in treating COVID-19 and to ensure all eligible patients receive the best available treatment.



A modelling study estimated that corticosteroids could save approximately 12 000 lives between July and December, 2020, in the UK.9
However, for this treatment to save lives it has to be successfully implemented. As implementation of a new intervention relies on behavioural change, it benefits from an understanding of baseline behaviours and detailed and explicit recommendations that consider factors relevant to decision making.10
Common challenges include complexity of the intervention and difficulty gaining consensus with colleagues.10
Success in implementing a new intervention is usually defined as an uptake of 80–90%.11

As of May, 2021, only an intermediate report from October, 2020, from the International Severe Acute Respiratory and Emerging Infections Clinical Characterisation Protocol UK (ISARIC4C CCP-UK) investigators had explored corticosteroid uptake in the UK, estimating that 55% of adult patients on oxygen in hospital had received corticosteroids.12
It is unknown how the changing guidelines and potential barriers have affected the transition from evidence to practice. We aimed to evaluate the implementation of corticosteroids into UK clinical practice since the announcement of the RECOVERY trial findings.
MethodsStudy design and participantsWe did an audit of clinical implementation using data from the ISARIC WHO Clinical Characterisation Protocol UK (CCP-UK), a prospective, observational cohort study representing nearly half of UK COVID-19 hospital admissions.13
We included patients aged 18 years or older who were admitted to 237 acute general hospitals with PCR-confirmed COVID-19 (or with high likelihood of disease if supporting PCR results were not available) from assumed community-acquired infection between March 16, 2020, and April 14, 2021. Community-acquired infection was defined as symptom onset 5 days or less after admission to hospital. Patients who received any supplementary oxygen at any point during their hospital stay were included in analyses.
Patient data, including patient demographics, comorbidities, treatments, complications, and outcomes, were recorded into the secure REDCap database. The detailed study protocol and ethics approval are described elsewhere.13
Under the Control of Patient Information notice 2020 for urgent public health research, processing of demographic and routine clinical data from medical records for research does not require consent in England and Wales.14
In Scotland, a waiver for consent was obtained from the Public Benefit and Privacy Panel.15
Reporting of this study conforms to the STROBE statement.16

VariablesWe collected information using the ISARIC4C case report form for key variables, including age (categorised into <50 years, 50–59 years, 60–69 years, 70–79 years, and ≥80 years, corresponding to the ISARIC4C Mortality Score17
categories), sex, self-reported ethnicity, deprivation (according to the Index of Multiple Deprivation, with the first quintile being the least deprived and the fifth quintile the most deprived), Clinical Frailty Score (scores of 1–2 indicate fit, 3–4 indicate vulnerable, but not frail, 5–6 indicate initial signs of frailty but with some degree of independence, and 7–9 indicate severe or very severe frailty),18
and comorbidities (presence of any one or more of hypertension, chronic cardiac disease non-asthmatic chronic pulmonary disease, asthma, type 1 diabetes, type 2 diabetes, obesity, chronic neurological disease, dementia, chronic kidney disease, moderate or severe liver disease, mild liver disease, malignancy, rheumatological disease, pre-admission immunosuppressants including corticosteroids, and HIV/AIDS). Physiological parameters of the ISARIC4C Mortality Score (SpO2, respiratory rate, C-reactive protein [CRP], blood urea nitrogen, Glasgow Coma Scale score)17
within 24 h of hospital admission were used as markers of illness severity. Admitting hospitals were mapped to the NHS regions to create the NHS region variable. These are reported for the patients with moderate or severe COVID-19 to account for the differences in patient cohort severity and thus eligibility for corticosteroid therapy. The ISARIC4C case report form collected information on whether or not patients had an admission to an intensive care or high dependency unit (these were not separated). We further categorised patients in critical care by receipt of invasive ventilation. The any oxygen variable represents patients who were recorded to receive any supplementary oxygen or any invasive ventilation (this was assumed to involve supplementary oxygen), or to have daily fraction FiO2 of more than 0·21 on any day of hospital admission. Corticosteroid administration, maximum level of respiratory support (no oxygen, supplemental oxygen, non-invasive ventilation, or invasive mechanical ventilation), and critical care admission were recorded at any timepoint during admission. We have provided further detail on variables in the appendix (pp 1–2).
Patients were recorded to have symptoms at admission if they reported any one or more of the following: cough, fever, sore throat, runny nose, ear pain, wheezing, chest pain, myalgia, joint pain, fatigue, shortness of breath, disturbance or loss of taste, lower chest wall indrawing, headache, altered consciousness or confusion, seizures, abdominal pain, vomiting or nausea, diarrhoea, conjunctivitis, skin rash, skin ulcers, lymphadenopathy, bleeding, or anosmia. If none of these were reported, patients were considered to be asymptomatic.
Corticosteroid treatment was recorded as a free text entry, which we interpreted using an algorithm described in the appendix (p 1) and checked manually. Dexamethasone and hydrocortisone, and prednisolone in pregnant women, are recommended by NICE,8
but methylprednisolone is also considered an appropriate alternative to these drugs.1
We created a variable, any corticosteroid, signifying administration of any of these corticosteroids during the admission; patients were therefore stratified by those who received once-daily 6 mg dexamethasone orally or intravenously, those who received any dose or frequency of dexamethasone, those who received any corticosteroid, and those who received none.
COVID-19 severitySince the initial guidance considered all patients requiring supplementary oxygen to be eligible for corticosteroid treatment,5
we primarily investigated corticosteroid administration in patients recorded to have received supplementary oxygen. To account for the severity criteria added in September, 2020, we further categorised these patients into those with mild COVID-19, moderate COVID-19, or severe COVID-19 by clinical severity on hospital admission. Severe COVID-19 reflects the WHO criteria:2
SpO2 of less than 90% or a respiratory rate of more than 30 breaths per min. Moderate COVID-19 includes patients with clinical respiratory distress (respiratory rate >20 breaths per min) and SpO2 threshold for supplementary oxygen (<94%).19
Patients not fulfilling these criteria might have transiently received oxygen at admission with minimal respiratory distress, whom we categorised as having mild COVID-19. The appendix (pp 16–20) shows the severity stratification of patients by various severity markers, demographics, and comorbidities.
OutcomesWe defined two time-based cohorts: admissions between March 16 and June 16, 2020 (baseline cohort), and between June 17, 2020, and April 14, 2021 (after the RECOVERY press release4
and allowing 28-day follow-up; second cohort).
The primary outcome was the proportion of patients in the second cohort who received any oral or intravenous corticosteroid (dexamethasone, prednisolone, hydrocortisone, or methylprednisolone). Patients who received supplementary oxygen were considered eligible, but we also explored the effect of the COVID-19 severity criteria. The secondary outcome was the change in administration of corticosteroids before (ie, in the baseline cohort) and after the publication of the RECOVERY trial results (ie, the second cohort), in relation to the RECOVERY trial and NICE guidance. The second cohort was further characterised and studied for factors associated with corticosteroid administration.
Statistical analysisContinuous data are summarised as median (IQR) and categorical data as frequency (percentage). We used statistical disclosure control measures to protect patient confidentiality and anonymity. Cells with fewer than five patients were either removed or replaced with not applicable or merged with other levels manually (not applicable could be 0 or suppressed).
We modelled corticosteroid use with a multiple logistic regression model, adjusting for demographic variables and variables previously shown to be associated with disease severity: age, sex, ethnicity, deprivation quintile, and comorbidities (hypertension, chronic cardiac disease, non-asthmatic chronic pulmonary disease, asthma, diabetes, chronic neurological disease, dementia, chronic kidney disease, moderate or severe liver disease, mild liver disease, malignancy, rheumatological disease, pre-admission immunosuppressants, and HIV/AIDS), with the aim to explain corticosteroid implementation. We also adjusted for time (week of admission) and the COVID-19 severity criteria. The model was built using a parsimonious criterion-based approach.20
This approach incorporated geographical clustering of patients through the inclusion of a random effect at the level of the admitting hospital, checking for all first-order interactions, including the effect of time (week of admission as linear and quadratic terms), and final model selection by the Akaike information criterion. We report C statistics as measures of model discrimination. We set statistical significance at 5%. We checked that the data were coded correctly, which identified the potential erroneous coding of all patients in some hospitals with an intensive care unit admission. We excluded these patients from the analysis. We identified missing values within each variable and analysed the patterns of missingness. We visually checked for associations between missing and observed data. For patients whose postcodes were missing, we used the average Index of Multiple Deprivation rank, weighted by population in each lower super output area for a given hospital catchment area. We considered comorbidity indicated as unknown as no comorbidity. We considered corticosteroid administration reported missing as no corticosteroid and did a sensitivity analysis of patients with a yes versus no entry.
We acknowledge the missing data in all our tables but did not perform any imputation for missing data, as given the nature of the study, the analysis team had concerns around interpretation if the corticosteroid administration were to be imputed.
We checked data for patterns of missingness, indicate missing data in the study tables, and describe missing data in the appendix (pp 6–29). The denominator for explanatory variables, such as comorbidities, is the number of patients with completed entries. The proportion of patients receiving any corticosteroid is reported as a percentage of the total number of participants, with the denominator including participants with missing corticosteroid entry.
We did sensitivity analyses: complete case analysis excluding patients with missing corticosteroid administration data, patients with recorded PCR-positive COVID-19, and a cohort excluding participants with an outcome of death or palliative discharge recorded within 2 days of admission to account for patients who might have been identified as palliative from the beginning and therefore not started on corticosteroid treatment. Frailty was only collected from Aug 1, 2020, onwards, and we did a sensitivity analysis for patients with frailty recorded.
We did an interrupted time-series analysis using segmented regression, with the timepoint of interest being June 16, 2020, when the RECOVERY trial findings and subsequent UK clinical guidance were published.4
, 5
The primary question was whether a change in absolute values (intercept) existed after the timepoint of interest. We considered time periods before (from March 16, 2020, to June 16, 2020; baseline cohort) and after (from June 17, 2020, and April 14, 2021; second cohort), for which we tested and reported trend lines with estimated 95% CIs. We investigated two subgroups with lower corticosteroid prescribing rates: patients with moderate or severe COVID-19 who were 80 years or older, or pregnant.
We undertook sensitivity analyses to evaluate the validity of these criteria relative to other reported severity markers,17
including CRP and fraction of inspired oxygen (FiO2). Aiming to avoid analysis of patients not requiring oxygen, and for whom there is a conditional recommendation against the use of corticosteroids,8
we modelled the factors associated with corticosteroid administration only in patients with moderate or severe COVID-19.
We analysed data using R (version 3.6.3), with packages including tidyverse, finalfit, and gridExtra.
Role of the funding sourceThe funders of this study had no role in the study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit for publication.
ResultsISARIC WHO CCP-UK enrolled 106 021 patients between June 17, 2020, and April 14, 2021 (figure 1). Of 96 708 eligible patients with COVID-19, 63 525 (65·7%) received supplementary oxygen and were included in analyses (figure 1; appendix pp 6–10). Of patients receiving oxygen, 16 593 (26·1%) had mild COVID-19, 26 776 (42·2%) had moderate COVID-19, and 19 600 (30·9%) had severe COVID-19 (figure 1).[size=0.938][size=0.938]Figure 1[size=0.938]Trial profile
[size=1.125][size=0.625][size=0.938]Show full caption



The proportion of patients on oxygen receiving corticosteroids increased from June, 2020, across levels of care and COVID-19 severity categories, with a clear step up in corticosteroid administration occurring immediately, and a subsequent continuing improvement plateauing in October, 2020 (figure 2). The intercepts of the segmented regression for daily proportion of patients on oxygen receiving any corticosteroid before and after June 16, 2020, showed a significant increase from 0·29 (95% CI 0·27–0·31) to 0·49 (0·47–0·52; p<0·0001; figure 3) This result parallels the observed increase in weekly proportion of patients receiving corticosteroids after publication of the RECOVERY trial results (appendix pp 49–50),4
which was similar across NHS regions (appendix p 51).[size=0.938][size=0.938]Figure 2[size=0.938]Corticosteroid administration in patients between the June 8, 2020, and April 14, 2021, stratified by supplementary oxygen, level of care, and COVID-19 severity at hospital admission
[size=1.125][size=0.625][size=0.938]Show full caption


[size=0.938][size=0.938]Figure 3[size=0.938]Fitted lines of the linear regression model for corticosteroid administration to patients who required oxygen, admitted to hospital between March 16, 2020, and April 18, 2021
[size=1.125][size=0.625][size=0.938]Show full caption



Of the 63 525 patients on oxygen, 42 442 (66·8%) received 6 mg dexamethasone once daily, 47 795 (75·2%) received any corticosteroid, 13 251 (20·9%) received no corticosteroid, and 2479 (3·9%) had missing corticosteroid data (table 1). Of the 47 795 patients who received any corticosteroid, 42 442 (88·8%) received 6 mg dexamethasone once daily, 4313 (9·0%) received another or unknown dose or frequency of dexamethasone, 558 (1·2%) received hydrocortisone, 456 (1·0%) received prednisolone, and 26 (0·1%) received methylprednisolone. Patients who received any corticosteroid were younger than those who received none (table 1).[size=1.125]Table 1[size=1.125]Baseline characteristics of patients admitted between June 17, 2020, and April 14, 2021, who received supplementary oxygen at any point in their admission, stratified by corticosteroid administration
[size=0.9375]6 mg once-daily dexamethasone group (n=42 442)
[size=0.9375]Any corticosteroid group*
[size=0.9375](n=47 795)
[size=0.9375]No corticosteroid group (n=13 251)
[size=0.9375]Missing corticosteroid group (n=2479)

[size=0.9375]Patient demographics
PCR-positive COVID-1938 424 (90·5%)43 287 (90·6%)11 927 (90·0%)1265 (51·0%)
Age on admission, years (n=63 525)68·0 (55·7–79·3)68·1 (55·7–79·4)77·8 (64·3–85·9)70·5 (56·6–81·2)
Age, years
<506584 (15·5%)7431 (15·5%)1418 (10·7%)358 (14·4%)
50–597729 (18·2%)8625 (18·0%)1244 (9·4%)408 (16·5%)
60–698602 (20·3%)9567 (20·0%)1652 (12·5%)449 (18·1%)
70–799517 (22·4%)10 786 (22·6%)3088 (23·3%)592 (23·9%)
≥8010 010 (23·6%)11 386 (23·8%)5849 (44·1%)672 (27·1%)
Sex (n=63 435)
Female17 285/42 380 (40·8%)19 558/47 723 (41·0%)6483/13 238 (49·0%)1039/2474 (42·0%)
Male25 095/42 380 (59·2%)28 165/47 723 (59·0%)6755/13 238 (51·0%)1435/2474 (58·0%)
Ethnicity
White29 880/36 897 (81·0%)33 663/41 515 (81·1%)10 304/11 659 (88·4%)1551/1821 (85·2%)
South Asian2972/36 897 (8·1%)3325/41 515 (8·0%)518/11 659 (4·4%)61/1821 (3·3%)
East Asian229/36 897 (0·6%)248/41 515 (0·6%)41/11 659 (0·4%)11/1821 (0·6%)
Black982/36 897 (2·7%)1111/41 515 (2·7%)202/11 659 (1·7%)46/1821 (2·5%)
Other ethnic minority2834/36 897 (7·7%)3168/41 515 (7·6%)594/11 659 (5·1%)152/1821 (8·3%)
Pregnancy (only recorded for women aged 12–55 years)
No3498/3582 (97·7%)3931/4051 (97·0%)772/937 (82·4%)165/183 (90·2%)
Yes84/3582 (2·3%)120/4051 (3·0%)165/937 (17·6%)18/183 (9·8%)
NHS region
East of England4101/42 164 (9·7%)4856/47 484 (10·2%)1775/13 172 (13·5%)170/2453 (6·9%)
London3260/42 164 (7·7%)3634/47 484 (7·7%)625/13 172 (4·7%)120/2453 (4·9%)
Midlands8986/42 164 (21·3%)10 346/47 484 (21·8%)3104/13 172 (23·6%)311/2453 (12·7%)
North East and Yorkshire6774/42 164 (16·1%)7703/47 484 (16·2%)1883/13 172 (14·3%)186/2453 (7·6%)
Northern Ireland58/42 164 (0·1%)61/47 484 (0·1%)NANA
North West8172/42 164 (19·4%)9042/47 484 (19·0%)2477/13 172 (18·8%)366/2453 (14·9%)
Scotland946/42 164 (2·2%)1002/47 484 (2·1%)196/13 172 (1·5%)86/2453 (3·5%)
South East5336/42 164 (12·7%)5914/47 484 (12·5%)1826/13 172 (13·9%)946/2453 (38·6%)
South West3436/42 164 (8·1%)3679/47 484 (7·7%)940/13 172 (7·1%)255/2453 (10·4%)
Wales1095/42 164 (2·6%)1247/47 484 (2·6%)346/13 172 (2·6%)13/2453 (0·5%)
[size=0.9375]Severity of illness at admission
Oxygen saturation (SpO2), % (n=62 726)92·0% (89·0–95·0)92·0% (89·0–95·0)94·0% (92·0–96·0)93·0% (90·0–95·0)
Respiratory rate, breaths per min (n=59 739)22·0 (20·0–28·0)22·0 (20·0–28·0)20·0 (18·0–24·0)22·0 (19·0–26·0)
C-reactive protein, mg/dL (n=50 470)93·0 (49·0–156·4)93·0 (49·0–157·0)52·2 (18·0–112·0)87·0 (39·0–150·0)
Blood urea nitrogen, mg/dL (n=50 591)6·5 (4·7–9·7)6·6 (4·7–9·8)7·3 (5·0–11·5)6·8 (4·8–10·6)
Glasgow coma scale†

1537 408/40 675 (92·0%)41 738/45 724 (91·3%)10 919/12 467 (87·6%)2006/2274 (88·2%)
<153267/40 675 (8·0%)3986/45 724 (8·7%)1548/12 467 (12·4%)268/2274 (11·8%)
Highest fraction of inspired oxygen (FiO2) on day of hospital admission (n=59 026)0·32 (0·24–0·50)0·32 (0·24–0·50)0·21 (0·21–0·28)0·32 (0·24–0·50)
Severity criteria
Mild COVID-198575/42 155 (20·3%)9757/47 470 (20·6%)6095/13 095 (46·5%)741/2404 (30·8%)
Moderate COVID-1919 092/42 155 (45·3%)21 165/47 470 (44·6%)4608/13 095 (35·2%)1003/2404 (41·7%)
Severe COVID-1914 488/42 155 (34·4%)16 548/47 470 (34·9%)2392/13 095 (18·3%)660/2404 (27·5%)
[size=0.9375]Comorbidities
Any comorbidity
No6766/40 263 (16·8%)7446/45 376 (16·4%)1299/12 608 (10·3%)293/1671 (17·5%)
Yes33 497/40 263 (83·2%)37 930/45 376 (83·6%)11 309/12 608 (89·7%)1378/1671 (82·4%)
Hypertension18 304/39 059 (46·9%)20 633/43 959 (46·9%)6155/12 033 (51·2%)680/1501 (45·3%)
Chronic cardiac disease10 268/39 118 (26·2%)11 650/44 069 (26·4%)4578/12 173 (37·6%)406/1558 (26·1%)
Non-asthmatic chronic pulmonary disease6540/39 133 (16·7%)7581/44 087 (17·2%)2388/12 154 (19·6%)261/1549 (16·8%)
Asthma6374/39 121 (16·3%)7256/44 078 (16·5%)1594/12 112 (13·2%)230/1541 (14·9%)
Type 1 diabetes797/38 651 (2·1%)894/43 555 (2·1%)314/11 964 (2·6%)53/1520 (3·5%)
Type 2 diabetes10 737/38 651 (27·8%)12 035/43 555 (27·6%)3131/11 964 (26·2%)391/1520 (25·7%)
Obesity7008/34 893 (20·1%)7846/39 170 (20·0%)1217/10 484 (11·6%)222/1369 (16·2%)
Chronic neurological disease3460/38 932 (8·9%)3992/43 848 (9·1%)1696/12 051 (14·1%)143/1543 (9·3%)
Dementia2989/38 847 (7·7%)3472/43 763 (7·9%)2058/11 920 (17·3%)122/1527 (8·0%)
Chronic kidney disease5329/39 017 (13·7%)6059/43 943 (13·8%)2506/12 119 (20·7%)219/1553 (14·1%)
Moderate or severe liver disease490/38 802 (1·3%)573/43 711 (1·3%)315/11 984 (2·6%)24/1536 (1·6%)
Mild liver disease583/38 697 (1·5%)661/43 578 (1·5%)238/11 930 (2·0%)27/1534 (1·8%)
Malignancy3017/38 938 (7·7%)3627/43 860 (8·3%)1518/12 041 (12·6%)123/1542 (8·0%)
Rheumatological disease4339/38 828 (11·2%)4982/43 754 (11·4%)1788/11 998 (14·9%)149/1529 (9·7%)
Pre-admission immunosuppressants, including corticosteroids4288/39 393 (10·9%)5264/44 314 (11·9%)1075/12 131 (8·9%)134/1419 (9·4%)
HIV/AIDS127/38 118 (0·3%)155/42 942 (0·4%)45/11 742 (0·4%)3/1510 (0·2%)
Data are n (%), median (IQR), or n/N %). Percentages are from complete cases and read vertically. Missing data from explanatory variables are omitted here and included in the appendix (pp 11–15). Percentages might not sum to 100 due to rounding. NA=not applicable (0 patients or suppressed).
[size=0.875em]* The any corticosteroid group includes 42 442 (88·8%) of 47 795 patients who received oral or intravenous dexamethasone 6 mg once daily, 3895 (8·1%) who received another or unknown dose or frequency of dexamethasone, 509 (1·1%) who received hydrocortisone, 406 (0·8%) who received prednisolone, and 24 (0·1%) who received methylprednisolone.
[size=0.875em]† A score of 15 indicates a fully awake state, and a score of less than 15 indicates any deficit in either the eye, motor, or verbal response used to assess conscious level.




Patients receiving any corticosteroid had a higher CRP than patients who did not receive corticosteroids, among other severity markers on admission (table 1). Patients receiving corticosteroids were more likely to have asthma and obesity, but less likely to have most other comorbidities, including chronic cardiac disease, chronic kidney disease, dementia, and chronic neurological disease (table 1). Of 44 314 patients receiving any corticosteroid, 5264 (11·9%) received some immunosuppressant medication (eg, oral corticosteroids or disease-modifying antirheumatic drugs) pre-admission (table 1).
Corticosteroid administration was higher among patients admitted to critical care (11 185 [86·6%] of 12 909) or requiring invasive ventilation (4882 [85·2%] of 5730) than in patients receiving ward-level care (36 415 [72·4%] of 50 278; figure 2; appendix pp 11–15). Of 27 226 patients not recorded to have received supplementary oxygen at any point during the hospital stay 4173 (15·3%) received corticosteroids (appendix pp 6–10).
Corticosteroid administration increased with higher COVID-19 severity: 9757 (58·8%) of 16 593 patients with mild COVID-19, 21 165 (79·0%) of 26 776 patients with moderate COVID-19, and 16 548 (84·4%) of 19 600 patients with severe COVID-19 received corticosteroids (figure 1).
Among 46 376 patients with moderate or severe COVID-19, 37 713 (81·3%) received any corticosteroid. Patients not receiving corticosteroids were older than those receiving corticosteroids (table 2). As among patients who received supplementary oxygen, patients with moderate or severe COVID-19 who had any corticosteroid had lower frequencies of chronic heart disease, chronic kidney disease, chronic neurological disease, and dementia than those who had no corticosteroid. In addition, of 591 patients with moderate or severe liver disease, 421 (71·2%) received corticosteroids. Rates of corticosteroid administration ranged from 4735 (74·8%) of 6333 patients in South East NHS regions to 3126 (88·1%) of 3550 patients in London NHS regions (table 2).[size=1.125]Table 2[size=1.125]Patients who received oxygen at any point in their admission and classified as having moderate or severe COVID-19 between June 17, 2020, and April 14, 2021, stratified by corticosteroid administration
[size=0.9375]Any corticosteroid group*
[size=0.9375](n=37 713)
[size=0.9375]No corticosteroid group (n=7000)
[size=0.9375]Missing corticosteroid group (n=1663)

[size=0.9375]Patient demographics
PCR-positive COVID-1934 158/41 212 (82·9%)6259/41 212 (15·2%)795/41 212 (1·9%)
Age on admission, years (n=46 376)67·3 (55·4–78·5)78·0 (66·0–86·0)69·6 (56·4–79·7)
Age, years
<506006/6867 (87·5%)619/6867 (9·0%)242/6867 (3·5%)
50–597037/7951 (88·5%)626/7951 (7·9%)288/7951 (3·6%)
60–697807/9041 (86·4%)922/9041 (10·2%)312/9041 (3·5%)
70–798543/10 690 (79·9%)1733/10 690 (16·2%)414/10 690 (3·9%)
≥808320/11 827 (70·3%)3100/11 827 (26·2%)407/11 827 (3·4%)
Sex
Female15 141/19 125 (79·2%)3317/19 125 (17·3%)667/19 125 (3·5%)
Male22 518/27 186 (82·8%)3674/27 186 (13·5%)994/27 186 (3·7%)
Ethnicity
White26 261/32 734 (80·2%)5458/32 734 (16·7%)1015/32 734 (3·1%)
South Asian2793/3119 (89·5%)280/3119 (9·0%)46/3119 (1·5%)
East Asian209/246 (85·0%)28/246 (11·4%)9/246 (3·7%)
Black912/1044 (87·4%)100/1044 (9·6%)32/1044 (3·1%)
Other ethnic minority2606/3020 (86·3%)298/3020 (9·9%)116/3020 (3·8%)
Pregnant (only recorded for women aged 12–55 years)
No3159/3597 (87·8%)328/3597 (9·1%)110/3597 (3·1%)
Yes84/155 (54·2%)61/155 (39·4%)10/155 (6·5%)
NHS region
East of England3728/4765 (78·2%)918/4765 (19·3%)119/4765 (2·5%)
London3126/3550 (88·1%)331/3550 (9·3%)93/3550 (2·6%)
Midlands8021/9888 (81·1%)1648/9888 (16·7%)219/9888 (2·2%)
North East and Yorkshire5997/7132 (84·1%)984/7132 (13·8%)151/7132 (2·1%)
Northern Ireland50/52 (96·2%)NANA
North West7146/8661 (82·5%)1269/8661 (14·7%)246/8661 (2·8%)
Scotland759/914 (83·0%)97/914 (10·6%)58/914 (6·3%)
South East4735/6333 (74·8%)1012/6333 (16·0%)586/6333 (9·3%)
South West2862/3507 (81·6%)487/3507 (13·9%)158/3507 (4·5%)
Wales1044/1265 (82·5%)210/1265 (16·6%)11/1265 (0·9%)
[size=0.9375]Severity of illness at admission
Oxygen saturation (SpO2), % (n=46 217)91·0% (88·0–93·0)92·0% (89·0–94·0)91·0% (88·0–93·0)
Respiratory rate, breaths per min (n=44 608)24·0 (21·0–28·0)23·0 (20·0–28·0)24·0 (20·0–28·0)
C-reactive protein, mg/dL (n=38 643)99·0 (53·0–164·0)63·0 (24·3–127·0)96·0 (47·0–163·0)
Blood urea nitrogen, mg/dL (n=38 396)6·6 (4·8–9·9)7·7 (5·2–12·1)7·0 (4·9–10·6)
Glasgow coma scale†

1533 136/40 165 (82·5%)5643/40 165 (14·0%)1386/40 165 (3·5%)
<153198/4375 (73·1%)1003/4375 (22·9%)174/4375 (4·0%)
Highest fraction of inspired oxygen (FiO2) (n=43 696)0·32 (0·24–0·60)0·24 (0·21–0·32)0·32 (0·24–0·60)
[size=0.9375]Comorbidities
Any comorbidity
No5957/6760 (88·1%)587/6760 (8·7%)216/6760 (3·2%)
Yes30 253/37 425 (80·8%)6187/37 425 (16·5%)985/37 425 (2·6%)
Hypertension16 382/20 242 (80·9%)3371/20 242 (16·7%)489/20 242 (2·4%)
Chronic cardiac disease9105/11 967 (76·1%)2578/11 967 (21·5%)284/11 967 (2·4%)
Non-asthmatic chronic pulmonary disease6668/8599 (77·5%)1718/8599 (20·0%)213/8599 (2·5%)
Asthma5953/7072 (84·2%)947/7072 (13·4%)172/7072 (2·4%)
Type 1 diabetes693/875 (79·2%)145/875 (16·6%)37/875 (4·2%)
Type 2 diabetes9645/11 731 (82·2%)1798/11 731 (15·3%)288/11 731 (2·5%)
Obesity6674/7563 (88·2%)726/7563 (9·6%)163/7563 (2·2%)
Chronic neurological disease2985/4000 (74·6%)919/4000 (23·0%)96/4000 (2·4%)
Dementia2559/3788 (67·6%)1144/3788 (30·2%)85/3788 (2·2%)
Chronic kidney disease4617/6134 (75·3%)1366/6134 (22·3%)151/6134 (2·5%)
Mild liver disease522/645 (80·9%)105/645 (16·3%)18/645 (2·8%)
Moderate or severe liver disease421/591 (71·2%)154/591 (26·1%)16/591 (2·7%)
Malignancy2742/3615 (75·9%)795/3615 (22·0%)78/3615 (2·2%)
Rheumatological disease3869/4960 (78·0%)974/4960 (19·6%)117/4960 (2·4%)
Pre-admission immunosuppressants, including corticosteroids4299/5079 (84·6%)678/5079 (13·3%)102/5079 (2·0%)
HIV/AIDS117/141 (83·0%)21/141 (14·9%)<5/141 (<5%)
Data are n/N (%) or median (IQR). Proportions read horizontally. Percentages might not sum to 100 due to rounding.
[size=0.875em]* The any corticosteroid group includes 33 580 (89·0%) of 33 713 patients who received oral or intravenous dexamethasone 6 mg once daily, 3366 (8·9%) who received another or unknown dose or frequency of dexamethasone, 392 (1·0%) who received hydrocortisone, 353 (0·9%) who received prednisolone, and 22 (0·1%) who received methylprednisolone.
[size=0.875em]† A score of 15 indicates a fully awake state, and a score of less than 15 indicates any deficit in either the eye, motor, or verbal response used to assess conscious level.




Univariable and multivariable associations with corticosteroid administration are described in the appendix (pp 32–34). After adjusting for sex, deprivation quintile, ethnicity, comorbidities, and admitting hospital, increasing age was strongly associated with patients not receiving corticosteroids (figure 4). Other factors associated with lower rates of corticosteroid administration included chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic neurological disease, dementia, moderate or severe liver disease, and malignancy. We found no association with diabetes and rate of corticosteroid administration. Severe illness, male sex, obesity, and pre-admission immunosuppressants were associated with higher rates of corticosteroid administration. No relevant first-order interactions were identified or incorporated into the models. Week of admission (both linear and quadratic term) did not contribute significantly. C statistic, as a measure of model discrimination, was 0·743 (95% CI 0·736–0·751).[size=0.938][size=0.938]Figure 4[size=0.938]Multivariable multilevel regression model of any corticosteroid administration among 30 670 patients with moderate or severe COVID-19 receiving supplementary oxygen and admitted to hospital between June 16, 2020, and April 14, 2021
[size=1.125][size=0.625][size=0.938]Show full caption



These results were consistent in the sensitivity analyses in which we excluded patients with missing corticosteroid (appendix pp 35–37), in patients with a recorded PCR-positive COVID-19 (appendix pp 38–40), and in which we excluded patients with death or palliative discharge within 2 days of admission (appendix pp 41–43). For the subgroup of 16 902 patients with recorded clinical frailty, significant associations with lower rates of corticosteroid prescribing included age 80 years or older (adjusted OR 0·80 [95% CI 0·66–0·97], p=0·021), increasing clinical frailty, and the aforementioned comorbidities (appendix pp 44–48).
Corticosteroids were administered to 8320 (70·3%) of 11 827 patients aged 80 years or older with moderate or severe COVID-19 (table 3). Rates of corticosteroid administration varied across the NHS regions from 1071 (61·0%) of 1756 patients in NHS South East to 416 (80·3%) of 518 patients in NHS London (table 3). Rates increased with level of care: 6381 (68·0%) of 9387 patients on oxygen alone, 1320 (85·4%) of 1546 patients on non-invasive ventilation, 456 (85·4%) of 534 patients in critical care, and 64 (82·1%) of 78 patients invasively ventilated. Within this older cohort, the proportion receiving corticosteroids decreased with increasing Clinical Frailty Scale17
score, but less so with comorbidities: the pattern in specific comorbidities mirrored the overall cohort.[size=1.125]Table 3[size=1.125]Subgroup analysis of patients aged 80 years or older with moderate or severe COVID-19, admitted to hospital between June 17, 2020, and April 14, 2021
[size=0.9375]Any corticosteroid group*
[size=0.9375](n=8320)
[size=0.9375]No corticosteroid group (n=3100)
[size=0.9375]Missing corticosteroid group (n=407)

[size=0.9375]Patient demographics
Age on admission, years (n=11 827)85·7 (82·8–89·5)86·9 (83·5–90·8)86·4 (83·6–90·3)
Sex
Female3865/5699 (67·8%)1623/5699 (28·5%)211/5699 (3·7%)
Male4442/6111 (72·7%)1473/6111 (24·1%)196/6111 (3·2%)
Ethnicity
White6666/9556 (69·8%)2607/9556 (27·3%)283/9556 (3·0%)
South Asian328/389 (84·3%)59/389 (15·2%)2/389 (0·5%)
East Asian26/31 (83·9%)4/31 (12·9%)1/31 (3·2%)
Black97/123 (78·9%)24/123 (19·5%)2/123 (1·6%)
Other ethnic minority323/420 (76·9%)85/420 (20·2%)12/420 (2·9%)
NHS region
East of England1026/1490 (68·9%)436/1490 (29·3%)28/1490 (1·9%)
London416/518 (80·3%)96/518 (18·5%)6/518 (1·2%)
Midlands1900/2692 (70·6%)734/2692 (27·3%)58/2692 (2·2%)
North East and Yorkshire1379/1901 (72·5%)491/1901 (25·8%)31/1901 (1·6%)
North West1462/2004 (73·0%)490/2004 (24·5%)52/2004 (2·6%)
Scotland126/168 (75·0%)34/168 (20·2%)8/168 (4·8%)
South East1071/1756 (61·0%)508/1756 (28·9%)177/1756 (10·1%)
South West649/905 (71·7%)211/905 (23·3%)45/905 (5·0%)
Wales227/310 (73·2%)82/310 (26·5%)1/310 (0·3%)
[size=0.9375]Severity of illness on admission
Oxygen saturation (SpO2), % (n=11 809)92·0% (88·0–94·0)92·0% (89·0–94·0)92·0% (88·0–93·0)
Respiratory rate, breaths per min (n=11 409)24·0 (20·0–28·0)22·0 (20·0–27·0)24·0 (20·0–27·0)
C-reactive protein, mg/dL (n=9346)89·0 (45·0–152·0)60·2 (24·0–123·0)77·0 (35·0–135·9)
Blood urea nitrogen, mg/dL (n=9408)9·6 (6·9–13·9)9·5 (6·7–14·8)9·4 (6·6–14·3)
Glasgow coma scale†

156722/9453 (71·1%)2409/9453 (25·5%)322/9453 (3·4%)
<151275/1903 (67·0%)562/1903 (29·5%)66/1903 (3·5%)
Highest fraction of inspired oxygen (FiO2; n=10 984)0·28 (0·24–0·40)0·24 (0·21–0·32)0·32 (0·24–0·40)
Severity criteria
Moderate COVID-194841/7182 (67·4%)2076/7182 (28·9%)265/7182 (3·7%)
Severe COVID-193479/4645 (74·9%)1024/4645 (22·0%)142/4645 (3·1%)
[size=0.9375]Comorbidities
Any comorbidity
No343/454 (75·6%)92/454 (20·3%)19/454 (4·2%)
Yes7697/10 868 (70·8%)2921/10 868 (26·9%)250/10 868 (2·3%)
Hypertension4848/6742 (71·9%)1762/6742 (26·1%)132/6742 (2·0%)
Chronic cardiac disease3908/5568 (70·2%)1551/5568 (27·9%)109/5568 (2·0%)
Non-asthmatic chronic pulmonary disease2095/2925 (71·6%)762/2925 (26·1%)68/2925 (2·3%)
Asthma1000/1369 (73·0%)337/1369 (24·6%)32/1369 (2·3%)
Type 1 diabetes133/181 (73·5%)41/181 (22·7%)7/181 (3·9%)
Type 2 diabetes2183/3001 (72·7%)756/3001 (25·2%)62/3001 (2·1%)
Obesity458/611 (75·0%)139/611 (22·7%)14/611 (2·3%)
Chronic neurological disease961/1433 (67·1%)440/1433 (30·7%)32/1433 (2·2%)
Dementia1755/2681 (65·5%)866/2681 (32·3%)60/2681 (2·2%)
Chronic kidney disease2281/3205 (71·2%)852/3205 (26·6%)72/3205 (2·2%)
Mild liver disease66/93 (71·0%)27/93 (29·0%)0
Moderate or severe liver disease62/102 (60·8%)36/102 (35·3%)4/102 (3·9%)
Malignancy1017/1467 (69·3%)414/1467 (28·2%)36/1467 (2·5%)
Rheumatological disease1295/1900 (68·2%)561/1900 (29·5%)44/1900 (2·3%)
Pre-admission immunosuppressants, including corticosteroids906/1163 (77·9%)228/1163 (19·6%)29/1163 (2·5%)
HIV/AIDS14/21 (66·7%)7/21 (33·3%)0
Clinical frailty‡

1–2164/196 (83·7%)26/196 (13·3%)6/196 (3·1%)
3–41207/1539 (78·4%)300/1539 (19·5%)32/1539 (2·1%)
5–62082/2885 (72·2%)753/2885 (26·1%)50/2885 (1·7%)
7–91250/1938 (64·5%)646/1938 (33·3%)42/1938 (2·2%)
Missing3617/5269 (68·6%)1375/5269 (26·1%)277/5269 (5·3%)
[size=0.9375]Level of care and escalation plans
Level of respiratory support
Oxygen alone6381/9387 (68·0%)2669/9387 (28·4%)337/9387 (3·6%)
High-flow nasal cannula555/816 (68·0%)218/816 (26·7%)43/816 (5·3%)
Non-invasive ventilation1320/1546 (85·4%)201/1546 (13·0%)25/1546 (1·6%)
Invasive ventilation64/78 (82·1%)12/78 (15·4%)2/78 (2·6%)
Critical care admission
Yes456/534 (85·4%)65/78 (12·2%)13/78 (2·4%)
No......
Not indicated3630/5176 (70·1%)1514/5176 (29·3%)32/5176 (0·6%)
Not appropriate3310/4308 (76·8%)985/4308 (22·9%)13/4308 (0·3%)
Missing1380/2343 (58·9%)601/2343 (25·7%)362/2343 (15·5%)
Death within 2 days of admission
Death or palliative discharge within 2 days of admission407/600 (67·8%)175/600 (29·2%)18/600 (3·0%)
Longer length of hospital stay or survival7913/11 227 (70·5%)2925/11 227 (26·1%)389/11 227 (3·5%)
Data are median (IQR), n/N (%), or n (%). Proportions read horizontally. Proportions read horizontally. Percentages might not sum to 100 due to rounding.
[size=0.875em]* The any corticosteroid group includes 7305 (87·8%) of 8320 patients who received oral or intravenous dexamethasone 6 mg once daily, 780 (9·4%) who received another or unknown dose or frequency of dexamethasone, 120 (1·4%) who received hydrocortisone, 114 (1·4%) who received prednisolone, and fewer than five who received methylprednisolone.
[size=0.875em]† A score of 15 indicates a fully awake state, and a score of less than 15 indicates any deficit in either the eye, motor, or verbal response used to assess conscious level.
[size=0.875em]‡ Clinical frailty reference: scores of 1–2 indicate fit, 3–4 indicate vulnerable, but not frail, 5–6 indicate initial signs of frailty but with some degree of independence, and 7–9 indicate severe or very severe frailty.




Among 4308 in this cohort in whom critical care admission was not considered appropriate, 3310 (76·8%) received corticosteroids. Fewer patients with a Glasgow Coma Scale score of less than 15 received corticosteroid therapy than those with a score of 15 (1275 [67·0%] of 1903 vs 6722 [71·1%] of 9453). Of the 11 827 patients aged 80 years or older, 600 (5·1%) died or were deemed palliative within 2 days of hospital admission. These patients had slightly lower rates of corticosteroid administration than those with a longer hospital stay or who survived (407 [67·8%] of 600 vs 7913 [70·5%] of 11 227).
Corticosteroid administration rates were lower in pregnant patients with moderate or severe COVID-19 compared with non-pregnant women with moderate or severe COVID-19 aged 18–55 years (84 [54·2%] of 155 vs 3159 [87·8%] of 3597). Pregnant and non-pregnant patients with moderate or severe COVID-19 were similar regarding proportions of symptomatic versus asymptomatic patients and moderate versus severe COVID-19 (appendix pp 30–31).

作者: indy    时间: 2023-1-9 22:11
indy 发表于 2023-1-9 09:10
(PART I)

SummaryBackgroundDexamethasone was the first intervention proven to reduce mortality in  ...

(PART II)


DiscussionWe observed a rapid and significant increase in the administration of corticosteroids since publication of the RECOVERY trial results on June 16, 2020. However, not all patients who fulfilled the criteria of oxygen therapy and additional severity criteria received corticosteroids. Ages of 70 years or older were associated with consistently lower rates of corticosteroid administration. Patients with dementia, chronic neurological disease, chronic cardiac disease, moderate or severe liver disease, and pregnant patients were also less likely to receive corticosteroids, regardless of severity of illness.
Considering the knowing–doing gap between evidence and implementation, which gets averaged at 17 years,21
the implementation of this programme has been rapid. This fast implementation could have been facilitated by the timing of the evidence, communication, the simplicity of the intervention, and the global focus on the COVID-19 pandemic. In June, 2020, in-hospital mortality from COVID-19 was around 20–25% overall, and up to 38% among patients receiving invasive mechanical ventilation,22
with no proven treatments to reduce mortality. For clinicians, corticosteroids are widely used across hospitals and specialties, and their administration is simple, and the widespread coverage of the trial results in the UK media might have helped to make corticosteroids acceptable among patients. This perceived high benefit-to-risk ratio, familiarity, and simplicity might have aided the achievement of the accepted 80–90% target reliability.23

However, this target was not achieved universally. Age of 70 years or older, clinical frailty, and the aforementioned comorbidities were associated with lower rates of corticosteroid administration. There were also regional differences in corticosteroid uptake. In December, 2020, there seemed to be a reduction in corticosteroid prescribing, which could reflect the increase in hospital burden of patients with COVID-19. These discrepancies highlight the importance of process mapping and exploring potential barriers in addition to quantifying rate of change, to better understand the implementation process.24

Clinicians might have been hesitant to prescribe corticosteroids in patients with advanced age or multiple comorbidities, especially if care was primarily palliative. We found a significant reduction in corticosteroid administration among patients who were 70 years or older, independent of patient demographics, illness severity, and comorbidities, which persisted when adjusting for frailty in the smaller cohort of patients for whom frailty was recorded. However, we did not find that treatment escalation plans affected the administration of corticosteroids or that patients who died in the first 2 days of hospital admission, or who were potentially on a palliative pathway, had lower rates of corticosteroids prescribed.
Other reasons for lower rates of corticosteroid prescribing in patients aged 70 years or older could include concerns of cognitive adverse effects and initial limited evidence in the RECOVERY trial subgroup analysis,3
although the REACT meta-analysis showed benefit in patients older than 60 years.6
The known corticosteroid-induced effects on cognition, delirium, and agitation, might have led clinicians to be cautious when prescribing them for patients with pre-existing cognitive decline or delirium.25
As the prevalence of delirium increases with age,26
clinicians might perceive patients older than 70 years to be at higher risk of such adverse effects. Although delirium was not recorded in this dataset, a Glasgow coma score of less than 15 was associated with lower rates of corticosteroid administration in patients with moderate or severe COVID-19 and in the subgroup of patients aged 80 years or older with moderate or severe COVID-19. This strong independent association of older age and lower rates of corticosteroid administration should be further explored.
Concerns over safety and scarce evidence could also disadvantage patients with diabetes27
and pregnant patients. Although we did not see significant differences in corticosteroid administration associated with diabetes, the uptake in pregnant patients was considerably lower than in non-pregnant women of reproductive age. This result could be explained by the limited and changing COVID-19 guidance for the use of corticosteroids in pregnancy.5
, 28
Although the most recent guidance from the Royal College of Obstetricians and Gynaecologists recommends use of corticosteroids in pregnant patients with COVID-19 requiring oxygen supplementation or ventilation,29
the initial concern of harm and controversies around the ideal corticosteroid30
might have compromised effective implementation. Although there might be a lower threshold to admit pregnant patients resulting in a less unwell cohort overall, the persistent poor uptake in pregnant patients with markers of high illness severity warrants further exploration.
Pre-admission immunosuppressants were associated with higher rates of corticosteroid administration, potentially reflecting indications for pre-existing conditions or lower thresholds to start corticosteroids. Some pre-existing comorbidities for which corticosteroids are occasionally indicated, such as malignancy or rheumatological conditions, were associated with lower rates of corticosteroid administration, which could reflect proven or potential concern about associated immunosuppression. Immunosuppression might present a relative contraindication to corticosteroids; therefore, the risk of secondary infection with corticosteroids should be explored further to ensure safe and appropriate prescribing.31
Alternatively, clinicians might perceive there to be less benefit from corticosteroids because of a potential effect of existing immunosuppression.
Corticosteroids are also indicated in exacerbations of asthma and other chronic pulmonary diseases. However, patients with moderate or severe COVID-19 and non-asthmatic chronic pulmonary disease received fewer corticosteroids, which persisted after adjusting for age and comorbidities. This finding could reflect lower baseline SpO2 and higher respiratory rates resulting in misclassification of some patients into artificially higher severity groups.
The rates of corticosteroid administration increased with markers of severity, such as high respiratory rate, low SpO2, and high CRP, and increasing level of care, but corticosteroids were also administered to patients not recorded to have received supplementary oxygen or without markers of severe COVID-19. Despite the WHO severity criteria,7
the initial clinical guidelines and the principal message from the RECOVERY trial recommended corticosteroids to anyone needing supplementary oxygen,5
and this message might have persisted as a simple decision aid. Contrarily, both the RECOVERY and the Metcovid trials reported a potential signal to harm among patients not receiving oxygen,3
, 32
which might have persuaded clinicians to err to the side of caution among patients with less severe COVID-19. Despite this signal to harm among patients receiving no oxygen, the rate of corticosteroid administration in the non-oxygen cohort observed here did not change after RECOVERY trial publication. To account for the less clear indication for patients with milder disease, we focused on patients with moderate or severe COVID-19 when identifying the discussed factors independently associated with lower corticosteroid administration.
The comprehensive clinical data collected allowed detailed analysis of subgroups to explore administration of corticosteroids. However, there are some limitations. There were more missing data than would be expected for a prospective cohort study, due to the nature of the pandemic, but this issue was handled using appropriate methods. Although the ISARIC WHO CCP-UK study captured a third of the patients admitted to hospital with COVID-19 in the UK after June 16, 2020, and therefore offers a generalisable estimate of the national uptake of corticosteroids, selection bias might still exist. Fewer hospital admissions before June 16 could be partly contributing to the slight premature increase in corticosteroid administration. We cannot comment on the duration of corticosteroid treatment or supplementary oxygen, or the time to prescription. We were also unable to determine the type of non-critical care ward, which could contribute to differences in rates of corticosteroid prescribing due to a range of skills, preparedness, or knowledge in treating patients with COVID-19. As the indication for the corticosteroid therapy was not recorded, a proportion of patients might have received corticosteroids for other indications; therefore, our corticosteroid administration rates for patients with COVID-19 are probably overestimates of the true administration rate for COVID-19. Similarly, cautions with corticosteroids, such as peptic ulcer disease or risk of gastrointestinal bleeding,33
were not collected. Although the severity criteria were robust, derived from commonly used clinical markers on admission, and reflected the current clinical guidelines, they could not capture all criteria for severe or critical COVID-19,2
such as clinical trend. Finally, there might be unmeasured confounders that we were either unaware of or unable to measure.
Rates of corticosteroid administration in COVID-19 have increased substantially since the publication of the RECOVERY trial results and updated clinical guidelines, with the greatest rates seen among patients with higher severity of illness. However, this study highlighted a marked difference in corticosteroid uptake based on age, with patients aged 70 years or older much less likely to receive corticosteroids, even after accounting for illness severity, comorbidities, and clinical frailty. The presence of chronic cardiac disease, chronic neurological disease, dementia, or pregnancy was also associated with lower rates of corticosteroid administration. A decision not to administer a cheap, simple, and potentially life-saving therapy such as low-dose corticosteroids in COVID-19 might benefit from a consensus approach, whereby any decision not to adhere to a guideline requires discussion and sense checking with another clinical colleague. This approach might provide reassurance to patients of equitable access and support clinicians in potentially challenging decision making. Future qualitative research should evaluate whether there were systematic barriers or enablers to implementation, overall or in specific subgroups of patients, across a range of institutions, settings, and practitioners. Such work should aim to understand to what extent the results presented here represent appropriate clinical judgement or potentially modifiable barriers to receiving life-saving treatments.
ISARIC Coronavirus Clinical Characterisation Consortium (ISARIC4C)
J Kenneth Baillie, Malcolm G Semple, Peter JM Openshaw, Gail Carson, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Annemarie B Docherty, Jake Dunning, Ana da Silva Filipe, Tom Fletcher, Christopher A Green, Julian A Hiscox, Antonia Ying Wai Ho, Peter W Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Laura Merson, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Clark D Russell, Vanessa Sancho-Shimizu, Janet T Scott, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, Ryan S Thwaites, Lance C W Turtle, Maria Zambon, Hayley E Hardwick, Chloe Donohue, Jane Ewins, Wilna Oosthuyzen, Fiona Griffiths, Lisa Norman, Riinu Pius, Tom M Drake, Cameron J Fairfield, Stephen Knight, Kenneth A Mclean, Derek Murphy, Catherine A Shaw, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Gary Leeming, Andrew Law, Ross Hendry, William Greenhalf, Victoria Shaw, Sarah McDonald, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, David Brealey, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Graham Cooke, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Antonia Ho, Maria Hobrok, Luke Hodgson, Anita Holme, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Igor Otahal, Mark Pais, Selva Panchatsharam, Hassan Paraiso, Brij Patel, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wooton, Andrew Workman, Bryan Yates, Peter Young.
Contributors
JKB, JD, JSN-V-T, PJMO, and MGS contributed to conceptualisation of the study. FN, EMH, MGS, and ABD did the formal analysis. FN, SRM, SDS, EMH, MGS, and ABD wrote the original draft. FN, SRM, SDS, TMD, RHM, JD, CJF, AH, JSN-V-T, RP, CDR, CAS, LT, PJMO, JKB, EMH, MGS, and ABD contributed to review and editing of the report. CD, HEH, AH, MG, GL, and RGS were responsible for project administration. JKB, PJMO, and MGS were responsible for funding acquisition. FN, EMH, and ABD verified all the data. All authors had full access to all data, and have seen and approved of the final text. EMH, MGS, and ABD had final responsibility for the decision to submit for publication.
Data sharingData, protocols, and all documentation around this analysis will be made available to academic researchers after authorisation from the ISARIC independent data management and access committee.
Declaration of interestsABD reports grants from the UK Department of Health and Social Care (DHSC) during the conduct of the study, and grants from the Wellcome Trust outside the submitted work. JSN-V-T reports grants from the DHSC during the conduct of the study, and is seconded to the DHSC. PJMO reports personal fees from consultancies and from the European Respiratory Society; grants from the UK Medical Research Council (MRC), the MRC Global Challenge Research Fund, the EU, the NIHR Biomedical Research Centre, MRC–GSK, the Wellcome Trust, and the NIHR (Health Protection Research Unit in Respiratory Infections at Imperial College London); and is an NIHR senior investigator outside the submitted work; his role as President of the British Society for Immunology was unpaid but travel and accommodation at some meetings was provided by the society. JKB reports grants from the MRC. MGS reports grants from DHSC, NIHR UK, MRC UK, HPRU in Emerging and Zoonotic Infections, and University of Liverpool, during the conduct of the study; and is chair of the Infectious Diseases Science Advisory Board and minority shareholder of Integrum Scientific, Greensboro NC, and Independent external and non-remunerated member of Pfizer's External Data Monitoring Committee for their mRNA vaccine program(s) outside the submitted work. All other authors declare no competing interests.
Acknowledgments
This study is supported by grants from the NIHR (award CO-CIN-01), the MRC (grant MC_PC_19059), the NIHR Imperial Biomedical Research Centre (grants P45058 and IS-BRC-1215-20013), the NIHR HPRU in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at the University of Liverpool, both in partnership with Public Health England (NIHR award 200907), the Wellcome Trust and the UK Department for International Development (215091/Z/18/Z), the Bill & Melinda Gates Foundation (OPP1209135), the Liverpool Experimental Cancer Medicine Centre (grant reference C18616/A25153), and the EU Platform for European Preparedness Against (Re-)emerging Epidemics 1 (FP7 project 602525). The NIHR Clinical Research Network provided infrastructure support for this research. This research was funded, in part, by the Wellcome Trust. RHM reports grants from BREATHE, the health data research hub for respiratory health (MC_PC_19004). BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and is delivered by Health Data Research UK. ABD acknowledges funding from the Wellcome Trust (216606/Z/19/Z0). LT is supported by a Wellcome Trust fellowship (205228/Z/16/Z). PJMO is supported by a NIHR Senior Investigator Award (award 201385). The views expressed are those of the authors and not necessarily those of the DHSC, the Department for International Development, the NIHR, the MRC, the Wellcome Trust, or Public Health England. Investigators were independent from funders. ISARIC4C CCP-UK data are provided by patients and collected by the UK National Health Service as part of their care. Although there was no direct involvement from patients or the public, quality improvement is paramount in ensuring the reliability of the health-care system that aims to maximise benefit and minimise harm to patients. This research was conducted as part of an urgent public health study in response to an emergency, meaning there was insufficient time for public involvement before data collection commenced. We are extremely grateful to the 2648 front-line NHS clinical and research staff and volunteer medical students who collected these data under challenging circumstances, and the generosity of the participants and their families for their individual contributions in these difficult times. We also acknowledge the support of Jeremy J Farrar (Wellcome Trust, London, UK) and Nahoko Shindo (WHO, Geneva, Switzerland).
Supplementary Material

ReferencesArticle InfoPublication HistoryPublished: April 2022

Identification
DOI: https://doi.org/10.1016/S2589-7500(22)00018-8
Copyright© 2022 The Authors. Published by Elsevier Ltd.
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作者: 老福    时间: 2023-1-9 22:42
易水 发表于 2023-1-9 21:34
5mg地米，相当于133mg氢化可的松，比常用的大剂量冲击疗法略低，但高于一般剂量。 ...

刚看到你引用文章里提到的激素用药量是每天口服6mg地米，所以差不多是一个级别，张文宏提到的用药量是没问题的。至于临床适用范围这个问题，我没有知识基础，就不参与讨论了。
作者: 常挨揍    时间: 2023-1-9 22:56
landlord 发表于 2023-1-7 08:55
这话说的条理很清楚嘛。搞不懂为啥这么多人骂他

水平明显比吴尊友饶毅差一截。



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