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MarkHoofnagle's profile
Mark Hoofnagle
Mark Hoofnagle
Mark Hoofnagle
@MarkHoofnagle

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Mark Hoofnagle

@MarkHoofnagle

Trauma/Critical Care/Acute Care Surgeon. MD/PhD. FACS. UVa/UMD/UPenn. Asst Professor of Surgery at Wash U. Blocking is curating.

St Louis, MO
surgery.wustl.edu/people/mark-ho…
Joined March 2012

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    1. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

      Unfortunately, by the time you are symptomatic with a virus, you are usually already high/peak viral load. So, when you give an antiviral to someone who is already ill, the damage from the virus is largely done. It’s there in big numbers and in the cells.

      17 replies 154 retweets 864 likes
      Show this thread
    2. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

      Consistent with this, the Lancet paper on the remdesivir trial in China shows no impact on viral load clinically.pic.twitter.com/ITifhKB8w2

      14 replies 221 retweets 925 likes
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    3. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

      Pick your metaphor. The cat is out of the bag. The damage is done. At this point the host response to virus is activated, and your body is suppressing replication through a variety of mechanisms (which also make you feel terrible).

      12 replies 78 retweets 669 likes
      Show this thread
    4. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

      So how could inhibiting RDRP after the fact help? The answer is, it probably doesnt. It certainly didn’t in this trial - no difference, not even a trend in mortality, but in subgroup analysis maybe shortened disease duration in early/mild disease.https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext …

      8 replies 119 retweets 651 likes
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    5. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

      Now, critics of stupid drugs that should never have been stockpiled by govts say, “sounds like Tamiflu!” Yes. This is the same as Tamiflu, which also maybe shortens flu by a day, but otherwise is a largely useless antiviral (and actually harmful with bad side effect profile).

      7 replies 148 retweets 967 likes
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    6. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

      Fortunately, side effects of remdesivir did not seem severe in this trial with only about 3x as many patients stopping than placebo, some rashes, nothing life threatening.

      5 replies 59 retweets 499 likes
      Show this thread
    7. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

      Where do the Shenanigans come in? Well, remember how maybe this Chinese trial showed a shortened course in a subset of patients? Like tamiflu? But didn’t change mortality? Well a month ago the NIAID trial changed their endpoints to remove death and instead look at dz duration.

      8 replies 138 retweets 798 likes
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    9. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

      This is like declaring a race and then when you realize you’re not going to win, declaring the destination was actually wherever you are standing at the moment.

      6 replies 124 retweets 1,003 likes
      Show this thread
    10. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

      Then, even more fishy, *the same day* as this Lancet trial is release, Gilead and NIAID claim a “positive trial” and they’ve “shortened the course of the disease significantly”. Notably, the mortality benefit did not reach significance.

      11 replies 133 retweets 789 likes
      Show this thread
      Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

      By the end of the day, reports that FDA is going to emergently approve remdesivir for treatment of COVID. Gilead gets what they want. No one will want to be in a control arm in further trials and they will argue all future trials must be noninferiority.

      8:20 AM - 1 May 2020
      • 135 Retweets
      • 747 Likes
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      9 replies 135 retweets 747 likes
        1. New conversation
        2. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

          Before we have the answer whether this drug actually changes anyone’s destiny, it’s going to become the gold standard therapy. We will likely now never know if (the unlikely possibility) it changes mortality.

          3 replies 121 retweets 698 likes
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        3. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

          Absolute genius. You have to salute them. On the day a negative trial of their drug is reported, based on a press release they took over the news cycle, and with some midstream edits to their endpoints their now “positive” trial wins them FDA approval and a halted trial.

          8 replies 221 retweets 956 likes
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        4. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

          It’s an infusion, once symptomatic, you need an admission, a test, etc., really even symptoms are probably too late a goal for such a therapy to work. Prophylaxis (like Gilead’s Truvada/PreP would be better - but unworkable in its current form.

          9 replies 73 retweets 532 likes
          Show this thread
        5. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020

          Either way, a big win for Gilead, but I’m unimpressed with any if the evidence presented so far that this is a game changer.

          67 replies 124 retweets 1,011 likes
          Show this thread
        6. End of conversation
        1. Colby White‏ @pianospike 1 May 2020
          Replying to @MarkHoofnagle

          Aren't there ongoing clinical trials that will give us more information as to its potential effectiveness?

          0 replies 0 retweets 0 likes
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        2. Massena1‏ @Massena1 1 May 2020
          Replying to @MarkHoofnagle

          You're really bumming me out w/this thread. I'm not a science person. Is there anything you've seen reported that you ARE hopeful about to treat/prevent Covid 19?

          1 reply 0 retweets 0 likes
        3. Mark Hoofnagle‏ @MarkHoofnagle 1 May 2020
          Replying to @Massena1

          No. If anything we persistently are going in the wrong directions, have not ramped testing and tracing, and have schizo leadership that, if anything, appear hell bent on killing us by stopping lockdown too soon and pursuing only the answers they want to hear.

          2 replies 0 retweets 2 likes
        4. Show replies
        1. Jeanne Sommerfeld‏ @mjsommerfeld 1 May 2020
          Replying to @MarkHoofnagle

          It changes the destiny and wealth of Gilead

          0 replies 0 retweets 0 likes
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        2. Félix Balazard‏ @felbalazard 2 May 2020
          Replying to @MarkHoofnagle

          That's overlooking the other trials that already have been studying the drug. We will be able to do a meta analysis to have better estimates. Also Gilead has made commendable commitments to make the drug affordable

          1 reply 0 retweets 0 likes
        3. Félix Balazard‏ @felbalazard 2 May 2020
          Replying to @felbalazard @MarkHoofnagle

          The time to recovery endpoint is quite relevant when you're in a pandemic situation and your hospitals threaten to be overrun

          0 replies 0 retweets 1 like
        4. End of conversation

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