COVID-19 medical discussion

[utee94 15811]

Not sure if this was already posted here or not?  I follow a couple of different forums for COVID medical info.  

 

Scientists See Signs of Lasting Immunity to Covid-19, Even After Mild Infections

New research indicates that human immune system cells are storing information about the coronavirus so they can fight it off again.

https://www.nytimes.com/2020/08/16/health/coronavirus-immunity-antibodies.html

Quote

Antibodies also come with an expiration date: Because they are inanimate proteins and not living cells, they can’t replenish themselves, and so disappear from the blood just weeks or months after they are produced. Hordes of antibodies appear shortly after a virus has breached the body’s barriers, then wane as the threat dissipates. Most of the B cells that produce these early antibodies die off as well.

But even when not under siege, the body retains a battalion of longer-lived B cells that can churn out virus-fighting antibodies en masse, should they prove useful again. Some patrol the bloodstream, waiting to be triggered anew; others retreat into the bone marrow, generating small amounts of antibodies that are detectable years, sometimes decades, after an infection is over. Several studies, including those led by Dr. Bhattacharya and Dr. Pepper, have found antibodies capable of incapacitating the coronavirus lingering at low levels in the blood months after people have recovered from Covid-19.

“The antibodies decline, but they settle in what looks like a stable nadir,” which is observable about three months after symptoms start, Dr. Bhattacharya said. “The response looks perfectly durable.”

Seeing antibodies this long after infection is a strong indication that B cells are still chugging away in the bone marrow, Dr. Pepper said. She and her team were also able to pluck B cells that recognize the coronavirus from the blood of people who have recovered from mild cases of Covid-19 and grow them in the lab.
Multiple studies, including one published on Friday in the journal Cell, have also managed to isolate coronavirus-attacking T cells from the blood of recovered individuals — long after symptoms have disappeared. When provoked with bits of the coronavirus in the lab, these T cells pumped out virus-fighting signals, and cloned themselves into fresh armies ready to confront a familiar foe. Some reports have noted that analyses of T cells could give researchers a glimpse into the immune response to the coronavirus, even in patients whose antibody levels have declined to a point where they are difficult to detect.

 

[Captainant 27642]

RIP triple

 

Turns out the lack of evidence of efficacy actually DOES matter! Whodathunkit

[Bevo 13571]

On 8/19/2020 at 2:26 PM, utee94 said:

Several studies, including those led by Dr. Bhattacharya and Dr. Pepper, have found antibodies capable of incapacitating the coronavirus lingering at low levels in the blood months after people have recovered from Covid-19.

This looks like fake news.

[JohnLocke 115]

2 hours ago, Captainant said:

RIP triple

 

Turns out the lack of evidence of efficacy actually DOES matter! Whodathunkit

You are johnny on the spot with this info.

[Captainant 27642]

1 hour ago, JohnLocke said:

You are johnny on the spot with this info.

Lolz that's on me. I did not look at the date, and I accept all shame given

[washparkhorn 9939]

On 8/19/2020 at 12:18 PM, Borachio said:

I had my first appointment yesterday at one of the research labs here in Austin doing the vaccine trial for Moderna. The nasal swab was as uncomfortable as advertised. They took 8 vials of blood, which seemed excessive. Then I got the injection.

The injection site started to get sore last night and was a little worse this morning, but it felt about the same as when I get the flu shot.  Pretty tender when I raise my arm. Since there is a decent amount of soreness maybe I did get the actual vaccine?  I hope so, anyway, I go back in a month to get the second injection, plus another nasal swab.

How is the soreness?

I assume the injection was intramuscular. If you can remain relaxed and your muscles unflexed during the injection, the post injection pain is usually better. 

Good luck and godspeed.

[ChiTownDoc 21144]

On 8/19/2020 at 2:26 PM, utee94 said:

Not sure if this was already posted here or not?  I follow a couple of different forums for COVID medical info.  

 

Scientists See Signs of Lasting Immunity to Covid-19, Even After Mild Infections

New research indicates that human immune system cells are storing information about the coronavirus so they can fight it off again.

https://www.nytimes.com/2020/08/16/health/coronavirus-immunity-antibodies.html

 

So glad this is coming out.  One of the more tiring aspects of digesting all the info out there has been the BS with re-infections.  Have said that's BS since day one.  And also as someone who has to get tested every fucking week, good on Yale...they can only scrape my brain so many more times before causing permanent damage. 

[Bevo 13571]

3 hours ago, ChiTownDoc said:

So glad this is coming out.  One of the more tiring aspects of digesting all the info out there has been the BS with re-infections.  Have said that's BS since day one.  And also as someone who has to get tested every fucking week, good on Yale...they can only scrape my brain so many more times before causing permanent damage. 

yep

[dcar00 14160]

3 hours ago, ChiTownDoc said:

So glad this is coming out.  One of the more tiring aspects of digesting all the info out there has been the BS with re-infections.  Have said that's BS since day one.  And also as someone who has to get tested every fucking week, good on Yale...they can only scrape my brain so many more times before causing permanent damage. 

of course it was BS with anyone with a brain but saying maybe only 3 months helps to scare everyone.

[ChiTownDoc 21144]

9 minutes ago, dcar00 said:

of course it was BS with anyone with a brain but saying maybe only 3 months helps to scare everyone.

Yep.  People act like there’s only bullshit on one side.  The ‘we are all gonna die’ bozos deserve to catch some hell too.  

Edited August 23, 2020 by ChiTownDoc

[Borachio 416]

6 hours ago, washparkhorn said:

How is the soreness?

I assume the injection was intramuscular. If you can remain relaxed and your muscles unflexed during the injection, the post injection pain is usually better. 

Good luck and godspeed.

The soreness was pretty much all gone today. The second day was the worst, very similar to when I get the flu shot.  Raising my hand above my head and just applying slight pressure to the injection site was quite sore. Didn't have any redness or noticeable swelling.

Yup, the injection was done into the side of my upper arm, just below the shoulder.

[MNLonghornFUKM 8817]

I’m just relieved after the vaccine, we’re guaranteed at least 4 more days of life.. and counting

[ABSR 5308]

On 8/22/2020 at 5:55 PM, ChiTownDoc said:

So glad this is coming out.  One of the more tiring aspects of digesting all the info out there has been the BS with re-infections.  Have said that's BS since day one.  And also as someone who has to get tested every fucking week, good on Yale...they can only scrape my brain so many more times before causing permanent damage. 

Can you or another doctor explain if having anti-bodies and having T cell resistance are the same thing?  Does the antibody test (assuming it is accurate) capture both of these or just anti-bodies...assuming they are not the same thing?

[ChiTownDoc 21144]

30 minutes ago, ABSR said:

Can you or another doctor explain if having anti-bodies and having T cell resistance are the same thing?  Does the antibody test (assuming it is accurate) capture both of these or just anti-bodies...assuming they are not the same thing?

No.  AB testing would NOT necessarily be positive if you fought infection off w T cells.  In many/most cases they would not trigger a positive ab test.  

[triplehorn 2664]

On 8/22/2020 at 9:18 AM, Captainant said:

RIP triple

 

Turns out the lack of evidence of efficacy actually DOES matter! Whodathunkit

Your confusion over timelines is consistent with  how checked out most in the US are about "what direction the evidence is growing."  The evidence continuing to accumulate today shows a clear and undeniable benefit when applied early in disease course.  Perhaps more significantly evidence continues to show that it is safe when applied with covid infection.  

Yesterday, this large study from Belgium with 8,075 subjects was published.  It found that mortality hazard ratio was down 32% in multivariate analysis for patients treated with hydroxychloroquine vs standard of care.  Again, no sign whatsoever of safety issues in the >4,500 subjects in the hcq group.

Less than one week old, this large retrospective study from Spain focused on eosinophil recovery with 9,644 hospitalized patients and showed lower mortality for HCQ (14.7% vs 29.2%, p<0.001), and AZ (15.3% vs. 18.4%, p<0.001). With a multivariate model including potential confounding factors, HCQ and AZ are associated with lower mortality, HCQ OR 0.662, p=0.057.

In light of the recent Yale immunology revelations regarding Covid gene products hacking our immune signaling pathways to amplify dangerous maladaptive immune responses, I really like this one month old study:  

Quote

HCQ 1-4 days from diagnosis was the only protective factor against prolonged viral shedding found, OR 0.111, p=0.001. 57.1% viral clearance with 1-4 days delay vs. 22.9% for 5+ days delayed treatment. Authors report that early administration of HCQ significantly ameliorates inflammatory cytokine secretion and that COVID-19 patients should be administrated HCQ as soon as possible. 42 patients with HCQ 1-4 days from diagnosis, 48 with HCQ 5+ days from diagnosis.

Critically, note that treatment with HCQ is associated with lowered levels of inflammatory cytokines IL-1B and IL-6.  This lends support to an anti-inflammatory mechanism of action of HCQ in reducing Covid mortality, the earlier the better.

Also the other week, news from India reported 108 Million doses of HCQ have been distributed to its population for free since March.  At 3.2M cases today,  India has the third most cases in the world behind the US (5.9M cases) and Brazil.  Deaths per 1M population?  India=43  US=548. 

RIP indeed.

 

 

[dcar00 14160]

32 minutes ago, triplehorn said:

Your confusion over timelines is consistent with  how checked out most in the US are about "what direction the evidence is growing."  The evidence continuing to accumulate today shows a clear and undeniable benefit when applied early in disease course.  Perhaps more significantly evidence continues to show that it is safe when applied with covid infection.  

Yesterday, this large study from Belgium with 8,075 subjects was published.  It found that mortality hazard ratio was down 32% in multivariate analysis for patients treated with hydroxychloroquine vs standard of care.  Again, no sign whatsoever of safety issues in the >4,500 subjects in the hcq group.

Less than one week old, this large retrospective study from Spain focused on eosinophil recovery with 9,644 hospitalized patients and showed lower mortality for HCQ (14.7% vs 29.2%, p<0.001), and AZ (15.3% vs. 18.4%, p<0.001). With a multivariate model including potential confounding factors, HCQ and AZ are associated with lower mortality, HCQ OR 0.662, p=0.057.

In light of the recent Yale immunology revelations regarding Covid gene products hacking our immune signaling pathways to amplify dangerous maladaptive immune responses, I really like this one month old study:  

Critically, note that treatment with HCQ is associated with lowered levels of inflammatory cytokines IL-1B and IL-6.  This lends support to an anti-inflammatory mechanism of action of HCQ in reducing Covid mortality, the earlier the better.

Also the other week, news from India reported 108 Million doses of HCQ have been distributed to its population for free since March.  At 3.2M cases today,  India has the third most cases in the world behind the US (5.9M cases) and Brazil.  Deaths per 1M population?  India=43  US=548. 

RIP indeed.

 

 

while I'm on board that after all this(when the politics goes away) HCQ is going to be seen as potential treatment that should have been used, the death numbers in India have to be taken with a HUGE grain of salt, IMO.  There are about 15-20 countries in the world we can reasonably assume the numbers are accurate.

[Anastasis 23464]

HCQ adherence is like a game of whack a mole. 

[Mitch Cumsteen 18547]

1 hour ago, Anastasis said:

HCQ adherence is like a game of whack a mole. 

Not true. Triplehorn is adhering to it like a motherfucker.

[Anastasis 23464]

14 minutes ago, Mitch Cumsteen said:

Not true. Triplehorn is adhering to it like a motherfucker.

Must be the zinc. 

[ChiTownDoc 21144]

I’m totally confused on random people being so hellbent on showing hcq works.  It’s mind boggling to me.  As if it really worked without serious SE the medical community would be against using it? 

[Brisketexan 105086]

4 hours ago, ChiTownDoc said:

I’m totally confused on random people being so hellbent on showing hcq works.  It’s mind boggling to me.  As if it really worked without serious SE the medical community would be against using it? 

Do you even deep state/big Pharma/(((Soros)))/DNC bro?

 

 

[triplehorn 2664]

Large studies are now rolling in:  

Italian retrospective study (n=3,451) concludes that hydroxychloroquine reduces risk of death by 30% in COVID-19 hospitalized patients

especially notable considering late stage application.  

 

What we really need to know is how much of the observed benefit from CQ/HCQ is due to early upstream anti-inflammatory actions.  Yale immuno lab found that this virus codes to immediately start driving maladaptive immune responses at the outset.  The viral genome is programmed to drive abnormal immune responses regardless of age or health status.  Inability to clear virus quickly can lead to further maladaptive immune amplification and variably death.  But looking at studies like this one: Signs of Cardiac Damage Even in Younger, Nonhospitalized COVID-19 Patients , where biopsy showed lymphocytic infiltration without presence of virus, it raises questions about broader application beyond those targeted as being at highest risk of death. As someone of low risk of death from this virus, I would be hard pressed not to briefly utilize this medication early if shown to minimize the process leading to even a glancing kiss of inflammatory myocarditis.  The comparative risk of the med here is next to zero.

 

 

[Anastasis 23464]

MRNA just read out some additional results from their phase I work.  Apparently, immune response in older subjects 55+ was very similar to younger subjects. 

https://www.bloomberg.com/news/articles/2020-08-26/moderna-will-present-vaccine-data-in-older-people-at-cdc-meeting

Moderna Inc. presented new safety data from an early trial that provides the first evidence that its Covid-19 vaccine stimulates the immune systems of older people.

In a phase 1 trial, Moderna’s coronavirus vaccine produced “consistently high levels” of neutralizing antibodies -- a key component of the body’s protective response -- in older adults, the company said in a statement. Antibody levels produced in people more than 55 years old were comparable to those seen in younger adults, the company said in a statement.

The results from Moderna’s early-stage trial, which include data from 20 people in the older age group, were presented Wednesday to the U.S. Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices. The findings are important because older adults often don’t respond as well to vaccines as younger adults.

The trial used a dose of the vaccine that has advanced to a final-stage trial. The dose produced antibody levels higher than those typically seen in people recovering from the virus, Moderna said.

[dcar00 14160]

24 minutes ago, Anastasis said:

MRNA just read out some additional results from their phase I work.  Apparently, immune response in older subjects 55+ was very similar to younger subjects. 

https://www.bloomberg.com/news/articles/2020-08-26/moderna-will-present-vaccine-data-in-older-people-at-cdc-meeting

Moderna Inc. presented new safety data from an early trial that provides the first evidence that its Covid-19 vaccine stimulates the immune systems of older people.

In a phase 1 trial, Moderna’s coronavirus vaccine produced “consistently high levels” of neutralizing antibodies -- a key component of the body’s protective response -- in older adults, the company said in a statement. Antibody levels produced in people more than 55 years old were comparable to those seen in younger adults, the company said in a statement.

The results from Moderna’s early-stage trial, which include data from 20 people in the older age group, were presented Wednesday to the U.S. Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices. The findings are important because older adults often don’t respond as well to vaccines as younger adults.

The trial used a dose of the vaccine that has advanced to a final-stage trial. The dose produced antibody levels higher than those typically seen in people recovering from the virus, Moderna said.

Lets go smart guys!!

[Brisketexan 105086]

1 hour ago, Anastasis said:

stimulates the immune systems of older people.

Man.....my quick eyes reading just latched on to "stimulates older people".....at first, I was disgusted.  But then, I thought of my own age, and......

[Sandman 3403]

I hope this is the right topic for this, apologies if not.

I was checking the CDC website and it has a list of medical conditions that would cause someone to be "at increased risk of severe illness from COVID-19". One of these is obesity, which they determine as someone with a BMI of 30+. Obesity is on the same list as cancer, COPD, sickle cell and diabetes. Our office has listed diabetics as "at risk" and working from home 100% but we have people in the office who I know are obese. Is this something that should be adressed? Would it be an HR nightmare? (I say yes).  If a person brought up osesity as a reason to work from home for their own safety, should their concern be taken seriously?

[triplehorn 2664]

Here's a useful table comparing the large scale studies to date:

Guess which study above had the key major impact on public perception early on?  Yes, the one where the investigators may be facing criminal investigation for dosing subjects at 2400mg HCQ in the first 24hrs.  It looks like a strong case can be made that they negligently overdosed patients possibly resulting in death.  The other study that shaped American perception?  That would be the fraudulent study published by Lancet and NEJM, later retracted. 

The US developed a permanent allergy to HCQ/CQ from early bad info and mistrust of leadership (not misplaced).  The result appears to translate into tens of thousands of American lives that could otherwise be with us today.  And not for one second do I blame any physician for avoiding treating their patients with this in the US.  Even if is were green-lighted here, there's no way it would be applied to make a difference.  The chaos and confusion, and lack of a coherent federal response means that the greater population, and docs, have largely been on their own.  Very few docs are going to go out on a limb by themselves in this environment.  Tragic, but understandable.

Posting about it now almost feels like a post-mortem because indications are that globally this is a one and done pandemic that is burning out.  The need for a vaccine for SARS-CoV-2 may well be obsolete by Nov/Dec.  A vaccine that can help knock out annual common cold coronaviruses would be nice.

 

[kevwun 15770]

I'd rather discuss HCQ with a shithouse rat.

[Anastasis 23464]

Which of those studies are RCTs versus observational studies consisting of retrospective analyses?  Why does that graphic present the observational data but none of the negative RCTs (other than recovery)? 

The issue with the observational studies is one of control for the many potential confounding influences.  All of the US-based RCTs and many ex-US have been negative. The explanations for those findings ranged from "but not early intervention, hospitalized patients" to "what about the zinc?".  The observational studies being promoted consist of data from patients who are...wait for it...hospitalized and not receiving zinc. Some of the retrospective analyses are really well done from a statistical analysis plan perspective (Belgium study in particular); however, the reality is that the potential confounding here is complex and multifactorial (immortal time bias, confounding by indication, confounding by other treatments...steroids in particular, confounding by time of treatment relative to pandemic onset, etc.), and may be difficult to control via statistical methods such as IPTW, PS methods, or regression adjustment.  Read the conclusions of the observational studies and almost all of them reflect their conclusion that prospective RCTs are necessary to support the use of HCQ.

This twitter thread from an ID pharmacist explains the RCT findings. He discusses the initial head fake re: HCQ that came from the wrong animal cell model, and goes through the RCT data that addressed various points in the spectrum of treatment. 

 

And this one discussed specifically the challenges with observational data in this particular setting.

 

Here are the links to the observational studies cited in that graphic if you are interested.  Triple quotes a lot of shit that gets the basics wrong (e.g.: With a multivariate model including potential confounding factors, HCQ and AZ are associated with lower mortality, HCQ OR 0.662, p=0.057.), so I encourage a read of the actual research methods, results, and conclusions. In most of these studies, the authors explicitly acknowledge that they are limited in their control for confounding, and that prospective studies with random assignment are necessary.

Sbidian: https://www.medrxiv.org/content/10.1101/2020.06.16.20132597v1

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

Castelnouvo: https://www.ejinme.com/article/S0953-6205(20)30335-6/fulltext

Rosenberg (this one is actually miscited, the rosenberg study was published in JAMA and was negative): https://www.ncbi.nlm.nih.gov/research/coronavirus/publication/32607928

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

Gonzales: https://www.medrxiv.org/content/10.1101/2020.08.18.20172874v1

 

 

Edited August 26, 2020 by Anastasis

[triplehorn 2664]

In this matter, not even a shithouse rat would understand what you're talking about.

 

In other news, it took until late August for it come out: study from New Jersey posted yesterday shows the risk of needing hospitalization is down a massive 47% with early outpatient tx with HCQ.  Not 5% less, not 10% less, almost 50% less likely to end up hospitalized with severe covid with outpatient initiation of HCQ.

Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational study

 

 

[Anastasis 23464]

Do you actually read anything other than the abstracts?  Or the tweets?

 

I would sincerely like to hear your critical review of that study's methods (in particular their methods for confounding control, selection of variables for inclusion in their models, statistical analysis plan, etc.) as well as the manuscript more generally.

 

This should be fun. 

Edited August 27, 2020 by Anastasis

[Scheiss Meister 8407]

At this point I just assume that triple and others of his ilk invested their life's savings in hydroxychloroquin early on, when it looked like it was a promising prospect, and are now desperately trying to drum up support so that they might recover some of what they threw into it.

[Anastasis 23464]

2 hours ago, Scheiss Meister said:

At this point I just assume that triple and others of his ilk invested their life's savings in hydroxychloroquin early on, when it looked like it was a promising prospect, and are now desperately trying to drum up support so that they might recover some of what they threw into it.

Nah, triple is just a quack. 

[Captainant 27642]

21 hours ago, triplehorn said:

In this matter, not even a shithouse rat would understand what you're talking about.

 

In other news, it took until late August for it come out: study from New Jersey posted yesterday shows the risk of needing hospitalization is down a massive 47% with early outpatient tx with HCQ.  Not 5% less, not 10% less, almost 50% less likely to end up hospitalized with severe covid with outpatient initiation of HCQ.

Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational study

 

 

On the other hand....

Quote

 

Effect of hydroxychloroquine with or without azithromycin on the mortality of COVID-19 patients: a systematic review and meta-analysis

Study eligibility criteria

We included published and unpublished studies comparing the mortality rate between patients treated with chloroquine or hydroxychloroquine with or without azithromycin and patients managed with standard of care.

Participants

Patients ≥18 years old with confirmed COVID-19.

 

Results

The initial search yielded 839 articles, of which 29 articles met our inclusion criteria. All studies except one were conducted on hospitalized patients and evaluated the effects of hydroxychloroquine with or without azithromycin. Among the 29 articles, 3 were randomized controlled trials (RCT), one was a non-randomized trial and 25 were observational studies, including 10 with a critical risk of bias and 15 with a serious or moderate risk of bias. After excluding studies with critical risk of bias, the meta-analysis included 11,932 participants for the hydroxychloroquine group, 8,081 for the hydroxychloroquine with azithromycin group and 12,930 for the control group. Hydroxychloroquine was not significantly associated with mortality: pooled Relative Risk RR=0.83 (95% CI: 0.65-1.06, n=17 studies) for all studies and RR=1.09 (95% CI: 0.97-1.24, n=3 studies) for RCTs. Hydroxychloroquine with azithromycin was associated with an increased mortality: RR=1.27 (95% CI: 1.04-1.54, n=7 studies). We found similar results with a Bayesian meta-analysis.

Conclusion

Hydroxychloroquine alone was not associated with reduced mortality in hospitalized COVID-19 patients but the combination of hydroxychloroquine and azithromycin significantly increased mortality.

 

tldr: HCQ+AZ == 27% increase in rate of death in practice

Edited August 27, 2020 by Captainant

[triplehorn 2664]

22 hours ago, Scheiss Meister said:

At this point I just assume that triple and others of his ilk invested their life's savings in hydroxychloroquin early on, when it looked like it was a promising prospect, and are now desperately trying to drum up support so that they might recover some of what they threw into it.

HCQ seemed possibly promising early on, but it was still misunderstood and misapplied -late - in severe hospitalized patients.  The meta-analysis @Captainant linked just above includes studies ONLY involving severely ill hospitalized covid patients.  Can't say if it's plain useless or just unfortunate they stopped including studies published after July 25.  Numerous large studies have come out since then showing mortality reduction even in hospitalized patients, not to mention this week a US study showing that hazard risk of even being hospitalized is reduced almost in HALF with early outpatient use of HCQ.  I know you're not posting to talk medical science, but whatever.

oh, and I'm not a stock jockey.  the one quoted below is.  

 

19 hours ago, Anastasis said:

Nah, triple is just a quack. 

 

I get some satisfaction from this.  It's what Ana does when he's out of answers.  That, and gifs.  Ana is a smart fool and occasional un-closeted misanthrope who's a sucker for the quick high.  Whether it relates to subjects where he's wrestling with political betrayal or incomplete science, over time as a different reality emerges, it devolves into both-sides anastasis and evasive garden style bullshittery.  Time to unblock!  lollol

 

We've thought we've had nothing to offer after testing positive yet aren't very sick or short of breath.  Just stay home and hope for the best.  Now we have multiple large studies in the last week (NJ n=1,067, Italy n=3,451, Belgium n=8,075) building a very solid foundation showing we have a safe available option that can save lives when started in the early stages of infection. The Belgian researchers have concluded that the mortality reducing effect of HCQ in covid is anti-inflammatory.   Some will remain allergic to considering it, and some will make a call.  People make personal choices affecting their health every day.  It's just good to know there is even a good, safe, available choice supported by medical science.

 

 

[Anastasis 23464]

43 minutes ago, triplehorn said:

It's what Ana does when he's out of answers. 

I'm out of answers?

 

You are a total clown. Everybody sees it triple.

[triplehorn 2664]

you and sheister.

[Anastasis 23464]

Just now, triplehorn said:

you and sheister.

Once again, I would love to see your critical analysis of the last observational study you posted. I would sincerely like to hear your critical review of that study's methods (in particular their methods for confounding control, selection of variables for inclusion in their models, statistical analysis plan, etc.) as well as the manuscript more generally.

Let's see it triple.  And then we can see who is out of answers, clown. 

[triplehorn 2664]

tasking now?  that's plain dodge.  it's what you do when you've got nothing.  all too familiar.

[Anastasis 23464]

Tasking?  I am just asking you to actually think critically about the evidence you present for once.

Weak, but not unexpected, clown. 

 

 

Edited August 28, 2020 by Anastasis

[Scheiss Meister 8407]

I am not a doctor, or a research scientist.  I am just a shit plant operator with over 30 years experience.  I have to look at data and try to figure out why the bacteria in my plant aren't happy and what I have to do to get them happy.  I learned a long time ago that if you try to correlate an effect to only one variable when there are many other variables present, and you do not account for those variables, whatever you find will be trash.  These studies looking at HCQ but not adjusting for all of the myriad variables inherent in the human population cannot come to valid conclusions.  Designed and controlled studies can and have shown valid evidence that HCQ is not effective enough to outweigh the risks that come with it.  

I want there to be a magic bullet for this, too, but it is clear as a bell that no one has found one yet, and HCQ is out of the running.  Well, at least to most of us.

[triplehorn 2664]

9 hours ago, Scheiss Meister said:

 I learned a long time ago that if you try to correlate an effect to only one variable when there are many other variables present, and you do not account for those variables, whatever you find will be trash.  These studies looking at HCQ but not adjusting for all of the myriad variables inherent in the human population cannot come to valid conclusions. 

 Keeping it understandable for me and anyone else, this is a useful study that addresses your concerns:

US Food and Drug Administration Approvals of Drugs and Devices Based on Nonrandomized Clinical TrialsA Systematic Review and Meta-analysis

helpful descriptive part of intro:

Quote

A well-designed randomized clinical trial (RCT) is widely considered the most reliable approach for evaluating the efficacy of clinical interventions or assessing the probable benefit of a medical device. However, RCTs often face practical limitations, such as difficulties in accruing patients, or other logistical or feasibility issues. As a result, alternative methods for the evaluation of treatments are increasingly considered, such as the assessment of a health interventions’ effects in nonrandomized, observational studies.1 Although such evaluations often provide results similar to those seen in RCTs,2,3 exceptions are not uncommon.4 The main concern about non-RCTs is that it is currently challenging to predict with confidence when the results of RCTs will be concordant with those of observational studies. The consequences of such a discordance can sometimes be disastrous.5,6

It is essential to explore when observational studies are considered sufficiently credible. Regulatory agencies, such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have accepted that large treatment effects can sometimes obviate the need for RCTs. They have accepted that non-RCTs can be considered reliable sources of evidence, ie, produce results with a low risk of bias, when they generate sufficiently large or dramatic effects that are thought to rule out the combined effects of bias and random errors.7 Therefore, an approach for evaluating when findings in observational studies can be considered credible because of sufficiently dramatic treatment effects is to analyze the approval decisions of the drug licensing authorities. Based on theoretical and simulation studies, several definitions have been proposed to categorize dramatic effects as those treatments displaying relative risks (RRs) of 5 or greater8 or 10 or greater9 or odds ratios (ORs) of 12 or greater.10

Using these definitions, we showed that the EMA approved 7% of treatments based on non-RCTs; between 2% and 4% of these approvals displayed dramatic effects.10 Like the EMA Priority Medicines and Adaptive Pathways programs, the FDA has a program called the Breakthrough Therapy designation (BTD), designed to support the approval of drugs demonstrating substantial (ie, dramatic) improvement over existing therapies and which may not require further testing in RCTs.7

results of this meta: 

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Among 677 drug and medical device applications, 68 (10.0%) were approved by the FDA based on non-RCTs. Estimates of effects were larger when no further RCTs were required (mean natural logarithm of the odds ratios, 2.18 vs 1.12; odds ratios, 8.85 vs 3.06; P = .03).   [...]

Overall, 9 of 677 total applications (1.3%) that were approved on the basis of non-RCTs had relative risks of 10 or greater and 12 (1.7%) had relative risks of 5 or greater. No clear threshold above which the FDA approved interventions based on the magnitude of estimated effect alone was detected.

 

So about 1 of every 10 drug and med device FDA approvals occur based off of non-RCT data.  The size of treatment effect plays a critical role when bodies like the FDA and EMA are evaluating a treatment for formal use approval with non-RCT data.  The greater the size of treatment effect, the smaller the extent to which effects of covariates and bias can be attributable as the cause of a positive outcome.  In this study "dramatic effects" were defined as relative risks (RRs) of 5 or greater or 10 or greater, or odds ratios (ORs) of 12 or greater.

With a "dramatic effects" threshold for FDA approval using a Relative Risk of 5 or 10, look back at this table:

These RR values are big - even for treatments that gain FDA use approval.  6 studies across 5 nations, involving a combined 34,619 subjects, all with highly consistent findings in direction and magnitude which further support a benefit not due to bias or covariates.  Keep in mind we're not talking about getting FDA approval for HCQ use to treat Covid in a crowded field of therapeutics.  We're desperately looking for anything that could offer benefit when there is no alternative.  And at first glance, this body of large studies goes way beyond positive thresholds in non-RCT studies used by FDA to freaking grant approval.  FDA approval for safety with HCQ has existed for over 50 years.

 

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 Designed and controlled studies can and have shown valid evidence that HCQ is not effective enough to outweigh the risks that come with it.  

Careful with your imprecise language.  Are you referring to early stage HCQ application, or initiating HCQ in severely ill hospitalized patients with glass lungs?  Show me the studies, RCT or not, where early stage application had no benefit.  That's the main error that keeps looping in peoples' minds.  Even Fauci is guilty of this imprecise language when drawing conclusions.  RCT's that show no benefit of HCQ initiated in hospitalized patients with advanced illness are useful - no benefit of HCQ if started too late.  Critically, that ignores the growing number of large studies finding dramatic positive effects appearing when HCQ is started very early in disease course.  There are myriad examples in medicine where timing of the intervention entirely determines outcome effects.

 

[Anastasis 23464]

51 minutes ago, triplehorn said:

So about 1 of every 10 drug and med device FDA approvals occur based off of non-RCT data. 

Triple doesn't read nor comprehend what he cites here.  That is a subset analysis of breakthrough treatment applications for the period from 2012-2018.  It is not reflective of FDA approvals generally.  It reflects a small subset of approvals, tilted towards devices and with the drug approvals represented by mostly cancer drugs. There are good reasons why comparison groups may be unavailable, or randomization untenable in those settings. The current situation is totally dissimilar. This is the kind of out right misrepresentation of data that he traffics in constantly and is frustrating. 

Edited August 28, 2020 by Anastasis

[triplehorn 2664]

31 minutes ago, Anastasis said:

Triple doesn't read nor comprehend what he cites here.  That is a subset analysis of breakthrough treatment applications for the period from 2012-2018.  It is not reflective of FDA approvals generally.  It reflects a small subset of approvals, tilted towards devices and with the drug approvals represented by mostly cancer drugs. There are good reasons why comparison groups may be unavailable, or randomization untenable in those settings. The current situation is totally dissimilar. This is the kind of out right misrepresentation of data that he traffics in constantly and is frustrating. 

You're being presumptuous.  I presented it not to draw a granular comparison.  I presented it not to make a case for FDA approval.  The simple point is that regulatory bodies like the FDA and EMA grant use approval using non-RCT data when the effect size is large - larger than thresholds needed for RCT based data - in order to offset effects of bias and covariates in observational studies.  The comparison may be a mismatch wrt FDA approvals, but you have not shown that with other relevant data.  To the extent there is a mismatch, the FDA threshold RR difference in this example, 5 or 10 vs. 30-40,  is large.

What is the FDA approval threshold for non-RCT positive RR findings in your context?  

 

Edited August 28, 2020 by triplehorn

[Anastasis 23464]

2 minutes ago, triplehorn said:

The simple point is that regulatory bodies like the FDA and EMA grant use approval using non-RCT data when the effect size is large - larger than thresholds needed for RCT based data - in order to offset effects bias and covariates in observational studies.

They will use observational data when RCT data is not available. And typically in those cases will not rely on observational data exclusively, but will assess within the full context of the available information. And if they are looking at your observational study, they will get elbow deep up in your ass on your methods and statistical analysis. Which is why I asked you to critically review those aspects of the last pre-print you posted.  

[triplehorn 2664]

Just now, Anastasis said:

They will use observational data when RCT data is not available. And typically in those cases will not rely on observational data exclusively, but will assess within the full context of the available information. And if they are looking at your observational study, they will get elbow deep up in your ass on your methods and statistical analysis. Which is why I asked you to critically review those aspects of the last pre-print you posted.  

Still waiting on you to present your non-RCT FDA approval threshold data in your context.  

 

 

[Anastasis 23464]

2 minutes ago, triplehorn said:

Still waiting on you to present your non-RCT FDA approval threshold data in your context.  

Are you asking me what is my threshold for non-RCT data when RCT results are available and informative to the question at hand? Stop being a clown triple. 

[JohnLocke 115]

Ok, I'll bite. There is not RCT results available that A) use hydroxychloriquine with zinc and azithromycin and B) are given early as an outpatient and C) have a large enough sample size of high risk patients to yield statistically significant results.

I tend to be influenced when I see dishonesty and what I have seen is HCQ being discarded as a treatment based on the fact A) it doesn't work well on very sick patients and B) statistically insignificant results, although positive, and needing larger sample sizes, are reported in the mainstream media as if they were negative results.

The 2nd layer of dishonesty has been the attack on the safety of HCQ, a widely used and well understood drug that is OTC in much of the world.  In Harvey Risch's words: The combination of hydroxychloroquine and azithromycin has been used for decades in hundreds of thousands of people with rheumatoid arthritis. There is a concern that these medications do change the heart pacing a little and could cause cardiac arrhythmias. However, these arrhythmias are still very rare in people using these medications. People who already have heart arrhythmias or are predisposed to them or have family histories of them should discuss this with their health care providers and see if using hydroxychloroquine plus doxycycline or some other medications would be a better choice. 

There is almost no downside to trying this drug if you are at high risk. In Dr. Risch's words again: Hydroxychloroquine alone is not the whole story. It needs to be combined with azithromycin or doxycycline and probably with zinc to make it most effective. The game changer is to aggressively treat people as soon as possible, before they are hospitalized, to keep them from becoming hospitalized in the first place. Hydroxychloroquine plus the other medications is what we know about now. In a few months we may have data on other medications that also work. We just have to start with something now.

The medical profession has been slow to act on data that is not based on RCT's. Shamefully so, when the data can be conclusive in and of itself. I point again to the rather shameful behavior of the medical profession in adopting antibiotics to treat ulcers as exhibit A.

When you are in the middle of a pandemic, you don't have time for RCT results. However, there is a huge mass of data available to sift through that is significant. I give the CDC an F for being prepared and able to do the heavy lifting in that regard. 

We'll have much better data in six months. And hopefully, better treatment options to go along with a vaccine.

[triplehorn 2664]

1 hour ago, Anastasis said:

Are you asking me what is my threshold for non-RCT data when RCT results are available and informative to the question at hand? Stop being a clown triple. 

Nope, and you know it.  The FDA gives approval for drugs and medical devices based off of non-RCT observational studies, albeit with a higher threshold for efficacy than RCT-based applications.  This is known.  You dismissed it pointing out that it related to a subset of applications.  I'm asking if you have evidence that there is a different (higher) efficacy threshold for drugs and devices for approval outside of the referenced subset.  You've ignored that so far, and your default to name calling is a huge tell.  You may be right, but until you can back it up with anything, you're running another bluff.  And again this is going above and beyond consideration of a drug that already has FDA safety approval and is widely applied for off-label use.  

And to your the point of your latest diversion, what RCT trial shows that early stage initiation of HCQ carries no benefit ?  There are real world reasons observational studies are employed.  When they are replicated 6 times using 35,000 subjects with a relative risk reduction of DEATH by 20-50%, and FDA safety approval has remained intact for over 50 years, it carries a powerful meaning in a pandemic where we're still at 40,000 new cases and >1000 deaths per day with no other early outpatient alternative.

[Anastasis 23464]

1 minute ago, triplehorn said:

I'm asking if you have evidence that there is a different (higher) efficacy threshold for drugs and devices for approval outside of the referenced subset.

The referenced subset being discussed, which you brought up, is by definition a set aside group where different thresholds of evidence are used for compassionate use situations. You make it really hard to take you serious. 

If you want to stop being a clown, I am happy to read your critical review of the methods and SAP of the last observational study you posted.