Coronavirus thread

[ccmdfd]

We have a significant tendency to want to have everything wrapped up with a nice little bow before the 11 o'clock News starts.

That's just not how it works with medical research though. It's going to take quite some time to get well-designed, prospective studies, performed in multiple centers done. Then even more time for others to analyze the data and point out further flaws, which almost always leads to even more prospective studies.

In the meantime, there will be further observational studies and such. That's good, nothing wrong with that but we can't come to any significant conclusions anytime soon

[Nephrology]

We have a significant tendency to want to have everything wrapped up with a nice little bow before the 11 o'clock News starts.

That's just not how it works with medical research though. It's going to take quite some time to get well-designed, prospective studies, performed in multiple centers done. Then even more time for others to analyze the data and point out further flaws, which almost always leads to even more prospective studies.

In the meantime, there will be further observational studies and such. That's good, nothing wrong with that but we can't come to any significant conclusions anytime soon

I will say I'm generally gloomy about the prospect for the current drugs under investigation. Sure we might get lucky, but none of the antivirals were designed specifically for SARS CoV2, so I am not incredibly hopeful they will be a slam dunk just because there is theoretical mechanistic support for their re-purposing for COVID19. I am even less hopeful for the "anti-ARDS" drugs they are pitching (i.e. the anti-inflammatory cytokine biologics like toculizumab, sarilumab, etc). All of the best data driven therapies for ARDS are basically just maximizing the yield of supportive care - if we don't have targeted therapies for ARDS already, I don't know why we'll find them now.

I may be wrong, but in wrapping up a thesis on the pathobiology of ARDS & critical illness, I've stepped over the corpses of a lot of putative therapies with strong preclinical data. E.g. Vitamin D in sepsis/ARDS. The PETAL network trials are the product of years of thoughtful labor from some of the country's biggest names in acute care. It just sort of beggars belief that in the span of 3 months we'd somehow do better, you know?

[45dotACP]

The heads of some of the departments at my hospital broadcasted a webinar yesterday...so basically the Pulm/Crit, CV surgery, Infectious Disease, Hematology, and Cardiology.

Our hospital has seen more volume than any other in our state with about 1086 COVID-19 admissions, 414 (38%) requiring ICU care 275 (25%) required intubation of which 88 died (32%) 169 died overall (15.6% hospital mortality overall) and 111 of those in the ICU (27% ICU mortality)

I'm told these numbers are fairly in line with national averages, though I haven't looked too deeply into it.

I wish I knew our ECMO data but I'm not going anywhere near that unit, as some 36 of their nurses were infected due to poor adherence to infection control practices, but last I heard about two weeks ago they had 27 ECMO circuits up and running.

Overall, it seems like our medical team is all in agreement that HCQ and particularly the HCQ/AZT treatment regimen is more harm than good.

I got the chance to pick the brain of our MICU medical director, and he mentioned that there were some meds that might improve the odds or buy us some time (Toci, Remdesivir, Convalescent plasma being the main ones alongside vitamin supplementation with Zinc, Vit D and Vit C, ) but the overall course of the patient is going to depend on A.) How healthy they are/how severe their case is, and B.) How much time we can buy them to recover with excellent ICU management. Proning, even of non intubated patients, has become a key strategy to buying time, as you can no doubt tell, intubation is not associated with a great outcome.

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[Wingate's Hairbrush]

https://www.google.com/amp/s/amp.the...s-for-covid-19

Yup.

Help me understand -- from the article, it seems a data collating error occurred that does account for a minor inconsistency but that has no impact on the overall implications of the study. The link, rather than reinforcing the "it doesn't add up" and "someone's pushing an agenda" assertions, seems to directly refute them.

[ccmdfd]

I will say I'm generally gloomy about the prospect for the current drugs under investigation. Sure we might get lucky, but none of the antivirals were designed specifically for SARS CoV2, so I am not incredibly hopeful they will be a slam dunk just because there is theoretical mechanistic support for their re-purposing for COVID19. I am even less hopeful for the "anti-ARDS" drugs they are pitching (i.e. the anti-inflammatory cytokine biologics like toculizumab, sarilumab, etc). All of the best data driven therapies for ARDS are basically just maximizing the yield of supportive care - if we don't have targeted therapies for ARDS already, I don't know why we'll find them now.

I may be wrong, but in wrapping up a thesis on the pathobiology of ARDS & critical illness, I've stepped over the corpses of a lot of putative therapies with strong preclinical data. E.g. Vitamin D in sepsis/ARDS. The PETAL network trials are the product of years of thoughtful labor from some of the country's biggest names in acute care. It just sort of beggars belief that in the span of 3 months we'd somehow do better, you know?

I too am not overly optimistic.

Man, i hate to sound like the "it's the flu crowd ", but they like to point out the large number of flu deaths. What's not often said with that is that large number of deaths occur for a disease which we have an effective vaccine for, as well as effective antivirals for. We have neither for Covid right now.

[MickAK]

Help me understand -- from the article, it seems a data collating error occurred that does account for a minor inconsistency but that has no impact on the overall implications of the study. The link, rather than reinforcing the "it doesn't add up" and "someone's pushing an agenda" assertions, seems to directly refute them.

Ok, here's a couple of articles from a Columbia statisticians blog.
https://statmodeling.stat.columbia.e...a-do-about-it/
https://statmodeling.stat.columbia.e...quine-perhaps/

I'm not sure how you're implying that refutes anything I said. I smelled horseshit and there is indeed horseshit. Again, the issue I have isn't with the Lancet study but with the push to use it as evidence for something it isn't.

[Nephrology]

I too am not overly optimistic.

Man, i hate to sound like the "it's the flu crowd ", but they like to point out the large number of flu deaths. What's not often said with that is that large number of deaths occur for a disease which we have an effective vaccine for, as well as effective antivirals for. We have neither for Covid right now.

Yes, precisely. It is not the flu, but in some ways, bears importance gross resemblance. That's also why I kept bringing up Tamiflu - "effective" is a highly relative word. Tamiflu is without a doubt more efficacious and well vetted for flu than any drug we have right now for COVID-19, but that's still not saying much. It's hard to combat the public notion that medications are a magic wand, particularly for infections, when the average person's closest analogous experience is taking augmentin for a soft tissue infxn or similar.

Because I am doing my PhD in the pulm world, I often think of 2 drugs you are probably familiar with too - Ofev and Esbriet. Let's just say that if the "cure" for COVID-19 works as well as either of those two, I'm not sure I'd take it.

[Wingate's Hairbrush]

Ok, here's a couple of articles from a Columbia statisticians blog.
https://statmodeling.stat.columbia.e...a-do-about-it/
https://statmodeling.stat.columbia.e...quine-perhaps/

I'm not sure how you're implying that refutes anything I said. I smelled horseshit and there is indeed horseshit. Again, the issue I have isn't with the Lancet study but with the push to use it as evidence for something it isn't.

Those quoted in the article you provided agree that the essential findings of the Lancet study are correct and their implications are that there's no evidence that HCQ is a safe or effective treatment for COVID-19.

[MickAK]

However, this doesn't have anything to do with your previous criticism of the article, which remains baseless.

It certainly doesn't change the fact that in order to meaningfully critique the findings of clinical literature, you have to be able to read and understand the thrust of their argument first.

Another direction this conversation could go would be 'Hmm, how did you know do fast something was up with their data' and we could talk about how I did that and how you could do it too and how it might help your interactions with the unwashed masses vis-a-vis medical research and we might both learn something.

I think that might be a more productive direction but if you want to double down on the Priest-King stuff that's cool too.

[Nephrology]

Ok, here's a couple of articles from a Columbia statisticians blog.
https://statmodeling.stat.columbia.e...a-do-about-it/

This article doesn't really say anything except bring up the controversy and repeats the well trodden truisms about how being from Harvard doesn't make you a genius. "These major institutions are big places, and you can’t necessarily trust a paper, just because it comes from a generally respected medical center." That's not a controversial statement.

https://statmodeling.stat.columbia.e...quine-perhaps/

Here are plausible rebuttals to Watson's critiques:

1/ Small margins of error from different datasets means exactly nothing. Not only is this common, but it is unlikely to influence their statistical results

2/ Responded to by authors in the Guardian article you linked

3/ I have no idea why this person is surprised that there are doses of HCQ being given higher than FDA recommendations. The study pulls patient data from hospitals all across the world, many of which I am sure are not aware of or interested in the FDA guidelines for the use of an experimental drug. besides, ~530mg per day is not much over the FDA recommended maintenance dose of 400mg qD.

None of these critiques is really particularly damning, but who knows, maybe these critiques will carry water down the line. Fortunately the investigation of HCQ in COVID-19 is not limited to a single retrospective study.

I'm not sure how you're implying that refutes anything I said. I smelled horseshit and there is indeed horseshit. Again, the issue I have isn't with the Lancet study but with the push to use it as evidence for something it isn't.

Do you smell horseshit here?

How about here?

here?

Or here? ( for those of you who wanted more studies on HCQ in mildly ill patients, give this one a read!)

And so on.

My point is that "smelling horseshit" isn't a valid criticism of a published article. The concerns you link in the Columbia blog post are valid criticisms, and they merit discussion. However, to say something "smells like horseshit" without specific criticism based in the text simply implies that you've arrived at your conclusion without any evidence to support it.

Furthermore, to focus on the Lancet article is to miss the forest for the trees: the lions share of evidence is stacking up against HCQ. While it is still too early to say this definitively, it seems inarguable to me that HCQ should not be used outside of prospective clinical trials which provide patients with an appropriate degree of cardiac monitoring and medical support.