Interesting observation concerning hydroxychloroquine

[Ygggdrasil]

I just realized my mistake. Sorry about that.

I just find it strange that number of deaths/ number of reported cases is still used as a type of "mortality rate" even though it is in no way related to the actual mortality rate of the illness.

As a somewhat bored retiree, I've been following this fairly closely since the beginning. I've generated over 130 spreadsheets, the oldest was created January 31st. It wasn't until the middle of April when I realized "reported case numbers" were useless, and I started ignoring them. And if you think about it, "mortality rates" are also kind of useless. I think CFR is used as it generates the highest fear factor, and that's probably a good thing, as some people don't seem to take this disease very seriously.

CFR is used because it is based on actual concrete numbers. There is a verifiable, measurable number of confirmed deaths and a verifiable, measurable number of confirmed cases. IFR is not a concrete number as estimating the number of infected individuals requires modeling and making many assumptions.

People who work in these areas known the limitations of CFR, but unfortunately, things get mangled when non-expert journalists attempt to communicate things to the general populace.

 

[nsaspook]

Anyone have an idea about how valid a evaluation this is of the company?
https://www.theguardian.com/world/2...-world-health-organization-hydroxychloroquine

The World Health Organization and a number of national governments have changed their Covid-19 policies and treatments on the basis of flawed data from a little-known US healthcare analytics company, also calling into question the integrity of key studies published in some of the world’s most prestigious medical journals.
...
Data it claims to have legitimately obtained from more than a thousand hospitals worldwide formed the basis of scientific articles that have led to changes in Covid-19 treatment policies in Latin American countries. It was also behind a decision by the WHO and research institutes around the world to halt trials of the controversial drug hydroxychloroquine. On Wednesday, the WHO announced those trials would now resume.
...
The Guardian’s investigation has found:

• A search of publicly available material suggests several of Surgisphere’s employees have little or no data or scientific background. An employee listed as a science editor appears to be a science fiction author and fantasy artist. Another employee listed as a marketing executive is an adult model and events hostess.

...
At a press conference on Wednesday, the WHO announced it would resume its global trial of hydroxychloroquine, after its data safety monitoring committee found there was no increased risk of death for Covid patients taking it.

http://freerangestats.info/blog/2020/05/30/implausible-health-data-firm

EDIT: add another critique.

 

[atyy]

Anyone have an idea about how valid a evaluation this is of the company?
https://www.theguardian.com/world/2...-world-health-organization-hydroxychloroquine

I think it is worth pointing out that when they WHO halted trials, they indicated that it was temporary to allow safety data to be reviewed.

https://www.who.int/news-room/q-a-detail/q-a-hydroxychloroquine-and-covid-19

"In light of recent publications of evidence on the safety and efficacy of hydroxychloroquine as a treatment for COVID-19 patients, the Executive Group of the Solidarity Trial decided to implement a temporary pause of the hydroxychloroquine arm within the trial as a precaution while the safety data is being reviewed.
...
Those patients previously randomized to hydroxychloroquine treatment should continue to receive hydroxychloroquine until they finish their course of treatment. The use of hydroxychloroquine and chloroquine are accepted as generally safe for use in patients with autoimmune diseases or malaria"

 

[Vanadium 50]

I think CFR is used as it generates the highest fear factor, and that's probably a good thing, as some people don't seem to take this disease very seriously.

I think the idea that The Wise need to deliberately mislead The Plebs because they are too stupid to do the right thing when told the truth is, at a minimum, un-democratic. I suspect it is also ineffective, counter-productive, and likely to lead to undesired outcomes.

That said, CFR answers as very specific question: "Doc, what are my chances?" - that is, once diagnosed, what are the likely outcomes. It just happens that most people are interested in an entirely different question.

It may be better to consider IFR and CFR more like functions than numbers, since they depend on age, sex and underlying conditions. If you are 20, female, and in good health, you have very different probabilities than if you are 85, male, with a bunch of other problems.

 

[Ygggdrasil]

The Lancet just published an "expression of concern" about the Mehra study:
This, of course, has no bearing on other papers.

The Mehra et al. study has now been officially retracted from The Lancet over the data integrity issues.

After publication of our Lancet Article, several concerns were raised with respect to the veracity of the data and analyses conducted by Surgisphere Corporation and its founder and our co-author, Sapan Desai, in our publication. We launched an independent third-party peer review of Surgisphere with the consent of Sapan Desai to evaluate the origination of the database elements, to confirm the completeness of the database, and to replicate the analyses presented in the paper.

Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis as such transfer would violate client agreements and confidentiality requirements. As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process.

We always aspire to perform our research in accordance with the highest ethical and professional guidelines. We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologise to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.

Official retraction notice: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31324-6/fulltext
Popular press coverage: https://www.sciencemag.org/news/202...onavirus-papers-over-data-integrity-questions

 

[Nik_2213]

Slightly tangential, I've been having an on-going argument with a HCQ supporter on another, non-physorg forum. First, he claimed it was a panacea. Then, he claimed Trumpotus endorsement as 'holy writ'. Then he claimed HCQ had to be taken at much higher dosage than routine anti-malarial. Then he claimed it had to be synergised with zinc supplements. Then he claimed it also had to be synergised with Vit-D...

I quoted the MontyPython 'Inquisition' sketch...
Ximinez: Nobody expects the Spanish Inquisition ! Our chief weapon is surprise...surprise and fear...fear and surprise... Our two weapons are fear and surprise...and ruthless efficiency... Our *three* weapons are fear, and surprise, and ruthless efficiency...and an almost fanatical devotion to the Pope... Our *four*...no... *Amongst* our weapons... Amongst our weaponry...are such elements as fear, surprise... I'll come in again. (Exit and exeunt)

 

[Rhyo9]

You'll notice when looking at per capita death rates from Covid-19 on worldometer, assuming the data are at least somewhat accurate, that industrialized, wealthier countries are more affected. One possible explanation (and there are probably a number of explanations worth exploring) is that per capita protein consumption is typically higher in these countries, leading to higher baseline mTOR activation. A number of viruses are known to exploit the mTOR pathway and mTOR inhibition has been suggested as treatment for covid-19:
https://pubmed.ncbi.nlm.nih.gov/32313883/

Also note that most of the risk factors for severe Covid-19 all have an underlying theme of dysfunctional AMPK signalling and perhaps sedentary habits are more prevalent in wealthier nations, leading to lower baseline AMPK activation. Resistant starch consumption also affects AMPK activation.

 

[Nik_2213]

You'll notice when looking at per capita death rates from Covid-19 on worldometer, assuming the data are at least somewhat accurate, that industrialized, wealthier countries are more affected.

Sadly, tragically, this could change very rapidly now Covid has become rampant in the impoverished and too-often malnourished favellas, shanty-towns etc etc of South America, Africa and India.

I hope you are correct, and those areas don't suffer deaths by the bazillion. I fear their losses will dwarf ours...

 

[jim mcnamara]

Edit - redirect my ping to Nik_2213

@Nik_2213 - you pretty much summed up the problems of presenting Science about drug tests and getting a raspberry (spelled "plplpl" ) back saying 'I know that Tide detergent enemas cure Covid-19'. The underinformed folks, mostly trolls, who do this kind of thing know: create enough noise about 'I am right' and you will give up. So I did.

I gave up on most of the dialogue like that about the Biology/Medicine re: the pandemic. He/She/It/troll will not relent and is generally immune to demonstrable facts.

So I stay on PF. Why?

You do not see much of that on PF. Because - There are a lot of us who spend time vetting poor posts from almost okay posts in order to keep crud out of sight. Most of the time.

We also have low tolerance for political slants that creep into Science Forums from time to time.

 

[Rhyo9]

Sadly, tragically, this could change very rapidly now Covid has become rampant in the impoverished and too-often malnourished favellas, shanty-towns etc etc of South America, Africa and India.

I hope you are correct, and those areas don't suffer deaths by the bazillion. I fear their losses will dwarf ours...

I hope so; sometimes I get stuff right, sometimes I don't. I managed to correctly predict the disproportionate effect on the African American and Southwest Native American populations, just based on the AMPK thing - that's something I wish I had not been correct about.

Vitamin D supplementation could help to reduce risk in the African American population - the relationship between ARDS (caused by both infection and trauma) and vitamin D status is well-established from interventional studies and it seems like a no-brainer to encourage people in general to mind their vitamin D status. However, I don't think that vitamin D is the whole story wrt the Af Am population and covid.

The recall on metformin could not have come at a worse time; I hope people can still get their metformin Rx's filled. OTOH I have not heard of people on metformin doing better (or worse) than people on other diabetes medications - though such comparisons would have to correct for degree of disease control (by controlling for markers such as HbA1c and fasting glucose) and might not 'jump out' at someone doing a preliminary analysis. Glitazones could possibly offer protection, also.

 

[Laroxe]

I have to say that following the information from the Oxford medical centre and the WHO, I thought that the issue of hydroxychloroquine had largely been settled. It was considered ineffective and was associated with some important side effects.

Unfortunately there have been some recent publications that have raised some issues over this research and the results. It appears that the data used in these studies was from patient groups treated with very high doses of HCQ, none appeared to have received doses consistent with prescribing guidelines. This would explain the side effects they described at the very least, but there seems no real justification provided for the very high doses used.

A recently published paper from Belgium of a large (8000+ subjects) retrospective analysis of hospital mortality comparing those given HCQ at normal doses to those who received supportive care only, provides some very different conclusions. They report an inpatient mortality rate of 17.7% for those treated with HCQ compared to a mortality rate of 27.1% in those not given the drug, the researchers had also built in controls for demographic variables and other risk factors. This is a significant difference that cannot be explained by any limitation in the methods and must be a cause for concern about the studies that stopped HCQ being widely used.
There has also been some other studies using HCQ + some other treatments that appear to offer support to this finding.

Main study;

https://www.sciencedirect.com/science/article/pii/S0924857920303423

other evidence;

https://www.sciencedirect.com/science/article/pii/S1477893920302817?via=ihub

https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext

 

[Vanadium 50]

You cannot use an antimalarial to treat an antiviral infection.

By that logic, you can't use blood pressure medication to regrow hair. And yet...

 

[Rhyo9]

Good news on HCQ. Dose makes the poison - and the medicine.

More good news is that type 2 diabetes patients on metformin have a 70% reduced risk of death from Covid as compared to T2D patients on other anti-diabetes drugs:
https://reference.medscape.com/viewarticle/935386
{ good news and also a relief to finally get a question answered that has been itching me since March }
Metformin's MOA is generally thought to be via AMPK activation though recently there is some debate in the literature on this point. However, there seems to be pretty good evidence that is does improve AMPK signalling overall. There are some aging researchers (e.g. David Sinclair ) who take metformin for life extension, but it seems like the safest way to improve AMPK signalling is through regular exercise.

Also, Kenya does not seem to be having as much of a problem with covid:
https://www.medrxiv.org/content/10.1101/2020.07.27.20162693v1

This could be due to low protein consumption > low baseline mTOR activation as I had suggested, however, there's another interesting possibility - high seroprevalence for hepatitis A:
http://www.ectrx.org/forms/ectrxcontentshow.php?year=2020&volume=18&issue=2&supplement=0&makale_no=0&spage_number=141&content_type=FULL TEXT

My daughter's doctor had her vaccinated for pneumococcus and hep A; she has Celiac so the pneumovax was expected but I did not know about hep A until I read up on it. Good doctor.