OtherGround Forums OG doc. AMA on COVID-19

3/29/20 6:31 PM
10/23/05
Posts: 3146
jcblass - Why hasn't this ravaged the homeless population. Here in LA they are all cooking out on the side of the road...they have terrible hygiene and are immune compromised yet have not experienced anything as a population. Los Angeles is still under 50 deaths despite having one of the largest and most concentrated homeless communities in the country.

Weather might be a factor. LA is also a lot less densely populated that NY. But there surely are other factors. Perhaps NY had several "super carriers". I'm guessing the numbers will start creeping up this week.

3/29/20 6:32 PM
10/23/05
Posts: 3147
stillmatic - Death rate for younger people keeps being brought up frequently but it is not the most relevant issue here. The hospitalization rate for people under 40 is still about 30% of all the cases meaning even if you are in that healthy under 40 category, it's not a rare instance that you will need treatment at a Hospital if you get this.

As has been said a million times, the concern is overwhelming Hospitals. Patients in for other stuff won't be able to get the treatment they need as well. On top of this, you will have health care workers themselves getting sick, needing treatment and we simultaneously lose the people we need fighting this while also taking an extra bed which there already is a shortage of.

Exactly. I'm not sure why this has to be repeated ad nauseam.

3/29/20 6:39 PM
2/4/09
Posts: 10738
jcblass - Why hasn't this ravaged the homeless population. Here in LA they are all cooking out on the side of the road...they have terrible hygiene and are immune compromised yet have not experienced anything as a population. Los Angeles is still under 50 deaths despite having one of the largest and most concentrated homeless communities in the country.

Look at median age, hypertension, diabetes, cardiovascular, and population density maps. 

 

West Coast looks like it is much better shape for this than East Coast

3/29/20 7:23 PM
12/13/11
Posts: 9137

mataleo, 

 

I am planning to give it a try of coming off my entyvio medication for ulcerative colitis. about 3 weeks ago I got my last infusion. And I only got it because I was headed to mexico for 3 weeks and I didn't want to test coming off only to have a flare up and be unable to get medication. entyvio is given in 4 or 6 or 8 week Intervals. I have been delaying it to see if I get any symptoms.the last time I went 11 weeks and had no problems.  Do you think this is a good idea to try right now? will it immediately strengthen my immune system to help fight off the corona if I dont get another infusion? or is my immune system compromised for longer than the drug is in my system? 

3/29/20 8:03 PM
2/14/19
Posts: 304
mataleo1 -
Bot - 

Mataleo, what is the word on ACE Inhibitors blood pressure medication. Does it make Covid more dangerous? I take Ramapril 2.5 mg twice a day. Wondering if I should ask my dr about stopping it.


This is changing everyday. No clear answer.

I'd say if it is easy and safe for you to switch BP medications, it's reasonable to do so. It's not at all malpractice to continue them as there isn't much data.

This is a twitter journal club I follow. A lot of smart people participate. And the data is inconclusive:
http://www.nephjc.com/news/covidace2

Thanks so much!

3/30/20 12:40 AM
9/23/08
Posts: 10912

In

3/30/20 12:59 AM
11/23/10
Posts: 154
mataleo1 -
jcblass - Why hasn't this ravaged the homeless population. Here in LA they are all cooking out on the side of the road...they have terrible hygiene and are immune compromised yet have not experienced anything as a population. Los Angeles is still under 50 deaths despite having one of the largest and most concentrated homeless communities in the country.

Weather might be a factor. LA is also a lot less densely populated that NY. But there surely are other factors. Perhaps NY had several "super carriers". I'm guessing the numbers will start creeping up this week.

I would also guess that the first wave of COVID-19 is circling in the wealthier (and healthier) parts of the population, seeing as it was imported through international travelers. The homeless population in general is probably separated by more degrees from them than the rest of the population, so the disease will hit them later.This is all speculation on my part of cause.

3/30/20 1:07 AM
1/1/01
Posts: 49402

FDA issues emergency authorization to use hydrochloriquine and chloriquine for covid 19

https://www.politico.com/news/2020/03/29/fda-emergency-authorization-anti-malaria-drug-155095

3/30/20 1:17 AM
10/14/03
Posts: 30857

3/30/20 1:18 AM
1/2/20
Posts: 536
So is ibuprofen good or bad? Saw it mentioned a couple of weeks ago but now opinions have changed are most experts are saying that its fine and previous articles lacked any real science/data.
3/30/20 1:31 AM
12/12/07
Posts: 13882
Eskimo -
mataleo1 -
Eskimo - 
mataleo1 -
Eskimo - 
mataleo1 -
Eskimo - 
jcblass - Is anyone surprised that in the 5-6 months since this virus hit, we have no known vaccine or even treatment? Despite a legitimate global effort?

Doesn't seem to promising for future outbreaks...

As a world, we can't even make a damn ventilator.

The reality is the number of dead are totally insignificant thus far. If people really start dying, and they very well might, you’ll see a better effort for the ventilators. 
As far as the vaccine or treatment, I don’t think 5-6 months is a very long time. The flu vaccine has been worked on for quite a while and it’s still not very good. 


Don't want to get on this again and I know your position but to say that deaths are totally insignificant thus far is simply ridiculous.

What kind of mortality metric do you need to make this clinically relevant?

Just shy of 8000 people die per day on average in the US. This has caused about a 5% uptick in that on the worst death day(around 500). Most of those that died had one foot in the grave already. Maybe that’s time to panic for you, but it’s clearly not for most people.

I fully expect things to get worse and it’s absolutely sad. However, my point was that things will have to actually get bad before money is motivated to innovate. I was making a moral judgement, I was just being honest. 


It's not sad, nor do I think it's a time to panic.

The number of deaths is alarming. It's logarithmic. And the sheer number of healthy patients needing medical help is growing quickly and overloading our capacity to do our jobs. Our service is declining to see patients with non urgent kidney diseases because we're being overwhelmed by COVID.

You are allowed to think otherwise, but the rest of the medical world including pharma is sufficiently concerned to throw a TON of resources and money for a vaccine. This is happening now regardless of your beliefs.

I feel like I’m talking with a woman. My comment was directed towards someone asking why ventilators weren’t being made at breakneck speed. I simply said the death numbers aren’t YET motivating enough for money/industry to willingly jump on board. I wasn’t making a moral judgement, it was just a fact. Big pharma got a blank check from the government to find a vaccine and they know every government in the world will force their citizens to take that vaccine so there is a huge financial incentive. If you don’t understand the way things work that’s not my fault and it doesn’t mean I don’t care or I don’t think it’s a big deal. 
I fully expect the virus to kill 2-300 thousand people in the US. That’s definitely a serious thing. It remains to be seen what the fallout from shutting down the economy will be. I predict it’s far worse for the average person than the virus would’ve been. No way to ever prove that just like there’s no way to prove how many people will be saved from shutting things down. Everyone will base their opinions on what they thought was right. Obviously medical people will always side with whatever helps the them save patients and lots of people are super scared so they’ll agree to anything right now. My position is that in 3-5 years most people will wish we’d done things a little differently. Maybe I’m dead wrong, only time will tell. 


You mentioned you were making a moral judgement, which is why I responded in such, but now realize it was probably a typo.

Nobody has a crystal ball here. But you're wrong if you believe that epidemiologists and doctors are only looking at 1 side of the equation (save lives by social distancing, close everything). Robust models and recommendations also incorporate consideration of the other side of these measures (economic downfall, isolation, suicides).

You keep repeating that we can't ever prove that. No fuck. These are projections which will only have an answer later. But we don't have the leisure to stand on the sidelines. Decisions need to be taken decisions now, and these are supported by big data, by expert opinion, by modeling, by experience. Science has the ability to estimate the effect of these interventions (not just lives saved). They may turn out to be entirely off target, but I submit that these are more than guesses or opinion.

If you were in charge, how would you approach this? What decisions would you favor? What would you do differently?

Yes that was a typo, sorry.

I still think we should’ve put in these strict measures for the people most at risk, the old and sick. We could’ve set up programs to get them essential goods to their homes. That could’ve been done until good drugs were developed for treatment or a vaccine is available. 

We could’ve recommended social distancing and good hygiene for everyone else. 
Maybe my math is wrong but only 4% of people dying are under 60, and less than 1% of people dying are considered healthy and under 60. 
Therefore I see no reason to not allow healthy people under 60 to not work. Unless of course we’ve a adopted an attitude that zero losses are acceptable, which would certainly be a first. 
Everyone seems to get aggravated with comparisons to other factors causing death, but I see no reason those aren’t valid. We’d probably save 10x the number of healthy people under 60 if we’d really crack down on texting and driving as what we’re doing by not allowing these same people to work. Most experts are saying we’re going to have between 80-160,000 deaths in the US from this in 2020. That means by quarantining healthy people under 60 we’re probably saving 1000-2000 of them. That number wouldn’t overwhelm ERs and it’s not worth putting a large number of people into poverty imo. It’s sad to lose anyone, but most things we do have a small risk involved. 
 

You’re oversimplifying this by just using death percentages. There are already cases out there of people who have recovered from it with severe lung damage. And it’s also been very inconsistent with who it attacks severely and who it doesn’t. There’s not a target model other than it seems to kill the elderly and immunocompromised more than anyone else, at least from what I’ve read. 

3/30/20 1:36 AM
12/12/07
Posts: 13883
jcblass - Why hasn't this ravaged the homeless population. Here in LA they are all cooking out on the side of the road...they have terrible hygiene and are immune compromised yet have not experienced anything as a population. Los Angeles is still under 50 deaths despite having one of the largest and most concentrated homeless communities in the country.

I live in LA, too. Although there are a lot of homeless here, the majority of them are located in the same parts of town. And with Starbucks being shut down for everything but drive through, the only other place I can think where they could possibly have contact with an infected person would be outside of 7-Elevens.

3/30/20 1:43 AM
11/10/18
Posts: 6806
captainplanet -
Eskimo -
mataleo1 -
Eskimo - 
mataleo1 -
Eskimo - 
mataleo1 -
Eskimo - 
jcblass - Is anyone surprised that in the 5-6 months since this virus hit, we have no known vaccine or even treatment? Despite a legitimate global effort?

Doesn't seem to promising for future outbreaks...

As a world, we can't even make a damn ventilator.

The reality is the number of dead are totally insignificant thus far. If people really start dying, and they very well might, you’ll see a better effort for the ventilators. 
As far as the vaccine or treatment, I don’t think 5-6 months is a very long time. The flu vaccine has been worked on for quite a while and it’s still not very good. 


Don't want to get on this again and I know your position but to say that deaths are totally insignificant thus far is simply ridiculous.

What kind of mortality metric do you need to make this clinically relevant?

Just shy of 8000 people die per day on average in the US. This has caused about a 5% uptick in that on the worst death day(around 500). Most of those that died had one foot in the grave already. Maybe that’s time to panic for you, but it’s clearly not for most people.

I fully expect things to get worse and it’s absolutely sad. However, my point was that things will have to actually get bad before money is motivated to innovate. I was making a moral judgement, I was just being honest. 


It's not sad, nor do I think it's a time to panic.

The number of deaths is alarming. It's logarithmic. And the sheer number of healthy patients needing medical help is growing quickly and overloading our capacity to do our jobs. Our service is declining to see patients with non urgent kidney diseases because we're being overwhelmed by COVID.

You are allowed to think otherwise, but the rest of the medical world including pharma is sufficiently concerned to throw a TON of resources and money for a vaccine. This is happening now regardless of your beliefs.

I feel like I’m talking with a woman. My comment was directed towards someone asking why ventilators weren’t being made at breakneck speed. I simply said the death numbers aren’t YET motivating enough for money/industry to willingly jump on board. I wasn’t making a moral judgement, it was just a fact. Big pharma got a blank check from the government to find a vaccine and they know every government in the world will force their citizens to take that vaccine so there is a huge financial incentive. If you don’t understand the way things work that’s not my fault and it doesn’t mean I don’t care or I don’t think it’s a big deal. 
I fully expect the virus to kill 2-300 thousand people in the US. That’s definitely a serious thing. It remains to be seen what the fallout from shutting down the economy will be. I predict it’s far worse for the average person than the virus would’ve been. No way to ever prove that just like there’s no way to prove how many people will be saved from shutting things down. Everyone will base their opinions on what they thought was right. Obviously medical people will always side with whatever helps the them save patients and lots of people are super scared so they’ll agree to anything right now. My position is that in 3-5 years most people will wish we’d done things a little differently. Maybe I’m dead wrong, only time will tell. 


You mentioned you were making a moral judgement, which is why I responded in such, but now realize it was probably a typo.

Nobody has a crystal ball here. But you're wrong if you believe that epidemiologists and doctors are only looking at 1 side of the equation (save lives by social distancing, close everything). Robust models and recommendations also incorporate consideration of the other side of these measures (economic downfall, isolation, suicides).

You keep repeating that we can't ever prove that. No fuck. These are projections which will only have an answer later. But we don't have the leisure to stand on the sidelines. Decisions need to be taken decisions now, and these are supported by big data, by expert opinion, by modeling, by experience. Science has the ability to estimate the effect of these interventions (not just lives saved). They may turn out to be entirely off target, but I submit that these are more than guesses or opinion.

If you were in charge, how would you approach this? What decisions would you favor? What would you do differently?

Yes that was a typo, sorry.

I still think we should’ve put in these strict measures for the people most at risk, the old and sick. We could’ve set up programs to get them essential goods to their homes. That could’ve been done until good drugs were developed for treatment or a vaccine is available. 

We could’ve recommended social distancing and good hygiene for everyone else. 
Maybe my math is wrong but only 4% of people dying are under 60, and less than 1% of people dying are considered healthy and under 60. 
Therefore I see no reason to not allow healthy people under 60 to not work. Unless of course we’ve a adopted an attitude that zero losses are acceptable, which would certainly be a first. 
Everyone seems to get aggravated with comparisons to other factors causing death, but I see no reason those aren’t valid. We’d probably save 10x the number of healthy people under 60 if we’d really crack down on texting and driving as what we’re doing by not allowing these same people to work. Most experts are saying we’re going to have between 80-160,000 deaths in the US from this in 2020. That means by quarantining healthy people under 60 we’re probably saving 1000-2000 of them. That number wouldn’t overwhelm ERs and it’s not worth putting a large number of people into poverty imo. It’s sad to lose anyone, but most things we do have a small risk involved. 
 

You’re oversimplifying this by just using death percentages. There are already cases out there of people who have recovered from it with severe lung damage. And it’s also been very inconsistent with who it attacks severely and who it doesn’t. There’s not a target model other than it seems to kill the elderly and immunocompromised more than anyone else, at least from what I’ve read. 

Mataleo explained that to me in response to that post.

3/30/20 1:52 AM
11/23/10
Posts: 155
mataleo1 -
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NoNeed4aScreenName - 

Hes commenting of the fact there is no control. He says no control cause we are proposing to treat everyone. 

Also says what about the hippocratic oath. I always wondered about the ethics of giving someone near death or on a path to death a fucking placebo!


Good point but I'm not necessarily arguing to give controls placebo (although plenty of people are, they remain completely unimpressed with HCQ). At this point, no ethics committee would sign off on this. HCQ has risks and I could make an argument for clinical equipose, but I'm ok to accept HCQ as a treatment.

Could be HCQ vs HCQ + azithro. Or HCQ vs Remdesivir.

Here in Denmark the COVID-19 guidelines that just came out yesterday say nothing of antiviral treatment except that they will update them as soon as evidence becomes available, and I think there’s a study starting next week with a clean placebo group vs HCQ. Both the study and the guidelines are not targetted at ICU-patients though. HCQ and azithromycin have been made off-limits to prescribe for doctors outside of hospitals/specialist clinics though, so somebody must have been prescribing it off-label.

I just read there’s a global shortage of condoms coming up due to factory shutdowns. Without azithromycin for GPs we’ll soon have a chlamydia pandemic on our hands as well :)


Don't you find it weird that HCQ vs placebo wouldn't be tried on sick patients?

First, I'm assuming you'd need A LOT of patients to see a difference in outcomes in mildly sick individuals.

Second, doesn't it say something about our presumed interpretation of equipose?

Ah, I worded myself inaccurately regarding the guidelines: they were published by the danish college of pulmonologists and specify treatment of in-hospital patients outside of ICU units. The intensivist college hasn’t published a guideline (I’m guessing it’s because there is no evidence to support such a guideline, and they’d rather allow for individual assessments and for practice to be adapted to local conditions in the critically ill patients).

Regarding studies and equipoise, I don’t know in the case of COVID-19. It might turn out like Tamiflu and Influenza where you couldn’t show an effect of treatment in studies unless initiated shortly after symptom onset, which was rarely the case in studies based in ICU settings, so the evidence had to be based on study populations with milder presentations (IIRC, and that might have changed, I haven’t reviewed the literature in years). This is obviously an exception to the rule and speculation on my part - in general you’re right: studying the most severely sick would be the best way of making a feasible effect study. The study I was thinking of was part of a multinational one with I think 600 patients in each treatment arm (SoC, HCQ, remdesivir, lopinavir). That might be too few for statistical significance, but probably enough to get an estimate if any of the treatments have an impact of clinical significance.

Now, there’s one study planned here, for which I absolutely agree with you that it’s dumb as bricks: they’re planning to do an RCT with HCQ on covid-19 patients not admitted to a hospital AND their close household contacts in 50 families. I’ve only read about it in the media though, and it seems to be motivated by a GP who had started prescribing HCQ to vulnerable groups in his practice. It might be just a way for reaearchers/authorities to a least formalize that (mal)practice. Or to drag out time with false promises while shutting him up, I don’t know. Seems hopelessly underpowered to show anything but side-effects to me at least.

Regarding equipoise I’m probably more worried about all those small, quickly-set-up studies with non-PIOs which might skew it and make it harder to set up the big studies of PIOs. I’m doing observational studies though, and have little experience with intervention studies, so that’s somewhat of an uninformed opinion on my part.

3/30/20 2:12 AM
11/10/18
Posts: 6808
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mataleo1 -
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Hes commenting of the fact there is no control. He says no control cause we are proposing to treat everyone. 

Also says what about the hippocratic oath. I always wondered about the ethics of giving someone near death or on a path to death a fucking placebo!


Good point but I'm not necessarily arguing to give controls placebo (although plenty of people are, they remain completely unimpressed with HCQ). At this point, no ethics committee would sign off on this. HCQ has risks and I could make an argument for clinical equipose, but I'm ok to accept HCQ as a treatment.

Could be HCQ vs HCQ + azithro. Or HCQ vs Remdesivir.

Here in Denmark the COVID-19 guidelines that just came out yesterday say nothing of antiviral treatment except that they will update them as soon as evidence becomes available, and I think there’s a study starting next week with a clean placebo group vs HCQ. Both the study and the guidelines are not targetted at ICU-patients though. HCQ and azithromycin have been made off-limits to prescribe for doctors outside of hospitals/specialist clinics though, so somebody must have been prescribing it off-label.

I just read there’s a global shortage of condoms coming up due to factory shutdowns. Without azithromycin for GPs we’ll soon have a chlamydia pandemic on our hands as well :)


Don't you find it weird that HCQ vs placebo wouldn't be tried on sick patients?

First, I'm assuming you'd need A LOT of patients to see a difference in outcomes in mildly sick individuals.

Second, doesn't it say something about our presumed interpretation of equipose?

Ah, I worded myself inaccurately regarding the guidelines: they were published by the danish college of pulmonologists and specify treatment of in-hospital patients outside of ICU units. The intensivist college hasn’t published a guideline (I’m guessing it’s because there is no evidence to support such a guideline, and they’d rather allow for individual assessments and for practice to be adapted to local conditions in the critically ill patients).

Regarding studies and equipoise, I don’t know in the case of COVID-19. It might turn out like Tamiflu and Influenza where you couldn’t show an effect of treatment in studies unless initiated shortly after symptom onset, which was rarely the case in studies based in ICU settings, so the evidence had to be based on study populations with milder presentations (IIRC, and that might have changed, I haven’t reviewed the literature in years). This is obviously an exception to the rule and speculation on my part - in general you’re right: studying the most severely sick would be the best way of making a feasible effect study. The study I was thinking of was part of a multinational one with I think 600 patients in each treatment arm (SoC, HCQ, remdesivir, lopinavir). That might be too few for statistical significance, but probably enough to get an estimate if any of the treatments have an impact of clinical significance.

Now, there’s one study planned here, for which I absolutely agree with you that it’s dumb as bricks: they’re planning to do an RCT with HCQ on covid-19 patients not admitted to a hospital AND their close household contacts in 50 families. I’ve only read about it in the media though, and it seems to be motivated by a GP who had started prescribing HCQ to vulnerable groups in his practice. It might be just a way for reaearchers/authorities to a least formalize that (mal)practice. Or to drag out time with false promises while shutting him up, I don’t know. Seems hopelessly underpowered to show anything but side-effects to me at least.

Regarding equipoise I’m probably more worried about all those small, quickly-set-up studies with non-PIOs which might skew it and make it harder to set up the big studies of PIOs. I’m doing observational studies though, and have little experience with intervention studies, so that’s somewhat of an uninformed opinion on my part.

In the studies with HCQ are they also giving zinc? Isn’t that the whole point of HCQ? That it allows way more zinc than normal to pass the cell membrane and stop the virus from replicating as easily? Or am I totally wrong about this?

Edited: 3/30/20 3:48 AM
11/23/10
Posts: 156
Eskimo -
Job Security -
mataleo1 -
Job Security - 
mataleo1 -
NoNeed4aScreenName - 

Hes commenting of the fact there is no control. He says no control cause we are proposing to treat everyone. 

Also says what about the hippocratic oath. I always wondered about the ethics of giving someone near death or on a path to death a fucking placebo!


Good point but I'm not necessarily arguing to give controls placebo (although plenty of people are, they remain completely unimpressed with HCQ). At this point, no ethics committee would sign off on this. HCQ has risks and I could make an argument for clinical equipose, but I'm ok to accept HCQ as a treatment.

Could be HCQ vs HCQ + azithro. Or HCQ vs Remdesivir.

Here in Denmark the COVID-19 guidelines that just came out yesterday say nothing of antiviral treatment except that they will update them as soon as evidence becomes available, and I think there’s a study starting next week with a clean placebo group vs HCQ. Both the study and the guidelines are not targetted at ICU-patients though. HCQ and azithromycin have been made off-limits to prescribe for doctors outside of hospitals/specialist clinics though, so somebody must have been prescribing it off-label.

I just read there’s a global shortage of condoms coming up due to factory shutdowns. Without azithromycin for GPs we’ll soon have a chlamydia pandemic on our hands as well :)


Don't you find it weird that HCQ vs placebo wouldn't be tried on sick patients?

First, I'm assuming you'd need A LOT of patients to see a difference in outcomes in mildly sick individuals.

Second, doesn't it say something about our presumed interpretation of equipose?

Ah, I worded myself inaccurately regarding the guidelines: they were published by the danish college of pulmonologists and specify treatment of in-hospital patients outside of ICU units. The intensivist college hasn’t published a guideline (I’m guessing it’s because there is no evidence to support such a guideline, and they’d rather allow for individual assessments and for practice to be adapted to local conditions in the critically ill patients).

Regarding studies and equipoise, I don’t know in the case of COVID-19. It might turn out like Tamiflu and Influenza where you couldn’t show an effect of treatment in studies unless initiated shortly after symptom onset, which was rarely the case in studies based in ICU settings, so the evidence had to be based on study populations with milder presentations (IIRC, and that might have changed, I haven’t reviewed the literature in years). This is obviously an exception to the rule and speculation on my part - in general you’re right: studying the most severely sick would be the best way of making a feasible effect study. The study I was thinking of was part of a multinational one with I think 600 patients in each treatment arm (SoC, HCQ, remdesivir, lopinavir). That might be too few for statistical significance, but probably enough to get an estimate if any of the treatments have an impact of clinical significance.

Now, there’s one study planned here, for which I absolutely agree with you that it’s dumb as bricks: they’re planning to do an RCT with HCQ on covid-19 patients not admitted to a hospital AND their close household contacts in 50 families. I’ve only read about it in the media though, and it seems to be motivated by a GP who had started prescribing HCQ to vulnerable groups in his practice. It might be just a way for reaearchers/authorities to a least formalize that (mal)practice. Or to drag out time with false promises while shutting him up, I don’t know. Seems hopelessly underpowered to show anything but side-effects to me at least.

Regarding equipoise I’m probably more worried about all those small, quickly-set-up studies with non-PIOs which might skew it and make it harder to set up the big studies of PIOs. I’m doing observational studies though, and have little experience with intervention studies, so that’s somewhat of an uninformed opinion on my part.

In the studies with HCQ are they also giving zinc? Isn’t that the whole point of HCQ? That it allows way more zinc than normal to pass the cell membrane and stop the virus from replicating as easily? Or am I totally wrong about this?

Not from what I’ve read. I think the logic is that zinc - like potassium - is already a predominantly intracellular electrolyte due to a lot of transport proteins in cell membranes, and while intake of zinc is somewhat correlated to extracellular/plasma-levels of zinc, it is not related closely to intracellular levels under normal circumstances . And excess intracellular zinc has been associated with tissue damage in cell models of ischemia where the zinc homeostasis was disturbed. I’m far from a physiology professor though (they seem abundant on the internet somehow), so take that with a grain of salt.

I think mostly it’s a combination of a weak theoretic mechanism of action and wanting to keep the effects separate (testing the combination you don’t know which one is the cause of a beneficial/harmful effect or even cancelling each other out). And similarly to avoid zinc toxicity/side effects mixing with HCQ/covid-19 symptoms.

3/30/20 3:51 AM
11/10/18
Posts: 6817
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Eskimo -
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Job Security - 
mataleo1 -
NoNeed4aScreenName - 

Hes commenting of the fact there is no control. He says no control cause we are proposing to treat everyone. 

Also says what about the hippocratic oath. I always wondered about the ethics of giving someone near death or on a path to death a fucking placebo!


Good point but I'm not necessarily arguing to give controls placebo (although plenty of people are, they remain completely unimpressed with HCQ). At this point, no ethics committee would sign off on this. HCQ has risks and I could make an argument for clinical equipose, but I'm ok to accept HCQ as a treatment.

Could be HCQ vs HCQ + azithro. Or HCQ vs Remdesivir.

Here in Denmark the COVID-19 guidelines that just came out yesterday say nothing of antiviral treatment except that they will update them as soon as evidence becomes available, and I think there’s a study starting next week with a clean placebo group vs HCQ. Both the study and the guidelines are not targetted at ICU-patients though. HCQ and azithromycin have been made off-limits to prescribe for doctors outside of hospitals/specialist clinics though, so somebody must have been prescribing it off-label.

I just read there’s a global shortage of condoms coming up due to factory shutdowns. Without azithromycin for GPs we’ll soon have a chlamydia pandemic on our hands as well :)


Don't you find it weird that HCQ vs placebo wouldn't be tried on sick patients?

First, I'm assuming you'd need A LOT of patients to see a difference in outcomes in mildly sick individuals.

Second, doesn't it say something about our presumed interpretation of equipose?

Ah, I worded myself inaccurately regarding the guidelines: they were published by the danish college of pulmonologists and specify treatment of in-hospital patients outside of ICU units. The intensivist college hasn’t published a guideline (I’m guessing it’s because there is no evidence to support such a guideline, and they’d rather allow for individual assessments and for practice to be adapted to local conditions in the critically ill patients).

Regarding studies and equipoise, I don’t know in the case of COVID-19. It might turn out like Tamiflu and Influenza where you couldn’t show an effect of treatment in studies unless initiated shortly after symptom onset, which was rarely the case in studies based in ICU settings, so the evidence had to be based on study populations with milder presentations (IIRC, and that might have changed, I haven’t reviewed the literature in years). This is obviously an exception to the rule and speculation on my part - in general you’re right: studying the most severely sick would be the best way of making a feasible effect study. The study I was thinking of was part of a multinational one with I think 600 patients in each treatment arm (SoC, HCQ, remdesivir, lopinavir). That might be too few for statistical significance, but probably enough to get an estimate if any of the treatments have an impact of clinical significance.

Now, there’s one study planned here, for which I absolutely agree with you that it’s dumb as bricks: they’re planning to do an RCT with HCQ on covid-19 patients not admitted to a hospital AND their close household contacts in 50 families. I’ve only read about it in the media though, and it seems to be motivated by a GP who had started prescribing HCQ to vulnerable groups in his practice. It might be just a way for reaearchers/authorities to a least formalize that (mal)practice. Or to drag out time with false promises while shutting him up, I don’t know. Seems hopelessly underpowered to show anything but side-effects to me at least.

Regarding equipoise I’m probably more worried about all those small, quickly-set-up studies with non-PIOs which might skew it and make it harder to set up the big studies of PIOs. I’m doing observational studies though, and have little experience with intervention studies, so that’s somewhat of an uninformed opinion on my part.

In the studies with HCQ are they also giving zinc? Isn’t that the whole point of HCQ? That it allows way more zinc than normal to pass the cell membrane and stop the virus from replicating as easily? Or am I totally wrong about this?

Not from what I’ve read. I think the logic is that zinc - like potassium - is already a predominantly intracellular electrolyte due to a lot of transport proteins in cell membranes, and while intake of zinc is somewhat correlated to extracellular/plasma-levels of zinc, it is not related closely to intracellular levels under normal circumstances . And excess intracellular zinc has been associated with tissue damage in cell models of ischemia where the zinc homeostasis was disturbed. I’m far from a physiology professor though (they seem abundant on the internet somehow), so take that with a grain of salt.

I think mostly it’s a combination of a weak theoretic mechanism of action and wanting to keep the effects separate (testing the combination you don’t know which one is the cause of a beneficial/harmful effect or even cancelling each other out). And similarly to avoid zinc toxicity/side effects mixing with HCQ/covid-19 symptoms.

Thank you

3/30/20 7:07 AM
1/1/01
Posts: 24785


3/30/20 9:23 AM
10/23/05
Posts: 3148
Neil McCauley -

mataleo, 

 

I am planning to give it a try of coming off my entyvio medication for ulcerative colitis. about 3 weeks ago I got my last infusion. And I only got it because I was headed to mexico for 3 weeks and I didn't want to test coming off only to have a flare up and be unable to get medication. entyvio is given in 4 or 6 or 8 week Intervals. I have been delaying it to see if I get any symptoms.the last time I went 11 weeks and had no problems.  Do you think this is a good idea to try right now? will it immediately strengthen my immune system to help fight off the corona if I dont get another infusion? or is my immune system compromised for longer than the drug is in my system? 

Hey. Your immune system is likely not normal. These drugs affect immunity for an extended period of time. If you're young and otherwise healthy, the risk for you to be very sick from COVID is small. However, if you can delay that medication safely, I'd consider it. Weighing up balances here. Ulcerative colitis is no joke, as you know, and I wouldn't want you to have a flare up just to avoid the small risk of being very ill from COVID. What does your GI think?

3/30/20 9:26 AM
10/23/05
Posts: 3149
Dangerousdoug - So is ibuprofen good or bad? Saw it mentioned a couple of weeks ago but now opinions have changed are most experts are saying that its fine and previous articles lacked any real science/data.

My intuition tells me that it's fine, but there is indirect data suggesting risk of harm from NSAIDs. No definite data against it, but several clinicians are recommending against them for now. Wish I could give a more definite answer.

3/30/20 9:30 AM
10/23/05
Posts: 3150
Job Security -
mataleo1 -
Job Security - 
mataleo1 -
NoNeed4aScreenName - 

Hes commenting of the fact there is no control. He says no control cause we are proposing to treat everyone. 

Also says what about the hippocratic oath. I always wondered about the ethics of giving someone near death or on a path to death a fucking placebo!


Good point but I'm not necessarily arguing to give controls placebo (although plenty of people are, they remain completely unimpressed with HCQ). At this point, no ethics committee would sign off on this. HCQ has risks and I could make an argument for clinical equipose, but I'm ok to accept HCQ as a treatment.

Could be HCQ vs HCQ + azithro. Or HCQ vs Remdesivir.

Here in Denmark the COVID-19 guidelines that just came out yesterday say nothing of antiviral treatment except that they will update them as soon as evidence becomes available, and I think there’s a study starting next week with a clean placebo group vs HCQ. Both the study and the guidelines are not targetted at ICU-patients though. HCQ and azithromycin have been made off-limits to prescribe for doctors outside of hospitals/specialist clinics though, so somebody must have been prescribing it off-label.

I just read there’s a global shortage of condoms coming up due to factory shutdowns. Without azithromycin for GPs we’ll soon have a chlamydia pandemic on our hands as well :)


Don't you find it weird that HCQ vs placebo wouldn't be tried on sick patients?

First, I'm assuming you'd need A LOT of patients to see a difference in outcomes in mildly sick individuals.

Second, doesn't it say something about our presumed interpretation of equipose?

Ah, I worded myself inaccurately regarding the guidelines: they were published by the danish college of pulmonologists and specify treatment of in-hospital patients outside of ICU units. The intensivist college hasn’t published a guideline (I’m guessing it’s because there is no evidence to support such a guideline, and they’d rather allow for individual assessments and for practice to be adapted to local conditions in the critically ill patients).

Regarding studies and equipoise, I don’t know in the case of COVID-19. It might turn out like Tamiflu and Influenza where you couldn’t show an effect of treatment in studies unless initiated shortly after symptom onset, which was rarely the case in studies based in ICU settings, so the evidence had to be based on study populations with milder presentations (IIRC, and that might have changed, I haven’t reviewed the literature in years). This is obviously an exception to the rule and speculation on my part - in general you’re right: studying the most severely sick would be the best way of making a feasible effect study. The study I was thinking of was part of a multinational one with I think 600 patients in each treatment arm (SoC, HCQ, remdesivir, lopinavir). That might be too few for statistical significance, but probably enough to get an estimate if any of the treatments have an impact of clinical significance.

Now, there’s one study planned here, for which I absolutely agree with you that it’s dumb as bricks: they’re planning to do an RCT with HCQ on covid-19 patients not admitted to a hospital AND their close household contacts in 50 families. I’ve only read about it in the media though, and it seems to be motivated by a GP who had started prescribing HCQ to vulnerable groups in his practice. It might be just a way for reaearchers/authorities to a least formalize that (mal)practice. Or to drag out time with false promises while shutting him up, I don’t know. Seems hopelessly underpowered to show anything but side-effects to me at least.

Regarding equipoise I’m probably more worried about all those small, quickly-set-up studies with non-PIOs which might skew it and make it harder to set up the big studies of PIOs. I’m doing observational studies though, and have little experience with intervention studies, so that’s somewhat of an uninformed opinion on my part.

Great post, thx. I'm very concerned we are basing all of our chloroquine recs on soft non-clinical outcomes (non-PIOs). The media is already reporting a 100% cure rate for HCQ, when it's very clear it's nowhere near that. Looking forward to results 

3/30/20 9:41 AM
2/4/09
Posts: 10746
mataleo1 -
Job Security -
mataleo1 -
Job Security - 
mataleo1 -
NoNeed4aScreenName - 

Hes commenting of the fact there is no control. He says no control cause we are proposing to treat everyone. 

Also says what about the hippocratic oath. I always wondered about the ethics of giving someone near death or on a path to death a fucking placebo!


Good point but I'm not necessarily arguing to give controls placebo (although plenty of people are, they remain completely unimpressed with HCQ). At this point, no ethics committee would sign off on this. HCQ has risks and I could make an argument for clinical equipose, but I'm ok to accept HCQ as a treatment.

Could be HCQ vs HCQ + azithro. Or HCQ vs Remdesivir.

Here in Denmark the COVID-19 guidelines that just came out yesterday say nothing of antiviral treatment except that they will update them as soon as evidence becomes available, and I think there’s a study starting next week with a clean placebo group vs HCQ. Both the study and the guidelines are not targetted at ICU-patients though. HCQ and azithromycin have been made off-limits to prescribe for doctors outside of hospitals/specialist clinics though, so somebody must have been prescribing it off-label.

I just read there’s a global shortage of condoms coming up due to factory shutdowns. Without azithromycin for GPs we’ll soon have a chlamydia pandemic on our hands as well :)


Don't you find it weird that HCQ vs placebo wouldn't be tried on sick patients?

First, I'm assuming you'd need A LOT of patients to see a difference in outcomes in mildly sick individuals.

Second, doesn't it say something about our presumed interpretation of equipose?

Ah, I worded myself inaccurately regarding the guidelines: they were published by the danish college of pulmonologists and specify treatment of in-hospital patients outside of ICU units. The intensivist college hasn’t published a guideline (I’m guessing it’s because there is no evidence to support such a guideline, and they’d rather allow for individual assessments and for practice to be adapted to local conditions in the critically ill patients).

Regarding studies and equipoise, I don’t know in the case of COVID-19. It might turn out like Tamiflu and Influenza where you couldn’t show an effect of treatment in studies unless initiated shortly after symptom onset, which was rarely the case in studies based in ICU settings, so the evidence had to be based on study populations with milder presentations (IIRC, and that might have changed, I haven’t reviewed the literature in years). This is obviously an exception to the rule and speculation on my part - in general you’re right: studying the most severely sick would be the best way of making a feasible effect study. The study I was thinking of was part of a multinational one with I think 600 patients in each treatment arm (SoC, HCQ, remdesivir, lopinavir). That might be too few for statistical significance, but probably enough to get an estimate if any of the treatments have an impact of clinical significance.

Now, there’s one study planned here, for which I absolutely agree with you that it’s dumb as bricks: they’re planning to do an RCT with HCQ on covid-19 patients not admitted to a hospital AND their close household contacts in 50 families. I’ve only read about it in the media though, and it seems to be motivated by a GP who had started prescribing HCQ to vulnerable groups in his practice. It might be just a way for reaearchers/authorities to a least formalize that (mal)practice. Or to drag out time with false promises while shutting him up, I don’t know. Seems hopelessly underpowered to show anything but side-effects to me at least.

Regarding equipoise I’m probably more worried about all those small, quickly-set-up studies with non-PIOs which might skew it and make it harder to set up the big studies of PIOs. I’m doing observational studies though, and have little experience with intervention studies, so that’s somewhat of an uninformed opinion on my part.

Great post, thx. I'm very concerned we are basing all of our chloroquine recs on soft non-clinical outcomes (non-PIOs). The media is already reporting a 100% cure rate for HCQ, when it's very clear it's nowhere near that. Looking forward to results 

As much as I want HCQ to be a treatment/prophylaxis I have to agree with you guys. 

 

After doing more research about Didier and wondering why he didnt included any of the 1000's of other patients data that weren't treated (I guess really everyone that has the virus in a way is a form of control) the outcome could have simply tracked untreated patients. We dont know. 

 

I'm still a believer in using some type of binding inhibiting mechanism with ACE2, hopefully HCQ can be it. 

 

Also, in terms of pharmacokinetics is there any difference between the hydroxy form and the phosphate forms? 

3/30/20 10:41 AM
1/1/12
Posts: 1606

Why the change in the name? Why does everyone call it covid-19 but now there's this new name for it and not everyone is calling it that. So which is it?

3/30/20 10:57 AM
5/19/17
Posts: 10835

Hey Doc,

This may sound like an obvious question, and it may have already been asked, so I will make it quick.

How do you envisage/predict this will go away.

What I dont understand is how lockdown can get rid of it 100%, and why it wouldnt spike again.  If it arrived, say for example, the UK, on airplanes, and wasnt there 6 months before,  surely it will just get going again.

It seems to me only a vaccine, or herd immunity, can end this.  Or else it/we will be spiking and reacting for the next 18 months.  Do you agree?

 

3/30/20 11:07 AM
12/9/13
Posts: 27530
Soup and Beer -

FDA issues emergency authorization to use hydrochloriquine and chloriquine for covid 19

https://www.politico.com/news/2020/03/29/fda-emergency-authorization-anti-malaria-drug-155095

not good news, lots of side effects on the heart