Coronavirus

[Jurgis]

The outrageous part of the calcifediol issue is that it basically boils down to the most mundane recommendation:  "Be good and goddamned sure that you are not vitamin D deficient when there is covid floating around your community.  If you are white and in the middle of the winter, think hard about whether you are getting adequate vitamin D from dietary sources because you'll be getting nothing from exposure to the sun.  If you have a darker complexion, even in the middle of summer, think hard about whether your body will be producing adequate vitamin D from exposure to the sun."

For $10 per year, anybody can go to WalMart and buy vitamin D supplements.  Heads you win, tails you don't lose.

SJ

A potential win/not-lose aspect is that: "One pill every two weeks fights diabetes, cancers, heart failure, and 18 other diseases".  :)

Covid-19 was recently added to this list. Isn't there an analytical risk here?

Disclosure 1: over the years, i've had to periodically participate in committees which had to decide if the single payer should pay for certain propositions (there was typically a few participants whose main line of argument was: what is there to lose? a similar line of argument is used now to justify the 2T fiscal shot in the arm). Apologies: i tend to focus (too much?) on second and other higher order effects (the 'unseen' ones).

Disclosure 2: i'm in the process of being enrolled in a study (based on strong foundations) which will follow people at relatively high risk to be exposed and to contract covid over the next few months. One arm of the study will receive vitamin D supplementation and the other arm will get a placebo. (i may receive a placebo but will watch for the side effects; you must be aware that the placebo group will also report side effects?)

 

Should I tell you that high vitamin D can cause (? ) (is linked to?) kidney stone problems?

Now that I told you this, watch out for kidney stones in placebo group...  ::)

[StubbleJumper]

The outrageous part of the calcifediol issue is that it basically boils down to the most mundane recommendation:  "Be good and goddamned sure that you are not vitamin D deficient when there is covid floating around your community.  If you are white and in the middle of the winter, think hard about whether you are getting adequate vitamin D from dietary sources because you'll be getting nothing from exposure to the sun.  If you have a darker complexion, even in the middle of summer, think hard about whether your body will be producing adequate vitamin D from exposure to the sun."

For $10 per year, anybody can go to WalMart and buy vitamin D supplements.  Heads you win, tails you don't lose.

SJ

A potential win/not-lose aspect is that: "One pill every two weeks fights diabetes, cancers, heart failure, and 18 other diseases".  :)

Covid-19 was recently added to this list. Isn't there an analytical risk here?

Disclosure 1: over the years, i've had to periodically participate in committees which had to decide if the single payer should pay for certain propositions (there was typically a few participants whose main line of argument was: what is there to lose? a similar line of argument is used now to justify the 2T fiscal shot in the arm). Apologies: i tend to focus (too much?) on second and other higher order effects (the 'unseen' ones).

Disclosure 2: i'm in the process of being enrolled in a study (based on strong foundations) which will follow people at relatively high risk to be exposed and to contract covid over the next few months. One arm of the study will receive vitamin D supplementation and the other arm will get a placebo. (i may receive a placebo but will watch for the side effects; you must be aware that the placebo group will also report side effects?)

 

 

Yes, there is a big analytical risk here, but not a big practical risk.  The analytical risk is that you kind of need to twist yourself into a bit of a pretzel to make the logical jump from correlation to causation when considering vitamin D deficiency and adverse covid outcomes.  And for some (most?) of the conditions that are portrayed in that chart, the correlation is likely only that -- correlation.  On the other hand, there is approximately zero downside to taking 1000 IU of vitamin D during the period between the two equinoxes, which is my point of there being very little practical risk.  If you do go down that road of twisting yourself into a pretzel, at worst you are only out $10.

 

With respect to the study in which you are participating, why are they initiating a vitamin D supplementation study to coincide with the arrival of the spring equinox?  That is as silly as it gets when you are dealing with a city located on the 45th parallel with an overwhelmingly white population.  In three weeks, you'll be sitting in the sun in a sheltered area of your back yard, drinking a beer and wearing short-sleeves.  With the rapidly strengthening sun, your pasty-white skin will enable you to soak up more vitamin D in an hour of drinking beer in the sun than what your daily 1000 IU tablet could give you over a week.  The logical timing to conduct that study would have been from November 1 to February 28th, when the sun in Mtl is at its weakest and when nearly every square inch of our body is covered with insulating clothing.  Even pasty-white guys have trouble getting enough vitamin D during that period.

 

 

SJ

[Dalal.Holdings]

The outrageous part of the calcifediol issue is that it basically boils down to the most mundane recommendation:  "Be good and goddamned sure that you are not vitamin D deficient when there is covid floating around your community.  If you are white and in the middle of the winter, think hard about whether you are getting adequate vitamin D from dietary sources because you'll be getting nothing from exposure to the sun.  If you have a darker complexion, even in the middle of summer, think hard about whether your body will be producing adequate vitamin D from exposure to the sun."

For $10 per year, anybody can go to WalMart and buy vitamin D supplements.  Heads you win, tails you don't lose.

SJ

A potential win/not-lose aspect is that: "One pill every two weeks fights diabetes, cancers, heart failure, and 18 other diseases".  :)

Covid-19 was recently added to this list. Isn't there an analytical risk here?

Disclosure 1: over the years, i've had to periodically participate in committees which had to decide if the single payer should pay for certain propositions (there was typically a few participants whose main line of argument was: what is there to lose? a similar line of argument is used now to justify the 2T fiscal shot in the arm). Apologies: i tend to focus (too much?) on second and other higher order effects (the 'unseen' ones).

Disclosure 2: i'm in the process of being enrolled in a study (based on strong foundations) which will follow people at relatively high risk to be exposed and to contract covid over the next few months. One arm of the study will receive vitamin D supplementation and the other arm will get a placebo. (i may receive a placebo but will watch for the side effects; you must be aware that the placebo group will also report side effects?)

 

Though Vitamin D may be beneficial and there is an asymmetry to supplementation (low downside, potentially good upside), this is classic correlation does not necessarily imply causation fallacy. You have to be very careful in medicine from making wild associations like this and concluding that Vitamin D is some kind of silver bullet.

 

What is more likely to be the ultimate source in the graph you posted of healthiness and Vitamin D levels? Remember, sunlight --> increased Vitamin D. So what is really likely happening is you are looking at people who get more sunlight. Is the sunlight the reason they are healthier? Unlikely, unless they utilize photosynthesis. Sunlight is another correlation, not necessarily causation.

 

 

But people who get more sunlight are likely to be a certain type of person: these are people who are likely to be more active, "not sick", and physically fit.

 

So the causation is likely to be: better physical fitness --> less risk for medical conditions (which we already know: exercise is good for you); but also: better physical fitness --> more time in sunlight --> more vitamin D (the true causality for health likely comes from the physical fitness, not the Vitamin D which is merely an association).

 

 

We also know that lighter skin tone people produce more vitamin D in sunlight. We know in a lot of countries that ethnic minorities who are darker are more at risk of many medical conditions, partly due to socioeconomic status impacting lifestyle with genetics contributing as well (particularly in the countries where a lot of Vitamin D research is done).

 

SO the true causation is likely to be: pale skin tone --> better socioeconomic status --> healthier lifestyle --> less risk for medical conditions but also: pale skin tone --> more vitamin D generated due to less melanin in the skin (again, the vitamin D likely just a mere association)

 

 

 

And none of the above considers the bias present in "Grassroots Health", an organization likely heavily biased on the topic...

[Cigarbutt]

^To be fair, the potential 'link' between vitamin D levels and covid risk etc makes (anecdotal level assessment) more sense (slightly) than the 'link' with other conditions such as chronic fatigue, autism...etc, however the overall level of evidence is still in the basement of the hierarchy of evidence. So far, an obvious link between the transmission pattern of the virus and vitamin D (sunlight exposure as surrogate) appears to play a very secondary (if any) role.

For those interested, there are methodological ways to try to go around the correlation analytical risk that is embedded with the potential link between vitamin D and Covid risk. There was recently a genetic type of assessment that came out and there is this population level assessment that was carried out in Europe during 2020:

https://www.medrxiv.org/content/10.1101/2021.03.04.21252885v1.full.pdf

TLDR version: Once using a way to control the correlation risk, vitamin D levels or 'deficiencies' are not linked to Covid risk.

 

@StubbleJumper

Apologies for pursuing this 'policy' topic but there is an investment correlation: when people come here to share investment thoughts, various ideas may be 'recommended'. To be convinced, individual anecdotes may be interesting but a higher level of evidence may be necessary. Let's say someone in Ottawa notices your astute comments in this thread about the link between Covid and vitamin D, and you obtain the decision power to mutualize the cost of vitamin D supplementation for the 38M population. What do you decide? Now is a good time to suggest expenditures because there is a mountain of free money to distribute. 10 bucks per person is only 380M after all.

[StubbleJumper]

^To be fair, the potential 'link' between vitamin D levels and covid risk etc makes (anecdotal level assessment) more sense (slightly) than the 'link' with other conditions such as chronic fatigue, autism...etc, however the overall level of evidence is still in the basement of the hierarchy of evidence. So far, an obvious link between the transmission pattern of the virus and vitamin D (sunlight exposure as surrogate) appears to play a very secondary (if any) role.

For those interested, there are methodological ways to try to go around the correlation analytical risk that is embedded with the potential link between vitamin D and Covid risk. There was recently a genetic type of assessment that came out and there is this population level assessment that was carried out in Europe during 2020:

https://www.medrxiv.org/content/10.1101/2021.03.04.21252885v1.full.pdf

TLDR version: Once using a way to control the correlation risk, vitamin D levels or 'deficiencies' are not linked to Covid risk.

 

@StubbleJumper

Apologies for pursuing this 'policy' topic but there is an investment correlation: when people come here to share investment thoughts, various ideas may be 'recommended'. To be convinced, individual anecdotes may be interesting but a higher level of evidence may be necessary. Let's say someone in Ottawa notices your astute comments in this thread about the link between Covid and vitamin D, and you obtain the decision power to mutualize the cost of vitamin D supplementation for the 38M population. What do you decide? Now is a good time to suggest expenditures because there is a mountain of free money to distribute. 10 bucks per person is only 380M after all.

 

 

No, your policy observation is spot on.  Ignoring the constitutional inappropriateness of Ottawa providing vitamin D to citizens, it would certainly be a measure that should have been stacked-up and compared to the myriad of other spending and regulatory measures that the federal government has employed over the past year.  For all of those, cabinet should have been provided analysis to evaluate the costs and the potential benefits.  A vitamin D initiative would likely stack up favourably in the long list of measures that have been considered (at the top of the list would have been the covid app which held the potential to significantly facilitate trace-back at a trivial cost, and the bottom of the list would be the establishment of domestic vaccine production capacity not slated to come on line until December 2021 which is likely to be useless irrespective of cost).  Effectively, there is precious little difference between taking measures like mask mandates on the hope that it reduces transmission, shutting down outdoor events with the notion that it might help to some degree, and a vitamin D program.  Ex ante, there is scant evidence that any of them would work in practice, so you recognize that the costs and outcomes could quite possibly be asymmetric and you make a decision.

 

 

SJ

 

 

[Investor20]

^To be fair, the potential 'link' between vitamin D levels and covid risk etc makes (anecdotal level assessment) more sense (slightly) than the 'link' with other conditions such as chronic fatigue, autism...etc, however the overall level of evidence is still in the basement of the hierarchy of evidence. So far, an obvious link between the transmission pattern of the virus and vitamin D (sunlight exposure as surrogate) appears to play a very secondary (if any) role.

For those interested, there are methodological ways to try to go around the correlation analytical risk that is embedded with the potential link between vitamin D and Covid risk. There was recently a genetic type of assessment that came out and there is this population level assessment that was carried out in Europe during 2020:

https://www.medrxiv.org/content/10.1101/2021.03.04.21252885v1.full.pdf

TLDR version: Once using a way to control the correlation risk, vitamin D levels or 'deficiencies' are not linked to Covid risk.

 

@StubbleJumper

Apologies for pursuing this 'policy' topic but there is an investment correlation: when people come here to share investment thoughts, various ideas may be 'recommended'. To be convinced, individual anecdotes may be interesting but a higher level of evidence may be necessary. Let's say someone in Ottawa notices your astute comments in this thread about the link between Covid and vitamin D, and you obtain the decision power to mutualize the cost of vitamin D supplementation for the 38M population. What do you decide? Now is a good time to suggest expenditures because there is a mountain of free money to distribute. 10 bucks per person is only 380M after all.

 

 

No, your policy observation is spot on.  Ignoring the constitutional inappropriateness of Ottawa providing vitamin D to citizens, it would certainly be a measure that should have been stacked-up and compared to the myriad of other spending and regulatory measures that the federal government has employed over the past year.  For all of those, cabinet should have been provided analysis to evaluate the costs and the potential benefits.  A vitamin D initiative would likely stack up favourably in the long list of measures that have been considered (at the top of the list would have been the covid app which held the potential to significantly facilitate trace-back at a trivial cost, and the bottom of the list would be the establishment of domestic vaccine production capacity not slated to come on line until December 2021 which is likely to be useless irrespective of cost).  Effectively, there is precious little difference between taking measures like mask mandates on the hope that it reduces transmission, shutting down outdoor events with the notion that it might help to some degree, and a vitamin D program.  Ex ante, there is scant evidence that any of them would work in practice, so you recognize that the costs and outcomes could quite possibly be asymmetric and you make a decision.

 

 

SJ

 

Why would causation be an issue in prospective randomized clinical studies.  My main gripe is even after 8 months after the Spain pilot randomized study showing over 90% improvement with Calcifediol, no prospective randomized clinical study was done.

 

If you see the below link of a new Ivermectin meta-analysis, the authors on page 11 & 12 (Table 1) listed the RCT studies they identified of Ivermectin by a search of databases.

https://osf.io/k37ft/

 

They list Bangladesh, Nigeria, Spain, Pakistan, India, Bulgaria, Israel, Egypt, Argentina.....of locations of these studies they identified.

 

To resolve causation, one could do prospective randomized clinical studies which many countries did for Ivermectin.

 

I would hope they simply mimic the Calcifediol pilot randomized study to confirm the findings in a larger study.

 

Note:  For discussion only. Not a suggestion for treatment. Please consult your physician for any treatment.

[Cigarbutt]

...so you recognize that the costs and outcomes could quite possibly be asymmetric and you make a decision. ---) Pascal's wager argument

SJ

Why would causation be an issue in prospective randomized clinical studies.  My main gripe is even after 8 months after the Spain pilot randomized study showing over 90% improvement with Calcifediol, no prospective randomized clinical study was done.

...

@Investor20

i think this is not the place to argue about specifics unrelated to investments. For your own potential benefit though, you may want to take a look at this:

https://poseidon01.ssrn.com/delivery.php?ID=183110124086122101102097088025096087053071017088069085030106035014016005029027087109054039038069096025084085005094125105002042006001104046005072005101012083042059078008088037095080105104083120004038106070084060095065106024068114073027110069084125095117087006109028100094022026117111096105026&EXT=pdf&INDEX=TRUE

It's a study (labeled as high level evidence by the authors) looking for a peer review which has recently been released and that shares authors with the 'spectacular' Barcelona study that you mention. Let's see if you can come up with an objective opinion about the authors' conclusions and their significance.

-----

Easy paths (paths of least resistance) are great but can lead astray. The fundamental problem with the Pascal's wager analogy is that you need an underlying assumption that there is only one god. That's why some prefer to use a 'cocktail' approach (add selenium, zinc etc etc). The added level of uncertainty with Covid was significant but where do you draw the line? How do you balance the need to keep an open mind and the possibility of doing stupid things? And yes 'easy' solutions are popular these days but are 'we' on the right path?

[Investor20]

...so you recognize that the costs and outcomes could quite possibly be asymmetric and you make a decision. ---) Pascal's wager argument

SJ

Why would causation be an issue in prospective randomized clinical studies.  My main gripe is even after 8 months after the Spain pilot randomized study showing over 90% improvement with Calcifediol, no prospective randomized clinical study was done.

...

@Investor20

i think this is not the place to argue about specifics unrelated to investments. For your own potential benefit though, you may want to take a look at this:

https://poseidon01.ssrn.com/delivery.php?ID=183110124086122101102097088025096087053071017088069085030106035014016005029027087109054039038069096025084085005094125105002042006001104046005072005101012083042059078008088037095080105104083120004038106070084060095065106024068114073027110069084125095117087006109028100094022026117111096105026&EXT=pdf&INDEX=TRUE

It's a study (labeled as high level evidence by the authors) looking for a peer review which has recently been released and that shares authors with the 'spectacular' Barcelona study that you mention. Let's see if you can come up with an objective opinion about the authors' conclusions and their significance.

-----

Easy paths (paths of least resistance) are great but can lead astray. The fundamental problem with the Pascal's wager analogy is that you need an underlying assumption that there is only one god. That's why some prefer to use a 'cocktail' approach (add selenium, zinc etc etc). The added level of uncertainty with Covid was significant but where do you draw the line? How do you balance the need to keep an open mind and the possibility of doing stupid things? And yes 'easy' solutions are popular these days but are 'we' on the right path?

 

This is a coronavirus thread.  Not investment thread. 

 

The above study you gave the link is not a randomized study.  Instead they gave the medicine and placebo by ward, not randomized by individuals.  Upon realizing this Lancet removed the publication. This study came out in jan 2021.

 

The study I was citing is below and was published in Aug 2020 where they randomized individual hospitalized patients.

 

https://www.sciencedirect.com/science/article/abs/pii/S0960076020302764?via%3Dihub

 

And there is observational study I cited too, the Dubai hospital report

https://vitamindwiki.com/Vitamin+D+has+eliminated+ICU+COVID-19+in+hospital+in+Dubai+since+June+-+Sept+26%2C+2020

Vitamin D has eliminated ICU COVID-19 in hospital in Dubai since June - Sept 26, 2020

 

@SJ:  Blacks and other colored people are disproportionately effected by Covid, especially in colder areas such as NYC or Chicago.  One hypothesis is due to their skin color, they have much higher Vitamin D deficiency. Thanks for bringing up the issue of skin color and Vitamin D.

 

https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/covid19-racial-disparities

According to media reports, in Chicago, where African Americans comprise a third of the city’s population, they account for half of those who have tested positive for the coronavirus, and almost three-quarters of COVID-19 deaths.

 

Note: Not a suggestion for treatment. For discussion only.  Please consult a physician for any treatment.

[Cigarbutt]

...

This is a coronavirus thread.  Not investment thread. 

The above study you gave the link is not the study I am citing.  The above study you cite was not a randomized study.  Instead they gave the medicine and placebo by ward, not randomized by individuals.  Upon realizing this Lancet removed the publication. This study came out in jan 2021.

The study I was citing is below and was published in Aug 2020 where they randomized individual hospitalized patients.

https://www.sciencedirect.com/science/article/abs/pii/S0960076020302764?via%3Dihub

...

The Aug 2020 study shares several methodological flaws which are fundamental (there is a pattern).

From reported peer review, the study you mention has the following weaknesses: small number of patients, ICU admission as a subjective outcome, and the unusual dosing regimen. There are also many more that are easy to spot.

From a proprietary review (just complemented with short review and and an investment parallel):

In the study you mention, they report a comparison of some variables after randomization, but before actual 'blind' intervention:

D-Dimer (ng/mL) (mean +/-SD)     'treated' group: 650.92 +/- 405.61        control group: 1333.54 +/- 2570.50

Because of the wide dispersion in d-dimer levels and because of small numbers, they come to the conclusion that  there is no statistical difference for d-dimer levels between the two groups, a conclusion which is obviously very suspect. Any difference when comparing groups after randomization is suspicious and attempts to adjust results after the fact is even more suspicious. Also, the d-dimer variable is incredibly important. For the financially focused, the d-dimer level for somebody coming to the hospital is similar to the Altman Z-score for a company potentially entering distress. The importance of this aspect was sort of suspected when the study was published but the importance of elevated d-dimer levels for Covid has been consistently and repeatedly demonstrated since then. Higher d-dimer levels indicate that the the Covid disease process is more advanced, has entered an unfavorable immune response profile and has involved the coagulation profile. Higher d-dimer levels indicate that there is higher risk (exponential type of rise with linear rise in d-dimer levels) for disease severity, ICU admission, poor outcome and death. The difference in d-dimer levels in the two groups after randomization, in itself, goes a long way in explaining the measured differences in 'treatment' outcomes and makes this study essentially valueless.

Just for fun (in the unlikely event that there is one other person in the world who wonders), more recent reports about d-dimers and Covid show a very similar correlation matrix (sensitivity and specificity, but even more convincing for d-dimers) with area under the curve on the left showing excess risk between the d-dimer phenomenon and the excess bankruptcy risk described for the Altman Z-score:

From the covid stuff (2021):

From the bankruptcy stuff (2013):

 

The study you mention is like if the FED would have set up two groups last year, 'randomly' selected: one group receive support and the other group does not and they report that the group they supported did much better, forgetting to discuss that evaluation of their data indicates that the 'randomization' process resulted in the 'untreated' group starting out with wildly worse Altman Z-scores. An option then would be to keep on repeating the same mistakes, over and over again. What is there to lose?

[John Hjorth]

This is a coronavirus thread.  Not investment thread. ...

 

Now who defined this topic [and had the authority to so] this particular way?

[Investor20]

...

This is a coronavirus thread.  Not investment thread. 

The above study you gave the link is not the study I am citing.  The above study you cite was not a randomized study.  Instead they gave the medicine and placebo by ward, not randomized by individuals.  Upon realizing this Lancet removed the publication. This study came out in jan 2021.

The study I was citing is below and was published in Aug 2020 where they randomized individual hospitalized patients.

https://www.sciencedirect.com/science/article/abs/pii/S0960076020302764?via%3Dihub

...

The Aug 2020 study shares several methodological flaws which are fundamental (there is a pattern).

From reported peer review, the study you mention has the following weaknesses: small number of patients, ICU admission as a subjective outcome, and the unusual dosing regimen. There are also many more that are easy to spot.

From a proprietary review (just complemented with short review and and an investment parallel):

In the study you mention, they report a comparison of some variables after randomization, but before actual 'blind' intervention:

D-Dimer (ng/mL) (mean +/-SD)     'treated' group: 650.92 +/- 405.61        control group: 1333.54 +/- 2570.50

Because of the wide dispersion in d-dimer levels and because of small numbers, they come to the conclusion that  there is no statistical difference for d-dimer levels between the two groups, a conclusion which is obviously very suspect. Any difference when comparing groups after randomization is suspicious and attempts to adjust results after the fact is even more suspicious. Also, the d-dimer variable is incredibly important. For the financially focused, the d-dimer level for somebody coming to the hospital is similar to the Altman Z-score for a company potentially entering distress. The importance of this aspect was sort of suspected when the study was published but the importance of elevated d-dimer levels for Covid has been consistently and repeatedly demonstrated since then. Higher d-dimer levels indicate that the the Covid disease process is more advanced, has entered an unfavorable immune response profile and has involved the coagulation profile. Higher d-dimer levels indicate that there is higher risk (exponential type of rise with linear rise in d-dimer levels) for disease severity, ICU admission, poor outcome and death. The difference in d-dimer levels in the two groups after randomization, in itself, goes a long way in explaining the measured differences in 'treatment' outcomes and makes this study essentially valueless.

Just for fun (in the unlikely event that there is one other person in the world who wonders), more recent reports about d-dimers and Covid show a very similar correlation matrix (sensitivity and specificity, but even more convincing for d-dimers) with area under the curve on the left showing excess risk between the d-dimer phenomenon and the excess bankruptcy risk described for the Altman Z-score:

From the covid stuff (2021):

From the bankruptcy stuff (2013):

 

The study you mention is like if the FED would have set up two groups last year, 'randomly' selected: one group receive support and the other group does not and they report that the group they supported did much better, forgetting to discuss that evaluation of their data indicates that the 'randomization' process resulted in the 'untreated' group starting out with wildly worse Altman Z-scores. An option then would be to keep on repeating the same mistakes, over and over again. What is there to lose?

 

@Cigarbutt, You missed my specified gripe, no one tried to mimic this Calcifediol study and mimic it to confirm the result after 8 months.

 

These studies for treatment are mostly done outside US.  Here is another:

 

Kintor Pharmaceutical has reported top-line results from its investigator-initiated trial of Proxalutamide in Brazil, which showed a 92% reduction in mortality in hospitalised Covid-19 patients.

https://www.clinicaltrialsarena.com/news/kintor-proxalutamide-lowers-mortality/

 

"the placebo-controlled, double-blinded, randomised, parallel assignment, and multi-centre trial enrolled 588 patients within 48 hours of hospital admission."

 

"On 9 March, a preliminary analysis was conducted based on 294 patients in the Proxalutamide arm and 296 patients in the control arm.

 

"Results showed that the mortality in the Proxalutamide arm was 11 (3.7%) versus 141 (47.6%) in the control arm on day 14, indicating a 92% reduced mortality risk."

 

@John.  To say Coronavirus has no relationship to investment is ridiculous statement.  But my contention was from the description of General Discussion forum "Feel free to talk about anything and everything on this board". It has threads like " I Need a Laugh. Tell me a Joke. Keep em PC.", "When will you take a vaccine", and "Movies and TV shows (general recommendation thread)", etc.

[Cigarbutt]

...my specified gripe, no one tried to mimic this Calcifediol study and mimic it to confirm the result after 8 months.

...Kintor Pharmaceutical has reported top-line results from its investigator-initiated trial of Proxalutamide in Brazil, which showed a 92% reduction in mortality in hospitalised Covid-19 patients....

Just like when building an investment case, one should aim to build on previously established foundations. Occasionally, the process is a leap forward but often it is incremental but you need strong foundations. If you start with poor foundations, the likelihood of going in the wrong direction is high. The calcifediol study (IMO) has little or no value and it is hard to justify to build upon this work.

Also, why would you want to 'mimic' a study with such poor foundations? The idea of 'replication' of a study is not simply to repeat the study. The most cost-effective conceptual way to go about this is to try to repeat the study with the aim to disprove the conclusions, in a way. That's why this Board is so interesting for investment thoughts when ideas get confronted and opposed in a constructive way.

This is part fundamental analysis and part looking at incentives and incentives in those studies can be significant which is why independent replication is so important.

The 'hormonal' study (and general line of thought) starts with a much stronger foundation even if it's about repurposed drugs. There is a clear and plausible mechanism of action through the ACE receptor. The study appears to be very well done and is a clear signal for replication to be done as soon as possible. Results appear solid but it's a sponsored study and, very often, the rate of favorable replication of sponsored studies is disappointing.

All in all, there has to be a way to optimize the process (balance alternatives with established practices etc) but the Covid episode has shown that a huge amount of resources have been wasted because of poor foundations to start with and a poor process to follow.

You must realize that an incredibly high number of 'researchers' are about to look for the next popular target.

[Investor20]

...my specified gripe, no one tried to mimic this Calcifediol study and mimic it to confirm the result after 8 months.

...Kintor Pharmaceutical has reported top-line results from its investigator-initiated trial of Proxalutamide in Brazil, which showed a 92% reduction in mortality in hospitalised Covid-19 patients....

Just like when building an investment case, one should aim to build on previously established foundations. Occasionally, the process is a leap forward but often it is incremental but you need strong foundations. If you start with poor foundations, the likelihood of going in the wrong direction is high. The calcifediol study (IMO) has little or no value and it is hard to justify to build upon this work.

Also, why would you want to 'mimic' a study with such poor foundations? The idea of 'replication' of a study is not simply to repeat the study. The most cost-effective conceptual way to go about this is to try to repeat the study with the aim to disprove the conclusions, in a way. That's why this Board is so interesting for investment thoughts when ideas get confronted and opposed in a constructive way.

This is part fundamental analysis and part looking at incentives and incentives in those studies can be significant which is why independent replication is so important.

The 'hormonal' study (and general line of thought) starts with a much stronger foundation even if it's about repurposed drugs. There is a clear and plausible mechanism of action through the ACE receptor. The study appears to be very well done and is a clear signal for replication to be done as soon as possible. Results appear solid but it's a sponsored study and, very often, the rate of favorable replication of sponsored studies is disappointing.

All in all, there has to be a way to optimize the process (balance alternatives with established practices etc) but the Covid episode has shown that a huge amount of resources have been wasted because of poor foundations to start with and a poor process to follow.

You must realize that an incredibly high number of 'researchers' are about to look for the next popular target.

 

First of all everyone has their own style of investing.  I like to study something that interests me and even if I dont find anything that is investible, I learnt something and that is enough of ROI for me.

 

Regarding your issues with Calcifediol trial you said

 

"From reported peer review, the study you mention has the following weaknesses: small number of patients, ICU admission as a subjective outcome, and the unusual dosing regimen. There are also many more that are easy to spot.

From a proprietary review (just complemented with short review and and an investment parallel):

In the study you mention, they report a comparison of some variables after randomization, but before actual 'blind' intervention:

D-Dimer (ng/mL) (mean +/-SD)      'treated' group: 650.92 +/- 405.61        control group: 1333.54 +/- 2570.50"

Note: Emphasis in underline added

 

Your concern seems to be it is a small study.  The authors called it a "Pilot" study.  You are saying the intervention and placebo group are not matched well.  That could be because of the small study. I am not clear about your concern about subjective nature of ICU admission because the authors said the trial is a "double-masked clinical trial."

 

What I am hoping for is a randomized double blinded clinical trial which involves giving same dosage of Calcifediol, to same set of patients (at admission like in the pilot trial), but larger number of volunteers, using a randomized blinded study.  The blinding portion is to take care of the subjective part you were concerned about - which authors said they already used. This is what I mean by mimicking the "Pilot" study with a larger study to confirm the results. What I am asking is why was this not done long time back?

 

Note: Only for discussion.  Not a suggestion for treatment.  Please consult a physician for any treatment.

[Cigarbutt]

...What I am asking is why was this not done long time back?...

i don't know why but suspect that a lack of more convincing human and physical capital into the venture may be related to the poor risk-reward profile (amount invested versus potential benefits).

There are a few relevant trials underway which will be made available for review between April and June 2021, hoping we learn something.

[backtothebeach]

...What I am asking is why was this not done long time back?...

... may be related to the poor risk-reward profile...

 

Let's address the elephant in the room: There is no money to be made in cheap, early-onset treatment, therefore no political interest in the developed world. If studies are funded publicly, ultimately it becomes a question of politics. Studies in developing countries are all flawed of course...(kinda racist if you ask me - not referring to board members here).

 

Lot's of money to be made with treatment of more severe cases, so no problem to emergency approve Remdesivir with only a doubtful Gilead sponsored study.

 

 

[Gregmal]

Just wanted to bump this on the one year anniversary of some of the greatest contrarian indicators of all time here of COBF. The genius authors of these can remain nameless however the March-June pages here were quite something!

Third and fourth weeks of April last year there were folks making claims such as( some paraphrasing):

"I hope you & your kind are active participants in the market for sure"    April 26, 56% return had you listened!

Better answer for him: "If you truly think the whole world is wrong and you are right, the futures market opens at 6 pm EST"      March 15-basically the bottom

"If you are as confident as you are that you are correct, the financial markets are providing you plentiful opportunities to profit handsomely. "          Mid March....Yup, plentiful indeed.

"President Cuomo"....this didnt age well!

"I don't commit to numbers in the face of rapid compounding and wide uncertainty, but I do sell my stocks and go to cash when I sensed this disaster unfolding".      Thats too bad

 

On Michael Burry and Mr. Cuomo: 

"Well he went in big on Gamestop and Tailored Brands, so not surprising." 

"Galileo's investments in Gamestop and Tailored Brands need the Church to listen! Galileo may be suffering from an acute case of incentive caused bias (Even Newton wasn't immune to the whims of the South Sea Company)...

But yes, what Pres Cuomo is already planning...a strategic reopening."

"Presidential--with a capital 'P'. Somebody jelly of President Cuomo, wants to capture the political upside of Cuomo's stellar management".     LMFAO! Ooops!

"The market has provided ample opportunity for those who missed this in March to cash out with the S&P now where it was in October 2019. There should be no valid excuse for these people if they lose their shirts."           Late April..sooo prescient 

"So Sam Zell, Buffett, and Icahn are cautious on the sidelines and on the other side you have folks like Bill Ackman. Take your pick..."  Well...Ackman did 70%. Buffett barely broke even, Icahn sucked wind, and Zell...who cares?

 

"and then they'll cry and talk about "who could have predicted this".   Whelp....obviously some of us could have, but not all of us!

 

 

 

S&P since then? One of the truly great, generational, perhaps even once in a lifetime buying opportunities... ~+56% over the next 12 months

The cream eventually rises to the top and the turds get flushed down the toilet and go away. As they say, never in doubt! Nostradamus! Always certain!

I hope you all were invested in the markets! If not, just remember, an ounce of prevention is worth a pound of cure! Just ask Taleb. Buffett and Icahn were both bearish. Only stooopid people buy stonks during a pandemic! Dumb aphorisms for the win!

 

And yea, I 100% did flag these posts at the time to throw them in peoples faces down the road. When people run their mouths they deserve accountability. 

 

Cheers

[DocSnowball]

Greg, thanks for refreshing this thread. It is a time to reflect isn't it. Humility and confidence is the winning dichotomy in the age of Coronavirus, if that makes any sense. All those posters were wrong about the markets and not humble enough about what the future holds, myself included.

On the medical side, things are turning out very differently than imagined in 2021. I'm just returning back from Delhi, India, where I lost my father to this current wave. It is an order of magnitude worse than 2020, who could have ever imagined? Everything we feared last year has come true now in terms of loss of life. Every third home has someone sick (usually entire families), every 10th home someone is in the hospital - if lucky enough to find a bed, every 20-25th home someone has died. The hospitals are completely full, in the last two days I know of two people who died just looking for a bed all day and not finding it. Doctors don't have a place where they can admit family members, and are taking care of them at home with Dexamethasone, anticoagulant injections, and the odd oxygen cylinder if you can find one at all. It is tragic beyond description. 

The only key metric that the Government cared about was collapse of the healthcare system, and the magnitude of the wave made it happen. Hospitals ran out of oxygen killing 20-30 people over minutes. This led to mass closure of excess admissions, as no hospital now wants to admit sick people and have them die in house due to lack of oxygen. Given no beds available for sick people, Government had to call a lockdown - now into its second week in Delhi. A few more states have had to do the same. The situation is no better across the country, with peak expected in the next week or two. 

I know of two other physicians who were there from the US, fully mRNA vaccinated - both got symptomatic disease. Scores of Astra Zeneca vaccinated folks who died or are in the hospital critically ill. A significant chunk under 50 years. A new variant, the double mutant strain, appears to be behind a lot of this. Flights have been flying out the entire last month, now taking this strain across the world. 

I can't even think of second order impact at this time, but I'm sure others can. There is a certain sense of deja vu to what happened in Wuhan early 2020.   

[Gregmal]

Sorry to hear of your loss. 

I do actually recall, IIRC it was John Hjorth, probably back around this time a year ago, having significant concerns  for India specifically. 

What puzzles me, is that considering how globally connected everything is, as far as information goes...how does a year pass and yet we still the level of pure chaos that is currently being seen in India? How dont we have adequate supplies? I am by no means an expert on India, but to think this has been around for over a year and the worst is still happening in places is bizarre. Brazil was another puzzling one although I think different factors were at work there. Conversely, we havent really heard all that much out of Asia anymore. 

Without getting into it too severely as I always feel Im treading on ice with respect to covid and Sanjeev's tolerance for politics, but is the issue with covid really the politics of it? Its seems(again not specific to red/blue) that many of the areas that have been outliers suffered from lack of flexibility in terms of adapting on the political front. 

 

In respect to the markets, I dont recall you being an obnoxious ass about it. Everyone is obviously entitled to their opinions. Some are more skilled in their ability to forecast than others, but there were a few folks here who went out of their way to viscously disparage, mock, and even attempt to bully people whom disagreed with them...and those are the people who happened to be hilariously wrong and quoted above. If you are going to behave like that, at the least, you better be right. There were lot of folks who underestimated the markets, but they were humble about it and generally cordial and didnt make total fools of themself. Others, not so much. 

Edited April 25, 2021 by Gregmal

[Libs]

>I know of two other physicians who were there from the US, fully mRNA vaccinated - both got symptomatic disease. Scores of Astra Zeneca vaccinated folks who died or are in the hospital critically ill. A significant chunk under 50 years. A new variant, the double mutant strain, appears to be behind a lot of this. Flights have been flying out the entire last month, now taking this strain across the world. <

Doc

Really sorry for your loss. What's going on there is unimaginable.

Regarding the above, this is not what is being reported....we are told the vaccines are effective against new strains. Hopefully we'll get some decent data on this soon. From what I can tell, Moderna, Pfizer and JNJ shots have not been given in India, which leads me to wonder if we really know if they protect. Ugh.

 

 

 

 

 

 

[DocSnowball]

44 minutes ago, Libs said:

>I know of two other physicians who were there from the US, fully mRNA vaccinated - both got symptomatic disease. Scores of Astra Zeneca vaccinated folks who died or are in the hospital critically ill. A significant chunk under 50 years. A new variant, the double mutant strain, appears to be behind a lot of this. Flights have been flying out the entire last month, now taking this strain across the world. <

Doc

Really sorry for your loss. What's going on there is unimaginable.

Regarding the above, this is not what is being reported....we are told the vaccines are effective against new strains. Hopefully we'll get some decent data on this soon. From what I can tell, Moderna, Pfizer and JNJ shots have not been given in India, which leads me to wonder if we really know if they protect. Ugh.

 

 

 

 

 

 

Thank you for your kind words. Sorry for the long posts, perhaps just looking for a release valve. I went in believing the vaccine will protect me (should have been more humble) -spent two weeks also taking care of my sick mom and brother at home. Had two days of symptoms but PCR never turned positive. The other two US physicians I talked with had documented disease. I tried to talk to the Government lab folks to get their viruses sequenced, but too much red tape was involved. 

I think the cases were down so low mid-March, both Govt. and people lowered their guard. Public gatherings, religious festivals, election rallies, markets and malls, along with early vaccine euphoria contributed. Preparedness was eased, including getting rid of additional hospital beds and supplies etc and focusing on vaccination efforts. Unfortunately the AZ vaccine didn't bring the results hoped, esp with one dose which most people had received. Then the new variants took hold and the rise in cases was exponential - nearly 100 fold in Delhi within 4-5 weeks (200 cases a day early-mid March to 25,000 cases a day mid-April)

Trying to make my brain work a little now and looking back at vaccine info vs variants. Attaching two summary slides from mid-Feb from our society's presentation about vaccines vs variants- pay attention to the B.1351 (S African strain) or the E484K/Q mutation results - approx. two fold drop in antibody titers with mRNA vaccines but still some efficacy is expected. Limited trial results from across the world for other three vaccines - note the poor AZ results in S. Africa, no different than placebo really.

What we know/ What we don't know:

1- terrible epidemic in India overwhelming the healthcare system - medicines, beds, oxygen shortage/ ?how long this will last and what it will do to the economy

2- new doubt mutant strain identified, more infectious plus has E484Q mutation conferring some vaccine resistance/ ?is this strain the reason or was it behavior or ineffective vaccine

3- lot of documented severe cases who had AZ vaccine, mostly one dose, some two doses - implications for countries relying on this esp other developing countries. Consistent with S Africa trial with this vaccine showing poor efficacy. /? will the vaccine be similarly ineffective in Europe

4- lot of documented cases in those who had disease last year, raises question of duration and effectiveness of natural immunity beyond 1 year/ against this strain - implications for places relying on "herd immunity"/ ? depends on whether these were mostly just mild cases or severe cases. 

5- ? anecdotes of failure of mRNA vaccine, but the only way to know is when a population gets exposed (?Israel or a US state likely to be first placed with good data capture). /?The hope is that even partial immunity may be enough to prevent a collapse of the healthcare system, fingers crossed, although the unvaccinated may suffer disproportionately. Implications for mRNA vaccines becoming preferred vaccines, both because a bit more protective now and because they can be adapted quickly for booster doses. 

6 - ? we don't know how these variants will spread in different weather and population conditions. What happened in one place may not/ will not happen everywhere. But it could happen in a few other places unfortunately. 

Edited April 25, 2021 by DocSnowball

[cubsfan]

Fun reading about all the apocalyptic predictions again. People were so so sure of themselves - and vicious about it too - especially if you disagreed with them.

[Gregmal]

^Yup! Lot of lessons to be learned. If nothing else though, when it comes to financial markets, dont be afraid to think for yourself and go against the crowd. Dont be scared of being on the unpopular side of the trade. Dont let hysteria influence you. And especially, dont just blindly say "Buffett thinks....." and follow suit. 

The truth is, some people, seem to refuse to learn or adapt. They'll just head into the next generational opportunity singing tunes like "an ounce of prevention is worth a pound of cure" and once again miss it. Even Buffett swiftly pivoted after his disastrous AGM showing and saw the greater picture mid summer. An ounce of prevention may be worth a pound of cure, but a pound of cure aint +56% on S&P in 12 months(or more if you got creative)....always certain!

[Spekulatius]

It might be time to have an ounce of prevention and vaccinate the portfolio a bit just in case this has consequences beyond just India.

it is not that we never have seen this before.

[ANP301191]

Speaking to family in Mumbai (who thankfully are safe), the situation in Dehli is replicated in Mumbai. Even in April/May 2020 at the peak of it in Mumbai, there was some availability of oxygen or beds, today even doctors are unable to get family members admitted.  While respecting the need to keep politics out of it, the gross incompetence shown by officials in opening up India and declaring victory so early while not replenishing oxygen or other necessary healthcare supplies has really shown a weakness in governance in India from public health officials/politicians.

What frightens me even more than the actual case counts in India is the food inflation, which has begun to skyrocket, which will lead to a vicious cycle of people who are hand to mouth needing to work to feed their families and then getting sick and spreading the disease even further.

Another question I have been asking: where else has this strain migrated to? I have read of cases in Belgium, HK, France, UK all linked to India via people who have travelled in the past few days. I would guess its only a matter of time till it starts showing up in local populations or other countries.

[Cigarbutt]

Warm thoughts and good luck to India.

Reaching herd immunity has proven to be a tough challenge in correlation to the speed of vaccine rollouts.

In many places, results have shown various levels of resurgence but the hospitalization numbers have tended to show variable levels of muted impact in correlation to vaccine rollouts (priority rules vs age groups).

Opinion: it's not the inefficacy of vaccines that was a primary factor for recent India's developments (it was the residual distance to herd immunity) but the virus (and variants) is benefiting from an unusual opportunity to create new variants (from mutations and recombination). It's a natural experiment with basic biology as the driving force and variable levels of human behavior having a marginal impact.

'Triple mutant' coronavirus variant discovered in India? What it means - The Week

From an odds basis and applying what is known presently about Covid-19, it's unlikely that the new variants will significantly escape vaccines (or variants of vaccines) but the odds are not zero.

 

Edited April 26, 2021 by Cigarbutt