Here’s my conspiracy theory for the day - hydroxychloroquine

[Frances]

4 hours ago, Skippy said:

This recent poll by Reuters/Ipsos reminded me of some of the things being discussed here regarding the politicizing of things that aren't inherently political (like medications).

Question: How would the following developments impact your interest in taking a coronavirus/COVID19 vaccine, if at all?...President Trump says the vaccine is safe:

More interested: Republicans 26%

No more or no less interested: Democrats 26%; Republicans 51%

Less interested: Democrats 55% 

https://www.ipsos.com/sites/default/files/ct/news/documents/2020-05/writeup_reuters_2020_coronavirus_vaccine_05_21_2020.pdf

There are several other equally interesting responses in this survey. I think it's a regrettable development in our culture that seemingly everything has to be politicized these days.

I think that question found what it was designed to find. I mean who looks to any president, R or D, generally mature, honest, and trustworthy or not, for healthcare advice? We generally don’t elect people to that office who have science or healthcare backgrounds. The results across party were much more similar when asked about FDA, personal doctor, and scientific studies. Rather than asking about the president, it seems like the Surgeon General or Dr. Fauci would make more sense in this case.

Edited to add that it also asked, if President Trump says it is safe rather than something like, if President Trump says the CDC or FDA believes the vaccine is safe. Why would anyone care about any president’s personal opinion on the vaccine? It’s like his comments about HCQ. Many were personal and off the cuff rather than referring specifically to experts or studies or federal agencies in charge of regulating such things.

Edited May 24, 2020 by Frances

[Pen]

@Ktgrok  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461643/

a place to start.  

And from its links you could find some more that is related to potential direct virus replication inhibition aspects of chloroquine type drugs.

(That is, this a reason that HCQ itself may help early on completely separate from zinc ionophore aspects.) 

 

(then in addition there are potential benefits in reducing cytokines storm...     perhaps more on this tomorrow, but I suspect lack of help from HCQ late in game suggests either that damage is too far gone, or that there is more direct blood cell and circulatory system damage going on. Because if it mostly cytokines storm alone I think HCQ would be doing better than it is later into illness.) 

[Pen]

@Ktgrok though in a different grouping of viruses dengue is also a single RNA  strand encapsulated virus:

https://www.nature.com/articles/s41598-017-07023-z

and the same mechanism of endocytosis could likely apply to both

as well, hcq might be able to interfere with the spike proteins in coronavirus from being able to attach to the ACE2 receptors on cells (as very probably does vitamin D interfere with spike protein attachment). 

 

so possibly HcQ would be a help to block attachment

and then possibly be a help to slow replication inside the cell ...

 

However, nb, use for both those potential benefits would have to be quite early, or even

prophylactic 

It would not be especially helpful once lots of virus has already attached and already replicated itself numerous times 

is what my reading (largely having to do with other viruses) indicates. 

 

But, contrary to this, HCQ, probably has not helped with HIV, maybe even makes AIDS  worse for some reason.

so if there are actually meaningful bits of HIV in the SARS2 genome / RNA, that might make SARS2 able to resist HCQ like HIV seems to do, rather than to be more like SARS1 and Dengue where Hcq seems to be likely to be able to help decrease attachment and replication .  

Edited May 25, 2020 by Pen

[Corraleno]

6 hours ago, happysmileylady said:

The Lancet analysis, IMO, has a lot of problems.

First.....it wasn't a drug trial.....it was just analysis of a bunch of data.  Which, can certainly be useful, but ultimately isn't really much evidence.  The data came from countries all over the world, and we all know that the accuracy of the data across the world is highly variable.  It also goes all the way back to December 20th......and that's like the most brand newest time we have for this thing.  (though I am going to be honest, it did surprise me that HCQ was being used as far back as 12/20/19.)

Second.....it was only for hospitalized patients.  I think our primary goal in treatment of this....treatment vs cure vs vaccine....is to find a treatment that keeps people out of hospitals.  I mean, ultimately, a cure or vaccine would be great, but since those are pretty much NOT going to happen any time soon (if at all) then the best hope we have is a treatment that keeps people out of the hospital in the first place.  Studying hospitalized people doesn't really advance us toward that goal.

Third....as I said before, within 48 hours of diagnosis simply IS NOT the same as within 48 hours of symptoms.  So again, the analysis really isn't addressing the goals.  It has nothing to do with preventative treatment or early intervention.  Especially when you consider that in many places, it took SO LONG to get test results back, especially in early days.  

 

The Lancet paper is an analysis of 15,000 cases, all of whom received HCQ or CQ within 48 hours of diagnosis, and many scientists find that data more reliable and trustworthy than the data from the small and very flawed French study that started all the HCQ hype. That study (Gaudret et al) (1) was not randomized or blind, the "control group" consisted of patients who had preexisting conditions that contraindicated use of HCQ as well as those who refused HCQ treatment, (2) they were only tested for a period of 6 days, (3) it included only 26 patients, and (4) 6 of those 26 were excluded from the results because 3 were transferred to ICU, 1 died, 1 stopped treatment due to side effects, and 1 left the hospital for undisclosed reasons. So ALL of the patients who had underlying conditions that would have made HCQ treatment dangerous were put in the control group, and then they excluded ALL of the patients in the treatment group who did not get better, and claimed that HCQ treatment reduced viral load in all patients who completed the very brief treatment. And if those issues weren't damaging enough, there were other anomalies with testing dates reported, serious questions about the control group (who were at 4 different hospitals, while the treatment group were all at the Marseille hospital, and some of the control patients were missing test data because of differences in data collection at different hospitals), and various other issues that raised red flags after the study was mysteriously rushed through "peer review" in only 24 hours.

So the "best" evidence we have so far that HCQ is effective against CV19 is one very small study that put all the patients with underlying conditions in the "control group" AND excluded from the treatment results all the patients who did worse. And that is the study that prompted Trump to call HCQ + AZ "one of the biggest game changers in the history of medicine."

So a meta-analysis of 15,000 patients doesn't count because it's not a double-blind study, but a tiny French study (neither blind, nor legitimately controlled) does? The VA study showing worse outcomes with HCQ doesn't count, because only severely ill patients received the treatment; and studies showing negative results for HCQ + AZ don't count because AZ is the dangerous part (except that combination actually got better results in the French study than HCQ alone), and studies showing negative results for CQ + AZ don't count, because everyone knows CQ is more dangerous than HCQ (except the Lancet analysis showed that CQ + AZ was actually less dangerous than HCQ + AZ), and studies showing negative results when HCQ is given more than 48 hours after diagnosis don't count, but the Lancet analysis of 15,000 patients who did get HCQ or CQ within 48 hours of diagnosis also doesn't count because they actually should have gotten the drug within 48 hours of the first symptoms.

So none of the results from multiple studies showing negative results for HCQ treatment count, because the only acceptable evidence would have to come from a large, randomized, double-blind study where healthy patients with no underlying conditions were given HCQ + zinc within 48 hours of their very first symptom, before they ever tested positive. But the vast majority of people with "Covid-like symptoms" turn out to be negative, and you really can't just indiscriminately give a drug with potentially dangerous side effects to anyone with a sniffle or cough on the off chance they actually do have Covid, so you kind of need to wait for a confirmed test (i.e. a diagnosis). And until a study that meets all of these criteria is published that shows negative results for HCQ, people will continue to believe that HCQ is an effective treatment and the only reason so many studies show seriously negative results, and the FDA is warning against its use outside of clinical trials, is because scientists all over the world care more about making Donald Trump look stupid than actually saving lives.

 

[Ausmumof3]

https://www.recoverytrial.net/files/professional-downloads/recovery_noticetoinvestigators_2020-05-24_1422.pdf

at least one randomised trial is taking place although it looks like they had to check to make sure it was safe to go ahead 

Edited May 25, 2020 by Ausmumof3

[Pen]

7 hours ago, Corraleno said:

 

The Lancet paper is an analysis of 15,000 cases, all of whom received HCQ or CQ within 48 hours of diagnosis, and many scientists find that data more reliable and trustworthy than the data from the small and very flawed French study that started all the HCQ hype. That study (Gaudret et al) (1) was not randomized or blind, the "control group" consisted of patients who had preexisting conditions that contraindicated use of HCQ as well as those who refused HCQ treatment, (2) they were only tested for a period of 6 days, (3) it included only 26 patients, and (4) 6 of those 26 were excluded from the results because 3 were transferred to ICU, 1 died, 1 stopped treatment due to side effects, and 1 left the hospital for undisclosed reasons. So ALL of the patients who had underlying conditions that would have made HCQ treatment dangerous were put in the control group, and then they excluded ALL of the patients in the treatment group who did not get better, and claimed that HCQ treatment reduced viral load in all patients who completed the very brief treatment. And if those issues weren't damaging enough, there were other anomalies with testing dates reported, serious questions about the control group (who were at 4 different hospitals, while the treatment group were all at the Marseille hospital, and some of the control patients were missing test data because of differences in data collection at different hospitals), and various other issues that raised red flags after the study was mysteriously rushed through "peer review" in only 24 hours.

So the "best" evidence we have so far that HCQ is effective against CV19 is one very small study that put all the patients with underlying conditions in the "control group" AND excluded from the treatment results all the patients who did worse. And that is the study that prompted Trump to call HCQ + AZ "one of the biggest game changers in the history of medicine."

So a meta-analysis of 15,000 patients doesn't count because it's not a double-blind study, but a tiny French study (neither blind, nor legitimately controlled) does? The VA study showing worse outcomes with HCQ doesn't count, because only severely ill patients received the treatment; and studies showing negative results for HCQ + AZ don't count because AZ is the dangerous part (except that combination actually got better results in the French study than HCQ alone), and studies showing negative results for CQ + AZ don't count, because everyone knows CQ is more dangerous than HCQ (except the Lancet analysis showed that CQ + AZ was actually less dangerous than HCQ + AZ), and studies showing negative results when HCQ is given more than 48 hours after diagnosis don't count, but the Lancet analysis of 15,000 patients who did get HCQ or CQ within 48 hours of diagnosis also doesn't count because they actually should have gotten the drug within 48 hours of the first symptoms.

So none of the results from multiple studies showing negative results for HCQ treatment count, because the only acceptable evidence would have to come from a large, randomized, double-blind study where healthy patients with no underlying conditions were given HCQ + zinc within 48 hours of their very first symptom, before they ever tested positive. But the vast majority of people with "Covid-like symptoms" turn out to be negative, and you really can't just indiscriminately give a drug with potentially dangerous side effects to anyone with a sniffle or cough on the off chance they actually do have Covid, so you kind of need to wait for a confirmed test (i.e. a diagnosis). And until a study that meets all of these criteria is published that shows negative results for HCQ, people will continue to believe that HCQ is an effective treatment and the only reason so many studies show seriously negative results, and the FDA is warning against its use outside of clinical trials, is because scientists all over the world care more about making Donald Trump look stupid than actually saving lives.

 

 

I do not think the studies are good, no. 

None are very good.

the French one for reasons you give

others I have been able to read had HcQ given to

1)sicker people 

and/or

2) too late in disease for HcQ ‘s most likely mode of possible action to work (aside from zinc ionophore aspect) 

eta: 

(actually, 48 hours after might even also often  be too late for zinc ionophore aspect too ...  if there’s already substantial tissue damage, or movement into tissues that are hard for drugs to reach)

HCQ alone may (based on SARS1 and Dengue  experimenting) be helpful to stop / decrease spike protein bonding to ACE2 receptors

and might be helpful to slow down or decrease replication inside cells. 

But by 48 hours after diagnosis there pretty much has to have been enough virus already bonded, entered into cells, replicated, and being shed to get a positive test result.which probably means the illness is at a stage already past when many people would be helped by HCQ alone. 

Thus even 50,000 cases would not be  especially meaningful if they are all set up in a way that won’t work well for the probable mode of action of the drug.  

(It seems kind of like concluding seatbelts don’t work if they are only fastened after the crash has already happened.  

Like saying, “You see, we fastened seatbelts on all these car crash victims within 48 minutes after the crash,  and  yet they died at the same rate or more than car crash victims with no seatbelts.”

...and even more useless if the small print reveals that seatbelts were applied too late on the more seriously injured  )

Edited May 25, 2020 by Pen

[ktgrok]

12 hours ago, Pen said:

@Ktgrok  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461643/

a place to start.  

And from its links you could find some more that is related to potential direct virus replication inhibition aspects of chloroquine type drugs.

(That is, this a reason that HCQ itself may help early on completely separate from zinc ionophore aspects.) 

 

(then in addition there are potential benefits in reducing cytokines storm...     perhaps more on this tomorrow, but I suspect lack of help from HCQ late in game suggests either that damage is too far gone, or that there is more direct blood cell and circulatory system damage going on. Because if it mostly cytokines storm alone I think HCQ would be doing better than it is later into illness.) 

yeah...that's not particuarly impressive, especially given how small most of the sample sets were. The larger ones and the RCT ones look like they show it wasn't very effective. This is the link to the chart with results of the various studies mentioned in the article if people want to look.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461643/table/prp2293-tbl-0001/?report=objectonly

[Pen]

Another problem with HCQ in terms of timing would be its effects on interferon production.

 If it were given too late to stop bonding of spike protein to ACE2 receptors and too late to help halt intracellular replication, but instead just at the time to inhibit the Toll-like receptors, so that interferon production were not signaled at the time when it was needed to fight massive intracellular viral production, then it might well make CV19 worse. 

 

This might even mean its potential best use might be on an as needed prophylactic basis, 1) for high risk CV19 situations similar to prophylactic use going into malarial areas,, or 2) if people were known to be exposed, as part of contact tracing to offer them HCQ if they did not have contraindications and with clear disclosure of very real severe risks with the medicine (ideally to be taken then also with zinc) as close to an exposure as possible when it might help prevent spike protein bonding to ACE2 receptors in the first place.  

Before there were symptoms.  Even before a positive test result. 

 

(Or, speculating, and this could relate to some people where it does seem by word of mouth to help later, if timing is **after** the Toll-like receptor s have already signaled for interferon such that the body’s own interferon is busy fighting virus and the the HCL is helping to stop spike protein attachments to yet more cells’s ACE2 receptors and helping to slow or stop yet more virus being manufactured in cells already infected so that the interferon has a chance to cope.)

 

Edited May 25, 2020 by Pen

[Skippy]

13 hours ago, Frances said:

I mean who looks to any president, R or D, generally mature, honest, and trustworthy or not, for healthcare advice?

 

13 hours ago, Frances said:

Why would anyone care about any president’s personal opinion on the vaccine?

Exactly! It's so obvious to us, but (taking out the D and R and looking at all respondents to the question), only 37% are able to think rationally about this question.

Question: How would the following developments impact your interest in taking a coronavirus/COVID19 vaccine, if at all?...President Trump says the vaccine is safe:

All respondents:

More interested 14%

Less interested 36%

No more or no less interested 37% 

Not sure 13%

[Frances]

36 minutes ago, Skippy said:

 

Exactly! It's so obvious to us, but (taking out the D and R and looking at all respondents to the question), only 37% are able to think rationally about this question.

Question: How would the following developments impact your interest in taking a coronavirus/COVID19 vaccine, if at all?...President Trump says the vaccine is safe:

All respondents:

More interested 14%

Less interested 36%

No more or no less interested 37% 

Not sure 13%

I guess I just don’t find it surprising that when you take a controversial topic like vaccines and a controversial leader and combine them that rationality goes out the window for some. And if you combine not sure and no more or less, you do get to 50%, so in some respects that’s not too bad for such a long survey.

[Pen]

 

Quote

(then in addition there are potential benefits in reducing cytokines storm...     perhaps more on this tomorrow,

 

So here’s the some more “tomorrow “

 

I think in re “cytokine storm” stage of CV19, HCQ has low level likely help in that because it would help at the Toll-cell receptor stage of signaling for interferon.  But Interferon is needed to fight virus.

Thus a “cytokine storm” like event can be stopped for autoimmunity this way, and when there is not actually a virus present that would help. However,  if there were an actual virus infection, especially a severe one, then stopping the interferon production would be a problem.  Instead for CV19 type cytokine storm, it seems like it would be the interleukine production stage that would need to be stopped, and afaik that isn’t when/where in the whole cytokine process the HCQ acts. 

It also seems increasingly likely that the huge damage being seen may not be cytokine storm, but rather primary viral attachment to ACE2 receptors in numerous tissues not just lungs and damage to those tissues.

Particularly attachment to and damage in circulatory system and blood, so that low O2 at the blood level is actually causing much of the damage to body in numerous ways. Hypoxia. Or also now clots and results of clots. 

And in that case, things that can likely reduce coronavirus spike protein (that’s the crown ends that stick out and fit like keys into the ACE2 receptors) from bonding in first place are likely to be hugely important.  

So D is in that category. And I am taking D3 at upper safe level amount because I think its benefits hugely outweigh risks to me.  

And So too probably from the studies on other viruses is HCQ a substance that reduces spike protein bonding to ACE2 receptors, but I am not taking it because I think it has some serious risks greater than my current immediate risk of infection.  Though with underlying conditions for which HCQ is often prescribed, yes, it is something I would try for if timing were right...  for the CV19 itself very likely, and also in my case to possibly prevent an AI flare up which I tend to get when I get sick with anything. 

 

Edited May 25, 2020 by Pen
Clarity maybe? Still seems unclear...

[Wheres Toto]

5 hours ago, Pen said:

 

I do not think the studies are good, no. 

None are very good.

the French one for reasons you give

others I have been able to read had HcQ given to

1)sicker people 

and/or

2) too late in disease for HcQ ‘s most likely mode of possible action to work (aside from zinc ionophore aspect) 

eta: 

(actually, 48 hours after might even also often  be too late for zinc ionophore aspect too ...  if there’s already substantial tissue damage, or movement into tissues that are hard for drugs to reach)

HCQ alone may (based on SARS1 and Dengue  experimenting) be helpful to stop / decrease spike protein bonding to ACE2 receptors

and might be helpful to slow down or decrease replication inside cells. 

But by 48 hours after diagnosis there pretty much has to have been enough virus already bonded, entered into cells, replicated, and being shed to get a positive test result.which probably means the illness is at a stage already past when many people would be helped by HCQ alone. 

Thus even 50,000 cases would not be  especially meaningful if they are all set up in a way that won’t work well for the probable mode of action of the drug.  

(It seems kind of like concluding seatbelts don’t work if they are only fastened after the crash has already happened.  

Like saying, “You see, we fastened seatbelts on all these car crash victims within 48 minutes after the crash,  and  yet they died at the same rate or more than car crash victims with no seatbelts.”

...and even more useless if the small print reveals that seatbelts were applied too late on the more seriously injured  )

But these limitations may be exactly the reason why it is NOT an effective and safe treatment.    You don't give potentially dangerous medications to people who you aren't even sure are sick.    That's part of the safety/efficacy assessment.   

[Pen]

1 hour ago, Ktgrok said:

yeah...that's not particuarly impressive, especially given how small most of the sample sets were. The larger ones and the RCT ones look like they show it wasn't very effective. This is the link to the chart with results of the various studies mentioned in the article if people want to look.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461643/table/prp2293-tbl-0001/?report=objectonly

 

I wasn’t looking for large numbers. I was looking for likely understanding of the metabolic pathways and other immunological aspects that would be relevant to me. 

Large numbers are really helpful if there’s a well done prospective study with well matched control cohorts.

 I don’t find large numbers especially relevant to trying to understand potential biochemical mechanisms.

If the study I linked was not one about the likely ways that the HCQ works then, in my dealings with mice and electric issues being more my focus yesterday (and is about to be again today), I may have linked a wrong one.  It was in my saved file, but I didn’t reread before linking here.  I’ll look later if I can. 

[ktgrok]

15 minutes ago, Pen said:

 

 

 

It also seems increasingly likely that the huge damage being seen may not be cytokine storm, but rather primary viral attachment to ACE2 receptors in numerous tissues not just lungs and damage to those tissues.

 

 

That does seem to be what we are seeing. 

2 minutes ago, Pen said:

 

I wasn’t looking for large numbers. I was looking for likely understanding of the metabolic pathways and other immunological aspects that would be relevant to me. 

later if I can. 

Right, but those theoretical metabolic pathways are not important if in actual use it doesn't work. Which, in the larger random control trial in that link, as well as other smaller ones, it didn't. 

[Pen]

On 5/25/2020 at 7:06 AM, Where's Toto? said:

But these limitations may be exactly the reason why it is NOT an effective and safe treatment.    You don't give potentially dangerous medications to people who you aren't even sure are sick.    That's part of the safety/efficacy assessment.   

 

Otoh, Lots of people have taken HCQ prophylactically for malaria over the years without knowing which person would develop malaria .   Sometimes even chloroquine which had more risks was taken for months by missionaries and others in malarial areas (before malaria developed resistance), and many did  just fine with it. 

(Or also similar with Amodiaquine, which I think has more risks yet, but seems also to have antiviral effects such as for Ebola )

Edited May 26, 2020 by Pen

[Pen]

33 minutes ago, Ktgrok said:

That does seem to be what we are seeing. 

Right, but those theoretical metabolic pathways are not important if in actual use it doesn't work.

I agree.  If it doesn’t work then it doesn’t.

 

 But I do not agree that any trials that I have read about have thus far proved it does not work.  When I have read the studies that I have been able to read thus far, they have all been seriously flawed as to patients given HCQ being sicker or timing being too late, or both. 

 

 

 

 

 

[ktgrok]

1 minute ago, Pen said:

I agree.  If it doesn’t work then it doesn’t.

 

 But I do not agree that any trials that I have read about have thus far proved it does not work.  When I have read the studies that I have been able to read thus far, they have all been seriously flawed as to patients given HCQ being sicker or timing being too late, or both. 

 

 

 

 

 

Right..but there are no studies showing it does work. 

I have no well done double blind studies showing vanilla ice cream doesn't cure COVID 19. But that doesn't mean that it should be promoted as something that DOES cure COVID 19. Which is sort of where we are with HCQ. And those studies you linked using it on other viruses don't give any impression it generally works for that. Sort of like I don't have any showing ice cream works. 

And given how varied the responses to this illness are, we really can't trust much anecdotal evidence. Someone taking it and getting better isn't really saying anything, given how many people take nothing and get better. You'd need a really large sample size to see a statistical difference, so anecdotes really don't help. 

[Pen]

10 minutes ago, Ktgrok said:

Right..but there are no studies showing it does work. 

I have no well done double blind studies showing vanilla ice cream doesn't cure COVID 19. But that doesn't mean that it should be promoted as something that DOES cure COVID 19. Which is sort of where we are with HCQ. And those studies you linked using it on other viruses don't give any impression it generally works for that. Sort of like I don't have any showing ice cream works. 

And given how varied the responses to this illness are, we really can't trust much anecdotal evidence. Someone taking it and getting better isn't really saying anything, given how many people take nothing and get better. You'd need a really large sample size to see a statistical difference, so anecdotes really don't help. 

 

Do you have anything even in vitro suggesting that ice cream might work?

 

I am not wanting you or anyone else to have HCQ, especially not against your will or sense of what would be right for you personally.

But I would like to be able to have it myself if I had an exposure.   Even for a significant likelihood of exposure, but not certain . Well before a need for hospital stage.  At the right timing, I don’t think it would take the sort of extended use that results in retinal damage etc. Not even close.  I realize heart issues can be sooner, but are pretty rare.  

 

Edited May 25, 2020 by Pen
Fixing error... are there actually any studies whatsoever in cell cultures, in mice, anything that actually puts ice cream on same footing of possibility as HCQ?

[Pen]

https://www.sciencedaily.com/releases/2018/11/181129085538.htm

Amodiaquine antimalarial re ebola. 

[Guest]

One of my musings (definitely not really a theory, and possibly not even a hypothesis) is that maybe HcQ works for people who had an underlying autoimmune disorder, and didn't know it, since it is effective at calming down the immune system for different disorders. So many of the ways CoVID acts seem familiar to me as someone with an autoimmune disorder that has had different symptoms at different times that I'm wondering if that makes a difference in how it is presented. If so, maybe testing for at least the more common antibodies that indicate autoimmune disorders (via bloodwork) would let us know who would best benefit from taking HcQ, especially for people who are in jobs where they have to have close contact with other people. 

[Pawz4me]

30 minutes ago, happysmileylady said:

Does anyone have any experience with how a drug moves from research into clinical trials?  I don't, but another poster mentioned having experience with clinical trials, maybe she has some more info on that transition?  

My assumption is that in order for a drug to enter a clinical trial, there has to be some research on it first.....there has to be enough data to make starting a clinical trial worth it, right?  Clearly, HCQ and remdesivir and some other drugs have shown enough positive data in that research to get trials started, right?  Or is there usually very little data before the trials are started?  

 

ETA:  Should have googled first, I found this

https://www.fda.gov/patients/drug-development-process/step-2-preclinical-research

Presumably, because HCQ is not something brand new from scratch, but something we already had, I would presume that step 1 was skipped, but I would presume that they would have had to do the preclinical research before the trials were actually started.  

This might be helpful

Most drugs would have animal studies done and then move on to a Phase 1 clinical trial in people.

 

[Pawz4me]

6 minutes ago, dmmetler said:

One of my musings (definitely not really a theory, and possibly not even a hypothesis) is that maybe HcQ works for people who had an underlying autoimmune disorder, and didn't know it, since it is effective at calming down the immune system for different disorders. So many of the ways CoVID acts seem familiar to me as someone with an autoimmune disorder that has had different symptoms at different times that I'm wondering if that makes a difference in how it is presented. If so, maybe testing for at least the more common antibodies that indicate autoimmune disorders (via bloodwork) would let us know who would best benefit from taking HcQ, especially for people who are in jobs where they have to have close contact with other people. 

A registry has been set up to try to study how people with rheumatological diseases react to Covid 19. I would hope that would help researchers sort through whether HCQ or other common medicines used to treat AI illnesses might help (or hurt) those who become infected with Covid 19. At this point I think all we have are guesses and conjecture. My own rheumy thinks the medication I'm on might reduce the likelihood of a cytokine storm reaction if I contracted Covid 19. But he was very clear that's just a guess.

[Pen]

13 minutes ago, dmmetler said:

One of my musings (definitely not really a theory, and possibly not even a hypothesis) is that maybe HcQ works for people who had an underlying autoimmune disorder, and didn't know it, since it is effective at calming down the immune system for different disorders. So many of the ways CoVID acts seem familiar to me as someone with an autoimmune disorder that has had different symptoms at different times that I'm wondering if that makes a difference in how it is presented. If so, maybe testing for at least the more common antibodies that indicate autoimmune disorders (via bloodwork) would let us know who would best benefit from taking HcQ, especially for people who are in jobs where they have to have close contact with other people. 

 

Interesting idea! 

 

As a person with autoimmunity etc, I have had a tendency to meet or particularly bond with (out of many people met ) some others with similar problems too.  I think it may be that the irl people I know who have had particular success with HCQ have had either AI or porphyria which is also related to HcQ action, and has some overlap in heme/porphyria disregulation with CV19.  This may explain why I might tend to know people for whom HCQ seems to have worked really well and why it might also for me. 

Perhaps different than general population. 

 

[Pawz4me]

1 minute ago, happysmileylady said:

Thank You.

So the in vitro is in cells, in the little dishes right?  And then the in vivo are the animal studies?  So, generally, before moving on to phase one trials, a drug would have some research done, both in dishes, and in animal testing, am I understanding that right?  

 

 

 

That's my understanding for new drugs. I don't know how it applies to a new use for a drug that has already been FDA approved for treating other conditions.

[Wheres Toto]

 

2 hours ago, happysmileylady said:

Thank You.

So the in vitro is in cells, in the little dishes right?  And then the in vivo are the animal studies?  So, generally, before moving on to phase one trials, a drug would have some research done, both in dishes, and in animal testing, am I understanding that right?  

 

 

 

 

2 hours ago, Pawz4me said:

That's my understanding for new drugs. I don't know how it applies to a new use for a drug that has already been FDA approved for treating other conditions.

 

Generally a brand new compound is studied in vitro on cells, if that is appropriate, then animal studies, safety studies, efficacy studies, large-scale studies, and post release studies.    Some drugs can skip various of these steps for various reasons.  Drugs for conditions that have no current treatments but are fatal or life-debilitating may be fast-tracked.   Sometimes a drug is being studied for one thing, isn't going well but they notice it works for something else (viagra is a good example of this).   If a drug is already available for a different indication, what trials are needed will depend on the differences in the how it is being used.  A big increase in dosage or frequency of dosing or method of administration (in hospital under close monitoring versus by prescription versus OTC) may require additional safety trials before going to efficacy trials.   Sometimes all that's needed is a Phase III trial to make sure it works well for the new indication.   

I worked on a drug that had an indication as an alternative to heparin for anticoagulation during heart surgery for patients with heparin-induced thrombocytopenia.  Since there were limited options for this indication, and it could be a life-threatening situation, they were able to get approval for this comparatively easier.   They then went for a bigger indication ($$$$) as an acute treatment for patients with acute ischemic stroke.   They were able to use the data from the previous Phase I and II studies and start with Phase III studies on stroke patients.  

[Corraleno]

Case study series on 17 patients with lupus who had been taking HCQ for an average of 7.5 yrs before they contracted Covid-19. The results were not good:

Over the course of hospitalization, 76% of the cohort developed viral pneumonia, 65% experienced complications due to respiratory failure, and 29% had acute respiratory distress syndrome. A total of 65% of patients required oxygen therapy, including nasal cannula in five individuals, mechanical ventilation in five, and high-flow nasal cannula in one. Data for the cohort were collected between 29 March and 6 April, and on 7 April half remained in hospital, 36% had been discharged, and 14% had died.

[Wheres Toto]

34 minutes ago, Corraleno said:

Case study series on 17 patients with lupus who had been taking HCQ for an average of 7.5 yrs before they contracted Covid-19. The results were not good:

 

 

I was wondering if they were seeing patients already taking HCQ for other things and then coming down with Covid-19 and how that looked.   

[Vida Winter]

5 hours ago, Pen said:

 

Otoh, Lots of people have taken HCQ prophylactically for malaria over the years without knowing which person would develop malaria .   Sometimes even chloroquine which had more risks was taken for months by missionaries and others in malarial areas (before malaria developed resistance), and many did  just fine with it. 

 

In Oregon it may not be prescribed as a preventative. You have to be admitted to a hospital to receive it.

https://www.oregon.gov/omb/statutesrules/Documents/855.007.0085 Prescriptions for Chloroquine.pdf

[Pen]

6 minutes ago, Vida Winter said:

 

In Oregon it may not be prescribed as a preventative. You have to be admitted to a hospital to receive it.

https://www.oregon.gov/omb/statutesrules/Documents/855.007.0085 Prescriptions for Chloroquine.pdf

 

Yeah. In Oregon, I can hardly even get Sudafed. 

I will do what I can not to be in hospital.  

[Ausmumof3]

WHO temporarily pauses studying hydroxychloroquine due to safety concerns

From CNN's Jacqueline Howard

A bottle and pills of Hydroxychloroquine sit on a counter at Rock Canyon Pharmacy in Provo, Utah. George Frey/AFP/Getty Images

The World Health Organization has temporarily halted studying hydroxychloroquine as a potential Covid-19 treatment in its Solidarity Trial due to safety concerns, WHO Director-General Tedros Adhanom Ghebreyesus said during a briefing in Geneva on Monday.

The decision was made after an observational study was published in the medical journal The Lancet on Friday, which described how seriously ill Covid-19 patients who were treated with hydroxychloroquine and chloroquine were more likely to die.

Tedros said that an independent executive group is now reviewing the use of hydroxychloroquine in WHO's Solidarity Trial. The trial, which involves actively recruiting patients from more than 400 hospitals in 35 countries, is a global research effort to find safe and effective therapeutics for Covid-19.

"The Executive Group of the Solidarity Trial, representing 10 of the participating countries, met on Saturday and has agreed to review a comprehensive analysis and critical appraisal of all evidence available globally," Tedros said on Monday.

"The review will consider data collected so far in the Solidarity Trial and, in particular robust randomized available data, to adequately evaluate the potential benefits and harms from this drug," Tedros said. "The Executive Group has implemented a temporary pause of the hydroxychloroquine arm within the Solidarity Trial while the data is reviewed by the Data Safety Monitoring Board." 

Tedros added that the other arms of the trial are continuing.

"This concern relates to the use of hydroxychloroquine and chloroquine in Covid-19," Tedros said. "I wish to reiterate that these drugs are accepted as generally safe for use in patients with autoimmune diseases or malaria."

[Pen]

Conclusions in India seem to go back and forth

(Some Quotes From articles and google:) 

 

 

New Delhi: A revised government advisory on Friday recommended use of hydroxychloroquine as a preventive medication for asymptomatic healthcare workers working in non-COVID-19 hospitals, frontline staff on surveillance duty in containment zones and paramilitary/police personnel involved in coronavirus infection related activities.

...

Highlighting the studies on prophylaxis of SARS-CoV-2 infection, the advisory stated that a retrospective case-control analysis at ICMR has found that there is a significant dose-response relationship between the number of prophylactic doses taken and frequency of occurrence of SARSCoV-2 infection in symptomatic healthcare workers who were tested for coronavirus infection.

...

 

As was mentioned in the earlier advisory, the drug against the infection is also recommended for all asymptomatic healthcare workers involved in containment and treatment of COVID-19 and household contacts of laboratory confirmed cases.

...

Another investigation from three central government hospitals in New Delhi indicates that amongst healthcare workers involved in COVID-19 care, those on HCQ prophylaxis were less likely to develop SARS-CoV-2 infection, compared to those who were not on it.

The benefit was less pronounced in healthcare workers caring for a general patient population. ...

Besides, an observational prospective study of 334 healthcare workers at AIIMS, out of which 248 took HCQ prophylaxis in New Delhi also showed that those taking HCQ prophylaxis had lower incidence of SARS-CoV-2 infection than those not taking it.

 

...

 

ICMR issues revised advisory on use of hydroxychloroquine - Livemint

3 days ago · The revised advisory issued by the ICMR, however, cautioned that the intake of the medicine should not instill a sense of false ...

 

 

 

 

Hydroxychloroquine (HCQ) study shows increased mortality in COVID-19 patients just ...

16 hours ago · According to the guidelines laid by the Indian Council of Medical Research (ICMR) on the prophylactic use of hydroxychloroquine on ...

 

 

 

 

HCQ breakthrough: ICMR finds it's effective in preventing coronavirus, expands its use

3 days ago · Three studies find that hydroxychloroquine reduces chances of contracting Covid, so ICMR allows more frontline workers to take it as ...

Edited May 26, 2020 by Pen

[Pen]

@Ktgrok  @Quill

https://timesofindia.indiatimes.com/india/no-major-side-effects-of-hcq-should-be-continued-as-preventive-treatment-for-covid-19-icmr/articleshow/76006748.cms

 

Edited May 26, 2020 by Pen

[Pen]

@Quill

https://www.sciencedirect.com/science/article/pii/S092485792030145X

[ktgrok]

So, looking at what we have, seems it is showing it may work for prevention, in people not yet sick, but not good in patients who are already symptomatic. THAT is helpful information. It also looks like it was only worth it as a preventative in high risk situations - those directly caring for COVID patients, or those living with people who are positive, etc. 

[Pen]

23 minutes ago, Ktgrok said:

So, looking at what we have, seems it is showing it may work for prevention, in people not yet sick, but not good in patients who are already symptomatic. THAT is helpful information. It also looks like it was only worth it as a preventative in high risk situations - those directly caring for COVID patients, or those living with people who are positive, etc. 

 

Which is also what I was trying to explain was largely the thrust of the in vitro evidence. HCQ seemed to be able to stop the spike protein, the crown tips that fit like a key into the lock key hole of the ACE2 receptors and allow the virus to enter cell where it can replicate, HCQ first of all seems to be able to stop it from being able to do that key fitting into lock bonding thing. That’s prophylactic very best probable thing it can help with.  Not a complete stop 100% of time, but hugely reduced such that illness could be expected to be milder. 

(ETA not sure how to say this clearly—when it stops the virus from connecting it is apparently a complete stop as far as that virus’s affected protein spike goes, but some other virus / protein spike might still do the bonding.

Still, virus reduction, whether by SD, or masks, or stopping spike protein-ACE2 bond so that virus can’t enter cells, all likely to help outcome.  The HCQ seems probably to change the viruses ‘ protein spikes by ? adding a sugar molecule ? so they no longer fit the receptor so perfectly, not by changing the ACE2 receptors.  Since ACE2 receptors are important for various life functions I prefer treatment to change the virus spike, not wipe out the ACE2 receptors. There is also an acid-base change that seems significant in terms of likely mode of action.) 

2nd, for virus that does get in, the in vitro studies strongly suggest that HCQ can reduce replication speed.

So both of these start as early events in course of illness.  Though they do continue as disease progresses and more cells are affected. 

And it does look like real world evidence is fitting the in vitro studies even in vitro evidence on similar viruses. 

 

It would probably help most the earlier it can be given.  It would help least late and in cases already severe (which is what it was used for in most studies) or bad enough to be in hospital as has been pointed out is all being allowed as “compassionate “ use I guess in my state. I don’t see that there is much compassionate about giving a medicine when it is at a probably too late for it point. And when reading the in vitro studies would show that late stage (and being in hospital is pretty much already late stage in my state) is too late. 

Which, idk, @Quill — how does that fit with your thread title and op?

 

 

Edited May 26, 2020 by Pen

[Guest]

@Pen, it jibes. I don’t know what will happen when the dust settles but I will not be surprised if HCQ *does* have a medically-acknowledged role. 

I do think “they” don’t want people to clamor for the drug; that has already happened at least once. 

[Pen]

18 minutes ago, Quill said:

@Pen, it jibes. I don’t know what will happen when the dust settles but I will not be surprised if HCQ *does* have a medically-acknowledged role. 

I do think “they” don’t want people to clamor for the drug; that has already happened at least once. 

 

It **is** really bad if people who can get access buy it up and stockpile maybe in a garage like some were doing with TP and hand sanitizer etc .  And that supply then probably doesn’t even ever get used because the stockpiles don’t need it and who would want to buy a black market drug that’s been in some jerk’s garage stockpile. .

And I’d not be at all surprised if we someday were to learn that Beijing has been prophylactically treating VIPs with it. 

 

In re stockpiling, or people randomly using it when not needed, I’d just as soon people think it doesn’t work at all when it does help significantly 

But I would like to be able to more easily obtain it ***at right time, which is to say at first serious inkling that even thoytrying to be careful I have been exposed ***  if I feel aI need it.  

It almost seems like opioid pain relievers where actions of criminals and addicts result in people with real pain needs not being able to get it. 

 

[Pen]

From the long thread:

 

o,  Ausmumof3 said: 

https://www.the-scientist.com/news-opinion/disputed-hydroxychloroquine-study-brings-scrutiny-to-surgisphere-67595
 

significant questions raised over the data In the lancet hydroxychloroquine study.  
 

On May 28, an open letter, which has now accrued more than 180 signatories at research institutions around the world, laid out multiple other problems with the study data and analyses. In addition, readers of the study are beginning to ask about the nature and history of Surgisphere, and how it managed to obtain such a complex dataset in a relatively short period of ti

[Amy in NH]

On 5/23/2020 at 8:33 AM, Quill said:

You have a point. But clearly, he must believe it’s protecting him, unless he’s straight up lying about taking it himself, which is certainly possible, but I think, not likely. 

The dude is a pathological liar.  As of April 14, 2020 he has made 18,000 verifiably false or misleading statements since the start of his presidency.

 

[Terabith]

14 minutes ago, Amy in NH said:

The dude is a pathological liar.  As of April 14, 2020 he has made 18,000 verifiably false or misleading statements since the start of his presidency.

 

He is a pathological liar, but I doubt he's lying about this.  Given that there have been some decent studies out of South Korea about its efficacy used as prophalaxis for people exposed, and given when he said he was finishing up a two week course, it lines up with exposure to his valet, who tested positive.  I could totally see a White House doctor prescribing it for that purpose under that circumstance, especially given how excited Trump is about the stuff.  

[Guest]

5 hours ago, Amy in NH said:

The dude is a pathological liar.  As of April 14, 2020 he has made 18,000 verifiably false or misleading statements since the start of his presidency.

 

Well, sure. No disagreement from me there. But, as they say, even a broken clock is right twice a day. 

[ktgrok]

Bummer. https://www.cbsnews.com/news/hydroxychloroquine-coronavirus-prevention-covid-19-study/

[EmseB]

1 hour ago, Danae said:

Don’t worry, advocates will soon explain why this study doesn’t count. 

Did you read the article?

[Joker]

I’m sad it didn’t show to be helpful against Covid but happy it didn’t show to be deadly like so many have been saying. 

[EmseB]

10 minutes ago, Danae said:

Yes.

Just wondering if you saw this part:

"There are some big caveats: The study enrolled people through the Internet and social media, relying on them to report their own symptoms rather than having them tracked in a formal way by doctors. Participants were not all tested for the coronavirus but were diagnosed as COVID-19 cases based on symptoms in many cases. And not all took their medicines as directed."

[ktgrok]

26 minutes ago, Joker said:

I’m sad it didn’t show to be helpful against Covid but happy it didn’t show to be deadly like so many have been saying. 

Same. Was hoping for better news. 

[EmseB]

2 hours ago, Danae said:

So, what part of my post do you think makes it look like I didn’t see that part?  
 

I’d say I was dead on.

That you thought there were some sort of advocates of the drug that would find a reason to discount the study when the flaws are reported right in the article. Those things seem significant and I'm not an advocate of any particular drug. Or are they not significant?

[Penelope]

The Lancet meta analysis has been retracted. Big scandal.

https://www.thelancet.com/lancet/article/s0140673620313246

[PrincessMommy]

37 minutes ago, Penelope said:

The Lancet meta analysis has been retracted. Big scandal.

https://www.thelancet.com/lancet/article/s0140673620313246

just about to post this.  They've been dupped and it was a lie.  The "company" putting out data was a front.  Good grief.  It wasn't just the WHO, etc... but also several prestigious peer-reviewed medical journals. 

"A Guardian investigation can reveal the US-based company Surgisphere, whose handful of employees appear to include a science fiction writer and an adult-content model, has provided data for multiple studies on Covid-19 co-authored by its chief executive, but has so far failed to adequately explain its data or methodology."

https://www.theguardian.com/world/2020/jun/03/covid-19-surgisphere-who-world-health-organization-hydroxychloroquine

Edited June 4, 2020 by PrincessMommy

[Guest]

14 minutes ago, PrincessMommy said:

just about to post this.  They've been dupped and it was a lie.  The "company" putting out data was a front.  Good grief.  It wasn't just the WHO, etc... but also several prestigious peer-reviewed medical journals. 

"A Guardian investigation can reveal the US-based company Surgisphere, whose handful of employees appear to include a science fiction writer and an adult-content model, has provided data for multiple studies on Covid-19 co-authored by its chief executive, but has so far failed to adequately explain its data or methodology."

https://www.theguardian.com/world/2020/jun/03/covid-19-surgisphere-who-world-health-organization-hydroxychloroquine

Well, dang. Curiouser and curiouser. 

I am beginning to think there is no such thing as the truth. Or, that none of us can really expect to get it from any quarter.