Cancel Order? Because of Corona Virus Fallout?
06-07-2020, 06:40 PM
#286
It doesn’t hurt, and may work. Just be careful to not overdose on D. We cant give medical advice over the internet as you know.
06-07-2020, 06:43 PM
#287
The 4600 patient UK RECOVERY study had a second randomization to toculizumide or not in the control if CRP > 75. HCQ lowers inflammatory markers like CRP, no toci likely not given, since CRP likely less than 75 in a lot of HCQ treated patients. We need to see that data before making any broad declarations.
That being said, it’s not just about HCQ. It’s about a theory of disease that explains that a lot of stuff may work. Obviously we need to do the trials as we are doing. The point is that the physicians and scientists are on it, and there is hope.
That being said, it’s not just about HCQ. It’s about a theory of disease that explains that a lot of stuff may work. Obviously we need to do the trials as we are doing. The point is that the physicians and scientists are on it, and there is hope.
Are you making assumptions that HCQ is dropping CRP levels or is this backed by data?
I'm more impressed by the potential for biologics and small molecule therapy. Cytokine release syndromes have been treated by IL-6 and IL-1 inhibition and there is a theoretical role for JAK/STAT inhibitors. So much of this disease seems to present like decompensated systemic vasculitis and there may be lessons to be learned in how we treat these types of conditions and apply them to COVID19.
Incidentally, I have a number of COVID19 patients on biologics who did remarkably well, despite significant comorbidities (ie diabetes), and they fully recovered. This is anecdotal of course, like the NY data indicating the same experience, but I find it compelling.
06-07-2020, 06:56 PM
#288
Banned
Have you guys seen a difference in outcomes for Type 1 diabetics compared to Type 2s? All of the stories I’ve read about this virus just mention “diabetes.” I’m wondering if a Type 1 diabetic with good blood sugar control would really have a worse outcome than a non-diabetic.
06-07-2020, 08:01 PM
#289
No worries, dude. Sorry for snapping back.
At this stage of the game, I want to see meaningful clinical outcome measures from an RCT vs studies reporting CT values. I have no axe to grind about HCQ -- I write thousands of prescriptions for it. The drug is very safe and has an exceedingly low toxicity profile. It would be the ideal drug. But I'm waiting to see real clinical data. And yes, I'm a rheumatologist in the south -- we use HCQ for numerous autoimmune conditions, not just SLE. India has opened up exportation, which makes a real difference in the supply and was probably the biggest bottleneck. Yet, even then, we still deal with rationed refills and numerous PA requests. Bottleneck after bottleneck. It is getting better, though.
Are you making assumptions that HCQ is dropping CRP levels or is this backed by data?
I'm more impressed by the potential for biologics and small molecule therapy. Cytokine release syndromes have been treated by IL-6 and IL-1 inhibition and there is a theoretical role for JAK/STAT inhibitors. So much of this disease seems to present like decompensated systemic vasculitis and there may be lessons to be learned in how we treat these types of conditions and apply them to COVID19.
Incidentally, I have a number of COVID19 patients on biologics who did remarkably well, despite significant comorbidities (ie diabetes), and they fully recovered. This is anecdotal of course, like the NY data indicating the same experience, but I find it compelling.
At this stage of the game, I want to see meaningful clinical outcome measures from an RCT vs studies reporting CT values. I have no axe to grind about HCQ -- I write thousands of prescriptions for it. The drug is very safe and has an exceedingly low toxicity profile. It would be the ideal drug. But I'm waiting to see real clinical data. And yes, I'm a rheumatologist in the south -- we use HCQ for numerous autoimmune conditions, not just SLE. India has opened up exportation, which makes a real difference in the supply and was probably the biggest bottleneck. Yet, even then, we still deal with rationed refills and numerous PA requests. Bottleneck after bottleneck. It is getting better, though.
Are you making assumptions that HCQ is dropping CRP levels or is this backed by data?
I'm more impressed by the potential for biologics and small molecule therapy. Cytokine release syndromes have been treated by IL-6 and IL-1 inhibition and there is a theoretical role for JAK/STAT inhibitors. So much of this disease seems to present like decompensated systemic vasculitis and there may be lessons to be learned in how we treat these types of conditions and apply them to COVID19.
Incidentally, I have a number of COVID19 patients on biologics who did remarkably well, despite significant comorbidities (ie diabetes), and they fully recovered. This is anecdotal of course, like the NY data indicating the same experience, but I find it compelling.
I do think that what is happening is that the dendritic cell is being infected by the virus, and going into a stress autophagy response that the virus then uses to complete its lifecycle. Anything that interrupts this stress response may work. Additionally, at about day 7-8, if you don't clear the virus, go can get a substantial and in some cases overwhelming neutralizing antibody response which can cause cytokine storm. Happens in monkeys infected with SARS. Biologics can act on both this inflammatory response as well as the dendritic cell. A lot of stuff out there inhibits cellular autophagy, so it may work.
Someone should report on people taking biologics and their response to COVID infection.
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kwikit356 (06-07-2020)
06-07-2020, 08:03 PM
#290
Have you guys seen a difference in outcomes for Type 1 diabetics compared to Type 2s? All of the stories I’ve read about this virus just mention “diabetes.” I’m wondering if a Type 1 diabetic with good blood sugar control would really have a worse outcome than a non-diabetic.
https://www.sciencedirect.com/scienc...50413120302382
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kwikit356 (06-07-2020)
06-07-2020, 08:06 PM
#291
I too am irritated by the whole HCQ mess. It either works for COVID or it doesn't. We test it in a well controlled RCT to find out one way or the other. It became way to political, with everyone rooting for one side or the other. This isn't a political game, it is medicine and people's lives. I am saddened by people with SLE not getting the drug and flaring. Hopefully they got their scripts filled and are OK now.
I do think that what is happening is that the dendritic cell is being infected by the virus, and going into a stress autophagy response that the virus then uses to complete its lifecycle. Anything that interrupts this stress response may work. Additionally, at about day 7-8, if you don't clear the virus, go can get a substantial and in some cases overwhelming neutralizing antibody response which can cause cytokine storm. Happens in monkeys infected with SARS. Biologics can act on both this inflammatory response as well as the dendritic cell. A lot of stuff out there inhibits cellular autophagy, so it may work.
Someone should report on people taking biologics and their response to COVID infection.
I do think that what is happening is that the dendritic cell is being infected by the virus, and going into a stress autophagy response that the virus then uses to complete its lifecycle. Anything that interrupts this stress response may work. Additionally, at about day 7-8, if you don't clear the virus, go can get a substantial and in some cases overwhelming neutralizing antibody response which can cause cytokine storm. Happens in monkeys infected with SARS. Biologics can act on both this inflammatory response as well as the dendritic cell. A lot of stuff out there inhibits cellular autophagy, so it may work.
Someone should report on people taking biologics and their response to COVID infection.
Also, there are much cheaper markers of cytokine storm and death than IL-6. https://www.nature.com/articles/s42256-020-0180-7
Sorry, Porsche guys for hijacking this thread! I'll stop now and go drive mine!
06-07-2020, 08:12 PM
#292
Your point being? If your hospitalized COVID 19 patient has a fever of 102, is on low flow oxygen (say 2-3 liters/min), and could tip over that night into the ICU, what would you do? Try to call the FDA and get remdesivir by compassionate use, knowing it would take at least 24-48 hours possibly, and with supplies limited and likely next to impossible to get? Wring your hands and worry about offending someone by doing something that the NY Times says tonight on their front page is "unscientific?" Or give hydroxychloroquine 400 mg (2 pills) orally immediately, with 400-600 mg (2-3 pills daily for 3-4 days after that), for a total cost of $10 and low risk of any side effects (do an EKG do be sure of no long QT)? What is the darn downside risk? What do you have to lose, even if it in the end it may not work? At least you left nothing on the table--and that is what we owe our patients.
This is what docs right now are dealing with EVERY SINGLE HOUR (sorry for the caps, but I am worked up, and I know I'm not supposed to cuss) in wards in downtown NYC. Guidelines in several countries suggest its use for exactly the patient above.
The trials will come out, hopefully shortly, and be either positive or negative, or in between (how's that for clarity
). This drug is so cheap and so relatively non-toxic it's a no brainer unless the trials are dead negative.
Prophylaxis--meaning that the drug can work in asymptomatic people to block acquisition of the virus or reduce viral load in airway secretions to reduce or prevent transmission? Preclinical modeling suggests that a single 400 mg dose (two pills, $2) weekly can generate enough HCQ in the lungs to reduce viral load for several days to a week. It doesn't have to be 100% reduction of viral load, and not 100% of people have to take it--just enough to reduce transmission below an R0 < 1, and this whole mess goes away. Randomized controlled trials are ongoing in health care workers exposed to COVID 19, as well as family members of COVID 19 positive patients living in the same house.
I think with the potential catastrophic damage to the economy looming with each consecutive day of lockdown, the pressure will build to try something like this on a large scale, perhaps without waiting for the trials to be complete. That, my friends, is the true endgame. Do we roll the dice with incomplete data? Or do we continue to wait in total lockdown for a fuller dataset (the proper scientific way to do it) and tank our way of life, possibly for a long time?
I for one would at least want to see data from a larger controlled randomized population than what we have right now (perhaps 100-500 patients or unaffected people). But I for one would not want to wait for more than another few weeks of lockdown, with perhaps a better idea of the shape of the epidemic to guide me.
That's my opinion, ranting on a Porsche 992 site (probably not the right venue), and I apologize. I hope beyond hope that we don't have to make these decisions in the absence of evidence, but events may force us to.
This is what docs right now are dealing with EVERY SINGLE HOUR (sorry for the caps, but I am worked up, and I know I'm not supposed to cuss) in wards in downtown NYC. Guidelines in several countries suggest its use for exactly the patient above.
The trials will come out, hopefully shortly, and be either positive or negative, or in between (how's that for clarity
). This drug is so cheap and so relatively non-toxic it's a no brainer unless the trials are dead negative.Prophylaxis--meaning that the drug can work in asymptomatic people to block acquisition of the virus or reduce viral load in airway secretions to reduce or prevent transmission? Preclinical modeling suggests that a single 400 mg dose (two pills, $2) weekly can generate enough HCQ in the lungs to reduce viral load for several days to a week. It doesn't have to be 100% reduction of viral load, and not 100% of people have to take it--just enough to reduce transmission below an R0 < 1, and this whole mess goes away. Randomized controlled trials are ongoing in health care workers exposed to COVID 19, as well as family members of COVID 19 positive patients living in the same house.
I think with the potential catastrophic damage to the economy looming with each consecutive day of lockdown, the pressure will build to try something like this on a large scale, perhaps without waiting for the trials to be complete. That, my friends, is the true endgame. Do we roll the dice with incomplete data? Or do we continue to wait in total lockdown for a fuller dataset (the proper scientific way to do it) and tank our way of life, possibly for a long time?
I for one would at least want to see data from a larger controlled randomized population than what we have right now (perhaps 100-500 patients or unaffected people). But I for one would not want to wait for more than another few weeks of lockdown, with perhaps a better idea of the shape of the epidemic to guide me.
That's my opinion, ranting on a Porsche 992 site (probably not the right venue), and I apologize. I hope beyond hope that we don't have to make these decisions in the absence of evidence, but events may force us to.
https://www.nejm.org/doi/full/10.1056/NEJMoa2012410
CONCLUSIONS
In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.)
06-07-2020, 08:18 PM
#293
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Forgot this reference. HCQ drops IL-6 in this study. https://www.medrxiv.org/content/10.1....27.20073379v1
Also, there are much cheaper markers of cytokine storm and death than IL-6. https://www.nature.com/articles/s42256-020-0180-7
Sorry, Porsche guys for hijacking this thread! I'll stop now and go drive mine!
Also, there are much cheaper markers of cytokine storm and death than IL-6. https://www.nature.com/articles/s42256-020-0180-7
Sorry, Porsche guys for hijacking this thread! I'll stop now and go drive mine!
06-07-2020, 09:14 PM
#294
I too am irritated by the whole HCQ mess. It either works for COVID or it doesn't. We test it in a well controlled RCT to find out one way or the other. There may be subgroups that benefit. It became way too political, with everyone rooting for one side or the other. This isn't a political game, it is medicine and people's lives. I am saddened by people with SLE not getting the drug and flaring. Hopefully they got their scripts filled and are OK now.
I do think that what is happening is that the dendritic cell is being infected by the virus, and going into a stress autophagy response that the virus then uses to complete its lifecycle. Anything that interrupts this stress response may work. Additionally, at about day 7-8, if you don't clear the virus, go can get a substantial and in some cases overwhelming neutralizing antibody response which can cause cytokine storm. Happens in monkeys infected with SARS. Biologics can act on both this inflammatory response as well as the dendritic cell. A lot of stuff out there inhibits cellular autophagy, so it may work.
Someone should report on people taking biologics and their response to COVID infection.
I do think that what is happening is that the dendritic cell is being infected by the virus, and going into a stress autophagy response that the virus then uses to complete its lifecycle. Anything that interrupts this stress response may work. Additionally, at about day 7-8, if you don't clear the virus, go can get a substantial and in some cases overwhelming neutralizing antibody response which can cause cytokine storm. Happens in monkeys infected with SARS. Biologics can act on both this inflammatory response as well as the dendritic cell. A lot of stuff out there inhibits cellular autophagy, so it may work.
Someone should report on people taking biologics and their response to COVID infection.
Regarding biologics - there has been a small case study exploring this question. Definitely not conclusive data, but it's interesting. ACR guidelines now allow RA patients to remain on Tocilizumab if they become infected w/COVID19.
https://www.nejm.org/doi/full/10.1056/NEJMc2009567
06-08-2020, 01:55 AM
#295
In March you claimed HQC on its own reduced viral without any evidence and it’s been thoroughly debunked.
https://www.nejm.org/doi/full/10.1056/NEJMoa2012410
https://www.nejm.org/doi/full/10.1056/NEJMoa2012410
CONCLUSIONS
In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.)In terms of the viral load stuff, if you read carefully my statement from two months ago, I said reduction in viral load did not have to be 100% for pre-exposure HCQ prophylaxis to work. in fact, in an Indian study it does http://www.ijmr.org.in/preprintarticle.asp?id=285520;type=0 after six weeks of 400 mg of HCQ weekly.
As early therapy of symptomatic patients with COVID like illness in Brazil, HCQ reduces hospitalizations. https://pgibertie.files.wordpress.co...ript-final.pdf
OK, time to go now. I'm not shilling HCQ here, just so you know. I'm just saying there's a decent theory of the disease, and possibly lots of things that can work.
This gives people hope that there is an end in sight. There is indeed an end to this soon I believe, which is good.
06-08-2020, 02:00 AM
#296
I'm intrigued by longer term prophylaxis with HCQ - it does take some time for it to become meaningfully effective to treat rheumatic disease. I'll be interested to see data on patients taking HCQ long term as it pertains disease prevalence, severity and outcomes. The politics of HCQ has been a real PITA - I've done my best to ignore it. I really could not care less whether Trump takes it or not. If it works, it works. Unfortunately, some do have a vested interest to make sure "their side" wins. Can't scratch your *** nowadays without it becoming a political debate.
Regarding biologics - there has been a small case study exploring this question. Definitely not conclusive data, but it's interesting. ACR guidelines now allow RA patients to remain on Tocilizumab if they become infected w/COVID19.
https://www.nejm.org/doi/full/10.1056/NEJMc2009567
Regarding biologics - there has been a small case study exploring this question. Definitely not conclusive data, but it's interesting. ACR guidelines now allow RA patients to remain on Tocilizumab if they become infected w/COVID19.
https://www.nejm.org/doi/full/10.1056/NEJMc2009567
Though there are these two trials:
Pre-exposiure prophylaxis in India http://www.ijmr.org.in/preprintarticle.asp?id=285520;type=0 after six weeks of 400 mg of HCQ weekly.
As early therapy of symptomatic patients with COVID like illness in Brazil, HCQ reduces hospitalizations. https://pgibertie.files.wordpress.co...ript-final.pdf
06-08-2020, 11:11 AM
#297
Three Wheelin'
FWIW, I find this discussion fascinating. It’s definitely way outside of the bounds of my expertise (business guy) but it’s nevertheless very interesting to read, especially compared to the spun articles in MSM sources.
06-08-2020, 07:46 PM
#298
Banned
I also really appreciate all of this information. It's so much nicer to hear information about this virus from actual doctors rather than a story on the news.
Now that we've heard about some of the things that could possibly help people with the virus, how about some information on things that could possibly effect people in a negative way. I'm specifically curious about Ibuprofen and ACE Inhibitors. Early on, it sounded like both of these types of drugs could be bad for people with the virus. Later, we were told Ibuprofen is fine to take and ACE Inhibitors might actually help protect people's lungs. Do you guys have any real information one way or the other about these drugs?
Now that we've heard about some of the things that could possibly help people with the virus, how about some information on things that could possibly effect people in a negative way. I'm specifically curious about Ibuprofen and ACE Inhibitors. Early on, it sounded like both of these types of drugs could be bad for people with the virus. Later, we were told Ibuprofen is fine to take and ACE Inhibitors might actually help protect people's lungs. Do you guys have any real information one way or the other about these drugs?
06-08-2020, 09:07 PM
#299
Have you guys seen a difference in outcomes for Type 1 diabetics compared to Type 2s? All of the stories I’ve read about this virus just mention “diabetes.” I’m wondering if a Type 1 diabetic with good blood sugar control would really have a worse outcome than a non-diabetic.
06-09-2020, 04:45 AM
#300
I too find this conversation incredibly interesting. I've spent a ton of time looking at the numbers behind all this, but have absolutely zero knowledge of medicine, so it's fascinating to see what's been happening on that side of things.
There are so many insane statistics of how overblown the Coronavirus panic has been, but a few of my favorites:
1) The current CDC Excess Mortality stats by "provisional counts" show the entire country at 101% out of 100%. The CDC has already counted nearly 93k of the 110k reported, so it's very likely this year ends up being under the threshold for excess deaths.
2) Many, many states, either never had any excess mortality or significantly lower levels of excess mortality than during flu season in 2018, regardless of intervention strategy.
3) Not many states actually upload consistently good Long Term Care facility data, but of the ones that do, there are 5 states where nursing homes are 70% or higher of the total reported fatalities.
4) The average age of death in Massachusetts is 82, or essentially older than the average life expectancy.
It's infuriating how bad the data reporting is too. States do focused testing on meatpacking plants or nursing homes or jails, don't publicly announce they're doing it, then everyone panics when there's a rise in cases. Well no, nothing's changed in the general population, they're just testing outbreaks. Which is fine, just say you're doing it. The data we're seeing now is a compilation of dates. I live in Los Angeles, and LA County is reporting test results every day from literally weeks ago. Deaths reported today generally occurred weeks or even months ago. The Indiana state dashboard specifies this, but most states don't. You can see this by comparing what the CDC has counted vs. what tracking sites have counted. The peak was much earlier and higher than people think, and the decline has been faster and steeper. The mask or "face covering" stupidity...the flip flopping by Fauci...the fact that politicians believed that modeling data from the horrendous failures at the IHME and Imperial College was fact, so they cleared hospital space, expecting to be overrun with patients, which of course never happened....they cleared hospital space by sending patients back to nursing homes, creating mass death...it's just all infuriating.
One of the best is Cuomo's 140,000 hospital beds claim...NY state is the hardest hit region in the world, and it peaked at 18,800 hospital beds. Only off by 90%. And of course the answer is lockdowns worked, because lockdowns work. No evidence, no proof, they just worked because they must have worked. Except all these areas that never locked down fared better, in many cases significantly better, than those that did. But lockdowns work because lockdowns work.
People panicked, politicians panicked, caved to peer and media pressure, and operated on the "doing something is better than doing nothing" philosophy. Which was absolutely wrong.
On that note, I'm not getting a new 911 yet, but my wife is getting a 2020 Macan S...so far we've been able to get 9% off on a lot car. So that's good.
There are so many insane statistics of how overblown the Coronavirus panic has been, but a few of my favorites:
1) The current CDC Excess Mortality stats by "provisional counts" show the entire country at 101% out of 100%. The CDC has already counted nearly 93k of the 110k reported, so it's very likely this year ends up being under the threshold for excess deaths.
2) Many, many states, either never had any excess mortality or significantly lower levels of excess mortality than during flu season in 2018, regardless of intervention strategy.
3) Not many states actually upload consistently good Long Term Care facility data, but of the ones that do, there are 5 states where nursing homes are 70% or higher of the total reported fatalities.
4) The average age of death in Massachusetts is 82, or essentially older than the average life expectancy.
It's infuriating how bad the data reporting is too. States do focused testing on meatpacking plants or nursing homes or jails, don't publicly announce they're doing it, then everyone panics when there's a rise in cases. Well no, nothing's changed in the general population, they're just testing outbreaks. Which is fine, just say you're doing it. The data we're seeing now is a compilation of dates. I live in Los Angeles, and LA County is reporting test results every day from literally weeks ago. Deaths reported today generally occurred weeks or even months ago. The Indiana state dashboard specifies this, but most states don't. You can see this by comparing what the CDC has counted vs. what tracking sites have counted. The peak was much earlier and higher than people think, and the decline has been faster and steeper. The mask or "face covering" stupidity...the flip flopping by Fauci...the fact that politicians believed that modeling data from the horrendous failures at the IHME and Imperial College was fact, so they cleared hospital space, expecting to be overrun with patients, which of course never happened....they cleared hospital space by sending patients back to nursing homes, creating mass death...it's just all infuriating.
One of the best is Cuomo's 140,000 hospital beds claim...NY state is the hardest hit region in the world, and it peaked at 18,800 hospital beds. Only off by 90%. And of course the answer is lockdowns worked, because lockdowns work. No evidence, no proof, they just worked because they must have worked. Except all these areas that never locked down fared better, in many cases significantly better, than those that did. But lockdowns work because lockdowns work.
People panicked, politicians panicked, caved to peer and media pressure, and operated on the "doing something is better than doing nothing" philosophy. Which was absolutely wrong.
On that note, I'm not getting a new 911 yet, but my wife is getting a 2020 Macan S...so far we've been able to get 9% off on a lot car. So that's good.