1) In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Xueting Yao, Fei Ye, Miao Zhang, Cheng Cui, Baoying Huang, Peihua Niu, Xu Liu, Li Zhao, Erdan Dong, Chunli Song, Siyan Zhan, Roujian Lu, Haiyan Li, Wenjie Tan, Dongyang Liu
Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than chloroquine (EC50=5.47 μM) in vitro.
Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquinephosphate when given 500 mg twice daily 5 days in advance.
【 在 obamaasia (ohyeah) 的大作中提到: 】 : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108130/pdf/ciaa237.pdf : Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than : chloroquine (EC50=5.47 μM) in vitro. : Based on PBPK models results, a loading dose of 400 mg twice daily of : hydroxychloroquine sulfate given orally, followed by a maintenance dose of : 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, : as it reached three times the potency of chloroquinephosphate when given : 500 mg twice daily 5 days in advance.
发表的临床试验是200mg/天三天；而后给予800mg/天，重症患者给予3周，轻中症患者 给予2周。 这篇论文的推荐是Hydroxychloroquine sulfate 400 mg given twicedaily for 1 day, followed by 200 mg twice daily for 4 more days
你认为哪个方案的剂量大？
【 在 obamaasia (ohyeah) 的大作中提到: 】 : There is clinical evidence to support the effect of hydrocholorquine in : clinical trial. : Read carefully, 200mg/天 is much less than the recommandated dosage of the : paper, : not 大很多. :
【 在 obamaasia (ohyeah) 的大作中提到: 】 : Very obviously. the problematic clinical trial has messed up the kinetics.: I am not sure the dosage in the clinical trial you mentioned ever reached : therapeutic plateau.
Interventions HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively).
发表的临床试验是1200mg/天三天；而后给予800mg/天，重症患者给予3周，轻中症患者给予2周。这篇论文的推荐是Hydroxychloroquine sulfate 400 mg given twicedaily for 1 day, followed by 200 mg twice daily for 4 more days
你认为哪个方案的剂量大？
没有谁的研究是problematic.也没有谁的方案是正确标准。更不存在谁 mess up 的问 题。
【 在 obamaasia (ohyeah) 的大作中提到: 】 : IS this the paper you are talking about ? : https://www.medrxiv.org/content/10.1101/2020.04.10.20060558v1 : 明明是1200 mg daily for three days. Why you say it is 200 mg for three day ? : : Really no need to continue if you do not read and cite correctly.
Risk Factors for Mortality in Patients with COVID-19 in New York City
Takahisa Mikami M.D., Hirotaka Miyashita M.D., Takayuki Yamada M.D., Matthew Harrington M.D., Daniel Steinberg M.D., Andrew Dunn M.D. & Evan Siau M.D.
Background New York City emerged as an epicenter of the coronavirus disease 2019 (COVID-19) pandemic.
Objective To describe the clinical characteristics and risk factors associated with mortality in a large patient population in the USA.
Design Retrospective cohort study.
Participants 6493 patients who had laboratory-confirmed COVID-19 with clinical outcomes between March 13 and April 17, 2020, who were seen in one of the 8 hospitals and/or over 400 ambulatory practices in the New York City metropolitan area
Main Measures Clinical characteristics and risk factors associated with in-hospital mortality.
Key Results A total of 858 of 6493 (13.2%) patients in our total cohort died: 52/2785 (1.9%) ambulatory patients and 806/3708 (21.7%) hospitalized patients. Cox proportional hazard regression modeling showed an increased risk of in- hospital mortality associated with age older than 50 years (hazard ratio [HR] 2.34, CI 1.47–3.71), systolic blood pressure less than 90 mmHg (HR 1.38, CI 1.06–1.80), a respiratory rate greater than 24 per min (HR 1.43, CI 1.13–1.83), peripheral oxygen saturation less than 92% (HR 2.12, CI 1.56–2.88), estimated glomerular filtration rate less than 60 mL/min/1.73m2 (HR 1.80, CI 1.60–2.02), IL-6 greater than 100 pg/mL (HR 1.50, CI 1.12–2.03), D- dimer greater than 2 mcg/mL (HR 1.19, CI 1.02–1.39), and troponin greater than 0.03 ng/mL (HR 1.40, CI 1.23–1.62). Decreased risk of in-hospital mortality was associated with female sex (HR 0.84, CI 0.77–0.90), African American race (HR 0.78 CI 0.65–0.95), and hydroxychloroquine use (HR 0.53, CI 0.41–0.67).
Conclusions Among patients with COVID-19, older age, male sex, hypotension, tachypnea, hypoxia, impaired renal function, elevated D-dimer, and elevated troponin were associated with increased in-hospital mortality and hydroxychloroquine use was associated with decreased in-hospital mortality.
【 在 obamaasia (ohyeah) 的大作中提到: 】 : 氯喹在纽约和底特律都证明降低死亡率 : 钟南山也证明氯喹降低死亡率 : ============================================== : Risk Factors for Mortality in Patients with COVID-19 in New York City : Takahisa Mikami M.D., Hirotaka Miyashita M.D., Takayuki Yamada M.D., Matthew : Harrington M.D., Daniel Steinberg M.D., Andrew Dunn M.D. & Evan Siau M.D. : Background : New York City emerged as an epicenter of the coronavirus disease 2019 ( COVID : -19) pandemic. : Objective : ...................
1) In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome
Coronavirus 2 (SARS-CoV-2)
Xueting Yao, Fei Ye, Miao Zhang, Cheng Cui, Baoying Huang, Peihua Niu, Xu
Liu, Li Zhao, Erdan Dong, Chunli Song, Siyan Zhan, Roujian Lu, Haiyan Li,
Wenjie Tan, Dongyang Liu
Clinical Infectious Diseases, ciaa237, https://doi.org/10.1093/cid/ciaa237
2). 钟南山在临床病人观察到氯喹的作用
数据呢？
体外作用的剂量用于体内基本等于杀人。
Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than
chloroquine (EC50=5.47 μM) in vitro.
Based on PBPK models results, a loading dose of 400 mg twice daily of
hydroxychloroquine sulfate given orally, followed by a maintenance dose of
200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquinephosphate when given
500 mg twice daily 5 days in advance.
I think this is the first direct evidence to support the anti-viral effect
of chloroquine and Hydroxychloroquine.
不太理解这篇论文的逻辑在哪里。
前期有临床试验发表，剂量比这篇文章的“推荐”大很多。给予3天200mg/天；而后给
予800mg/天，重症患者给予3周，轻中症患者给予2周。研究评价了28天新型冠状病毒转阴率和5个时间点的临床症状改善。结果发现羟氯喹并不改善主要指标-28天新型冠状病毒转阴率。其次，intent-to-treat分析显示28天两组的临床症状改善没有差异。
作为一种以杀伤病原体为目标的药物，如果有效理论上肯定是剂量越大效果越好。限制因k素是剂量越大不良反应也就越重，所以要在杀伤病原和不良反应之间权衡。这篇论
文是体外实验，不包括对不良反应的考虑。如果能够提出一个推荐剂量，也应该是基于最低有效剂量作出结论。但是，临床上已经证明剂量大很多的同种药物都无法改变临床结果。这篇论文的推荐剂量当然无效。
【 在 obamaasia (ohyeah) 的大作中提到: 】
: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108130/pdf/ciaa237.pdf
: Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than
: chloroquine (EC50=5.47 μM) in vitro.
: Based on PBPK models results, a loading dose of 400 mg twice daily of
: hydroxychloroquine sulfate given orally, followed by a maintenance dose of
: 200 mg given twice daily for 4 days is recommended for SARS-CoV-2
infection,
: as it reached three times the potency of chloroquinephosphate when given : 500 mg twice daily 5 days in advance.
There is clinical evidence to support the effect of hydrocholorquine in
clinical trial.
Read carefully, 200mg/天 is much less than the recommandated dosage of the
paper,
not 大很多.
【 在 nile (nile) 的大作中提到: 】
: 不太理解这篇论文的逻辑在哪里。
: 前期有临床试验发表，剂量比这篇文章的“推荐”大很多。给予3天200mg/天；而后给
: 予800mg/天，重症患者给予3周，轻中症患者给予2周。研究评价了28天新型冠状病毒转
: 阴率和5个时间点的临床症状改善。结果发现羟氯喹并不改善主要指标-28天新型冠状病
: 毒转阴率。其次，intent-to-treat分析显示28天两组的临床症状改善没有差异。
: 作为一种以杀伤病原体为目标的药物，如果有效理论上肯定是剂量越大效果越好。限制
: 因k素是剂量越大不良反应也就越重，所以要在杀伤病原和不良反应之间权衡。这篇论
: 文是体外实验，不包括对不良反应的考虑。如果能够提出一个推荐剂量，也应该是基于
: 最低有效剂量作出结论。但是，临床上已经证明剂量大很多的同种药物都无法改变临床
: 结果。这篇论文的推荐剂量当然无效。
: ...................
发表的临床试验是200mg/天三天；而后给予800mg/天，重症患者给予3周，轻中症患者
给予2周。
这篇论文的推荐是Hydroxychloroquine sulfate 400 mg given twicedaily for 1 day, followed by 200 mg twice daily for 4 more days
你认为哪个方案的剂量大？
【 在 obamaasia (ohyeah) 的大作中提到: 】
: There is clinical evidence to support the effect of hydrocholorquine in
: clinical trial.
: Read carefully, 200mg/天 is much less than the recommandated dosage of the
: paper,
: not 大很多.
:
Very obviously. the problematic clinical trial has messed up the kinetics.
I am not sure the dosage in the clinical trial you mentioned ever reached
therapeutic plateau.
没有谁的研究是problematic.也没有谁的方案是正确标准。更不存在谁 mess up 的问
题。
上海瑞金医院的方案第一周给药是200三天加上800四天。 第二三四周是每周800x7.
北医三院的方案第一天800，第二三四五天400。第五天后停药。
如果你认为的北医的方案具备“治疗平台”，不管怎么算，上海瑞金的剂量远远在你所谓的平台之上。
【 在 obamaasia (ohyeah) 的大作中提到: 】
: Very obviously. the problematic clinical trial has messed up the kinetics.: I am not sure the dosage in the clinical trial you mentioned ever reached : therapeutic plateau.
IS this the paper you are talking about ?https://www.medrxiv.org/content/10.1101/2020.04.10.20060558v1
明明是1200 mg daily for three days. Why you say it is 200 mg for three day ?
Really no need to continue if you do not read and cite correctly.
【 在 nile (nile) 的大作中提到: 】
: 没有谁的研究是problematic.也没有谁的方案是正确标准。更不存在谁 mess up 的问
: 题。
: 上海瑞金医院的方案第一周给药是200三天加上800四天。 第二三四周是每周800x7.
: 北医三院的方案第一天800，第二三四五天400。第五天后停药。
: 如果你认为的北医的方案具备“治疗平台”，不管怎么算，上海瑞金的剂量远远在你所
: 谓的平台之上。
我是没有看原始论文。只看了论坛转发消息。
【上海交通大学医学院附属瑞金医院在medRxiv上传了一个羟氯喹治疗COVID-19多中心
open label随机临床试验的结果。研究共入组了150个住院病人，75人接受羟氯喹+标准治疗，75人只接受标准治疗作为对照组。研究给予3天200mg/天；而后给予800mg/天，
重症患者给予3周，轻中症患者给予2周。】
http://www.mitbbs.com/article_t/Military/56686739.html
这个帖子中说的研究给予3天200mg/天，是错误的。你说对了。是1200mg/天，连续三天。后面连续三周（重症）和连续两周（轻症）每天800mg。你是不是没看到? 原文就在
这里：
Interventions HCQ was administrated with a loading dose of 1, 200 mg daily
for three days followed by a maintained dose of 800 mg daily for the
remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively).
即使我被误导把1200mg误当成200mg,至少我的基本观点没有错。瑞金医院的方案比北医三院的剂量大很多。如果你认为北医三院的剂量可以称”治疗剂量平台“，那么瑞金医院的剂量远远在“治疗剂量平台”之上。但是瑞金的剂量方案仍然没有临床效果。北医三院的体外实验推荐剂量效果可想而知。
好吧，把我之前给你的问题修改一下。
发表的临床试验是1200mg/天三天；而后给予800mg/天，重症患者给予3周，轻中症患者给予2周。这篇论文的推荐是Hydroxychloroquine sulfate 400 mg given twicedaily for 1 day, followed by 200 mg twice daily for 4 more days
你认为哪个方案的剂量大？
没有谁的研究是problematic.也没有谁的方案是正确标准。更不存在谁 mess up 的问
题。
上海瑞金医院的方案第一周给药是1200三天加上800四天。 第二三四周是每周800x7.
北医三院的方案第一天800，第二三四五天400。第五天后停药。
如果你认为的北医的方案具备“治疗平台”，不管怎么算，上海瑞金的剂量远远在你所谓的平台之上。
【 在 obamaasia (ohyeah) 的大作中提到: 】
: IS this the paper you are talking about ?
: https://www.medrxiv.org/content/10.1101/2020.04.10.20060558v1
: 明明是1200 mg daily for three days. Why you say it is 200 mg for three day ?
:
: Really no need to continue if you do not read and cite correctly.
免疫抑制剂可能有助于抑制炎症，减少重症
【 在 nile (nile) 的大作中提到: 】
: 不太理解这篇论文的逻辑在哪里。
: 前期有临床试验发表，剂量比这篇文章的“推荐”大很多。给予3天200mg/天；而后给
: 予800mg/天，重症患者给予3周，轻中症患者给予2周。研究评价了28天新型冠状病毒转
: 阴率和5个时间点的临床症状改善。结果发现羟氯喹并不改善主要指标-28天新型冠状病
: 毒转阴率。其次，intent-to-treat分析显示28天两组的临床症状改善没有差异。
: 作为一种以杀伤病原体为目标的药物，如果有效理论上肯定是剂量越大效果越好。限制
: 因k素是剂量越大不良反应也就越重，所以要在杀伤病原和不良反应之间权衡。这篇论
: 文是体外实验，不包括对不良反应的考虑。如果能够提出一个推荐剂量，也应该是基于
: 最低有效剂量作出结论。但是，临床上已经证明剂量大很多的同种药物都无法改变临床
: 结果。这篇论文的推荐剂量当然无效。
: ...................
氯喹是免疫抑制剂吗？
即使你一定要说它是，这里讨论的也不是可能性。而是实验结果。
【 在 Saudi (沙武帝) 的大作中提到: 】
: 免疫抑制剂可能有助于抑制炎症，减少重症
氯喹在纽约和底特律都证明降低死亡率
钟南山也证明氯喹降低死亡率
==============================================
Risk Factors for Mortality in Patients with COVID-19 in New York City
Takahisa Mikami M.D., Hirotaka Miyashita M.D., Takayuki Yamada M.D., Matthew Harrington M.D., Daniel Steinberg M.D., Andrew Dunn M.D. & Evan Siau M.D.
Background
New York City emerged as an epicenter of the coronavirus disease 2019 (COVID-19) pandemic.
Objective
To describe the clinical characteristics and risk factors associated with
mortality in a large patient population in the USA.
Design
Retrospective cohort study.
Participants
6493 patients who had laboratory-confirmed COVID-19 with clinical outcomes
between March 13 and April 17, 2020, who were seen in one of the 8 hospitals and/or over 400 ambulatory practices in the New York City metropolitan area
Main Measures
Clinical characteristics and risk factors associated with in-hospital
mortality.
Key Results
A total of 858 of 6493 (13.2%) patients in our total cohort died: 52/2785 (1.9%) ambulatory patients and 806/3708 (21.7%) hospitalized patients. Cox
proportional hazard regression modeling showed an increased risk of in-
hospital mortality associated with age older than 50 years (hazard ratio [HR] 2.34, CI 1.47–3.71), systolic blood pressure less than 90 mmHg (HR 1.38, CI 1.06–1.80), a respiratory rate greater than 24 per min (HR 1.43, CI 1.13–1.83), peripheral oxygen saturation less than 92% (HR 2.12, CI 1.56–2.88), estimated glomerular filtration rate less than 60 mL/min/1.73m2 (HR 1.80, CI 1.60–2.02), IL-6 greater than 100 pg/mL (HR 1.50, CI 1.12–2.03), D-
dimer greater than 2 mcg/mL (HR 1.19, CI 1.02–1.39), and troponin greater
than 0.03 ng/mL (HR 1.40, CI 1.23–1.62). Decreased risk of in-hospital
mortality was associated with female sex (HR 0.84, CI 0.77–0.90), African
American race (HR 0.78 CI 0.65–0.95), and hydroxychloroquine use (HR 0.53, CI 0.41–0.67).
Conclusions
Among patients with COVID-19, older age, male sex, hypotension, tachypnea,
hypoxia, impaired renal function, elevated D-dimer, and elevated troponin
were associated with increased in-hospital mortality and hydroxychloroquine use was associated with decreased in-hospital mortality.
https://link.springer.com/article/10.1007/s11606-020-05983-z
请就本文提出的论据和结论讨论，其他问题可以另行讨论。
【 在 obamaasia (ohyeah) 的大作中提到: 】
: 氯喹在纽约和底特律都证明降低死亡率
: 钟南山也证明氯喹降低死亡率
: ==============================================
: Risk Factors for Mortality in Patients with COVID-19 in New York City
: Takahisa Mikami M.D., Hirotaka Miyashita M.D., Takayuki Yamada M.D.,
Matthew
: Harrington M.D., Daniel Steinberg M.D., Andrew Dunn M.D. & Evan Siau M.D.
: Background
: New York City emerged as an epicenter of the coronavirus disease 2019 (
COVID
: -19) pandemic.
: Objective
: ...................