Posted on 03/29/2020 11:38:34 AM PDT by FreedomPoster
You are exactly right.
RE: did glance at the conclusions. I agree there is potential to show viral clearing to decrease progression of the disease to a more sever form. Let me spend some time reading this carefully.
It’s good to come to an agreement on something. Please return to this thread at your leisure and tell what you think.
RE:As I have said all along, there were people taking these drugs prior. How did they do?
There are NUMEROUS anecdotal evidences posted in this thread of people from Florida, NJ, North Carolina and other states who were rescued from death’s door and were saved as a result of taking the combination of hydroxychloroquine and azithromycin. I know that these do not count to you since they are not in a controlled clinical trial setting, but there’s at least a partial answer to your question. You want to see lives saved— were these stories are your answer.
See here:
and here:
The wife got distracted so I took a first pass. Everybody who has been bitching at me, look at this paper. THIS is what science looks like. Not some email from, well, whatever. This is gonna take me some time to digest.
OK. Ive been working on this for 20 min. Remember, Inf. Dis., not my speciality. The bench stuff, i dont understand the details. I shared some thoughts with semantic the other day, unless you are in healthcare this may seem silly and if you are. You probably already realize most of this. If so just skip it. It may help you understand what they are doing. I take back everything nasty I said about Raoult now I see the actual paper. That journalist clearly did him no favors but hell, IM struggling with this. Remember this is the first paper in at least 5 years that I have looked at, for years I have been trying to forget I was ever a doctor. Now this. Anyway...
How may virus particles (visions) does it take to start an infection?
I dont think anyone knows for sure but over the decades, at times like this, one ponders these things. My thoughts go along these lines, some things are known, much not. A lot of information is proprietary.
If one viral particle (virion) is inhaled and lands on a nasal epithelium cell, on a specific receptor, it can then do what it does and infect the cells by transmitting its genetic material. That cell replicates 800 or 1,000 or whatever new virions, the cell dies from it and releases all those particles to start already x800 or so on surrounding cells. But is that lone virion always successful. You can imagine there is a scenario in which the virus binds to a cell that is already about to die and in infecting the cell both perish, the cell dessicates the virus is wrapped in a shroud of dead cell, and both are sloughed off and blown out the nose.
So, theoretically, there is at least some risk the virion wont be successful. Now we can begin to talk about probabilities and thanks to Statistics we have an excellent tool to do so. So while we may not have the technology to see one virion do what it does, like Psycholgy needs not understand the brain in detail, it is the study of Behavior, we dont need to put our virion on a couch and ask questions about its childhood. We look for the behavior of the disease and theorize , if that were happening, this is what we would observe.
So how many virions does it take? AFAIK, no one knows this for any virus. I dont think its knowable. But it sort of stands to reason that if one got an inoculuum heavily loaded in multiple droplets that each, due to the relatively large size of the droplet compared to an aerosol, heavily laden with many, many viral particles a patient would have a serious jump start over the patient exposed to a lonely pioneer. The patient could get sicker, faster. Potentially it could make a real difference in the clinical course of the disease.
Lets assume two cases. One patient gets exposed by a massive droplet exposure where many droplets are inhaled and another where one little virus made it into the nose placed there by a contaminated finger from a doorknob. With just a little imagination you could easily see how the two exposures are so different the clinical course of the disease is likely different. The first may get very ill very quickly, the other have a longer prodrome, the immune system gets a chance to get off its back foot, and the patient has mild or no symptoms.
Once infected the new virions are released in every cough, sneeze, wiping of mucus on surfaces, etc. we know flu and cold are droplet spread. I believe the smart people are starting to realize (the one thing we learned in Med School about this previously considered to be of no clinical importance family of Coronaviruses) was they escaped detection for a long time because the are so small and compact. See if you can find an image to compare in scale toThe Dane Particle for instance. Why that was so gets technical but there it is. We know these virions are among the smallest virions out there.
So it stands to reason that there could be some people who were lightly infected who because they are young and healthy are able to produce Clouds of aerosol loaded with a lesser # of virions. Droplets are subject to temperature, humidity, sunlight, and gravity. Due to their small size aerosols float in air and linger for a very long time, immune to gravity.
I do believe the smart people (I say smart people because there is some disdain for clinicians among the people who strive for Revealed Truth in their Ivory Towers and it is returned for good reason, as clinicians we have to deal with the wreckage when they screw up, anyway) are beginning to realize this as through contact tracing they discover super spreaders.
So, it is possible that clinical progression of the illness could be a function of inoculuum, could produce a very mild illness with an astronomical Ro but no fatalities, but one superspreader can find those few people with diabetes or some other disease that makes it harder for their immune system to get off its back foot and those few get a very serious form of the disease even though it is aerosol. Now those patients become huge droplet spreaders.
So you can see how just based on largely theoretical arguments we can begin to see just how many different flavors of patients there are out there.
I like this guy’s attitude.
So, now we have established at least at a conjecture that tells us there are patients who have been exposed in different ways, how that could affect the course of the illness. There are patients with comorbidities who probably get into a situation where they are just overwhelmed with viremia, very high particle counts in their serum. So many cells dying and the immune system producing a lot of the different parts of the immune system, some of which are toxic to the human cells as well and they rapidly decompensate, become short of breath and turn blue. It seems that this only happens about 2-5% of cases which can sound trivial but isnt
You may recall my first question was Who are you gong to give it to? I conjectured that because of bench studies and anecdotes the drugs may very well have a significant effect at, say, preventing asymptomatic or mild cases from progressing and still have absolutely no impact on those patients who are rapidly decompensating from the very beginning.
Unfortunately, I am not that smart. I achieved by working my ass off for over a decade. But I know this: We have drugs we know to be highly effective, gentamicin comes to mind, that still cant save rapidly decompensating patients. I could go on and on about gentamicin, renal failure, tinnitus, etc. The question becomes does the drug help prevent the asymptomatic or mild from progressing to needs ET tube? We can know this right now. People were taking these drugs prior to the epidemic. Why dont we? The answers are there but they are not being shared.
Sent from my iPad
Notice the key is Zinc deficiency. Hydroxyquloroquine helps get zinc in the cells. High blood pressure meds can lower zinc. This can all be tied together. Time to get more zinc before falling ill!
First, look at the bottom of Introduction where they define their goals.
1) Outcomes. Clinical outcomes. Bravo! I love it but ten days closes the study but that may be fine for the purposes of answering our question do the drugs work? If one had time you would do longer, obviously we are out of time.
2) Contagiousness. Excellent goal. I havent been around cell or tissue culture since 1983, the bench stuff I cant begin to read critically. Sure, i can read it but you could sell me aquarium cleaner here. Not my table.
3) Length of stay.
Groups. They used URTI and LRTI. As a clinician I would want no Syx., mild, serious (O2), and intubated. But there may be a reasoning here that ID guys and Pulmonology. Guys understand that is escaping me because aint my table but remember one goal is to evaluate contagiousness. If you read all that crap I initially posted, there may be a difference in how the virus is spread, URTI emitting droplets, LRTI emitting aerosol. Since they dont state explicitly, I dont know. Remember, they are writing this for people who know everything they do.
They used the NEWS score (which I have never heard of but looks reasonable) not to define groups but to evaluate clinical progress. Elegant experimental design. My respect grows. Because one goal is to evaluate clinical progress.
Its going to take me hours to really unpack all this but at this point, i would say this, based on my thoughts to you earlier you can see how we are interested in Mortality. I am. My main concern is decreased mortality. This study cant really answer that but it can answer some other questions. If patients are shedding virus less they are less contagious. So as a Vet, herd doctor, epidemiologist, this is important. Decreases the Ro. It will have no impact on the patient but it will reduce the overall # of patients. Thats a good thing. So what this tells us is that there is at least a theoretical possibility that putting EVERYONE who tests positive on the drugs, n to for their sake, but others. There isnt enough drugs in the world to do that. I doubt there would be enough to put a bunch of essential personnel on them and quarantine everyone else.
So it stands to reason the people you want to put on drugs for their own benefit are the mild because, as I have stated, we want to decrease mortality. Obviously, this article cant really address mortality, really too few cases but there may be a suggestion here that it could change the course of the illness just enough that fewer people turn blue. Which is an end point not in the goals. Im going to have to make coffee and really read this entire thing again.
Anyway, for the moment it still doesnt answer my question but it does ask a bunch of good questions. An article like this has to really be read extremely carefully.
LOL. About now you are probably sorry you asked for my thoughts. Maybe now you see why I have a 5 second rule for the Medical Literature. If its worth reading it takes a while.
One thing. People with G6PD deficiency. Cant take it. So theres a built in control group for a larger study.
At this point in my understanding what this paper demonstrates is the role these drugs play may be (may be) is decreasing the hospital length of stay which could reduce the burden on the system by (pulling a number out of my...) as high as 30%. It may have no effect on mortality whatsoever but still be valuable and worth doing in those patients who pass the eligibility for the drug (many wont, see exclusions for yourself,G6PD Def, Hx of arrhythmia, etc.). So from a sense of is it worth doing? The answer may be yes but not for the reasons you think. The potential for reducing the mortality is there but you are putting some 3% of the people infected on the drug to prevent 1% or so from dying and the numbers to study that may take a while to accumulate the data.
But at least now we have a good place to start. Put eligible people on the drugs upon admission if they pass the screening. In a clinic like Dr Raoults with 75 Isolation beds over the next week or so he should, and will Im certain, be sharing more data on this. This is the Super Bowl of Medicine, folks.
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