Rational CoViD-19 Discussion Thread: Science vs. Politics

[babe]

Pretty sure now that the "Pandemic" is not exactly that.....more of a Political Panic or darkside Psy-op....

So in countries where malaria is a widespread concern, there is still no exponential outbreak, presumptively because of the prophylactic (preventative) action of hydroxychloroquine (Chloroquine).

In the US the reluctance of officials from the FDA and CDC to just push this well-understood preventative and curative chemical agent undoubtably is costing human lives. We do, however, have a large (1100 patient) clinical evaluation underway, and some of the governors who objective to the off-label use of it for their patients have now reversed themselves.

Choroquine is a very simple derivative of benzene, and can be made by the ton, literally speaking in a two-step synthesis, chlorination and oxidation reactions. It is generally prescribed with a 400 mg initial dose, followed by two 200 mg twice daily dose for ten days. CoVid-19 is not seen in patients who have been on this drug for other causes. Patients presenting with CoViD-19 who are treated with Chloroquine recover generally if they are not too far along and in ARDS condition, where the respiration machines are maxxed out and still the patient is not getting enough oxygen and is unconscious. In such patients, the drug is administered via fluid drops along with other life-sustaining stuff like dextrose. Some reports include cases where an antibiotic is co-administered.

The real seriousness of this virus cannot be overstated. It destroys lung tissue in the alveoli and impressively creates conditions for secondary infections with bleeding that means general whole-body spread of the infection, toxemia which damages vital organs and shuts them down.


Going over the testing data I can state that 98% of US citizens have no virus at present, and that 80% of people who have had the virus do not present as "serious". Of the serious cases, 80% are recovering, which means the death rate will turn out to be about 0.32% That calculates to a total death count of just under 200,000 Americans when we have all been through this./

Of continuing concern is the likelihood that we will not be able to produce an effective vaccine due to the HIV-like resistance to that. Still, even with HIV we now have combo therapies along with some vaccines that do fairly welll, if I have been properly informed.

The likelihood of achieving "herd immunity" is for similar reasons unlikely.

On the bright side, it looks to me like the CoViD-19 virus will not prove hardy enough to last in the real world, and our episode with it will turn out to be singular.

I might also point out that if we track patients and give everyone who has contacted a positive case of CoViD-19 a treatment with hydroxychloroquine, we can obliterate this disease completely,. like we did smallpox.

I am not convinced there ever was an animal source, more likely it was a lab rat error, some careless worker walking out of the Wuhan lab with the virus on his shoe, or clothes, or infected with it from his clumsy work . EVERY DAMN THING OUR SCIENTISTS EVER CREATE IN THE LAB WILL ONE DAY GET OUT ON THE STREET AND MAKE IT'S TURN AROUND THE WORLD.

And I say that as a one-time student of Mario Cappechi. Well I took his courses in genetic manipulations.

Still, folks, if you have any sort of compunction to eat uncooked critters like snakes, bats, fish, toads, lizards, I bless you and pray for a very quick Darwinian selection event. We just don't need humans that stupid/.

In that light, all of you true believer Darwinian Theorists might consider this. You have a religion disease based on homologies in the enzyme Cytochrome C. The evolutionary tree producted if you look at other fairly important functional genes/enzymes is NOT the same.

For example, we are with respect to insulin, brothers to the pigs. With respect to some neurological enzyme, we are cousins to the rattlesnake. And in quite a few respects we can claim fungal relatives.

Of course, these things can happen in nature with chronic host/parasite relations, occasional uncooked body fluid exchanges or uncooked digestive delicacies. Some proteins like antibodies can cross our gut and intestinal membranes and even get into cells elsewhere, and hey, if they produce something with some real survival value, it might not just get flushed or catabolized, and the same goes for DNA sequences.

 

[babe]

On the wild side, now..... hey, the above comments probably look wild enough...…. But "The Word On The Street" from China...… still lots of rumors about cremation factories, people being paid to keep quiet or removed from public contacts for re-education/whatever..... cremations still going on thousands per day, and rumor has it, over twenty million cell phone accounts disappeared.....


I am not willing to give full faith and credit to such things any more than I do to official reports, but Xi is out there bragging about how much better totalitarian governments can manage a pandemic. They are running a huge propaganda push all over the world with their offers of medical supplies and testing kits.

There is now a mobile cold storage unit outside I think every Utah hospital, and FedEx is hauling units all over the country for storing bodies which cannot easily be run through a morgue for a funeral. No kissing uncles Bob as the casket is closed.

 

[One Brow]

So in countries where malaria is a widespread concern, there is still no exponential outbreak, presumptively because of the prophylactic (preventative) action of hydroxychloroquine (Chloroquine).

In the US the reluctance of officials from the FDA and CDC to just push this well-understood preventative and curative chemical agent undoubtably is costing human lives. We do, however, have a large (1100 patient) clinical evaluation underway, and some of the governors who objective to the off-label use of it for their patients have now reversed themselves.

There is no reliable evidence chloroquine works, and the hospitals that are using don't see an effect. There is no reason it should work.

Meanwhile, prescribe something that doesn't work for COVID19 makes harder to get for the patients who have a genuine for chloroquine (malaria and lupus sufferers).

 

[infection]

There is no reliable evidence chloroquine works, and the hospitals that are using don't see an effect. There is no reason it should work.

Meanwhile, prescribe something that doesn't work for COVID19 makes harder to get for the patients who have a genuine for chloroquine (malaria and lupus sufferers).

There's anecdotal evidence (from physicians) regarding its use. Then there's one French study that's controversial. But the "reliable evidence" regarding it wouldn't, and couldn't, exist currently. At least the way we speak when we say that. It's impossible for that evidence to exist at this moment. You have to interpret availability of evidence, or lack thereof, within an appropriate context. Also an appeal to biological mechanism is often misleading, because the mechanisms by which many medications work isn't how a lot of medications actually work, but since we're human we like explanations and we choose the best available to ease our anxieties about the unknown. For instance, there's really no reason why hydrochlorothiazide (a diuretic) should work for diabetes insipidus (a condition characterized by frequent urination), but it does.

Anyhow, there's a huge conflation between the idea of "no evidence" and "negative evidence" and it misleads not just the general public, but a lot of otherwise intelligent people in healthcare and science related fields.

To suggest that there isn't evidence that it works would be true (but is not the same as negative evidence). But to suggest that because there isn't evidence that it works means it shouldn't be utilized is just as silly as saying it works and that everyone should take it. These decisions are best left to physicians with the relevant training who are managing sick patients, and not to bureaucrats.

 

[One Brow]

There's anecdotal evidence (from physicians) regarding its use. Then there's one French study that's controversial. But the "reliable evidence" regarding it wouldn't, and couldn't, exist currently. At least the way we speak when we say that. It's impossible for that evidence to exist at this moment. You have to interpret availability of evidence, or lack thereof, within an appropriate context. Also an appeal to biological mechanism is often misleading, because the mechanisms by which many medications work isn't how a lot of medications actually work, but since we're human we like explanations and we choose the best available to ease our anxieties about the unknown. For instance, there's really no reason why hydrochlorothiazide (a diuretic) should work for diabetes insipidus (a condition characterized by frequent urination), but it does.

Anyhow, there's a huge conflation between the idea of "no evidence" and "negative evidence" and it misleads not just the general public, but a lot of otherwise intelligent people in healthcare and science related fields.

To suggest that there isn't evidence that it works would be true (but is not the same as negative evidence). But to suggest that because there isn't evidence that it works means it shouldn't be utilized is just as silly as saying it works and that everyone should take it. These decisions are best left to physicians with the relevant training who are managing sick patients, and not to bureaucrats.

There are two French studies (both with no control groups, from the same guy), and two Chinese studies (one showing no effect, the other showing an effect at p value 0.045).

We known about corona viruses for decades (SARS, MERS, etc.). Did chloroquine ever work on them before? Doesn't chloroquine itself cause side effects?

You'll find physicians who prescribe coffee enemas for cancer and similar nonsense. That some physicians have a nice story doesn't make something true or likely.

 

[infection]

There are two French studies (both with no control groups, from the same guy), and two Chinese studies (one showing no effect, the other showing an effect at p value 0.045).

These studies are small. Too small. The Chinese studies are using mild patients (if you'll look at any of my comments, I qualify to discuss sick or hospitalized patients). With death rate anywhere from 1-4%, you need some really big sample sizes in studies to eliminate noise, and it does not appear that death were the primary outcomes of studies. And the point about the French study highlights the fact that you're in the middle of a pandemic and getting large sample sizes that are double-blinded and placebo controlled are nice because those are the buzzwords everyone mentally masturbating over literature loves, but its applicability on the ground-level isn't as applicable as it seems to those sitting in arm chairs critiquing data.

We known about corona viruses for decades (SARS, MERS, etc.). Did chloroquine ever work on them before? Doesn't chloroquine itself cause side effects?

It does, but you're looking at risk versus benefit. That's why I say these decisions are best left to people actively treating individuals because the variance in clinical situations are enormous, even if we like to distill everything down to "good/bad."

You'll find physicians who prescribe coffee enemas for cancer and similar nonsense. That some physicians have a nice story doesn't make something true or likely.

Sure, but where do you think medical treatments arise from before there's data to support it?

I have no skin in the game on hydroxychloroquine. I'm open to whatever it shows, and I'd prefer to hear of any solutions we could have that could improve things, hydroxychloroquine or not. If it has no benefit, I'm very open to that. If it's to be accepted, it would need to be on appropriate evidence for the circumstances. Likewise if it's rejected, it would have to be on appropriate evidence for the circumstances. People advocating that it's a miracle cure (not seeing tons [any] of those in the medical community) are just as ridiculous as those positive that there's no benefit (seeing a few of those). Essentially we're at a point of appropriate agnosticism. I don't have any belief one way or the other. I'm amused by those thinking there's certainty on either side, but there's a lot more perceived certainty on one side of the issue.

That's why I say that the decision for its application is best done by people on the ground level taking care of sick patients. There are a lot of things I do in my specialty that have insufficient evidence because situations are so unique. And too often people so far removed from anything I treat have strong opinions based on very incomplete information that has, at best, tangential relevance to situations I'm involved in. The only difference is that those strong opinion holders have no first hand experience actually managing the conditions I am.

Consider, for a moment, this systematic review from the British Medical Journal on the effectiveness of parachutes for preventing death and major trauma as a result of gravitational challenge:

https://www.bmj.com/content/327/7429/1459

But if we want a meaningless appeal to perceived authority, the FDA has authorized emergency use of hydroxychloroquine for COVID-19. That doesn't really mean anything to me. But what it should mean to others is that if an intensivist is treating patients in an ICU, it's certainly reasonable for them to use it if they feel it's warranted.

 

[infection]

My tl;dr on this is that I'm a very big proponent, with regard to anything, on doing the right thing for the right reasons. Too often we end up at the right conclusion but got their the wrong way, and we celebrate that, only to allow that same logic to fail us in the future because we think it's foolproof. Same thing about why you show your work on a math problem. Sure, perhaps one could arrive at the right answer. But if they got that answer going about it the wrong way, it's going to be problematic in the future. Hydroxychloroquine may not be beneficial. In fact, perhaps it's even harmful for use in COVID-19. But we haven't arrived at all reached a point where we know that. Perhaps we could. But if that's the case and we arrive there with the knowledge we have now, it' won't be because we've gotten the right answer the right way. I suppose we could blindly celebrate that, then allow our poor reasoning to lead us into poor future decisions.

 

[One Brow]

These studies are small. Too small. The Chinese studies are using mild patients (if you'll look at any of my comments, I qualify to discuss sick or hospitalized patients). With death rate anywhere from 1-4%, you need some really big sample sizes in studies to eliminate noise, and it does not appear that death were the primary outcomes of studies. And the point about the French study highlights the fact that you're in the middle of a pandemic and getting large sample sizes that are double-blinded and placebo controlled are nice because those are the buzzwords everyone mentally masturbating over literature loves, but its applicability on the ground-level isn't as applicable as it seems to those sitting in arm chairs critiquing data.

It does, but you're looking at risk versus benefit. That's why I say these decisions are best left to people actively treating individuals because the variance in clinical situations are enormous, even if we like to distill everything down to "good/bad."

I agree the studies are too small. Applicability at the ground level includes using treatments that you think have a chance of working.

There's been no testing on the effects of mega-doses of beta-carotene on COVID19, to my knowledge. So, if some person prescribes mega-doses of beta-carotene (or Vitamin C, etc.), why not? Is that all good? Perhaps you could toss in 15 different random things in the hope that works?

The notion of risk vs. benefit implies you have to have some reason to think there is a benefit.

Sure, but where do you think medical treatments arise from before there's data to support it?

IIRC, penicillin came from observations of mold in a dish. Your prior example, if I were to hazard a guess, came from someone being prescribed hydrochlorothiazide for blood pressure when they also happened to have diabetes. Both have since been extensively investigated.

There's been no testing on the effects of mega-doses of beta-carotene on COVID19, to my knowledge. So, if some person prescribes mega-doses of beta-carotene (or Vitamin C, etc.), why not? Is that all good? Perhaps you could toss in 15 different random things in the hope that works? I take Advair. If I report that my hair loss has slowed down/reversed, should doctors across the country start prescribing Advair for hair loss?

The notion of risk vs. benefit implies you have to have some reason to think there is a benefit.

I have no skin in the game on hydroxychloroquine. I'm open to whatever it shows, and I'd prefer to hear of any solutions we could have that could improve things, hydroxychloroquine or not. If it has no benefit, I'm very open to that. If it's to be accepted, it would need to be on appropriate evidence for the circumstances. Likewise if it's rejected, it would have to be on appropriate evidence for the circumstances. People advocating that it's a miracle cure (not seeing tons [any] of those in the medical community) are just as ridiculous as those positive that there's no benefit (seeing a few of those). ...

Consider, for a moment, this systematic review from the British Medical Journal on the effectiveness of parachutes for preventing death and major trauma as a result of gravitational challenge:

https://www.bmj.com/content/327/7429/1459

But if we want a meaningless appeal to perceived authority, the FDA has authorized emergency use of hydroxychloroquine for COVID-19. That doesn't really mean anything to me. But what it should mean to others is that if an intensivist is treating patients in an ICU, it's certainly reasonable for them to use it if they feel it's warranted.

I'm positive there's no scientific reason to suppose a benefit from chloroquine on COVID19, just as I'm positive there's a scientific reason to suppose a benefit of parachutes.

I agree that people relying on the FDA's guidelines are being reasonable in that they are not engaging in malpractice. I have an issue with the FDA ruling on that.

 

[infection]

I agree the studies are too small. Applicability at the ground level includes using treatments that you think have a chance of working.

There's been no testing on the effects of mega-doses of beta-carotene on COVID19, to my knowledge. So, if some person prescribes mega-doses of beta-carotene (or Vitamin C, etc.), why not? Is that all good? Perhaps you could toss in 15 different random things in the hope that works?

The notion of risk vs. benefit implies you have to have some reason to think there is a benefit.

This depends largely on the situation. For instance, if people are talking about "mega-doses of beta-carotene" for the treatment of prostate cancer with anecdotal reports, I'd overall be fairly skeptical. I wouldn't think much of it, but I'd surely be interested if there was a way to demonstrate what, if any, effect there may be. With mega-doses of Vitamin C, your risks are fairly minimal. It may translate to taking a more agnostic approach. Eg, patient has strong belief in this while undergoing treatment for prostate cancer. May take a hands off approach stating that the risk for harm is low, and they can try it if they want, but you're not necessarily recommending it but, rather, tolerating it.

Change mega-doses of vitamin C to mega-doses of lithium orotate and your equation completely changes. You know it would be harmful at those doses. In the absence of any evidence other than anecdotal, the risk outweighs the potential benefit.

Now change the scenario again where it's mega doses of vitamin C for COVID-19. It's cost is low and it's toxicity is low. Unless there was better evidence, I probably wouldn't do anything. If there was enough anecdotal evidence from treating physicians, then it will change your equation. The anecdotal evidence will precede large trials. That doesn't mean it will be consistent with it, but the fact that the evidence in the form of controlled trials would lag behind it shouldn't come as a surprise to anyone. So it again rolls down to risk vs. benefit. The risk is higher with hydroxychloroquine than with vitamin C, but the anecdotal evidence coming from treating physicians (which can be flawed, obviously) is greater than that of vitamin C. So this is where it's appropriate to defer to those treating the individual who can better weigh that possible risk. If you're talking about someone with low acuity receiving prostate cancer treatment, that's much different than someone currently intubated in the ICU. The virus is something we don't have familiarity with. Treating it is going to require more flexibility than things we have a long track record with. It's going to require a lot of guess work. It's a fluid environment that will require people on the ground to do things where they're in uncharted waters.

I take Advair. If I report that my hair loss has slowed down/reversed, should doctors across the country start prescribing Advair for hair loss?

Is your hair loss part of a pandemic that people are dying from for which there's currently no treatment and an active body count? If it is, it's worth getting that discussion out there.

The notion of risk vs. benefit implies you have to have some reason to think there is a benefit.

Used in other countries and anecdotal reports of many physicians. This is poor evidence for a lot of situations, but the threshold for "evidence" becomes lower in an unprecedented situation such as this. Again qualifying that this may very well be wrong. I don't have any opinion at all whether or not it is beneficial. But you have to understand what the current "best evidence" is, and currently "best evidence" doesn't exist at the level of a meta-analysis.

 

[infection]

I'm positive there's no scientific reason to suppose a benefit from chloroquine on COVID19, just as I'm positive there's a scientific reason to suppose a benefit of parachutes.

"Scientific reason" meaning what? Did you know there's no scientific proof that the flu vaccine, before its release, reduces morbidity or mortality? It's actually in the package insert. This leads a lot of dense people to poor conclusions, because they don't realize that the flu vaccine is different every year, and while it's technically true a priori, it definitely has proved to be true each year. But it technically isn't proved until it's out there. That doesn't mean that everything that doesn't have evidence eventually will have evidence, but do you not see the flaw in stating that because there's no evidence it means there won't be evidence? Anecdotal evidence isn't good evidence. But it's not no evidence. Especially if those anecdotes is a large plural of practicing physicians managing active COVID-19 cases, and not some backwoods grandpa with a new elixir. If a tree falls in the forest and there wasn't a double-blinded, placebo controlled trial observing it, did it happen?

 

[One Brow]

"Scientific reason" meaning what? Did you know there's no scientific proof that the flu vaccine, before its release, reduces morbidity or mortality? It's actually in the package insert. This leads a lot of dense people to poor conclusions, because they don't realize that the flu vaccine is different every year, and while it's technically true a priori, it definitely has proved to be true each year. But it technically isn't proved until it's out there. That doesn't mean that everything that doesn't have evidence eventually will have evidence, but do you not see the flaw in stating that because there's no evidence it means there won't be evidence? Anecdotal evidence isn't good evidence. But it's not no evidence. Especially if those anecdotes is a large plural of practicing physicians managing active COVID-19 cases, and not some backwoods grandpa with a new elixir. If a tree falls in the forest and there wasn't a double-blinded, placebo controlled trial observing it, did it happen?

I was aware of that for the flu, in particular, that there is scientific evidence it will be effective against the strains it is designed to combat, but little evidence those will be the strains you need protection from.

I understand that there might be evidence that springs up. I'm not opposed to, for example, actual clinical trials on chloroquine and COVID9. I suppose we principally disagree on the likelihood of a benefit for that usage, and as you pointed out, there is a small chance of toxicity. I suppose as long as the patients with a genuine need for chloroquine actually can acquire it, wasting medicine and money doesn't do a lot of harm.

 

[infection]

I was aware of that for the flu, in particular, that there is scientific evidence it will be effective against the strains it is designed to combat, but little evidence those will be the strains you need protection from.

Evidence meaning they haven't been able to actually test it in large scales of human populations because getting it out on the market to address an ongoing issue where time is of the essence is imperative. So they don't wait around to assess its true numbers for reduced morbidity and mortality because, if they did, by the time they had that data it would be completely worthless. We're in that kind of a situation right now.

I understand that there might be evidence that springs up. I'm not opposed to, for example, actual clinical trials on chloroquine and COVID9.

See above. Perhaps we could carry out a year or two of trials on each flu vaccine and get clear data before putting it out to market.

I suppose we principally disagree on the likelihood of a benefit for that usage, and as you pointed out, there is a small chance of toxicity.

You may be misreading me because I don't have any opinion on hydroxychloroquine. I'm just stating that of the available reasons of suspicion for it having benefit, the data is not at all conclusive demonstrating that it is not beneficial.

I suppose as long as the patients with a genuine need for chloroquine actually can acquire it, wasting medicine and money doesn't do a lot of harm.

I'll give you an example on a much lower scale. Currently there's some scant evidence out there of minocycline, an antibiotic, potentially having benefit for treating negative symptoms of schizophrenia. The data is very limited. Appreciate the fact that nobody stands to gain any benefit of minocyline being a recognized treatment for negative symptoms in schizophrenia. It's a generic drug. Absolutely no drug company is going to fund these studies (and for as much as people want to loathe the pharmaceutical companies, they certainly accept many conclusions in their views of medicine and healthcare based on a massive funding bias in the available literature, but I digress). So there's very limited data on this. There are no drugs that treat negative symptoms of schizophrenia. Really the only data, by and large, for treating schizophrenia is with medications that are treating positive symptoms of schizophrenia. There's very little discussion, pharmaceutically, regarding negative symptoms, when in reality these can be some of the most disabling. So minocycline does not have any mechanism of action belief behind it to suggest that it would work for this (and trying to look at mechanisms on paper is very misleading because it presumes we know way more about things than we actually do). But there's some scant, and sometimes conflicting evidence, regarding the use of minocycline in the early phases of a schizophrenia diagnosis. I don't have a strong belief in it. If I had to guess, it probably doesn't work. But consider that the treatment course is time limited, that the risks are very minimal, and that the medication is very cheap. If this were something I would be putting someone on indefinitely, then it changes the equation. But for 3 months? If I treat or if I don't treat, there's no way to say if there was a benefit and, if there was, to what extent it helped. I could never know in each individual. Several times I've used this because the risk is so small that the potential benefit of a treatment that one only takes for 3 months is reasonable when you're looking at someone who had otherwise been functional in their 20s but has now developed a psychotic disorder and its sequelae. Let's say in the future it's demonstrated that this does indeed have this benefit. Great. I was able to institute that within the window that it would be effective. Let's say in the future research shows that this does not have any effect. What are the patient and myself out? Very little.

Now you have a scenario where the potential outcome is death, especially as I'm talking about people in the hospital and intubated. Hydroxychloroquine certainly can have side-effects... but this is a very time limited course of medication you're talking about, and the potential for adverse issues is weighed by a treating physician. If research later shows this isn't beneficial, then what we're out is, as you mentioned, cost (<$10 worth of medication during a hospitalization that's going to be >$20k) and the potential disruption of supply. Now, who's on hydrochloroquine? In the US, people with certain autoimmune disorders such as lupus or RA. What's the risk to them going untreated? Well, being intubated an in the ICU wouldn't realistically be one of them. Now let's say research later verifies what many inpatient physicians are reporting. What would we have to lose if we withheld those treatments to later find out that it reduces mortality? To me, this is similar to the argument of shutting everything down to minimize spread. What if we're wrong and we didn't need to shut everything down? On the other hand, what if shutting everything down saved lives? I guess since we don't have any post hoc evidence that shutting everything down right now will save lives, it essentially means it can't/won't and we shouldn't, or at least that’s what it would mean if we followed that logic through.