Remdesivir III
The first Covid 19 case diagnosed in New Jersey
Around 3 a.m. on March 10, Balani arrived at the hospital. The medicine had come in, and she did not want to wait until the morning to administer it. With Balani in the room, a nurse woke Cai up so that he could sign the legal papers. Soon after, he was hooked up, intravenously, to the drug.
The next day Cai’s fever, which he’d had for at least nine days, finally broke. Even before he received the remdesivir, his oxygen levels started to stabilize. Now they indicated he was on the mend. He was still so weak in the following days that he could barely speak without exhaustion; every time he tried, he was racked by coughs. But the progress was steady
Chloroquine also ran, It was used for a day while the Remdesivir was in the mail,
Cai’s boss, Dr. George Hall, also made a call, not long after Huang spoke to the infectious-disease doctor on call. He spoke with another doctor on Cai’s caregiving team, a hospitalist named Danit Arad.
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Hall explained …that the Chinese National Health Commission had just published the seventh edition of guidelines on how to treat coronavirus. It was true that they were based more on clinical experience than on published studies, but he urged Arad to follow some of its protocols, which included prescribing two drugs that were commonly given to patients in China soon after they showed symptoms like shortness of breath: chloroquine, an antiviral drug once used to treat malaria, and Kaletra, another antiviral that had once been used to treat H.I.V.
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at the time that neither drug had been through extensive clinical trials or had F.D.A. approval. She listened patiently to Hall and expressed her concern that his suggestions did not conform to standard medical procedure or C.D.C. guidelines.
Hall understood the need for evidence-based medicine as well as she did, he told her. But this was life and death.
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That day, Cai was given chloroquine and Kaletra
I do not understand the need for “evidence-based medicine” or rather I do not understand how the phrase is used by doctors. There is no evidence that Covid 19 patients (without heart disease) do better without Chloroquine. I learn that “evidence based medicine” does not imply choosing the therapy that a fair balance of evidence suggests is best for the patient. Pharmaceuticals are presumed guilty until proven safe and effective. The evidence is treated as evidence in a criminal trial with the burden of proof on the pharmaceutical.
I have no idea what “standard medical procedure” might mean in the context of Covid 19. it appears that as soon as a new disease is discovered, there is a standard procedure for treating it, which can’t be based on data or evidence.
The story has a happy ending, but it is not reassuring. It also doesn’t surprise me.
Robert:
It baffles me too. If you come across someone who is bleeding badly, you do not preface your care by asking if they have HIV, You apply direct pressure to stop the bleeding or a tourniquet as another option.
Adapt, improvise and overcome using your tool box of remedies. Nice post.
Bill
And how are yoy Robert by the way. The radio silence from quarantine was worrying.
Gilead is using its 1.5 million doses remdesivir right now on compassionate care and phase III trials in all sorts of places. I just watched an interview with a doctor at Emory in Atlanta who has 400 patients on remdesivir. Gilead also plans to produce another 1 million doses by the end of the year. The thing is that it takes about 10 doses per patient so this will only cover 250 thousand patients assuming this treatment is effective. Hopefully we can find a way that other biopharma manufacturers to gear up production ASAP.
https://finance.yahoo.com/quote/GILD/community?p=GILD
The conversation board for Gilead over at yahoo finance has a lot of discussion on remdesivir. This morning the pre-market trading has pushed the share price above $80.
The idea of “evidence-based medicine” is that the practice is buttressed by evidence and not simply tradition.
Drugs and medical procedures don’t have Constitutional protection. The long history of quackery is a testament to the harm, direct and indirect, that unproven drugs and procedures can have.
In the specific case of hydroxychloroquine, decades of experience teach us that it is relatively benign when used at the proper dose, especially over short duration treatments. So even if it is ineffectual, which could well be the case (Donald Trump and your anecdote nonwithstanding), it wouldn’t do harm to give it off-label in a compassionate care setting. The one important downside if widespread adoption of an ineffective drug results in shortages for patients in which hydroxychloroquine as a proven effect. In that case, redirection for COVID-19 is not benign.
I don’t know, it seems to me that some hospitals are using hydroxychloroquine when desperate.
“Either way, his infomercials for this drug are not without consequences, as The New York Times found:
‘While many hospitals have chosen to use hydroxychloroquine in a desperate attempt to treat dying patients who have few other options, others have noted that it carries serious risks. In particular, the drug can cause a heart arrhythmia that can lead to cardiac arrest.
Dr. Megan L. Ranney, an emergency physician at Brown University in Rhode Island, said in an interview on Sunday night that she had never seen an elected official advertise a miracle cure the way Mr. Trump has.
“There are side effects to hydroxychloroquine,” Dr. Ranney said. “It causes psychiatric symptoms, cardiac problems and a host of other bad side effects.”’
That is to say—despite the president’s leading question—that you may, in fact, have something to lose by taking this thing. (Meanwhile, lupus patients certainly have something to lose. The drug is approved for them, and now there’s a run on it.) But now the whole right-wing grift-o-rama machine is oiled up and humming. The lackeys on State TV are peddling it in every segment they can, because he’s peddling it and their job is to peddle him. Yes, you’re supposed to believe Steve Doocy when he says this guy is doing a great job and you should ingest whatever he tells you to.”
https://www.esquire.com/news-politics/politics/a32050939/trump-hydroxychloroquine-coronavirus-miracle-cure/
A little more on this production issue as well as my part III on transfer pricing:
https://econospeak.blogspot.com/2020/04/remdesivir-and-transfer-pricing-iii.html
““There are side effects to hydroxychloroquine,” Dr. Ranney said. “It causes psychiatric symptoms, cardiac problems and a host of other bad side effects.”’”
There are side effects to COVID-19. It causes death.
The are side effects for every drug. In the case of hydroxychlorquine, you need to pay attention to the duration of treatment. If you are being treated for COVID-19, the duration will be short, so those side effects are unlikely. Let’s not play word games with people’s lives, m’kay?
Let say someone decides to rely on this malaria treatment thinking it works but it does not. That person may have had another option he choose not to try because of the false hope offered by someone who has zero clue what he is babbling about. Then the side effect would be this person dies from COVID19. And is no word game.
Of course there are side effects for every drug. I see no proof the Doctor is playing word games, and certainly not with people’s lives.
They don’t know if it helps, or if it will work.
Quite frankly there is only that small study from France, and I would pay absolutely no attention to what China reports. They are the most guilty party in this whole thing, as their reporting was a whitewash that delayed the worldwide response.
Covid 19 works by breaking down the lung tissue leading to a filling of the lungs with fluid, thus O2 does not get absorbed readily. Pneumonia. If the body can get the virus before it has caused damage to the extent that life can not continue, then you made it out. Ventilators push O2 through the fluid. It’s an artificial boost to the system to buy time for the immune system to do its thing.
This is most significant in the article: Even before he received the remdesivir, his oxygen levels started to stabilize.
If the O2 was stabilizing, then the person was on the up side. That the fever broke after the med means nothing unless you know others that have had their O2 stabilize and still died. Then you could theorize that the med helped such that the virus was further killed/deactivated as evidenced by the break in the fever within 24hrs of giving the med.
Next step, find the cases where the o2 was stabilizing prior to the med, who then had their fever break after the med and lived. Also, find those who had their O2 stabilize prior to the med, were given the med and died.
Evidence based medicine.
This is where our interconnected medical record systems can come into play and in a way an in real time study on the effects of the medicine. Of course, this depends on how well the people are entering the patient info in the record. Under such stressful situations as we are in, we may not be getting as complete a record as we would have in a true blinded drug trial.
I have recently read that studies looking at past pandemics, there is major under counting of the death rate during the time of the pandemic and that only much latter when numbers are crunched do we know the full extent. Thus, record keeping is not the best at the time of the crisis.
Daniel:
To your last point, I read that also. We still do not know how big the infestation is due to our low testing numeric in the beginning and even now.
Daniel – well said. That is why Gilead is doing a lot of phase III trials on their potential treatment. In other words, the very competent scientists at Gilead are working on evidence based medicine. That is a lot more than can be said about Trump, Navarro, and even RUDY as they hype those ant-malaria drug. A better term for what there three stooges are doing is snake oil salesmen promoting junk science.
Drug development is hard. Chloroquine killed HIV in vitro, but when they tried it in people it increased the viral load. The only way to find out what works is through controlled trials with N>>1.
Then, it’s all Bayesian statistics. Chlorqouine can cause potentially fatal heart problems and it can blind you. We only want to use it if it is effective enough to balance out these risks.
Sure, if someone is MFC, measure for coffin, you might want to try just about anything, but why chloroquine? Why not an artemisinin or pepto-bismol or gleevec? Based on what we know, they are just as likely to help.
Kalesburg:
I was in U of M hospital with a bout of ITP. For the record, my platelets disappeared for the second time of my life and this time almost 40 years later. Prednisone did not work and neither did a transfusion of platelets. I was a part of the walking dead. One bump and I would have bled out. A blood sucker came in to change a pick. He did not get the cap on correctly and my blood flowed like water. A whoa moment for him. I walked all over that hospital rather than sit in my room. The old hematologist would get anxious if I was walking around and he would be an asshole if I was reading on my laptop. Three weeks of confined and on steroids.
They finally got permission to use Rituxan on me, the second most expensive cancer drug after Humira. Two doses of Claritin plus some other stuff and I was dripped a litre on Rituxan. There are serious side effects to Rituxan also; but, what were my alternatives??? NONE, other than wait.
No Remdesivir available, so you go with the next best thing or die. If I am in such a situation, I will take the hydroxychloroquine early on when it has the best effect.
“Covid 19 works by breaking down the lung tissue leading to a filling of the lungs with fluid, thus O2 does not get absorbed readily.”
In many of the fatal cases, it appears that SARS-CoV-2 kills by provoking a cytokine storm. This contributes to the lung edema. IOW, the patient’s own immune response kills him. There was an early claim out of China that treatment with an IL-6 antagonist can blunt this reaction, although I haven’t seen it discussed since.
Recent article in Medscape: https://www.medscape.com/viewarticle/928236#vp_2 “Is Protocol-Driven COVID-19 Ventilation Doing More Harm Than Good?”
1. Reverse hypoxemia through an increase in FiO2 to a level at which the Type L patient responds well, particularly for Type L patients who are not experiencing dyspnea.
2. In Type L patients with dyspnea, try noninvasive options such as high-flow nasal cannula, continuous positive airway pressure, or noninvasive ventilation, and be sure to measure inspiratory esophageal pressure using esophageal manometry or surrogate measures. In intubated patients, determine P0.1 and P occlusion. High PEEP may decrease pleural pressure swings “and stop the vicious cycle that exacerbates lung injury,” but may be associated with high failure rates and delayed intubation.
3. Intubate as soon as possible for esophageal pressure swings that increase from 5-10 cmH2O to above 15 cmH2O, which marks a transition from Type L to Type H phenotype and represents the level at which lung injury risk increases.
4. For intubated and deeply sedated Type L patients who are hypercapnic, ventilate with volumes greater than 6 mL/kg up to 8-9 mL/kg as this high compliance results in tolerable strain without risk of ventilator-associated lung injury. Prone positioning should be used only as a rescue maneuver. Reduce PEEP to 8-10 cmH2O, given that the recruitability is low and the risk of hemodynamic failure increases at higher levels. Early intubation may avert the transition to Type H phenotype.
More in the article.
Joel, yes I should have mentioned it, but was keeping it simple.