7 ms·

> The major paper that drove most of this situation, and the meta analysis, appears to have been a straight up fraud. Umm, wat?! The vast majority of the stud

> The major paper that drove most of this situation, and the meta analysis, appears to have been a straight up fraud. Umm, wat?! The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians. Prior to 2020, basically everyone on earth agreed (including the WHO, who STILL agrees) that front-line clinicians and observational studies are excellent signals that can lead to scientific investigations that can lead to medical breakthroughs. The evidence for IVM as a treatment for covid (and many other viruses) is quite strong. There is, no, no large-scale RCT for IVM. However, it is inherently obvious that none will happen, none that give it a fair shake. The entire public health apparatus in the West has a huge desire to treat all illness with only on-patent, new medications. Do you not thin that this incentive influences what gets into the news? Do you think the public health authorities in Uttar Pradesh (https://indianexpress.com/article/cities/lucknow/uttar-pradesh-government-says-ivermectin-helped-to-keep-deaths-low-7311786/ https://indianexpress.com/article/cities/lucknow/uttar-prade...) are lying?

ashtonkem 5y ago
Feel free to actually read the article, it covers this.
mlyle 5y ago
> The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians. OK, so weak evidence. > Prior to 2020, basically everyone on earth agreed (including the WHO, who STILL agrees) that front-line clinicians and observational studies are excellent signals that can lead to scientific investigations that can lead to medical breakthroughs. Sure-- weak/crappy evidence and practitioner intuition can definitely point at worthwhile things to study rigorously, even if most of what they generate is trash. > The evidence for IVM as a treatment for covid (and many other viruses) is quite strong. ??? Quite a leap you made there.
- sjwalter 5y ago
  Calling the investigatory and experiential evidence of thousands of highly-trained doctors (some of whom pioneered the standard of care for covid) as "weak evidence" is something that only somebody carrying water for large pharmaceutical companies would say. Doctors in my area are prescribing IVM to treat covid because in their experience and that of their peers IT WORKS. They have fewer deaths, fewer complications. But it's "weak" evidence just because Pfizer didn't sponsor a gigantic RCT to "prove" it. "The only science is real is expensive science done by large corporations!"
  - dionian 5y ago
    Agreed, retract all the meta-analyses you want, but never dismiss actual front line results by physicians. If you have a regimen with zero deaths for a disease, I don't think we should be suppressing their clinical data. What a world...
    - ashtonkem 5y ago
      “Zero deaths” should have set off your alarm bells. That’s way too neat of a number for the real world; you only get that kind of result with small sample sizes or fraud. Even the vaccines, which are very effective, do not have a 0% death rate from infection.
      - chana_masala 5y ago
        Officially the FDA and CDC say there have been 0 deaths from adverse events. I agree, that's way too neat of a number for the real world.
        lamontcg 5y ago
        https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-Shimabukuro-508.pdf https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-... 3 deaths from TTS following J&J as of May 7th where there were 8.73 million doses of J&J administered.
        mlyle 5y ago
        You're saying re: vaccines? There's been several deaths believed to be caused by the vaccines and attributed as such by the FDA/CDC. And, you know, a few hundred thousand lives saved.
        pigeonhole123 5y ago
        Not a troll: how do you know that number? Pfizer’s own RCT showed no difference in all cause mortality after six months
- dionian 5y ago
  Given the recent fall from grace of prestigious journals like the Lancet on the Coronavirus evidence, I think it is useful for all of us to remain skeptical and purely science-based. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31958-9/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
tehjoker 5y ago
"Antiviral Effects of Ivermectin in COVID-19- Clinically Plausible?" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225296/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225296/ "In a study demonstrating the in vitro antiviral activity of ivermectin, upon incubation of infected Vero/hSLAM cells with 5 μM ivermectin, there was an approximately 5000-fold reduction of viral RNA by 48 hours in ivermectin treated samples as compared with control. The IC50 of ivermectin was found to be approximately 2.5 μM. Ivermectin seems to act on IMPα/β1 and inhibits the nuclear translocation of SARS-CoV-2 (Caly L et al., 2020). Further in-silico studies are required to confirm this target of ivermectin in SARS-CoV-2. The concentrations of 2.5 and 5 μM correspond to plasma concentrations of 2190 and 4370 ng/mL, respectively. These concentrations are 50–100 times the peak plasma concentration achieved with the 200 μg/kg of ivermectin (the US Food and Drug Administration recommended dose for treatment of onchocerciasis) (Chaccour C et al., 2017). Even with a dose 10 times greater than this dose (i.e., 2000 μg/kg), a peak plasma concentration of only ~250 ng/mL has been achieved (Guzzo CA et al., 2017)." "On the basis of the rationale above, any significant antiviral activity could not have been achieved with the dose used in the study and the resultant plasma concentration of the administered ivermectin. Thus, although ivermectin, in vitro, is a potent inhibitor of SARS-CoV-2 replication, in vivo, the plasma concentration required to achieve the antiviral effect far exceeds the therapeutically applicable dose." This thread discusses why the example of Uttar Pradesh's program isn't good evidence. https://twitter.com/GidMK/status/1440131176665006088 https://twitter.com/GidMK/status/1440131176665006088
- ashtonkem 5y ago
  Later studies have also shown that Vero cells are probably not a good choice for in vitro Covid tests, due to differences in how the virus infects those cells vs. human lung cells. This appears to be an innocent mistake; vero cells are very popular with virologists because they’re easy to work with and familiar. But unfortunately they are a very poor proxy for testing Covid cures on, given that they’re actually monkey kidney cells. But it’s a shame we’re still headed down this wrong path publicly. https://www.qps.com/2020/08/17/vero-cell-studies-misleading-results-in-the-fight-against-covid-19 https://www.qps.com/2020/08/17/vero-cell-studies-misleading-...
pacerwpg 5y ago
> Do you think the public health authorities in Uttar Pradesh (https://indianexpress.com/article/cities/lucknow/uttar-prade https://indianexpress.com/article/cities/lucknow/uttar-prade...) are lying? It's possible, the number of excess deaths in the region over a period (1 July 2020 and 31 March 2021) was measured at 197k compared to other years, but they only reported 4500 covid deaths.
eynsham 5y ago
Consider dexamethasone. > There is, no, no large-scale RCT for IVM. However, it is inherently obvious that none will happen, none that give it a fair shake. Well, the gold standard RCT Recovery (https://www.recoverytrial.net/ https://www.recoverytrial.net/) had a look. > The entire public health apparatus in the West has a huge desire to treat all illness with only on-patent, new medications. Dexamethasone is a cheap steroid. (For that matter, vaccines are incredibly cheap and yet nobody seems to have stopped them in favour of, say, monoclonal antibodies.) > Do you not thin that this incentive influences what gets into the news? Evidently not terribly much, given that dexamethasone was at least in all the British newspapers. > Do you think the public health authorities in Uttar Pradesh are lying? Quite plausibly. UP is perhaps the worst governed state in India and has been under all political parties. The case of Kafeel Khan is rather illustrative. More to the point, I don’t care whether they’re lying. The whole article is full of vague statements that are hardly a good basis to believe anything about ivermectin.
majormajor 5y ago
> The entire public health apparatus in the West has a huge desire to treat all illness with only on-patent, new medications. This and > The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians. > Prior to 2020, basically everyone on earth agreed (including the WHO, who STILL agrees) that front-line clinicians and observational studies are excellent signals that can lead to scientific investigations that can lead to medical breakthroughs. and > Doctors in my area are prescribing IVM to treat covid because in their experience and that of their peers IT WORKS. They have fewer deaths, fewer complications. Don't really add up. Best case interpretation of your argument is that you think doctors are split in half - not wholly aligned behind novel treatments - the "throw shit at the wall and see what sticks" group and the "only throw new custom expensive stuff at it" group, but even that doesn't really match what I'm seeing. A large number of doctors are out there throwing all sorts of things at a new disease because nobody knows what works yet. The data is going to be incredibly messy. One thing that has looked effective in many cases is steroids, very much not new. Other things that looked potentially effective haven't continued to look effective as more studies have been done. Where's the massive pushback against steroid treatment if this is an institutional greed thing? It looks to me much more like some people get married to their early hunches and dig in hard when the evidence doesn't pan out. Throw enough shit at the wall in enough places and all sorts of false leads are going to appear. Some of them getting shot down isn't a conspiracy. It's how we learn.
jjeaff 5y ago
Your assertion of the financial incentives of on patent vs off patent doesn't make sense for ivermectin. For one, the company that sells ivermectin in the US (Bayer) does not currently have an alternative covid treatment. They have publicly stayed that they do not believe ivermectin helps against covid. Secondly, an RX of ivermectin (for humans) appears to cost more ($35) than the vaccine ($20). Additionally, the vaccine is already paid for, whether or not people use it, many countries (especially the US) pre-purchased hundreds of millions of vaccine doses. Given that vaccines are already sold and adding ivermectin is pretty safe and is being added to the cocktail of treatments, already being used, I see no financial incentives for drug companies to discourage it.
- ImpressiveWebs 5y ago
  > I see no financial incentives for drug companies to discourage it. Then you’re not looking hard enough. You don’t think endless booster shots are an incentive to dismiss Ivermectin? Discouraging Ivermectin means, not billions, but trillions in revenue. And that’s not even considering the fact that the vaccines could never be legally approved for emergency use if Ivermectin works.
  - jjeaff 5y ago
    False. The existence of a therapeutic does not block approval of other treatments or vaccines. In fact, there were multiple emergency authorized therapeutics for c19 when the made the eua for the vaccine. And no one is talking about endless vaccines. We now have a 3rd booster for at-risk populations. It's possibly/likely that if they extend that recommendation to the rest of the population that 3 doses may be all that is needed for long term, strong immunity. Just like there are 3 doses for hep B and several other vaccines.
- jpadkins 5y ago
  If the FDA approves a therapeutics for covid19, then the emergency approval for experimental vaccines is gone. Not only do they lose vaccine mandates with that, but they also lose liability shield. There is a financial incentive to suppress covid19 therapeutics from pharma (and their stockholders).
unmole 5y ago
> Do you think the public health authorities in Uttar Pradesh are lying? Yes.
- ashtonkem 5y ago
  Heh, nobody is ever ready for that response.

ashtonkem 5y ago

Feel free to actually read the article, it covers this.

mlyle 5y ago

> The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians. OK, so weak evidence. > Prior to 2020, basically everyone on earth agreed (including the WHO, who STILL agrees) that front-line clinicians and observational studies are excellent signals that can lead to scientific investigations that can lead to medical breakthroughs. Sure-- weak/crappy evidence and practitioner intuition can definitely point at worthwhile things to study rigorously, even if most of what they generate is trash. > The evidence for IVM as a treatment for covid (and many other viruses) is quite strong. ??? Quite a leap you made there.

sjwalter 5y ago
Calling the investigatory and experiential evidence of thousands of highly-trained doctors (some of whom pioneered the standard of care for covid) as "weak evidence" is something that only somebody carrying water for large pharmaceutical companies would say. Doctors in my area are prescribing IVM to treat covid because in their experience and that of their peers IT WORKS. They have fewer deaths, fewer complications. But it's "weak" evidence just because Pfizer didn't sponsor a gigantic RCT to "prove" it. "The only science is real is expensive science done by large corporations!"
- dionian 5y ago
  Agreed, retract all the meta-analyses you want, but never dismiss actual front line results by physicians. If you have a regimen with zero deaths for a disease, I don't think we should be suppressing their clinical data. What a world...
  - ashtonkem 5y ago
    “Zero deaths” should have set off your alarm bells. That’s way too neat of a number for the real world; you only get that kind of result with small sample sizes or fraud. Even the vaccines, which are very effective, do not have a 0% death rate from infection.
    - chana_masala 5y ago
      Officially the FDA and CDC say there have been 0 deaths from adverse events. I agree, that's way too neat of a number for the real world.
      - lamontcg 5y ago
        https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-Shimabukuro-508.pdf https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-... 3 deaths from TTS following J&J as of May 7th where there were 8.73 million doses of J&J administered.
      - mlyle 5y ago
        You're saying re: vaccines? There's been several deaths believed to be caused by the vaccines and attributed as such by the FDA/CDC. And, you know, a few hundred thousand lives saved.
        pigeonhole123 5y ago
        Not a troll: how do you know that number? Pfizer’s own RCT showed no difference in all cause mortality after six months
dionian 5y ago
Given the recent fall from grace of prestigious journals like the Lancet on the Coronavirus evidence, I think it is useful for all of us to remain skeptical and purely science-based. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31958-9/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

tehjoker 5y ago

"Antiviral Effects of Ivermectin in COVID-19- Clinically Plausible?" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225296/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225296/ "In a study demonstrating the in vitro antiviral activity of ivermectin, upon incubation of infected Vero/hSLAM cells with 5 μM ivermectin, there was an approximately 5000-fold reduction of viral RNA by 48 hours in ivermectin treated samples as compared with control. The IC50 of ivermectin was found to be approximately 2.5 μM. Ivermectin seems to act on IMPα/β1 and inhibits the nuclear translocation of SARS-CoV-2 (Caly L et al., 2020). Further in-silico studies are required to confirm this target of ivermectin in SARS-CoV-2. The concentrations of 2.5 and 5 μM correspond to plasma concentrations of 2190 and 4370 ng/mL, respectively. These concentrations are 50–100 times the peak plasma concentration achieved with the 200 μg/kg of ivermectin (the US Food and Drug Administration recommended dose for treatment of onchocerciasis) (Chaccour C et al., 2017). Even with a dose 10 times greater than this dose (i.e., 2000 μg/kg), a peak plasma concentration of only ~250 ng/mL has been achieved (Guzzo CA et al., 2017)." "On the basis of the rationale above, any significant antiviral activity could not have been achieved with the dose used in the study and the resultant plasma concentration of the administered ivermectin. Thus, although ivermectin, in vitro, is a potent inhibitor of SARS-CoV-2 replication, in vivo, the plasma concentration required to achieve the antiviral effect far exceeds the therapeutically applicable dose." This thread discusses why the example of Uttar Pradesh's program isn't good evidence. https://twitter.com/GidMK/status/1440131176665006088 https://twitter.com/GidMK/status/1440131176665006088

ashtonkem 5y ago
Later studies have also shown that Vero cells are probably not a good choice for in vitro Covid tests, due to differences in how the virus infects those cells vs. human lung cells. This appears to be an innocent mistake; vero cells are very popular with virologists because they’re easy to work with and familiar. But unfortunately they are a very poor proxy for testing Covid cures on, given that they’re actually monkey kidney cells. But it’s a shame we’re still headed down this wrong path publicly. https://www.qps.com/2020/08/17/vero-cell-studies-misleading-results-in-the-fight-against-covid-19 https://www.qps.com/2020/08/17/vero-cell-studies-misleading-...

pacerwpg 5y ago

> Do you think the public health authorities in Uttar Pradesh (https://indianexpress.com/article/cities/lucknow/uttar-prade https://indianexpress.com/article/cities/lucknow/uttar-prade...) are lying? It's possible, the number of excess deaths in the region over a period (1 July 2020 and 31 March 2021) was measured at 197k compared to other years, but they only reported 4500 covid deaths.

eynsham 5y ago

Consider dexamethasone. > There is, no, no large-scale RCT for IVM. However, it is inherently obvious that none will happen, none that give it a fair shake. Well, the gold standard RCT Recovery (https://www.recoverytrial.net/ https://www.recoverytrial.net/) had a look. > The entire public health apparatus in the West has a huge desire to treat all illness with only on-patent, new medications. Dexamethasone is a cheap steroid. (For that matter, vaccines are incredibly cheap and yet nobody seems to have stopped them in favour of, say, monoclonal antibodies.) > Do you not thin that this incentive influences what gets into the news? Evidently not terribly much, given that dexamethasone was at least in all the British newspapers. > Do you think the public health authorities in Uttar Pradesh are lying? Quite plausibly. UP is perhaps the worst governed state in India and has been under all political parties. The case of Kafeel Khan is rather illustrative. More to the point, I don’t care whether they’re lying. The whole article is full of vague statements that are hardly a good basis to believe anything about ivermectin.

majormajor 5y ago

> The entire public health apparatus in the West has a huge desire to treat all illness with only on-patent, new medications. This and > The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians. > Prior to 2020, basically everyone on earth agreed (including the WHO, who STILL agrees) that front-line clinicians and observational studies are excellent signals that can lead to scientific investigations that can lead to medical breakthroughs. and > Doctors in my area are prescribing IVM to treat covid because in their experience and that of their peers IT WORKS. They have fewer deaths, fewer complications. Don't really add up. Best case interpretation of your argument is that you think doctors are split in half - not wholly aligned behind novel treatments - the "throw shit at the wall and see what sticks" group and the "only throw new custom expensive stuff at it" group, but even that doesn't really match what I'm seeing. A large number of doctors are out there throwing all sorts of things at a new disease because nobody knows what works yet. The data is going to be incredibly messy. One thing that has looked effective in many cases is steroids, very much not new. Other things that looked potentially effective haven't continued to look effective as more studies have been done. Where's the massive pushback against steroid treatment if this is an institutional greed thing? It looks to me much more like some people get married to their early hunches and dig in hard when the evidence doesn't pan out. Throw enough shit at the wall in enough places and all sorts of false leads are going to appear. Some of them getting shot down isn't a conspiracy. It's how we learn.

jjeaff 5y ago

Your assertion of the financial incentives of on patent vs off patent doesn't make sense for ivermectin. For one, the company that sells ivermectin in the US (Bayer) does not currently have an alternative covid treatment. They have publicly stayed that they do not believe ivermectin helps against covid. Secondly, an RX of ivermectin (for humans) appears to cost more ($35) than the vaccine ($20). Additionally, the vaccine is already paid for, whether or not people use it, many countries (especially the US) pre-purchased hundreds of millions of vaccine doses. Given that vaccines are already sold and adding ivermectin is pretty safe and is being added to the cocktail of treatments, already being used, I see no financial incentives for drug companies to discourage it.

ImpressiveWebs 5y ago
> I see no financial incentives for drug companies to discourage it. Then you’re not looking hard enough. You don’t think endless booster shots are an incentive to dismiss Ivermectin? Discouraging Ivermectin means, not billions, but trillions in revenue. And that’s not even considering the fact that the vaccines could never be legally approved for emergency use if Ivermectin works.
- jjeaff 5y ago
  False. The existence of a therapeutic does not block approval of other treatments or vaccines. In fact, there were multiple emergency authorized therapeutics for c19 when the made the eua for the vaccine. And no one is talking about endless vaccines. We now have a 3rd booster for at-risk populations. It's possibly/likely that if they extend that recommendation to the rest of the population that 3 doses may be all that is needed for long term, strong immunity. Just like there are 3 doses for hep B and several other vaccines.
jpadkins 5y ago
If the FDA approves a therapeutics for covid19, then the emergency approval for experimental vaccines is gone. Not only do they lose vaccine mandates with that, but they also lose liability shield. There is a financial incentive to suppress covid19 therapeutics from pharma (and their stockholders).

unmole 5y ago

> Do you think the public health authorities in Uttar Pradesh are lying? Yes.

ashtonkem 5y ago
Heh, nobody is ever ready for that response.