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Covid 19 virus inpacts sports, NHL,Season Tix other impacts

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2 hours ago, remkin said:

The actual remaining question is not are you immune if you've recovered? The real question, and it's answer is it's own kind of scary, is: "How long does your immunity last?". It's pretty obvious that it's at least 6 months. But after that speculation is wide. Some corona viruses immunity seems to last about one season or around a year give or take. Others appear to be a few years. This leads to the idea put out there that Covid will always be with us as it can flair up later after immunity may have faded. Most likely this is in pockets though as some will still have immunity. Also, there might be some attenuation from a vaccine, and there is a tenancy of long lasting viruses to mutate to a less virulent form.

rem, let me address this thought with another fact. We know that with "mutation" of a virus, like we see with influenza, the change frequently favors a more infectious form, as by virtue of that, it "outgrows" if you will, the lesser infectious form. A component of that mutation apparently, which by extension makes it "more infectious" is that its reduction in mortality spares more "targets" if you will in which to continue propagation. Simply put, the higher the virulence, the higher the mortality, the more quickly the virus dies out for lack of "targets". Thus virulence decreases in favor of sparing of "targets"? Weird how nature is, huh?

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1 hour ago, wxray1 said:

On a personal note, I have cold sores, a form of herpes.  I know all the ways to coax it out of its hiding, and have learned to avoid them.  Hope this beast doesn't decide to take up residence anywhere

I do too and at 1st sign of recurrence which we all quickly recognize don't we wxray, I keep Zovirax (presently Valacyclovir) in reserve to quickly take. Wipes it out after about 2 doses.

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28 minutes ago, wxray1 said:

There are something like over 200 tests developed for antibodies.  These all fall under an emergency measure by the FDA to allow them to be used.  I.E., there is no efficacy study on these.  It is th

Relative to this wxray, gradually, as more time allows, the FDA is pulling worthless tests operating under the EUA umbrella, and last I'd read, at least 20 have been pulled as less than worthless.

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29 minutes ago, KJUNKANE said:

Relative to this wxray, gradually, as more time allows, the FDA is pulling worthless tests operating under the EUA umbrella, and last I'd read, at least 20 have been pulled as less than worthless.

 

Let me double check my understanding of antibody testing. Even if the inferior tests are completely eliminated, the inverse relationship of disease prevalence to false positives means that antibody testing won't likely be a useful tool to identify those that are "safe" from the disease until a relatively large proportion of the population has actually had the disease.  Obviously, if tests with a higher degree of specificity were developed that would help, but is that take more or less correct?   

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5 hours ago, LakeLivin said:

 

Let me double check my understanding of antibody testing. Even if the inferior tests are completely eliminated, the inverse relationship of disease prevalence to false positives means that antibody testing won't likely be a useful tool to identify those that are "safe" from the disease until a relatively large proportion of the population has actually had the disease.  Obviously, if tests with a higher degree of specificity were developed that would help, but is that take more or less correct?   

Correct Lake, "prevalence" in this case trumps specificity, and further, as prevalence increases, specificity gains much more "positive predictive value", meaning one has more confidence in the accuracy/validity of a positive test. Not to beat a dead horse any further, but this then means that as prevalence goes up, meaning more of the population has been exposed to a disease (as in COVID-19), and has recovered, developing as they do, an antibody to that agent, then one has more confidence that a positive result from the antibody test actually indicates they've been exposed to the virus, or when a vaccine is developed and administered, that they've responded to it by developing the protective antibody.

To respond to one other debate, presently, as I'm sure many have discovered, there's debate as to how long this antibody will persist, however there's a well known facet to this debate, and that is even though an antibody appears to fade and eventually becoming "undetectable", we also believe this is a function of the sensitivity of "in vitro" testing (that is in a test tube if you will), and there's a phenomenon referred to as 2nd set reaction, meaning that "in vivo" (that is in the body) something else is felt to be operative. This involves memory stored of the viral antigen (the usual protein component of the virus recognized as foreign), which despite that antibody being sub detectable in vitro, nevertheless in vivo, a challenge by the viral antigen elicits a 2nd set antibody response, that occurs in a shorter period of time, is stronger than the 1st exposure and is longer lasting. We frequently observe this with several vaccines, thus the need for so called "booster" shot. 

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As an applied scientist (aka engineer), this discussion is a great diversion for me.  I have to admit, I had flashbacks to my Probability Theory 201 class.  Nothing but integral calculus!  Probability measured by the area under the curve, a nightmare.  The "flattening the curve" graphs were exactly the kind of crap we did in that class.  But anyway, the prevalence/specificity thing is part of it and I appreciate KJUN's input here.

 

I suspect in about 10 years we're going to have boom in PhD candidates in virology and epidemiology, just like I was part of the Apollo program boom.

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18 hours ago, KJUNKANE said:

Correct Lake, "prevalence" in this case trumps specificity, and further, as prevalence increases, specificity gains much more "positive predictive value", meaning one has more confidence in the accuracy/validity of a positive test. Not to beat a dead horse any further, but this then means that as prevalence goes up, meaning more of the population has been exposed to a disease (as in COVID-19), and has recovered, developing as they do, an antibody to that agent, then one has more confidence that a positive result from the antibody test actually indicates they've been exposed to the virus, or when a vaccine is developed and administered, that they've responded to it by developing the protective antibody.

To respond to one other debate, presently, as I'm sure many have discovered, there's debate as to how long this antibody will persist, however there's a well known facet to this debate, and that is even though an antibody appears to fade and eventually becoming "undetectable", we also believe this is a function of the sensitivity of "in vitro" testing (that is in a test tube if you will), and there's a phenomenon referred to as 2nd set reaction, meaning that "in vivo" (that is in the body) something else is felt to be operative. This involves memory stored of the viral antigen (the usual protein component of the virus recognized as foreign), which despite that antibody being sub detectable in vitro, nevertheless in vivo, a challenge by the viral antigen elicits a 2nd set antibody response, that occurs in a shorter period of time, is stronger than the 1st exposure and is longer lasting. We frequently observe this with several vaccines, thus the need for so called "booster" shot. 

 

Prevalence aside, any idea if the issue with false positives could be solved by serial testing?  Seems to me like that would depend on how much the false positives are a function of the test vs. how much they're a function of the person being tested. 

 

Here's the principle I'm trying to get at (and probably not very well, lol).  If the false positives are related mostly to the person being tested, it wouldn't matter how many times you retested a false-positive case; that person would show up as a false positive most of the time.  But if they were related mostly to the test, you could re-sample a person who tested positive multiple times, and with each iteration the probability of getting a false positive would go down and you would eventually end up with however much confidence you wanted that the person truly had the disease and was immune (let's ignore the length of immunity issue for now).  The number of iterations required to get to the confidence level you wanted would of course depend on the prevalence of the disease in the population at that time.  

 

Not sure if that makes sense;  if not, don't spend much time on trying to figure out what I'm saying.  I just re-read the post and I'm not sure it's 100% clear to me, lol.  

   

Edited by LakeLivin

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Beyond the above dialogue here’s a good 2 min read regarding the current CBA. Nothing at all, understandably, covered this sports disaster and there are many devils in the details. Didn’t see it in the article but about contracts ending or UFAs or RFAs playing after July 1?  Who would risk it? There zero provisions for any of this stuff not to mention a 10 week quarantine for the two who make the finals; life inside the Covid bubble that wouldn’t be impervious for any of the 24. If it comes together I’ll be watching for sure but this newly created re-start mess in the making just doesn’t look to have legs. 
 

https://nypost.com/2020/05/30/nhls-attempt-to-change-popular-rule-may-spark-restart-tension/amp/

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16 hours ago, LakeLivin said:

 

Prevalence aside, any idea if the issue with false positives could be solved by serial testing?  Seems to me like that would depend on how much the false positives are a function of the test vs. how much they're a function of the person being tested.

...

Not sure if that makes sense;  if not, don't spend much time on trying to figure out what I'm saying.  I just re-read the post and I'm not sure it's 100% clear to me, lol.  

 

 

LOL Lake!   From what I gather, you ask a good question.

 

For the MUSC test I took, they are going to get some data on that.  Plasma and platelet donors typically give frequently, as in multiple times per month.  I'm sure any change in status of a donor (neg->pos or pos->neg) is going to be scrutinized heavily.   The pos->neg change will be especially important for those donating convalescent plasma.

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On 5/28/2020 at 3:44 PM, wxray1 said:

The NHL is thinking about next season.  Not sure if ya'll got this survey.  Here's what I got.

covidsurvey.JPG

I got it too

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Just listened to most of the latest update from the EM Rap group. Most telling is how little new there is. Cases seem to be moving to South America globally. But most of the rest of it is fine tuning things we were at least previously onto. How to treat ICU patients, etc. Unfortunately the news on the treatment front is not as great as it seemed earlier.

 

First, yet another negative hydroxychloroquine study. Not an RCT, so the final nail is not been hammered yet, but the trends are not positive. 

 

Since that drug had already been trending pretty poorly, I'd say that for me the most disappointing news was actually a deep analysis of the remdesivir study. This is a pretty good example of part of what I've been on about. The establishment has jumped on board with the recently touted positive study on this drug. If you listen to some experts and most of the media, this is the first "proven" treatment. In fact, it says that very thing in an article right now on Yahoo life. So there it is right? 

 

Maybe, maybe not so fast. I mentioned a while ago that over my career I've found several scientific experts with a brilliant ability to break down the quality of studies. Maybe none has been as universally impressive as a guy named Jerome Hoffman in California. He is an academic ED doc with statistics background who has been breaking down 30 scientific articles/month for 30 years. He's retired now, but EM Rap brought him out of retirement to have a look at the latest remdesivir study. His opening line was, "It's even worse than I thought". 

 

Below is the entire hour and a half update, can't say it's worth watching the whole thing, but I include it here for the part that introduces Jerry Hoffman and his critique of the study, its worth a look, at around 27:00 to about 35:00. 7 minutes. 

 

 

 

It shows just some of the difficulties in "proving" something scientifically.  Bottom line, this latest remdesivir study is far from the proof it touts. About the only thing one can say with a study that is poorly done as this, is that the effect can't be monumental, because that would have shown up far far bigger. If this drug works, it will be a small effect, and there is still a strong chance this will end up being ineffective. 

 

But watch the experts, even the government ones, who will all have to respond to this seemingly positive study with a massive expansion of the use of this drug. Once that becomes standard care, it will be very very hard to stop it, even if it is increasingly proven ineffective, both because of how huge this whole Covid thing is, and the lack of alternative treatments. The only thing that would stop it, is a huge RCT proving no benefit or harm, or a clearly superior alternative. 

 

I still hope for it to work, but it is far from proven.

 

Really, listen to Jerry Hoffman's explanation if this issue interests you. It's 7 minutes of insight into how real scientists practice peer review, and why that is such a critical step in the scientific proof process.

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5 hours ago, remkin said:

Just listened to most of the latest update from the EM Rap group. Most telling is how little new there is. Cases seem to be moving to South America globally. But most of the rest of it is fine tuning things we were at least previously onto. How to treat ICU patients, etc. Unfortunately the news on the treatment front is not as great as it seemed earlier.

 

First, yet another negative hydroxychloroquine study. Not an RCT, so the final nail is not been hammered yet, but the trends are not positive. 

 

Since that drug had already been trending pretty poorly, I'd say that for me the most disappointing news was actually a deep analysis of the remdesivir study. This is a pretty good example of part of what I've been on about. The establishment has jumped on board with the recently touted positive study on this drug. If you listen to some experts and most of the media, this is the first "proven" treatment. In fact, it says that very thing in an article right now on Yahoo life. So there it is right? 

 

Maybe, maybe not so fast. I mentioned a while ago that over my career I've found several scientific experts with a brilliant ability to break down the quality of studies. Maybe none has been as universally impressive as a guy named Jerome Hoffman in California. He is an academic ED doc with statistics background who has been breaking down 30 scientific articles/month for 30 years. He's retired now, but EM Rap brought him out of retirement to have a look at the latest remdesivir study. His opening line was, "It's even worse than I thought". 

 

Below is the entire hour and a half update, can't say it's worth watching the whole thing, but I include it here for the part that introduces Jerry Hoffman and his critique of the study, its worth a look, at around 27:00 to about 35:00. 7 minutes. 

 

 

 

It shows just some of the difficulties in "proving" something scientifically.  Bottom line, this latest remdesivir study is far from the proof it touts. About the only thing one can say with a study that is poorly done as this, is that the effect can't be monumental, because that would have shown up far far bigger. If this drug works, it will be a small effect, and there is still a strong chance this will end up being ineffective. 

 

But watch the experts, even the government ones, who will all have to respond to this seemingly positive study with a massive expansion of the use of this drug. Once that becomes standard care, it will be very very hard to stop it, even if it is increasingly proven ineffective, both because of how huge this whole Covid thing is, and the lack of alternative treatments. The only thing that would stop it, is a huge RCT proving no benefit or harm, or a clearly superior alternative. 

 

I still hope for it to work, but it is far from proven.

 

Really, listen to Jerry Hoffman's explanation if this issue interests you. It's 7 minutes of insight into how real scientists practice peer review, and why that is such a critical step in the scientific proof process.

 

Thanks for posting rem, I'll have to listen to it later.

 

Even ignoring the problem with well controlled RCTs for the moment. When the medical experts first reported positive results with remdesivir, didn't they say it was more likely a "foot in the door" towards an "acceptably effective" treatment than the answer?  Similar to the early development of AIDs drugs?  That first study showed a decrease in length of hospital stays for remidesivir patients, and if I'm not mistaken the death rates for the two groups in that first positive study were 11% for placebo and 8% for remdesivir.  A 25% reduction in death rate would be great if it held up, but an 8% death rate in hospitalized covid patients never seemed like enough of an effect to "manage" the covid-19 problem.  I guess that never really registered to many?

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The study is interesting in that there were 8 groups and 3 of the worst groups were declared the bad outcomes.  Why not 2 he asks? 

 

That has a huge relevance to me.  I was once involved in a survey I had to pay attention to.  The responses were the usual 1 to 5.  1 being strongly like, 5 being strongly dislike and 3 being neutral.

 

The survey came out something like this:

1 - 10

2 - 40

3 - 5

4 - 5

5 - 40

 

So, the 1 and 2's were 50% of the responses, so the powers that be declared: VICTORY, you like it!  Thank you!

 

Meanwhile, the massive number of 5's were ignored.  The 4 and 5's together were 45, which is less than 50 for the like.  But the likes were all "sort of like" and the dislikes were all "strongly dislike."

 

It was purposefully ignored.  It was not a mistake.  What they were saying was true (more likes than dislikes), but the underlying numbers told a different story.   A simple average of the numbers could have been taken and a different result would emerge.


Anyway, as they say, there are lies, and then there are statistics.

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I can just forthrightly and honestly say this without the slightest hesitation. This board, complete with so many different forms of access, exposure, circumstantial to all our lives and what we've personally dealt with, and opinion from the whole spectrum concerning Covid, has been the most educational, reliable in many ways, and bare knuckles information that I have encountered in any other place where such discussions take place. ALL should be commended, thanked and given out prayers for, especially the front line people,(we have been shown who they are) who have personally had experience in what happened, how it happened and what the ramifications of the politics, business and personal involvement have shown to be in real time, real lives and communities spanning the state. I personally thank the MD personnel for sharing so much of your experience, expertise, and frankly, well informed opinions. My personal opinions have no place in the context of this enlightening, frank and better guided discussion than any I've seen and for that reason, as a man of humble intent concerning such matters when far more qualified "experts" IMO present theirs, have declined to offer any. I have followed and respectfully been impressed with the amount of knowledge, willingness to share, and overall the best example of a high IQ discussion that has been brought to my attention. Beyond that, I think it speaks volumes about the general intelligence level of hockey fans in this market, in particular those who have found a home in following the exploits of a small market, delicately balanced franchise between league stardom, popularity and being able to pay the bills through all the years of down for the previous decade. Thanks all who contribute here, who share a passion that we all have, and who rightfully and righteously respect the forum, even when we get a little chippy with attitudes and outlooks. It's a real pleasure and humbling hobby to be at least somewhat accepted here as well. I'm for hockey. As so well explained by several, the risk is minimal and some parts of life offer far more risks to the athletes in the sports of aggression in particular, as well as fans. I'd sit in PNC saturday night, beside anyone of you.

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12 hours ago, remkin said:

Just listened to most of the latest update from the EM Rap group. Most telling is how little new there is. Cases seem to be moving to South America globally. But most of the rest of it is fine tuning things we were at least previously onto. How to treat ICU patients, etc. Unfortunately the news on the treatment front is not as great as it seemed earlier.

 

First, yet another negative hydroxychloroquine study. Not an RCT, so the final nail is not been hammered yet, but the trends are not positive. 

 

Since that drug had already been trending pretty poorly, I'd say that for me the most disappointing news was actually a deep analysis of the remdesivir study. This is a pretty good example of part of what I've been on about. The establishment has jumped on board with the recently touted positive study on this drug. If you listen to some experts and most of the media, this is the first "proven" treatment. In fact, it says that very thing in an article right now on Yahoo life. So there it is right? 

 

Maybe, maybe not so fast. I mentioned a while ago that over my career I've found several scientific experts with a brilliant ability to break down the quality of studies. Maybe none has been as universally impressive as a guy named Jerome Hoffman in California. He is an academic ED doc with statistics background who has been breaking down 30 scientific articles/month for 30 years. He's retired now, but EM Rap brought him out of retirement to have a look at the latest remdesivir study. His opening line was, "It's even worse than I thought". 

 

Below is the entire hour and a half update, can't say it's worth watching the whole thing, but I include it here for the part that introduces Jerry Hoffman and his critique of the study, its worth a look, at around 27:00 to about 35:00. 7 minutes. 

 

It shows just some of the difficulties in "proving" something scientifically.  Bottom line, this latest remdesivir study is far from the proof it touts. About the only thing one can say with a study that is poorly done as this, is that the effect can't be monumental, because that would have shown up far far bigger. If this drug works, it will be a small effect, and there is still a strong chance this will end up being ineffective. 

 

But watch the experts, even the government ones, who will all have to respond to this seemingly positive study with a massive expansion of the use of this drug. Once that becomes standard care, it will be very very hard to stop it, even if it is increasingly proven ineffective, both because of how huge this whole Covid thing is, and the lack of alternative treatments. The only thing that would stop it, is a huge RCT proving no benefit or harm, or a clearly superior alternative. 

 

I still hope for it to work, but it is far from proven.

 

Really, listen to Jerry Hoffman's explanation if this issue interests you. It's 7 minutes of insight into how real scientists practice peer review, and why that is such a critical step in the scientific proof process.

 

Good stuff rem. Is it really possible that they didn't prospectively specify the primary efficacy endpoints for the remdesivir study that was reviewed in the video? :huh: Isn't there an IRB that would have had to review and approve the study protocol? I wonder if maybe in a rush to get the study started there were shortcuts taken.  

 

As far as the reviewer's other big point, they should have been able to adjust for differences in baseline severity in the analysis.  Although, "should have been able to" doesn't necessarily mean that they did. It would be interesting to see the actual full study report.  

 

I ended up listening to the whole video; some pretty interesting stuff in there.  I hadn't been aware of the covid-19 link to thrombosis. And I find it a bit discouraging that even in NYC they estimate infections at only 14-20%.  That leaves a long way to go to get to herd immunity. 

 

How often to they put out updates like that? Maybe you could give us a heads up next time one comes out?

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23 hours ago, remkin said:

Not an RCT

rem, what is this? I don't recognize the anacronym? 1st let me be upfront and state that I've not taken the time to listen thru that video as have been swamped with my own mess, and now a law firm wants to depose me on a private autopsy I performed on a sickle cell patient several years ago??? Don't they know there's more urgent things afoot?

 

A comment on these several drugs that were hurriedly thrown into the breach so to speak, particularly remdesivir. I never read them as being curative, and perhaps I was incorrect as I AM NOT A CLINICIAN, but at the most, I understood that they could shorten the length of hospital stay, as well as possibly shorten the length of viral shedding? That to my limited mind never said they were life sparing at the height of the illness(? cytokine storm), thus not the magic bullet we anxiously await? Was this wrong?

 

Most recently, I have been reading on several much more SARS COV-2 virocentric (not sure thats a word) approaches to an effective treatment, including a monoclonal antibody aimed a specific regions on the virion's capsid, and specifically at the now infamous "spike protein" and others, LY-CoV555. Other groups are working on "diverse antibodies", anticipating the possibility of this virus mutating like influenza. But these are being greatly rushed thru trials as I thought it was possible they might?

 

Finally Lake, regarding your comment on this link to "thrombosis", since the COVID virus appears to hone in on ACE-2 receptor sites, and they are globally found in many organs/sites throughout the human body, the coagulopathy(namely hypercoagulation=thrombosis) being observed is predictable as endothelial cells, those lining blood vessels, are one such cell with ACE-2 receptors. Ergo the source of microthrombi (clots) in vessels.

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Thanks for the kind words 2ndSacker. Lake, I know you have a stats background, so such things are not really shocking to you, but I think that very few non science people are really aware of how imperfect even "good" science is. I had an academic upbringing in EM, and as such have both reviewed and listened to reviews of close to 10,000 articles combined (the vast majority listened to Jerry Hoffman and others). After a while one gets a pretty good foundation for the shortcomings of much of science. It's an enlightened place to be, but it's also a very frustrating place to be as the vast majority of providers, let alone the general public understandably rely on a combination of certain experts and the media to get their sense of what is most true. It is wrong as often as it's right. 

 

This is a study that I mention to medical students I teach pretty frequently. It is so elegantly simple. A group of researchers went back 10 years in the New England Journal of Medicine and identified all of the studies in cardiology that claimed to have proven that a specific treatment was effective. Once they were all identified by specific criteria, they went forward up to the the present to determine how many of those claimed treatments had been thoroughly disproven. It was around 44%. Nearly all of those treatments had experts touting them. But the reality is worse than that since the NEJM is one of the most prestigious journals in the world getting to pick only the best studies. There are hundreds of lesser journals publishing studies that are laughable at the outset. 

 

But it's even worse than that overall because of publication bias: the big journals want to publish the new breakthroughs far more than publishing a negative study that shows a thing doesn't work.

 

But even the NEJM is easily corrupted by drug company studies, and even increasingly political biases. 

 

The famous line delivered to incoming medical students by the dean of the Harvard medial school is apt: "Half of what we are about to teach you is wrong. We just don't know which half". 

 

Beware of people claiming "settled science".  That phrase and others have become a political tool. It's tricky out there.

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36 minutes ago, KJUNKANE said:

rem, what is this? I don't recognize the anacronym? 1st let me be upfront and state that I've not taken the time to listen thru that video as have been swamped with my own mess, and now a law firm wants to depose me on a private autopsy I performed on a sickle cell patient several years ago??? Don't they know there's more urgent things afoot?

 

A comment on these several drugs that were hurriedly thrown into the breach so to speak, particularly remdesivir. I never read them as being curative, and perhaps I was incorrect as I AM NOT A CLINICIAN, but at the most, I understood that they could shorten the length of hospital stay, as well as possibly shorten the length of viral shedding? That to my limited mind never said they were life sparing at the height of the illness(? cytokine storm), thus not the magic bullet we anxiously await? Was this wrong?

 

Most recently, I have been reading on several much more SARS COV-2 virocentric (not sure thats a word) approaches to an effective treatment, including a monoclonal antibody aimed a specific regions on the virion's capsid, and specifically at the now infamous "spike protein" and others, LY-CoV555. Other groups are working on "diverse antibodies", anticipating the possibility of this virus mutating like influenza. But these are being greatly rushed thru trials as I thought it was possible they might?

 

Finally Lake, regarding your comment on this link to "thrombosis", since the COVID virus appears to hone in on ACE-2 receptor sites, and they are globally found in many organs/sites throughout the human body, the coagulopathy(namely hypercoagulation=thrombosis) being observed is predictable as endothelial cells, those lining blood vessels, are one such cell with ACE-2 receptors. Ergo the source of microthrombi (clots) in vessels.

RCT is Randomized Clinical Trial. It's a stand in for prospective double blind, placebo controlled trial in most cases. 

 

The rest of this if for those who want to read some of my take on aspects of medical research that aren't necessarily in the field:

 

One of the problems with many many medical studies is the use of "surrogate markers" in place of clinically significant outcomes. The more ineffective the treatment the more these surrogate markers are used. For those not familiar, say that the most important thing that a treatment could do is prevent death. Then say disability. But if a treatment can't affect those at all, maybe it can affect length of stay, or admissions to the hospital. If not that, maybe a pain scale or lowering the white blood cell count. It can be a slippery slope to rather insignificant things being measured. Another major related problem is studying many different possible outcomes. Statistics are applied in large part a way to predict how likely an effect is random rather than due to the treatment. Generally we accept about a 5% chance of a thing being random as the lowest bar. That's 1/20. If I study 15 different outcomes there's a pretty good chance that one or two will look positive just due to randomness. I can then pick those two after the study is completed, and focus my written article on that positive effect. I can stress it in title and the abstract. Especially if I'm a drug company. 

 

I've read many studies where the title and abstract and conclusion (the part most people skip to) say one thing, but the body of the study says the opposite. 

 

An example of surrogate marker use is a study for a drug called Atrovent. It is cheap and safe and added to some albuterol treatments for asthma or COPD. Studies showed that it increased a person's ability to forcefully exhale after treatment, called peak flow. Most experts used peak flows a lot because, well because we love numbers and that gives you a number. Never mind that it's pretty unreliable since patient effort varies. Anyways, experts mostly recommended adding it, and a company even came up with a treatment that had both albuterol and atrovent in it.  But that same study showed that adding atrovent to the treatment did not improve any meaningful outcomes: no change in death, no change in admission rates, no change in length of symptoms, no change in needing intubation, etc etc. And further, if you looked closer at the study (the way Jerry Hoffman looks at that table in the remdesivir study) you'd see that the authors of the atrovent study used substandard doses of the albuterol they were adding to, which is an unfair comparison (and another common study flaw, or trick depending on your point of view). That study is years old, but Atrovent, and the combined treatment with albuterol are still in wide spread use. It's cheap, its safe, it maybe adds a touch, so why not? But it's only been "proven" for that surrogate marker of peak flow, if that. 

 

So if a study picks a bunch of surrogate markers and then goes in and picks one or two that seemed to work after the fact, that's bad science. What's supposed to happen is that they use those seemingly effective markers as the basis for a new prospective study and try to actually prove the concept. But there's little motivation for a drug company to go out and disprove their own drug now touted by experts (often on their payroll).

 

Medical and other science is so messy already, with all kinds of bias baked in. And that's before the turbo charger of bias that is politics gets in there.

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10 hours ago, LakeLivin said:

 

Good stuff rem. Is it really possible that they didn't prospectively specify the primary efficacy endpoints for the remdesivir study that was reviewed in the video? :huh: Isn't there an IRB that would have had to review and approve the study protocol? I wonder if maybe in a rush to get the study started there were shortcuts taken.  

 

As far as the reviewer's other big point, they should have been able to adjust for differences in baseline severity in the analysis.  Although, "should have been able to" doesn't necessarily mean that they did. It would be interesting to see the actual full study report.  

 

I ended up listening to the whole video; some pretty interesting stuff in there.  I hadn't been aware of the covid-19 link to thrombosis. And I find it a bit discouraging that even in NYC they estimate infections at only 14-20%.  That leaves a long way to go to get to herd immunity. 

 

How often to they put out updates like that? Maybe you could give us a heads up next time one comes out?

Oh yes. As I pointed out above science studies are a messy business. My arm's length relationship with just accepting a thing because an expert said it, is borne of 30 years of watching them fail over and over. One boiled down description of science is a method of attempting to remove all bias from observing the world. But there are so many types of bias it's astounding. There are studies on just different types of bias. Listening to Jerry Hoffman and others for years has been pretty eye-opening. It is very common for especially drug companies to set things up in their favor. Hoffman was surprised since this was apparently a government study, but the government has bias too (like finding a treatment fast). 

 

EM Rap is an outstanding product. It actually grew out of a product called Emergency Medical Abstracts where for years Jerry Hoffman and his partner reviewed about 20+ articles per month from a huge spread of journals and answered letters. Not only informing of what seemed promising or even "proven" but what we were likely to be sold as proven that at best needed better studies. EM Rap was initially a separate product started by Mel Herbert, (the Australian guy that leads these updates). He had his own product that provided deep dives into important areas. When Jerry and his partner retired, they sold their business to Mel and he put it all together along with some other products into one hugely deep data base of EM continuing education. 

 

Anyways, EM Rap (which includes EMA) costs about $500/year, but they've made the covid stuff free. Way back at the start of this thread I included one or two of their earliest updates. They continue to put these out free, just search EM RAP Covid on You tube. I get notifications of new ones coming up, I'll try to put it on here if I do.

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3 hours ago, remkin said:

Oh yes. As I pointed out above science studies are a messy business. My arm's length relationship with just accepting a thing because an expert said it, is borne of 30 years of watching them fail over and over. One boiled down description of science is a method of attempting to remove all bias from observing the world. But there are so many types of bias it's astounding. There are studies on just different types of bias. Listening to Jerry Hoffman and others for years has been pretty eye-opening. It is very common for especially drug companies to set things up in their favor. Hoffman was surprised since this was apparently a government study, but the government has bias too (like finding a treatment fast). 

 

EM Rap is an outstanding product. It actually grew out of a product called Emergency Medical Abstracts where for years Jerry Hoffman and his partner reviewed about 20 articles per month from a huge spread of journals. Not only informing of what seemed promising or even "proven" but what we were likely to be sold as proven that at best needed better studies. EM Rap was started by Mel Herbert, (the Australian guy that leads these updates). He had his own product that provided deep dives into important areas. When Jerry and his partner retired, they sold their business to Mel and he put it all together along with some other products into one hugely deep data base of EM continuing education. 

 

Anyways, EM Rap costs about $500/year, but they've made the covid stuff free. Way back at the start of this thread I included one or two of their earliest updates. They continue to put these out free, just search EM RAP Covid on You tube. I get notifications of new ones coming up, I'll try to put it on here if I do.

 

Rem, I'm actually pretty familiar with the principles relating to good clinical trials.  I worked for Glaxo (before all the mergers) and was one of the primary statisticians for the first ondansetron NDA.  Part of my job was reviewing study protocols for exactly the type of flaws you're pointing out. I've been out of the field for quite a while now, and it's a bit surprising and very disconcerting that the science has apparently ended up where it's at.  Aren't reputable publications supposed to be peer reviewed?  Don't protocols for new drug studies still need to go through an IRB (institutional review board for those unfamiliar)? At the places I worked, part of the role of the statistician was to serve as a "check" on the clinicians, who often were so invested in a drug (emotionally, not financially) that subconscious bias could be viewed as understandable.

 

When I first started in the field (early '80s) the FDA had a huge presence.  It was significantly reduced in, what, maybe the early 90s? I wonder if the apparent degradation in standards might be linked to that?  Over regulation can be a big problem. But regulation can serve a valuable purpose.  Like many things, I wonder if the proper balance might have been lost?  

 

As an aside, the regulation thing could be viewed as one example of what I perceive as perhaps the biggest challenge our society now faces, and that's extreme polarization.  Black or white, all or nothing.  Only in an environment like that could a phrase like "alternative facts" could be viewed with anything but complete ridicule.

Edited by LakeLivin

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 Interesting, though if he's recovered it seems like a non-issue

 
 
 
 
Edited by legend-1

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20 minutes ago, legend-1 said:

 Interesting, though if he's recovered it seems like a non-issue

 
 
If a player or a few players contracting the Virus will push implementation of the playoffs back  then they have no business attempting this. Or the next season or any season.  There will be cases and this is here to stay, vaccine or no.  Same as the flu has always hit sports teams.   Just my opinion.
 

 

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That raises an issue which I've been pondering, for all sports really, not just ours. But what happens if these playoffs get rolling, everyone is swimmingly certified as "virus free", then 1 of the daily tests we're told they will be performing comes back positive? Wonder what contingencies they have for that? Shut that player, his contacts or the entire team down, both teams competing, all teams in that one venue or what? Then, what if it's one of the support staff, or alternately one of the coaches? This could get real interesting?

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4 hours ago, KJUNKANE said:

That raises an issue which I've been pondering, for all sports really, not just ours. But what happens if these playoffs get rolling, everyone is swimmingly certified as "virus free", then 1 of the daily tests we're told they will be performing comes back positive? Wonder what contingencies they have for that? Shut that player, his contacts or the entire team down, both teams competing, all teams in that one venue or what? Then, what if it's one of the support staff, or alternately one of the coaches? This could get real interesting?

This is The Big Issue, and I haven't seen a good answer from any league on this except Korean Baseball where they pledge to pause the league for weeks should a positive occur.

 

Bundesliga has started and is tip toeing around the issue.  Their equivalent minor league has a team on lockdown right now.   Competition suffers.  But it isn't playoffs, so some missing minor league games don't matter.  Meanwhile the big league looks like the are just praying.

 

For the Stanley cup playoffs, games can't go missing.  So...  More praying??

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15 hours ago, legend-1 said:

 Interesting, though if he's recovered it seems like a non-issue

 
 

 

Well, the Penguins have dealt with a virus rampaging through their team before in the fairly recent past.  Arguably the league‘s best player at the time, Sydney Crosby, even came down with the virus.  This was a highly infectious virus but it had a very effective vaccine and Crosby had been vaccinated, but still got the virus anyway.  Will the initial COVID-19 vaccine be anywhere near as effective as the mumps vaccine?  Unlikely, so even when there is a vaccine, figuring out the risk levels and those ‘what if’ contingency plans when someone gets sick will be on-going by the league planners perhaps for years...

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