Hydroxychloroquine Update for April 6

https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hydroxychloroquine-update-for-april-6

by hprotagonist • 6 years ago

76 94 6 years ago

blogs.sciencemag.org

kevingadd10• 6 years ago

The possible high-mortality interaction with metformin is a terrifying prospect. Diabetes is so common... hopefully it's something that doesn't apply to humans.

buboard3• 6 years ago

In mice. Hcq has been around for a long time, you d think that if it was so lethal in humans someone would have noticed

m0zg8• 6 years ago

Counterpoint: http://www.leparisien.fr/societe/sante/chloroquine-ne-perdon...

You can do double blind studies until your patients are literally blue in the face, or you can try what works now. That is literally the choice at the moment.

According to Peter Navarro, a good percentage of NYC patients are getting HCQ at the onset of symptoms now. Cuomo wants more of it, because it "appears to be working". Oklahoma is giving it to patients, too (https://www.news9.com/story/41972631/state-secures-possible-...), as does LA (https://twitter.com/ABC7/status/1246998628331163649). Italy saw its numbers of deaths stabilize once they started giving it. Marseille (where Raoult's hospital is) has the lowest fatality rate in all of France. If it works, we should see the recoveries shoot up in 5-7 days.

HCQ is also available _over the counter_ in some countries, and is given out like candy all over Africa where there's risk of malaria.

kevingadd10• 6 years ago

The fact that you can buy the drug over the counter doesn't mean it's universally safe. The people being hospitalized here are already doing poorly so exposing them to additional risk is not something you should just do on a whim. As the linked post mentions, there are clear signs of potential risks associated with the use of HCQ. I hope for the patients being dosed with it now that it both works and is safe, but it's incredibly reckless to go 'it's over the counter so it's fine'. A healthy person taking a reasonable dose as a malaria countermeasure is not the same as a person on a ventilator in the ICU. Their immune system is in a different condition, so is their heart.

m0zg8• 6 years ago

doesn't mean it's universally safe

_Table salt_ is not safe. Eat 100 grams of it and you will die. This does, however, mean that it's not as "dangerous" as the mainstream press wants you to believe. It's a 50 year old drug used all over the world. If it was "deadly", we'd know it by now.

CDC itself recommends taking it _as a prophylaxis_ when heading to the areas where malaria might be present: https://www.cdc.gov/malaria/travelers/drugs.html

Mountain_Skies2• 6 years ago

Is it being used as a treatment for those already on a ventilator? My impression is that it is being used as a way to help prevent patients from getting to the point of needing a ventilator.

xienze5• 6 years ago

A healthy person taking a reasonable dose as a malaria countermeasure is not the same as a person on a ventilator in the ICU.

Well I don’t think a person on a ventilator is in any position to self medicate, a doctor who presumably knows what they’re doing would be the one to direct the course of treatment. What’s the problem with that? There’s literally no “established” treatment for Covid 19 other than “hope we can keep you alive long enough for your immune system to beat it”, so under a doctor’s care I really don’t think there’s a lot of downside to trying to establish the efficacy of certain drugs in lieu of a long trial process.

tptacek10• 6 years ago

Substantial numbers of C19 patients are being given HCQ in C19 trials, but more than that, substantial numbers of newly-diagnosed C19 patients are already taking HCQ, since it's part of the standard of care for widespread conditions like rheumatoid arthritis. And those patients will of course have had the HCQ intervention before acquiring C19, not late in the course of their illness. It doesn't look like anyone is reporting unusual clinical success for those patients, while you can find clinical reports of QT disturbances (so: people are paying attention to this stuff).

strken• 6 years ago

Dosages for arthritis are pretty low, though.

ceejayoz3• 6 years ago

“You can do double blind studies until your patients are literally blue in the face, or you can try what works now.”

https://en.wikipedia.org/wiki/Politician%27s_syllogism

legostormtroopr• 6 years ago

Linking to wikipedia articles about logical fallacies isn't a debate tactic.

jonny_eh• 6 years ago

or you can try what works now

If you don't do studies, how else do you know if it works? Or what dosage? Or when to administer? Or downsides?

threeseed6• 6 years ago

Peter Navarro

An economist with zero medical background who from media reports is fighting against Fauci on this issue.

Any hint of a cure will be taken by people as a reason to ignore social distancing and stay at home rules. Which will directly cause an uptick in cases and deaths. Hence we need to be very, very sure that any cure is a real one.

bb88• 6 years ago

Any drug with a high efficacy should be seen in small sample sizes.

E.g. As a sample size of one, I know that consuming alcohol has a relaxing effect. And that's highly testable, one I wouldn't mind participating in.

If n=11 and there was no deviation from the normal expectation, it's possible that there was some undetectable effect, but it's far more likely there was no effect.

stri8ed• 6 years ago

Kentucky is giving it to patients, too.

Source?

Italy saw its numbers of deaths stabilize once they started giving it.

It appears the total number of cases also decreased. Which would suggest effect is likely due to social distancing.

Marseille (where Raoult's hospital is) has the lowest fatality rate in all of France

Source?

Klonoar2• 6 years ago

Opting to listen to Navarro over Fauci is a very odd choice.

Look, I get that certain discussions on this damn site resist dragging politics into it all, but this is pretty important: Navarro has nowhere near the qualifications that Fauci does and there is no reason to listen to him on this.

You're contributing to a larger problem with misinformation at a time when it's not needed. Listen to the medical professional, not the economist.

tptacek10• 6 years ago

I think he's just relying on Navarro's reporting that HCQ is being used in NYC, which, it clearly is; it looks like it's being tried all over the place. You can probably safely quote administration officials on something that simple. If he quoted Navarro saying HCQ was working, that would be problematic, especially because it doesn't seem to be working.

m0zg8• 6 years ago

Yale School of Medicine is onboard with HCQ as well. I guess they're total schmucks over there, nowhere close to the genius of Derek Lowe, who's not even a doctor. /s

Why can't you people admit that Trump was right?

https://files-profile.medicine.yale.edu/documents/7801c631-3...

ck2• 6 years ago

While other drugs are looking far more promising, there might be an obvious reason why despite lack of clear proof/results the president is pushing it so hard like everything else that motivates him: https://lawandcrime.com/covid-19-pandemic/major-producer-of-...

Mountain_Skies2• 6 years ago

Is it possible to corner the market on a generic drug that is produced across the world?

kevingadd10• 6 years ago

Given the widespread shortages of the drug, you could operate on a 'rising tide lifts all boats' model here and if you're one of only 3 large scale suppliers you know that you and your competitors will all be selling more product.

I don't think it makes sense as a reasoning for boosting HCQ, though, and there are more obvious reasons why he'd promote it. If you want to make money this isn't how you do it.

threeseed6• 6 years ago

Who says you need to corner the market ?

It's much easier to ramp up production than start an entirely new process with a new drug. And given we are talking about timeframes of weeks and months and not years all of the existing manufacturers will have a significant lead.

xienze5• 6 years ago

It’s a decades-old generic drug that multiple companies produce. Literally anyone with the means to do so can make it. There’s not a lot of money to be made with a drug that costs $5 for a course of treatment. You might have a point if he was pimping some brand new drug that cost $5000 a month.

dmh20002• 6 years ago

that wouldn't explain why Gov Cuomo is also a fan

raphlinus• 6 years ago

I'm a fan of this review, and of Derek Lowe in general. I especially like the way he explains effect size and also the reasons why we have to be cautious when looking at promising drugs.

Another take, by James Hamblin at the Atlantic: https://www.theatlantic.com/health/archive/2020/04/hydroxych...

This is written for a more general audience, and is not shy about taking on the more political aspects, including the clashing agendas of the people promoting HCQ and those urging a more skeptical approach.

mirimir3• 6 years ago

Yeah, I'm a huge fan too. And this is a great summary and perspective.

war1025• 6 years ago

My completely anecdotal experience with the Hydroxychloroquine story is that researchers keep pooh-poohing it and people in the field keep having success with it.

All I know is that based on the aggregate of information I've seen thus far, if I come down with Coronavirus, I want to be prescribed that stuff.

tptacek10• 6 years ago

Can you cite American clinical testimonials for HCQ? HCQ trials appear not to be controversial: they're being tried widely. Who's saying it's working?

benjohnson• 6 years ago

Quinine used to come from the bark of a tree - that bark is available as a nutritional supplement. It's also is used to make the bitter taste of Tonic Water.

buboard3• 6 years ago

Someone did the calculations. Ppl need to drink 200 gin tonics per day

hprotagonist• 6 years ago

it mostly still does. You _can_ synthesize it but the yield's godawful.

csours• 6 years ago

Regression to the mean is a huge problem with anecdotes. Some people get better. It may be due to some treatment, or they may just get better. This is why we have structured studies.

jschwartzi• 6 years ago

Yeah, I guarantee you that even with a 10% fatality rate 90% of people will get better spontaneously on their own. So any prospective treatment would have to do better than the recovery rate without treatment.

This is really a situation where the phrase "the plural of anecdote is not statistics."

pazimzadeh2• 6 years ago

Taking Chloroquine too soon might promote viral infection by inhibiting the anti-viral response. https://sciencedirect.com/science/article/abs/pii/S016635421...

CQ is for patients who have uncontrolled inflammation in response to the virus, not to be taken as a prophylactic.

dionian• 6 years ago

Chloroquine is more toxic than Hydrochloroquine, isn't it?

kevingadd10• 6 years ago

IIRC the addition of the hydroxy to the drug means it's going to be more water-soluble so it would be easier to excrete in urine and flush it out of the system, which would count as "less toxic" if you squint when reading the paper

I haven't seen any detailed discussions of the differences in toxicity, but one physician made a comment to that effect.

HarryHirsch3• 6 years ago

There is a clinical trial going on to check for just that. The hope is that when taken as a prophylactic it prevents entry into cells and give the immune system an advantage over the pathogen, but as you say, the immunosuppressive effects are a concern. We'll see soon enough.

tptacek10• 6 years ago

Repeating myself, but: there's an extent to which that trial has already been running naturally, since lots and lots of people take doses of HCQ comparable to the C19 protocol already, for rheumatoid arthritis. Lots of those people are getting C19. Are you seeing reports that arthritic patients who get C19 are faring better?

hexl2• 6 years ago

If I remember correctly, someone on twiv's podcast said that the inmune inhibition occurs months into treatment for lupus patients taking HCG. So, Could you explain in layman terms why this is not the case? Most of us have no clue about what's being discussed in the paper.

pazimzadeh2• 6 years ago

I haven't seen any evidence that (Xydroxy)chloroquine alone directly inhibits anything to do with the viral replication. The closest thing that I found is that Thymoquinone inhibits Mouse coronavirus replication and is generally protective of lungs:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933739/ https://erj.ersjournals.com/content/50/suppl_61/PA4935

Chloroquine is an antipyretic and relieves symptoms like fever from diseases like Malaria and dengue.

Chloroquine stops the inflammation from going out of control, which a good thing during an infection. But if you take it when you don't have an infection, it could stop you from detecting viruses in the first place.

The paper I cited in the previous comment mentions that Chloroquine is a TLR7 inhibitor. TLR7 is a receptor that senses of single-stranded viral RNA. https://www.sciencedirect.com/science/article/abs/pii/S01663...

dmh20002• 6 years ago

isn't it the azithromycin that causes the arrhythmia and i heard it is recommended to use doxycycline instead for anyone vulnerable to that side effect.

kevingadd10• 6 years ago

Erythromicin and azithromycin can have a negative effect but supposedly the chloroquine ALSO can have an effect, so subbing in doxycycline will help but might not be enough.

sunnyP• 6 years ago

I just read an article where Dr. Mohammud Alam in Long Island is treating covid19 patients that have heart issues with that combination. https://townhall.com/tipsheet/katiepavlich/2020/04/06/here-a...

moron4hire• 6 years ago

Why are we talking about drugs in the public media? This is like people demanding certain drugs from their doctors because they saw it in pharmaceutical commercial.

kevingadd10• 6 years ago

In part there's a desire to tell people that we have "a cure" or "a vaccine" ready to go because it suppresses panic and anxiety by creating the impression that the problem is solved. Naturally, telling people that before it's actually true causes new problems, so now we have people fighting to combat misinformation.

rsynnott• 6 years ago

Because various high profile idiots have been lying about them. In an ideal world maybe this would be staying out of the public eye, but it’s a bit late to put the genie back in the bottle now.

threeseed6• 6 years ago

Because it's actively being pushed by right-wing media and the President.

We have a Presidential election in November. And there is a proven, strong correlation between the strength of the economy and your chance of being elected. You can't have a strong economy and people feeling happy when they are stuck at home without a job and fearful of leaving the house.

So they need to get people back to work. And the only way that happens is if you can convince people that it's okay to get COVID-19 because there is some magical drug that will cure you if you end up in hospital.

seppin2• 6 years ago

Facts. Sad, depressing facts.

brandon272• 6 years ago

That might work if the election was say, within the next 15 to 30 days. Trying to scam the general population into believing that an unproven drug is some kind of "magic" cure is an awfully bold and risky move 7 months from an election, especially before a potentially staggering number of deaths has been realized.

tmaly• 6 years ago

The original research paper circulating on Hydroxychloroquine was from Tom Broker. He was a student of my good friend's father at Wesleyan University.

robocat• 6 years ago

“hydroxychloroquine itself actually lowers the activity of the innate immune system; that’s why people take it for lupus and for rheumatoid arthritis. Many people are saying that perhaps it will work best if taken early in the course of infection” (from article.)

Yet HCQ takes a very long time to act as an efficient immunosuppressant (1 to 3 months for Lupus) as per https://news.ycombinator.com/item?id=22798370 which seemed factual; but anyone have references to how long HCQ takes to become immunosuppressant?

Hydroxychloroquine has a long half life in the body, so you have to wonder what effects there will be from using it, especially if it turns out to be ineffective.

The original idea HCQ was useful was from long term users of HCQ, which may have quite different biological effects from short term usage in reaction to dosing.

Also perhaps Lupus has a confounding factor that makes Lupus sufferers less susceptible to Covid19?

treeman793• 6 years ago

I have Sjogrens. A cousin to Lupus.

One month after starting this drug I noticed a decrease in symptoms.

I stopped taking it for a couple weeks. Symptoms started again.

So works but is slow. The stimulant aspect however hits in an hour and last all day, and into the next morning. And oddly seems have some viagra like effects. I have to really be careful if I take other stimulants.

Antibiotics also keep symptoms at bay, but doctors won’t write script despite success.

This drug does a lot to the body. Good and bad.

nwah1• 6 years ago

Various doctors have been using chloroquine with high dose zinc. One idea is that chloroquine is simply a zinc ionophore, and its other effects aren't so relevant. Zinc has a long history of being recognized as an important nutrient for the immune system.

https://journals.plos.org/plosone/article?id=10.1371/journal...

m0zg8• 6 years ago

In the left corner we have Derek Lowe, who's not a doctor.

In the right corner we have the Yale School of Medicine which recommends HCQ for both the mild and severely ill patients: https://files-profile.medicine.yale.edu/documents/7801c631-3...

Let's see who will win.

zimpenfish2• 6 years ago

That Yale flowchat is basically "throw whatever we can at the patient and hope that something works". It's not a considered plan of treatment that has been thrashed out over years of trials and experiments.

m0zg8• 6 years ago

As opposed to Derek Lowe's "considered plan of treatment"?

Hydroxychloroquine Update for April 6

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