HCQ, azithro +/- zinc.
Remdisivir for more severe
earlier start the better
Remdisivir for more severe
earlier start the better
Hydroxychloroquine...........
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AG
How promising are early results?
And how confident are you that we can break through FDA bureaucratic red tape if it does continue to show promise?
And how confident are you that we can break through FDA bureaucratic red tape if it does continue to show promise?
https://blogs.sciencemag.org/pipeline/archives/2020/03/19/coronavirus-some-clinical-trial-data
Promising. Though small population studied. Based on Trump's press conference, I suspect FDA approval soon.
Promising. Though small population studied. Based on Trump's press conference, I suspect FDA approval soon.
I wonder what the scale up timeline will look like for Remdisivir. I am sure they are going as fast as they can...
https://www.gilead.com/purpose/advancing-global-health/covid-19
Gilead mass manufacturing. Despite large phase III trials. Desperate times. Liver toxicity is major concern with this drug. Conundrum because transaminitis commonly seen with COVID-19 infection to start with.
Gilead mass manufacturing. Despite large phase III trials. Desperate times. Liver toxicity is major concern with this drug. Conundrum because transaminitis commonly seen with COVID-19 infection to start with.
Anyone hearing anything about an anti-inflammatory called Actemra. Seems the Chinese are seeing good results with off label use of this as well.
Marcus: what do you see as a realistic timetable to get HCQ to the front lines such that this thing is blunted for economic recovery to begin? Also prior to this when will FDA and Trump be able to calm markets w full disclosure of ability of this drug to potentially end crisis 2020.
Wouldn't you expect them to start "trialing" this in NYC? Seems to be the current hot spot and most likely place to need any boost they can get.
2wealfth Man said:
Anyone hearing anything about an anti-inflammatory called Actemra. Seems the Chinese are seeing good results with off label use of this as well.
Matches the off-label use of bats and pangolins.
2wealfth Man said:
Anyone hearing anything about an anti-inflammatory called Actemra. Seems the Chinese are seeing good results with off label use of this as well.
Yes. Tocilzumab, not approved for use in USA. It's been used where able to fight the cytokine storm that attacks the lungs. On the USA there are some folks trying Kevzara off label to see if they get similar results as it has a similar mechanism of action.
Marcus Aurelius said:
HCQ, azithro +/- zinc.
Remdisivir for more severe
earlier start the better
Unfortunately for earlier start we have to get faster testing. Once we get to the point of confirming someone the same day as the test or even within a few hours, we can start this crap as soon as possible and lessen the need for hospitalization. Once we have fewer people needing hospitalization America's back in business.
Local pharmacies in the New York area are running out. People with lupus having a hard time finding what they need.
https://www.washingtonpost.com/business/2020/03/20/hospitals-doctors-are-wiping-out-supplies-an-unproven-coronavirus-treatment/
Edited out personal attack on doctor. Looks like his Rx probably legit.
https://www.washingtonpost.com/business/2020/03/20/hospitals-doctors-are-wiping-out-supplies-an-unproven-coronavirus-treatment/
Edited out personal attack on doctor. Looks like his Rx probably legit.
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Marcus Aurelius said:
https://www.gilead.com/purpose/advancing-global-health/covid-19
Gilead mass manufacturing. Despite large phase III trials. Desperate times. Liver toxicity is major concern with this drug. Conundrum because transaminitis commonly seen with COVID-19 infection to start with.
I'll preface this by saying that there's nowhere near enough evidence yet to say definitively any of these therapies have true benefit. Most of the trials are too small or lack truly adequate controls, and the situation being what it is we have essentially lowered the bar for what constitutes good literary evidence in an effort to get some treatment modalities in the pipeline. I'm also a skeptic at heart who has seen far too much prelim excitement crushed by the weight of large scale follow up and peer review. But like you said, desperate times.
That being said many (most?) physicians are way too conservative with regards to LFT elevations and stopping meds. I don't even consider holding a medication a asymptomatic patient truly needs until the LFTs are >5x the ULN, if symptoms present or bili bumps significantly then it's usually 3x. Many LFT elevations due to certain drugs aren't true hepatotoxicity but rather altered metabolism (like with statins, in which most elevations are transient and related to upregulatiion of AST/ALT) and in the absence of symptoms or significant changes in bilirubin or INR there's no real evidence for deleterious long term effects for short term therapies. The LFT elevations with COVID are mild (1.5-3x ULN usually) so it would require a bump outside the normal range of this disease to prompt me to worry about stopping a drug. That mindset helps limit potentially confounding LFT elevations from altering care. If the ALT is 500, assuming the patient isn't developing shock liver, you can assume there's more than the primary infectious process at play.
I get called all the time about stopping rifampin or INH for an ALT of 90 and I'm just like "why would I do that?"
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KidDoc said:Holy crap I never thought of that. Very interesting.longeryak said:
Explains why south of the equator malaria areas haven't been hit.
Most flavors of malaria in most parts of the world are resistant to chloroquine now and we don't use it for prophylaxis or treatment except for travelers to select areas. And keep in mind, it's generally not native citizens of the areas taxing malaria prophylaxis anyway.
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Shumba said:
What if you are allergic to z strips? I had an allergic reaction to erythromycin as an infant (at least that is what my mother has told me for years) and I've always avoided anything n the mycin family. Any alternatives for this treatment?
I have good news for you: 95% of patient reported drug "allergies" aren't real and the ones that were in childhood usually resolve with age anyway.
Nearly all drug allergies reported by patients are dirty filthy lies.
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Infection_Ag11 said:Shumba said:
What if you are allergic to z strips? I had an allergic reaction to erythromycin as an infant (at least that is what my mother has told me for years) and I've always avoided anything n the mycin family. Any alternatives for this treatment?
I have good news for you: 95% of patient reported drug "allergies" aren't real and the ones that were in childhood usually resolve with age anyway.
Nearly all drug allergies reported by patients are dirty filthy lies.
Been saying this to patients in the ER for years. Penicillin allergies are mostly BS. Cross reactivity with cephalosporins is not a thing for the large majority of patients. Let's stop claiming iodine allergies, as well.
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Dr. Not Yet Dr. Ag said:Infection_Ag11 said:Shumba said:
What if you are allergic to z strips? I had an allergic reaction to erythromycin as an infant (at least that is what my mother has told me for years) and I've always avoided anything n the mycin family. Any alternatives for this treatment?
I have good news for you: 95% of patient reported drug "allergies" aren't real and the ones that were in childhood usually resolve with age anyway.
Nearly all drug allergies reported by patients are dirty filthy lies.
Been saying this to patients in the ER for years. Penicillin allergies are mostly BS. Cross reactivity with cephalosporins is not a thing for the large majority of patients. Let's stop claiming iodine allergies, as well.
I've never, not once, seen a patient with a true allergic contraindication to both penicillins and cephalosporins. Even a real IgE mediated response like mild hives aren't a contraindication for short term therapy if no other options, just give them benadryl.
Unless a patient gives a great history for true anaphylaxis, we either trial them in the hospital or have allergy come and test them.
Oh, and nurses need to be banned from documenting "allergies" in patient charts. I get tired head reading all the "allergies" that consist of diarrhea, malaise, headache, etc.
No material on this site is intended to be a substitute for professional medical advice, diagnosis or treatment. See full Medical Disclaimer.
I can 100% guarantee you I am allergic to the drug "Western Cedar."
The greatest argument ever made against democracy is a 5 minute conversation with the average voter.
I took quinine pills once a week before and after my trip to India over the Christmas holidays. Local Indians don't take this malaria prevention pill.
Good post SCD.scd88 said:
I took quinine pills once a week before and after my trip to India over the Christmas holidays. Local Indians don't take this malaria prevention pill.
When I worked in West Africa we were given Malarone (which is similar). Started it before you left and when you got back. There are many Anti-Malaria meds out there (see below).
I took it for many years. Hopefully it or other Anti-Malaria's are out there soon to treat infected people and stop this stuff.
Supposedly it can stop it 4-5 days
https://www.drugs.com/condition/malaria.html
We have a solid decade plus of training physicians who know how to treat the labs and not the patient. Stopping the drug if it becomes the mainstay treatment for COVID 19 for a low level LFT abnormality would be a poor choice.
The South Korea number of cases is interesting. Have they plateaued? There seems to be little movement and what movement there is seems to be improvement. Why? They have been very aggressive in testing provding good date. If a hydoxychloroquine based regimen is their preferred treatment is this the reason? A population of 50 million should have had more cases than this. Also their mortality is something in the order of 0.4-0.6% Impressive and well done so far.
The South Korea number of cases is interesting. Have they plateaued? There seems to be little movement and what movement there is seems to be improvement. Why? They have been very aggressive in testing provding good date. If a hydoxychloroquine based regimen is their preferred treatment is this the reason? A population of 50 million should have had more cases than this. Also their mortality is something in the order of 0.4-0.6% Impressive and well done so far.
No material on this site is intended to be a substitute for professional medical advice, diagnosis or treatment. See full Medical Disclaimer.
PikesPeakAg said:
We have a solid decade plus of training physicians who know how to treat the labs and not the patient. Stopping the drug if it becomes the mainstay treatment for COVID 19 for a low level LFT abnormality would be a poor choice.
The South Korea number of cases is interesting. Have they plateaued? There seems to be little movement and what movement there is seems to be improvement. Why? They have been very aggressive in testing provding good date. If a hydoxychloroquine based regimen is their preferred treatment is this the reason? A population of 50 million should have had more cases than this. Also their mortality is something in the order of 0.4-0.6% Impressive and well done so far.
Marcus or someone else who can answer...if it's not airborne why the need for N95 masks for providers for patients who aren't on ventilation, BiPaP, etc? Thanks to all.
Primary method of transmission is respiratory droplets. So it is airborne. It has been shown to last viable in air for 3 hrs. BIPAP, high flow nasal cannula O2 and nebulizers are contraindicated as they have been shown to increase aerosolization of the virus.
CDC recommending N95 mask/respirators in cases of increased aerosolization. Otherwise, standard droplet masks due to shortage.
We are still having some flu and other cases like mycoplasma where we would obviously prefer to be wearing droplet masks as well.
We are still having some flu and other cases like mycoplasma where we would obviously prefer to be wearing droplet masks as well.
I think saying it is airborne gives the wrong impression of how contagious it is.Marcus Aurelius said:
Primary method of transmission is respiratory droplets. So it is airborne. It has been shown to last viable in air for 3 hrs. BIPAP, high flow nasal cannula O2 and nebulizers are contraindicated as they have been shown to increase aerosolization of the virus.
Just like the flue or cold. If you cough and don't cover it spreads droplets but it isn't being passed through Hvac systems etc.
Marcus, any moves to harvest plasma of recovered patients as treatment method?
yes it can be spread via fomites. But it's FAR less contagious that way.
I think that's been used successfully in China. Haven't read much on it.
Be careful with the French paper that is being passed around to support use of this treatment...it has a LOT of problems....
People actively reviewing the paper HERE
Some excerpts --
People actively reviewing the paper HERE
Some excerpts --
Quote:
Exceptionally poor design of a trial: Irrelevant choice of end point. How will an earlier negative swab translate into a reduced transmission rate if the shedding occurs while in the pre-symptomatic phase? How will this help the people who need treatment most - those with respiratory failure due to severe disease? Studies need to focus on significantly modifying survival in those with the most severe disease - not excluding the patients that go on to ITU.
Quote:
I attempted to reproduce Tables 2 and 3 (R code included at the end of the post), and obtained these results:
Table 2, Day 3: reported p=0.005, calculated p=0.0136 Table 2, Day 4: reported p=0.04, calculated p=0.0780 Table 2, Day 5: reported p=0.006, calculated p=0.0148 Table 2, Day 6: reported p=0.001, calculated p=0.0019
Table 3, Day 3: reported p=0.002, calculated p=0.0019 Table 3, Day 4: reported p=0.05, calculated p=0.0429 Table 3, Day 5: reported p=0.002, calculated p=0.0025 Table 3, Day 6: reported p<0.001, calculated p=0.0005
That is, Table 3 was more or less reproduced, but Table 2 wasn't; most of my p values are around twice the ones in the preprint.
Of the 8 tests, 5 produced warnings because chisq.test() doesn't like cell values of 0 or 1. Using fisher.test() from the "stats" package got rid of the warnings and caused some of the Table 2 p values to move towards the ones in the preprint, but only one (Day 6) got close. It isn't clear to me why one would use Fisher's Exact Test here --- my understanding is that it is not sufficient to invoke per-cell numbers of less than 6, as many authors seem to do, but I don't have a reference to hand for that.
Quote:
The study started with 26 patients who received Hydroxychloroquine (with or without Azithromycin), and 16 controls. Viral presence/absence at day 6 were considered the primary endpoint.
Data from only 20 treated patients are given. The data for these 20 patients looks incredibly nice; especially the patients who were given both medications all recovered very fast.
The other 6 treated patients dropped out of the study. Of these, 3 were transferred to the intensive care unit (presumably because they got sicker) and 1 died. The other two patients were either too nauseous and stopped the medication, or left the hospital (which might be a sign they felt much better).
Quote:
Here is another question.
The protocol for the treatment was approved by the French National Agency for Drug Safety on March 5th 2020. It was approved by the French Ethic Committee on March 6th 2020. The paper states that patients were followed up until day 14. The paper was published on March 20th.
Quote:
I extracted data from both figures and reconstructed sample sizes from Figure (1) ; proportions are shown; multiplied by the correct sample size, one should find integers. I found n=13 for the HQL-only treatment, and n=7 for the HQL+AZT treatment. The preprint however reports n=14 and n=6 respectively. What happened to the patient who was treated HQL+AZT in the talk and HQL-only in the preprint?
Quote:
To follow up the question above, how certain the authors are the negative results they have got are actually negative but not the false negative? This control group seemingly have high false negative results. Have you considered validating the PCR tests?
Agree. It's no "TIMI" level RPCT. But given the context, and relative safety of both drugs, I think it's worthy of using.
No doubt, and I would ask for it if I had to go to the ER right now with COVID-19, but the public needs to understand we are still in the testing phase and it is still far from a "cure", unlike what some public figures would like you to believe
That seems pretty shady to leave that info out of the summary.Ranger222 said:
Be careful with the French paper that is being passed around to support use of this treatment...it has a LOT of problems....
People actively reviewing the paper HERE
Some excerpts --Quote:
Exceptionally poor design of a trial: Irrelevant choice of end point. How will an earlier negative swab translate into a reduced transmission rate if the shedding occurs while in the pre-symptomatic phase? How will this help the people who need treatment most - those with respiratory failure due to severe disease? Studies need to focus on significantly modifying survival in those with the most severe disease - not excluding the patients that go on to ITU.Quote:
I attempted to reproduce Tables 2 and 3 (R code included at the end of the post), and obtained these results:
Table 2, Day 3: reported p=0.005, calculated p=0.0136 Table 2, Day 4: reported p=0.04, calculated p=0.0780 Table 2, Day 5: reported p=0.006, calculated p=0.0148 Table 2, Day 6: reported p=0.001, calculated p=0.0019
Table 3, Day 3: reported p=0.002, calculated p=0.0019 Table 3, Day 4: reported p=0.05, calculated p=0.0429 Table 3, Day 5: reported p=0.002, calculated p=0.0025 Table 3, Day 6: reported p<0.001, calculated p=0.0005
That is, Table 3 was more or less reproduced, but Table 2 wasn't; most of my p values are around twice the ones in the preprint.
Of the 8 tests, 5 produced warnings because chisq.test() doesn't like cell values of 0 or 1. Using fisher.test() from the "stats" package got rid of the warnings and caused some of the Table 2 p values to move towards the ones in the preprint, but only one (Day 6) got close. It isn't clear to me why one would use Fisher's Exact Test here --- my understanding is that it is not sufficient to invoke per-cell numbers of less than 6, as many authors seem to do, but I don't have a reference to hand for that.Quote:
The study started with 26 patients who received Hydroxychloroquine (with or without Azithromycin), and 16 controls. Viral presence/absence at day 6 were considered the primary endpoint.
Data from only 20 treated patients are given. The data for these 20 patients looks incredibly nice; especially the patients who were given both medications all recovered very fast.
The other 6 treated patients dropped out of the study. Of these, 3 were transferred to the intensive care unit (presumably because they got sicker) and 1 died. The other two patients were either too nauseous and stopped the medication, or left the hospital (which might be a sign they felt much better).Quote:
Here is another question.
The protocol for the treatment was approved by the French National Agency for Drug Safety on March 5th 2020. It was approved by the French Ethic Committee on March 6th 2020. The paper states that patients were followed up until day 14. The paper was published on March 20th.Quote:
I extracted data from both figures and reconstructed sample sizes from Figure (1) ; proportions are shown; multiplied by the correct sample size, one should find integers. I found n=13 for the HQL-only treatment, and n=7 for the HQL+AZT treatment. The preprint however reports n=14 and n=6 respectively. What happened to the patient who was treated HQL+AZT in the talk and HQL-only in the preprint?Quote:
To follow up the question above, how certain the authors are the negative results they have got are actually negative but not the false negative? This control group seemingly have high false negative results. Have you considered validating the PCR tests?
"According to the CDC, a health care worker taking care of COVID-19 suspected or confirmed patients should wear gloves, gowns surgical masks and face shield, which provides adequate protection against droplet transmission.
N95s should be used for critical patients during intermittent or continuous aerosol-generating procedures."
Then why is this the current recommendation from the hospital I am affiliated with. I must say I do not do inpatient medicine....
N95s should be used for critical patients during intermittent or continuous aerosol-generating procedures."
Then why is this the current recommendation from the hospital I am affiliated with. I must say I do not do inpatient medicine....