Covid analysis,,HCQ
Pre-Exposure Prophylaxis studies are very positive.
(PEP) Post Exposure Prophylaxis studies are positive.
One study reports a lack of significance,
but analysis shows significance, see detailed explanation.
Early treatment studies are very positive.
Late treatment studies are mixed, with effectiveness from slightly negative to very positive
Generally no significant harm except with higher than typical dosages
Interestingly UK performed 2x worse then Denmark and also germany performed worse then denmark in the lock down phase but not much worse
Hmm UK and sweden is very similar and although GB was late to implement lock down meassures the peak is about three weeks from the beginning as in basically all places I loocked at except india. What I do is to find the number of deaths at the earliest peak and divide by number of million in the population. Sweden and GB is 2x-2.5x worse than most other countries I looked at indicating a slow decay in those countries GB with lock down and Sweden without lockdown. There is a theory that in countries there is only a fraction that participate in the infection that can differ widely and create widly different responses depending on how large this fraction is. My hypothesis is the number that seeded the infection and got into the country that matters but why then is GB 2x worse than germany and denmark in the lockdown phase after the peak. The slow decay seam to be due to cluster outbreaks happening during a longer time frame, this is clearly seen in the Swedish data. Somehow I suspect that it might have something to do with immegrants. Swedish data suggest that immigrants have over 200% overdeath compared to maybe 40% of the overall normal swedish population and 20% of swedish population is from other countries. In sweden we have an elderly care where elderly is treated in their homes if they are a bit stronger. Some of those elderly have something like 15 different nurses that is a low wage position that is often held by immegrants. Also they had very little protective gears and 25% of the deaths where from this care. Hence an oppertunity to spread from region to region of areas with a high fraction immegrants. Yes we have areas or clusters with many immegrants. We also seam not to have reached them with recomendations and they may might have traveled to friends and family in other regions to a higher extent that normal Swedish population. This is speculations and I do not know if this is same as GB and different than denmark.
The slow decay seam to be due to cluster outbreaks happening during a longer time frame, this is clearly seen in the Swedish data. Somehow I suspect that it might have something to do with immegrants. Swedish data suggest that immigrants have over 200% overdeath compared to maybe 40% of the overall normal swedish population and 20% of swedish population is from other countries
It is not reported on much here in the US (politically incorrect), but part of the reason for the recent case increases in Texas, New Mexico, Arizona, and California are because of immigrants. Northern Mexico has been hard hit, and naturally they seek out the better care to the north. Their family members in the US, get infected, or vice versa, and also seek care.
In southern California as an example, during a one month period, there were over 500 helicopter medical flights transporting patients from the border hospitals, to hospitals further north with available beds.
But there are other hot spots too, such as our Native American reservations, jails, apartment complexes around universities, and yes...it is still getting into nursing homes after extraordinary precautions taken.
Northern Mexico has been hard hit, and naturally they seek out the better care to the north.
As far as I know, the border is closed, except for government officials and other high muckety-mucks. No one is crossing in either direction. The Canadian border is also closed. Really closed. We're talking so closed, their P.M. won't even come to Washington!
As far as I know, the border is closed, except for government officials and other high muckety-mucks. No one is crossing in either direction. The Canadian border is also closed. Really closed. We're talking so closed, their P.M. won't even come to Washington!
Are you serious? Yes, the border is officially closed, but it is very porous as you of all would, should know. Look, in their shoes I would be doing the same. This is not a political debate, and I do not understand why we can not speak honestly about the facts?
Yes, the border is officially closed, but it is very porous as you of all would, should know.
Is it? I have not read any news accounts. I read that the Canadian border has practically no traffic, except trucks hauling freight.
Anyway, the black and hispanic U.S. native population has a much higher incidence of infection, and more deaths per capita. It is not likely the black population is being infected by illegal immigrants. It would not be infected at a higher rate than the working class white population. I think the reasons why these minority groups have more casualties are clear:
They have more pre-existing health problems such as obesity.
Their jobs often require hands-on physical labor. You cannot do a factory job, or a grocery or warehouse job at home over the internet.
Many of their jobs, such as meatpacking, are prone to spreading infections.
Poor people tend to live in crowded houses, where infections often spread from one family member to another.
Poor houses often fail to meet modern standards of hygiene. In some Native American communities, more than half the houses lack indoor plumbing. Overall, 5.8% do, compared to 0.3% of white housing.
Hospitals in poor neighborhoods tend to have lower standards, fewer doctors, less equipment and so on. Especially in rural districts in Georgia, where many poor minorities live.
Display MoreIs it? I have not read any news accounts. I read that the Canadian border has practically no traffic, except trucks hauling freight.
Anyway, the black and hispanic U.S. native population has a much higher incidence of infection, and more deaths per capita. It is not likely the black population is being infected by illegal immigrants. It would not be infected at a higher rate than the working class white population. I think the reasons why these minority groups have more casualties are clear:
They have more pre-existing health problems such as obesity.
Their jobs often require hands-on physical labor. You cannot do a factory job, or a grocery or warehouse job at home over the internet.
Many of their jobs, such as meatpacking, are prone to spreading infections.
Poor people tend to live in crowded houses, where infections often spread from one family member to another.
Poor houses often fail to meet modern standards of hygiene. In some Native American communities, more than half the houses lack indoor plumbing. Overall, 5.8% do, compared to 0.3% of white housing.
Hospitals in poor neighborhoods tend to have lower standards, fewer doctors, less equipment and so on. Especially in rural districts in Georgia, where many poor minorities live.
Let the facts fall where they may, but let those facts be true. And let no man decide that his interpretation of those facts, are no less compassionate than the other.
Is it? I have not read any news accounts. I read that the Canadian border has practically no traffic, except trucks hauling freight.
It is a falacy that you need to test all combinations. Please read up about the statistical field of design of experiments but yes typically you do have an effect by individuals that is very common but not always and then interactin effects need to be included in the modell still not combinatorial in complexity but n^2 (Childs from Saphire fame is a proponent of the use of Design of Experiments also I am)
Well that is true - but n^2 is still too much.
My point - which it seems few here like - is that when you have lots of unknowns you start with drugs individually. If HCQ does not work, probably it will not work in combinations with otehr drugs. Whereas if it does work, it is worth seeing whether it works better with other drugs.
THHuxleynew: Your FUD of the day! Didn't you read the 10+ studies about HCQ AZT/doxy + Zinc ??
Can you show us one study using this combo that failed please ?
Or better stop to post false information!
So; the differnece between me and you (also a few others here) is that I change my mind.
I, too, was willing to see good Observational trials as quite strong but not conclusive evidence.
After going through the gamut of such evidence - pointing all directions - and having now enough RCT evidence - it is pretty clear that HCQ does not work as a treatment. Jury still out whether it works as prophylaxis.
There could be some weaker effect not showing up in the RCTs, true. But the whole reason people are stuck on it (otehr than politics) were some poor observtaiuonal trials that showed apparently strong effects. And still, people claim strong effect.
Strong effect just is not possible as treatment given the RCTs. Still a little wiggle room, you can perhaps argue as follows:
Add X + Y to HCQ (I guess X=zinc and Y=AZT)
There is no RCT evidence in that specific combo
It is possible that those two factors, and only those two, vastly increase effectiveness.
I can't say that is impossible till we get RCT evidence on that combo. Do we have it yet? If not we will get it soon. If those advocating this are correct it will be strongly positive.
There is evidence HCQ just does not help at 4-5 days after exposure (and typically before symptoms). You have to do a lot of hopeful thinking to have it working after symptoms with Zn and AZT added. And yet those 10+ studies rely on that.
On the other side, we can see practically (and can work out scientifically) how easy it is for observational studies of COVID mortality to give misleading results. Similarly how easy it is for doctors to think they have a miracle cure (because all their patients recover) when given demographics and file drawer effects that is expected.
I am just saying it as it is. Which is why most of the serious people looking at this say the same. No-one is saying that HCQ has no effect. You can never prove that of any substance. No-one is saying that there might be some long-odds conditions in which it works. Just that it has been tried, a lot, and does not work in the trials which can be trusted.
And there are so many other possible treatments we need to test...
THH
Display MoreWell that is true - but n^2 is still too much.
My point - which it seems few here like - is that when you have lots of unknowns you start with drugs individually. If HCQ does not work, probably it will not work in combinations with otehr drugs. Whereas if it does work, it is worth seeing whether it works better with other drugs.
So; the differnece between me and you (also a few others here) is that I change my mind.
I, too, was willing to see good Observational trials as quite strong but not conclusive evidence.
After going through the gamut of such evidence - pointing all directions - and having now enough RCT evidence - it is pretty clear that HCQ does not work as a treatment. Jury still out whether it works as prophylaxis.
There could be some weaker effect not showing up in the RCTs, true. But the whole reason people are stuck on it (otehr than politics) were some poor observtaiuonal trials that showed apparently strong effects. And still, people claim strong effect.
Strong effect just is not possible as treatment given the RCTs. Still a little wiggle room, you can perhaps argue as follows:
Add X + Y to HCQ (I guess X=zinc and Y=AZT)
There is no RCT evidence in that specific combo
It is possible that those two factors, and only those two, vastly increase effectiveness.
I can't say that is impossible till we get RCT evidence on that combo. Do we have it yet? If not we will get it soon. If those advocating this are correct it will be strongly positive.
There is evidence HCQ just does not help at 4-5 days after exposure (and typically before symptoms). You have to do a lot of hopeful thinking to have it working after symptoms with Zn and AZT added. And yet those 10+ studies rely on that.
On the other side, we can see practically (and can work out scientifically) how easy it is for observational studies of COVID mortality to give misleading results. Similarly how easy it is for doctors to think they have a miracle cure (because all their patients recover) when given demographics and file drawer effects that is expected.
I am just saying it as it is. Which is why most of the serious people looking at this say the same. No-one is saying that HCQ has no effect. You can never prove that of any substance. No-one is saying that there might be some long-odds conditions in which it works. Just that it has been tried, a lot, and does not work in the trials which can be trusted.
And there are so many other possible treatments we need to test...
sTHH
I also change if evidenses are there. And I can agree that in an initial phase to search for a treatment you could probably use a linear condition and work your way like you du with playing mastermind. It is not nessesary the best and fastest to search out one by one. Anyway in Sweden we do not focus much on HCQ and there we reduced deathrate for people strong enough for intensive care a factor of 5 times if you just go by stats from icu.
Safety of hydroxychloroquine in outpatients
https://www.medrxiv.org/conten…07.16.20155531v1.full.pdf
"
Data from three randomized clinical trials using hydroxychloroquine for the prevention and
43 treatment of COVID-19 did not suggest significant safety concerns. Gastrointestinal side effects
44 were common but arrhythmias were rare. There were no sudden deaths in any trial.
Randomized clinical trials can safely investigate whether hydroxychloroquine is efficacious for COVID-19.
I guess this study won't have a high media profile..
Japanese trials of Avigan inconclusive
https://www.reuters.com/articl…japan-trial-idUSKBN24B0M4
Japanese Prime Minister Shinzo Abe had said he hoped the drug would be approved as a COVID-19 treatment in May,
but a shortage of patients in Japan delayed the progress of clinical trials. It has been approved as a COVID-19 treatment in Russia and India.
Known generically as favipiravir, Avigan was developed by a subsidiary of Fujifilm
and it was approved in Japan as an emergency influenza treatment in 2014.
However Monash University in Australia is enrolling volunteers for another trial.
The current surge in the state of Victoria may help recruitment.
Up to now, drug trials in Australia have been handicapped because of lack of infections
https://www.alfredhealth.org.a…clear-covid-virus-faster/
Convalescent Plasma..for Covid19?
Currently there are well over 50 trials.. https://clinicaltrials.gov/ct2…cntry=&state=&city=&dist=
" A recent review underscores the lack of randomized, double-blind trials and highlight the importance of considering a “scale up” study in order to utilize CP once efficacy is established
The published cases suggest positive clinical outcomes in patients receiving CP in addition to antiviral therapy +/– corticosteroids "
https://www.frontiersin.org/ar…3389/fmed.2020.00435/full
However a recent review of 5 RCT s of CP with severe influenza showed
"The administration of convalescent plasma appears safe but may not reduce the mortality,
number of days in the intensive care unit, or number of days on mechanical ventilation in patients with severe influenza.
https://ccforum.biomedcentral.…N_bmcso_article_paid_XMOL
A potential cornucopia of drug treatments for Covid are being trialled
This website promises to keep an update..
https://www.pharmaceutical-jou…s=false#Remdesivir_257868
most of the... The xxxxxx-mabs are biologicals (proteins or polypeptides) and are much more expensive.. infliximab might be the cheapest.. ~$2000 upwards..
The simpler molecules .. even Remdesivir are simpler to make and manufacturing is much cheaper..
Back in April an estimate for the costs of these simpler existing drugs was made
https://www.pharmaceutical-jou…s=false#Remdesivir_257868
Remdesivir was priced at 9$... Avigan at $20 HCQ +AZi would be $2.40
Immune modulators:
Other or multiple mechanisms:
Display MoreSafety of hydroxychloroquine in outpatients
https://www.medrxiv.org/conten…07.16.20155531v1.full.pdf
"
Data from three randomized clinical trials using hydroxychloroquine for the prevention and
43 treatment of COVID-19 did not suggest significant safety concerns. Gastrointestinal side effects
44 were common but arrhythmias were rare. There were no sudden deaths in any trial.Randomized clinical trials can safely investigate whether hydroxychloroquine is efficacious for COVID-19.
I guess this study won't have a high media profile..
Difficult to know but my feeling is that the emphasis on HCQ side effects medically is:
(a) because no positive evidence
(b) as a push back from politicians deciding they know more than doctors and very strongly promoting certain treatments that most doctors would be reluctant to give.
(c) even though they are low, they do exist. And we have potentially the whole country wanting to be dosed with it. At say 1 in 100K deaths that is still 3,000 needless US deaths.
New drug on the block..not so new.. repurposed from osteoporosis..
Phase 2 trial (Safety)to commence for Apilimod
https://www.biospace.com/artic…ent-of-covid-19-patients/
"
“We all want to do our part to allow the people we love to get back to work, school, and play. At AI Therapeutics we feel we need to do all we can to make sure our drug, LAM-002, has the best shot to help and working with Yale is the perfect place to start,” said Jonathan Rothberg, AI Therapeutics’ co-founder and Recipient of the National Medal of Technology and Innovation for inventing high speed “Next-Gen” DNA sequencing.
As the clinical trial is progressing, AI Therapeutics is preparing to make the LAM-002 accessible; it has 70,000 doses ready to go, 70,000 on the way, and the compound in preparation for nearly 5 million more doses."
Rothberg sounds like a clever chap
Interesting thesis on small molecule screening for anti RNA virus activity
Recent thesis... another clever chap
The winter break in europe is very strong correlate to the size of the outbreak peak.
Norway,Denmark,Finland,Germany all with excellent low peaks had their holliday before week 9
France,Belgium,GB,Sweden,Netherlands all had their winter holliday partly or fully week 9 or 10
See the trend!
Finally GB has the same problem as Sweden with a slow downward slope after the peak and if Sweden is 2,5 times as bad as Denmark, GB is about 2,0 times as bad as Denmark whenit comes to the behavior after the peak. So it does not look like it's because of the lock down, more due to the fact that we had a critical mass of people that transmitted the virus so that new clusters continously crop up and delay the recovery. If you look at the media around Sweden, the next time around we will have close down italian style and punish all good people that followed the rule. This is like putting another sticker to a tire ontop of an old one to really make it hold although the tire is leaking elsewhere in a new hole.
Let the facts fall where they may, but let those facts be true.
Everything I listed is a well documented, uncontroversial fact:
[Poor people] have more pre-existing health problems such as obesity.
Their jobs often require hands-on physical labor. You cannot do a factory job, or a grocery or warehouse job at home over the internet.
Many of their jobs, such as meatpacking, are prone to spreading infections. . . .
And let no man decide that his interpretation of those facts, are no less compassionate than the other.
Why not? If a person unfairly blames the patients for the disease, surely that is less compassionate.
You do not blame the patients. Your hypothesis, that the disease is being spread by coming in from Mexico, does not lack compassion. But it seems far-fetched. There is a lot of evidence it is not true, or only marginally true. So you are probably wrong, for the reasons I listed.
There are some gray areas. It is clear that obese people suffer more from the disease and they die at higher rate. That is a fact. If you say that an obese person is responsible for his weight, then you are saying -- in effect -- they have brought illness and death upon themselves. That is less compassionate than saying: "obese people cannot help being fat" or "the food companies make people fat." It seems less compassionate to me. Less sympathetic. However, I think they are responsible for being overweight, so I guess I am less sympathetic. I would say they are partly responsible, and society, the food companies and the zeitgeist are partly responsible.
To take another example, is it less compassionate to say: "people who do not wear masks and who go to crowded bars are responsible for getting COVID-19"? I would say yes, they are responsible, and yes, that is less compassionate. I sympathize with them, but I am more sympathetic toward people who do all they can to avoid the disease, wearing masks, not going to bars, social distancing, and yet they still get it.
