Almost done.
Here is this.
https://academic.oup.com/aje/article...1/1218/5847586
Almost done.
Here is this.
https://academic.oup.com/aje/article...1/1218/5847586
You're just now coming to this conclusion? It took until December?Originally Posted by TheNewbie
Christ on a cracker, no wonder there's such a disconnect here between you and reality.
"Are you ready? Okay. Let's roll."- Last words of Todd Beamer
The high schoolers and college kids seem to be the ones most likely to ignore common sense precautions against spread, so I’d be very ok with this. Or, even better, sealing them up in shrinkwrap and putting them in the closet for the next year.
Ken
BBI: ...”you better not forget the safe word because shit's about to get weird”...
revchuck38: ...”mo' ammo is mo' betta' unless you're swimming or on fire.”
Let me know show you a couple of things here. The guy who published this is a collaborator with the guy who published this
https://www.wsj.com/articles/too-muc...238928?mod=mhp
Too Much Caution Is Killing Covid Patients
Doctors should follow the evidence for promising therapies. Instead they demand certainty.
By Joseph A. Ladapo
Nov. 24, 2020 12:28 pm ET
They both refer to different studies. They know that for doctors to listen to researchers, a word "randomized trial" must be used. So they reference a meta-analysis of five randomized trials as an evidence that HCQ works. They just happen to be the authors of that meta-analysis, bold is mine.
Randomized Controlled Trials of Early AmbulatoryHydroxychloroquine in the Prevention of COVID-19 Infection,Hospitalization, and Death: Meta-Analysis Joseph A. Ladapo, MD, PhD1; John E. McKinnon, MD, MSc2; Peter A. McCullough, MD, MPH3;Harvey A. Risch, MD, PhD4
The five trials they quote are
Mitjà O, Ubals M, Corbacho-Monné M, et al. A cluster-randomized trial ofhydroxychloroquine as prevention of COVID-19 transmission and disease. Preprints July 26,2020. h
Mitjà O, Corbacho-Monné M, Ubals M, et al. Hydroxychloroquine for early treatment ofadults with mild COVID-19: A randomized-controlled trial. Clin Infect Dis 2020 Jul 16:ciaa1009
Skipper CP, Pastick KA, Engen NW, et al. Hydroxychloroquine in nonhospitalized adultswith early COVID-19: A randomized trial. Ann Intern Med 2020 Jul 16:M20-4207.
Rajasingham R, Bangdiwala AS, Nicol MR, et al. Hydroxychloroquine as pre-exposureprophylaxis for COVID-19 in healthcare workers: a randomized trial. Preprints September 21,2020. h
Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial ofhydroxychloroquine as postexposure prophylaxis for Covid-19. N Engl J Med 2020 Aug6;383(6):517-25
When I clicked on each individual trial, all of them seem to be negative for HCQ benefits. You should double check that but I think I am right. So it seems like those dudes took five negative trials, reanalyzed them into one positive meta-analysis, and now publish everywhere quoting themselves.
I guess I invite you to be equally inquisitive and skeptical about what everybody says, whether proponents or opponents of any specific therapies and approaches.
Doesn't read posts longer than two paragraphs.
Damn lies and statistics indeed!!
Knowing how to look for stuff like this and even just knowing to look for stuff like this at all is one of the benefits of a formal education in a subject. I'm all for self education, but training does matter.
So, my genetics classes were decades before modern generic engineering...
It it the case that the vaccine contains X amount of mRNA, that gets taken into N cells which then display the relevant proteins, but no additional mRNA is produced in the body? I.e. only the original N cells ever contain the mRNA? And does the immune system then attack the cells that synthesized and are now displaying the relevant proteins?
My googling didn't find more than superficial answers...
With modern information availability and resources you can self-educate on a lot of subjects pretty fast if you're disciplined and motivated, but it only gives you a narrow beam flashlight. There's no shortcuts to a wide beam flashlight. There's nothing wrong with using your narrow beam flashlight to make decisions, but if you go wandering around with it you are likely to fall off a cliff.
I'm not 100% sure how this vaccine works, but you are correct that no additional mRNA is produced in the body. mRNA is basically the working copy of the instructions to make the protein that make it to the factory floor. It's printed on cheap paper, has grease stains from lunch, and a coffee cup ring. At the end of the day it gets shredded because nobody wants it cluttering up their desk. When the cell needs a copy of instructions, it prints straight from the document controlled server (DNA), instead of making a copy of a copy.
My knowledge of the intricacies of the immune system isn't enough to give a good answer about how the displaying cells may be attacked by an immune response.
Sorry for the delayed reply - had an important committee meeting this AM that has occupied my time until just now.
So, I'll try to organize my thoughts on this in a fashion that is logical and orderly.
As @pangloss mentioned, the default position is to assume no relationship between two variables of interest. This stems from the millenia-old conception of the scientific method, in which the purpose of scientific investigation is not to establish that something works, but to refute the null hypothesis. That is to say that the default hypothesis in any and every scenario is that A does not cause B. As a scientist, the mission is not to prove that A causes B, but to provide enough evidence that you can no longer say with certainty that A does NOT cause B.
In the world of drug development, this process occurs, grossly speaking, in two phases. The first being "pre-clinical" - i.e. mice and test tubes - and the second being clinical research using real human patients.
The pre-clinical phase primarily concerns itself with what is described as a mechanistic relationship. Think about this like the moving parts of a gun or a car. How does the ignition of the cartridge cause the ejection of the spent brass? This can be described very explicitly using relationships between moving parts: the cartridge ignites, which generates pressure from the combusting gasses, which causes the slide to move to the rear, and so on.
In the drug development world, this is where things begin, except we don't know all of the parts involved nor how they relate, because the machine in question has a quasi infinite number of parts. The challenge in building this relationship is 1) knowing what these parts are, and 2) knowing how they work together. If you have 1 and 2, you can arrive at your hypothesis: how might I exploit this relationship to achieve the desired effect in a living organism?
The problem with hydroxychloroquine and COVID-19 is that there has never been a persuasive mechanistic hypothesis. Ever. I would challenge you to find one, but you will not be able to. If you can find persuasive evidence to the contrary, I am open to listening to it, but I know that it does not exist because I've looked for it and what I've found is deeply lacking. I've covered this before in this thread and won't re-hash this now, but will cover this again if you desire more specifics.
This closes part one of my argument.
The second piece is clinical evidence. I.e., in real human beings, is there evidence that this works?
This appears to be your sticking point. There have been many, many, many , many, many, studies that show that plaquenil does not help patients with COVID-19 across a variety of settings: the severely ill, the mildly ill, those who have been exposed and are asymptomatic. With and without azithyromycin (which is again totally devoid of an evidence based mechanistic rationale). None of them have shown any effect to date. For fun, in case you don't have enough reading, here is a study looking at exactly what you requested: HCQ + zinc in mildly ill patients. Spoiler alert: it was negative.
There are exactly two trials that I have been able to find that support your position. The first is a retrospective analysis from the Marseille metro area in France. The second is also a retrospective study based out of the NY metro area. Both of these are deeply lacking in quality, which is why there have been very few other studies able to support their findings. To save myself some time, I will quote a paper that describes succinctly the issues with their methodology (i.e. how they designed their studies):
I am, as always, happy to run through each paper, figure by figure, to give you more specifics.Overall, the methodologies of the published studies are not robust, and the results are tempered largely by selection bias and residual confounding bias. At the design level, most studies lack the randomization, concealment of the generated sequence, and blinding/masking needed to generate sound evidence, when they are RCTs and not observational uncontrolled single-arm case series. At the analysis level, they lack the standard steps taken to minimize confounding such as prospective design, statistical adjustment for prognostic factors, (propensity) matching, or stratification [13]. Even with procedural and statistical controls, the evidence emerging from the COVID-19 research in general and using hydroxychloroquine research thus far as the example, cannot optimally achieve prognostic balance as would a large sample-sized RCT with optimal methodology. Our examination has found the reporting to be very sparse and lacking of the explicitness that is warranted, and the patient-important outcomes needed for decision-making are often not studied or not reported.
Finally, to address what appears to be your biggest sticking point ,it seems you are hung up on the fact that there is an absence of studies that have rigorously tested what you appear to believe is the "goldilocks zone" of treatment: "HCQ and Zinc (together), given in the early stages of the virus"
1. See the study cited above (which has its own limits I am also happy to discuss)
2. See my discussion re: mechanistic rationale
3. Assuming you're still not persuaded: let's talk a bit about how drug design.
There is no drug in the United States that has been tested against the infinity of possible confounding effects that exists in the world. This is why we rely on studies which are inherently unable to capture every possible outcome: we accept random chance is a factor in this world, and that there is no need to flip a coin an infinite number of times to understand that our odds for heads and tails are 50:50.
This ends part two of my argument. To conclude:
What I would ask you is this: what is the real source of your beliefs on this topic?
It is deeply obvious to me that they are not based on a rational or logical investigation of the peer-reviewed, Pubmed indexed evidence that is available. This is the currency of knowledge in the biomedical world, and as I have hopefully reviewed for the final time, it overwhelmingly contradicts your position.
I will finish this extremely long post by reiterating my challenge: why do you hold the beliefs that you do? Is it really based on a rational investigation of the available evidence? If not, what do you believe serves as its basis?
Do you really think that the hundreds of thousands of medical and scientific professionals in this world do not want to help patients with COVID-19? Do you truly believe that the millions of man-hours that went into all of the articles that I've cited in this post were part of a conspiracy to disprove the efficacy of this drug? Do you truly feel that the desperate and overworked clinicians in this country would actively work to discredit a drug that has real potential to treat those suffering from this terrible virus?
If your answer is yes, I'd sincerely ask you to do some soul searching as to why you feel this way.
Last edited by Nephrology; 12-04-2020 at 03:49 PM.
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