Dexamethasone is a serious drug and corticosteroid [1]. It was prescribed for a friend after eye-surgery and having skin / eye inflammation problems, I used it (with no doctors advice) recklessly albeit with very small quantities.
The drug was hyper-effective. An unbelievably tiny quantity can remove any inflammation (eye, skin, hair skin rash, etc...). But the fall out and side-effects are no joke even for seemingly super minuscule doses. It was a horror story for me with horrible eye inflammation, small inflammations in different parts of the body and a skin rash I still struggle with until today. Mind you I took small localized doses and not an injection. I wasn't aware that it can travel through your skin, get into your blood and make a mess.
I think the research will need to specify potential side-effects and their probabilities. It's trade-off at the end of the day.
PS: Do not ever think of trying it without medical advice and doctor supervision.
Well, yeah, steroids are incredible, shame they have such severe side effects. Following a parvovirus B19 infection I developed severe joint problems(basically got advanced arthritis at the age of 28, how fun), and all it took to sort out was one steroid injection. I won't lie, for the next few days after the injection I felt like a superhuman, all the issues went away and in general I felt super great. Obviously that's not something you can continue doing because the side effects get really bad after a while, my doctor warned me that if the issues come back I probably won't be able to get another injection because the risk is too great, but for a one-off thing it was like a miracle cure.
That's the problem with evolution. Any protein in the body ends up with multiple completely unrelated functions.
If it's in the blood stream for enough generations, the body will find some alternate use for it. It's like a compression algorithm on your DNA.
...and so when we try to use meds to counter certain proteins or block receptors, we discover that it has a dozen totally unrelated impacts. "Oh, that blood pressure medication? Well let's just have it also randomly give you prostate cancer!" (real example).
Organic evolved animals are the worst type of spaghetti code - if there was ever something you'd want to redesign from the ground up, it's us.
Then add to that that there isn't even any "standard" type of human. We're all different - and even different groups of us have different smatterings of genes. Sometimes it correlates with our ancestors background - sometimes it doesn't. Who knows! Evolution! We're all each just individual experiments running around to see which genes can procreate the most.
...and it's not even as though each of us is a single experiment on a specific gene, that would be too easy. We're each an experiment on a unique collection of thousands of genes that evolution hopes will average out the results across the entire population. Try to wrap your statistics PhD around that!
Then also factor in that modern human evolutionary pressures are totally different than they were even a couple of generations ago, and it becomes clearly evident that evolution is in a complete state of dysfunctional disarray.
Evolution is romanticized, but its ability are limited, not infinite.
The more complex a species, the less adaptivity it has to fundamental shifts in environmental pressures. The interconnections between protein functions are directly responsible for that trade-off, and become a liability.
The time scales for evolution far beyond our current level of genetic complexity, probably extend beyond the life span of the Earth.
Now the benefit of this speghetti-code situation is that no intelligent designer is required - obviously a fundamental ingredient of abiogenesis, but does it benefit an species that's capable of genetic editing?
Nope. At this point, it's really just a bottleneck to even repairing the most straight-forward genetic diseases.
As a species, we're approaching the time where we've obviated evolution. ...I won't say we've seen that yet because reproduction rates are still very uneven across population segments, but it's only a matter of a few more generations (cataclysms not withstanding).
It’s not spaghetti code... I just think your analogy is weak and misleading.
Not sure how you’re defining complex but humans pretty soundly refute that adaptability thing.
It’s not a “bottleneck” it’s just... life. Can you point to an animal anywhere near as successful as humans that doesn’t have.. genetic variability? No. It’s a requirement and precondition for our success, not some flaw we overcame despite.
Nonetheless, it's a very freeing view to consider that just by existing you've already succeeded. Everything that comes after is an adventure. You've already beaten far, far greater odds just by being here than anything you'll accomplish in life.
Something being more mysterious doesn't make it more interesting.
What's my private key? It's a mystery, but not a very interesting one.
Why does the universe exist? It's mysterious, maybe the most mysterious thing of all, and 8lit's interesting, but I'd say it's not the most interesting question of them all.
by mystery, i mean much more than that which is not known.
i mean to convey: something that is difficult or impossible to explain. something that is deeply interesting and provokes wonderment.
what is more difficult to explain and understand than the fundamental nature of existence?
perhaps it is not apparently immediately _useful_.
but in a cosmic sense, of what use is it to understand thought objects in the world when there is a complete lack of understanding of the consciousness in which these thought objects arise?
i’m curious what are some candidates for “most interesting question of them all” in your view. this is something which sparks a genuine curiosity in me and would love to hear your perspective.
it is evident that people don’t actually converge on singular sets of beliefs in this way. but for sake of argument let’s put that aside and suppose we actually do.
even with this, this doesn’t address the concern of actuality versus appearance.
consensus reality has been wrong in the past, and can be shown wrong again.
>As a species, we're approaching the time where we've obviated evolution.
This is hubris. Everything that humanity may accomplish in the future, from editing its own genome to creating general artificial intelligence, is a product of that same evolutionary process. We do all that out of our innate need for self preservation and reproduction—evolutionary imperatives for all organisms.
But it’s more accurate to think of evolution as a universal computational process occurring within the substrate of (bio)chemistry. That computation will yield further computation (intelligence and its products).
This way you can define evolution to mean absolutely anything, at which point the word loses its meaning.
If we stick to traditional, useful definition of biological evolution, then we can confidently say that it stopped being the driving force for plant and animal life no later than when we've first learned to communicate and remember ideas; we've made it irrelevant when we've learned to write. It still works on microscale, but that's mostly because things breed and die faster at that scale, there's more of it, and we can't efficiently poke at it with any sort of precision.
Well we’re constructed the same way that is: by an intern that is just copy pasting from examples he’s seen work plus occasionally typing it out himself and making an error.
“Spaghetti code“ doesn’t imply “buggy”, so I think is a decent description. Evolution found a good local optimum, but I think that the optimal design would be quite a bit better than what we have now.
> “Spaghetti code“ doesn’t imply “buggy”, so I think is a decent description. Evolution found a good local optimum, but I think that the optimal design would be quite a bit better than what we have now.
The matter is, the possibilities of DNA are infinite, you can create Godzilla if you knew how. The problem is, nobody knows how, so evolution is all we have - random mutations and survival will lead to /something/. Even genetical engineering now is in essence copy pasting of certain parts that we know work in a specific way, bound by what currently exists. But if you could really grasp biology, that works down to the single molecule and atomic levels, and actually dictate it however you like, I think it would be the final technology we would ever need.
Spaghetti code absolutely implies buggy because code != biology. They operate completely differently, in fact potentially opposites (logic is the opposite/complement of intuition, ie neural nets, of which our body operates far more like an adaptive/analog machine than a logical one which is brutally unforgiving).
In code, a single typo breaks the whole thing. So spaghetti code by definition is bad and breaks easily.
Sure, we have a fuck ton of complexity. But it’s only messy to us because we don’t understand all the conditions that led to it.
Humans certainly have flaws, but in general we are as well suited to surviving on Earth as you possibly can be, especially on the whole.
I’d say: we’re so so much better designed than any code that exists anywhere today, that it’s a farce. We are literally the opposite of spaghetti code. We’re Antifragile!
Memory leaks, data loss, intermittent bugs, bad edge case handling are all examples of bugs that could result from a typo and not break the whole system outright.
Furthermore, there are plenty of examples of single gene mutations/interventions that are deadly/crippling.
A single typo sometimes breaks the whole thing. Sometimes, it does not. The same is true for genetic mutations in humans - most typos are harmless, a few give us nasty cancers.
Yes, but that process is also what makes us live in the first place (variability). It definitely breaks, but on the majority it works better than anything we know of.
"The spaghetti code works fairly well" is a different claim than "it's not spaghetti code", though.
"Spaghetti code" doesn't mean "broken". It means "hard to maintain". Our modern medical system is pretty decent proof that maintaining a human is quite a bit of work.
Only in high-level languages, when you have to deal with grammar.
DNA is better compared to binary code fed to a CPU. There is no equivalent of "a single typo breaks the whole thing" there; whatever you feed the CPU, it will execute something. Whether you'll like the results or not is another question - but the same is true with biology. The DNA is there, physically, and it will interact with proteins in one way or another.
Spaghetti code is spaghetti code. It refers to to the code being essentially so interwoven with each other that changing a single thing has consequences for many other locations in the code. Spaghetti code can be 100% bug free.
There are myriad of examples of our body having feature which you could equate to biological spaghetti.
I donno, I am inclined to agree with the spaghetti code connotation. Humans are insanely adaptive, flexible, and efficient, but there are some serious design flaws. Here are some examples of a few things I could see improving: The need to inhale and exhale out of the same place that you need to eat and drink is bad engineering, too much risk of choking or drowning. The sexual reproductive organs sharing the space with waste elimination is unsanitary during copulation. Finally, bipedal upright legs. Legs are awkward and unbalanced, and the knees are extremely susceptible to injury, we would greatly benefit from a more robust mobility design.
Extra Credit: A prehensile tail would be extremely useful in many situations and I believe may decrease the risk of injury for elderly people. With an adequately strong prehensile tail, older people would be able to use it as a sort of a tripod leg to keep themselves upright with less risk of falling.
But, I think the double use of orifices (air, food, urine, semen) is a good idea. Minimizing orifices seems to be an advantage... fewer avenues for outside stuff getting in. (And I don't think human sexual organs are necessarily dirtier due their location; urine is more or less sterile, and feces shouldn't really come into play under ordinary circumstances... )
The problem with spaghetti code is that decently intelligent people are forced to work with it and they would be vastly more productive if it weren't spaghetti.
No such advantage with our bodies, as they are only "worked on" by probabilistic processes.
Well, the difference is that for programming you almost always have an enormous surplus of computing power, while evolution is a race to the bottom on who can do most with fewer resources.
Tell that to your immune system. It's necessary, but reasonably likely to kill you or at least make your life miserable.
If we're so insanely flexible and efficient, why do we have the same body plan as every other tetrapod? We walk upright, but our weight is cantilevered out from a spine that is manifestly not designed for that.
I mean, not yet. The days of "let's tweak it so the blood vessels go behind the retina" or "let's add a bit more cartilage to the knees" aren't here yet, but they're probably coming eventually.
Evolution doesn't really optimize for the "keep this body running at age 100" scenarios that we find ourselves in lately, and there's a lot of legacy code.
Evolution is dumb. What dictates evolution is who survives. People wish to live 100 years old and be like 20, but that would be very complex, and eventually, humans exist as a species just fine without it, that is, the DNA keeps existing and replicating without that advantage. If conditions dictated that the humans who are young for 100 years leave more of their DNA than those who do not, then eventually that is the path we would have taken - maybe that is the path we WILL take, if conditions allow. But it's just a selfish wish. It's like saying an ant worker should live decades. Good for itself, maybe, but adds little value to the survival of the species, the job gets done as it is.
You are assuming evolution leads to the best adaptation. That's simply not true. It finds a local minimum and that's it. It's evident that a human that stays fertile and young for 100 years leaves more offspring then the current human. But the way to get there might not be continous improvement of fitness and thus evolution will never get there by itself.
It does not "lead" anywhere. It's a wandering in the wild. Some paths lead to cliffs, some will keep you going for a long time. A vast number of paths will be taken, but in any given time you only see the species - better yet, the individuals - who have not fallen off a cliff.
I like the idea of evolution, because "it is what it is". It happens whether you believe it or not. It has no goal, it just happens. And, it's not that evolution "changes" species, it's that whoever survives becomes the definition of what a species is at all, therefore "evolution" is just the observable outcome, the process is natural selection. So, it's pointless to "blame" evolution, to say "it is not good enough". I, you, we don't even know what's "Good enough" and for whom. Even whatever we consider "humanity" is the outcome of our natural selection. Your very wish to live forever, is the outcome of our natural selection.
The wish to genetically engineer our species' future members, will only be judged good or bad by its outcome, not by our planning. What you see now is what works, and the proof it works is we are still here. For example, if we end up destroying the world and our species with nuclear weapons, the path of evolution giving us intellect will have proven to be a bad one for this branch of DNA called "human species".
I can only say I have a very bad gut feeling about conscious genetic altering of humans, and I trust there are many arguments to find if I analyze it. Perhaps it's only some aspect of my DNA's self preservation not wanting to lose over some made-up DNA.
Anyway, I agree there’s ways we can improve, only disagreed with the implication that we’re running on some sort of hacked together or sloppy system. The redundancy of biology is incredible, the opposite of easy to break.
Ureters come out near the vagina, causing UTIs. Our intestines are better suited for being on all fours, leading to hernias. We eat and breathe with the same orifice, and some of us choke to death from it. Our eyes have blind spots that lead to our brains filling in details, sometimes inaccurately. Goosebumps are vestigial, men have nipples, human embryos briefly make tails and gill slits, heads are too big for the birth canal, etc. etc. etc.
If we had the technology to design a human from the ground up, we'd make a lot of fixes.
As with many hacked together and sloppy codebases, it still works, fairly well. That doesn't mean it's not hacked together and sloppy, though.
Sloppy compared to what? What would you point to as better? Where would you put the urethra, for example?
Many of your examples are contrived. Sure they have some failure modes, but they also are succeeding trillions of times a day.
I’d bet a lot of money a “human designed human” would not perform better, except for taking ideas from other humans, and only when done in very limited cases.
> Sloppy compared to what? What would you point to as better?
Sloppy compared to, say, crocodiles, which largely haven't changed in hundreds of millions of years. We humans aren't well designed for our current use cases, as we changed a whole bunch of our behaviors in the last few hundred thousand years.
> Where would you put the urethra, for example?
I'd leave that up to a biomedical engineer. Perhaps they'd rig up a system like reptiles and birds have, where the useful water gets reabsorbed and they excrete urea crystals.
> Sure they have some failure modes, but they also are succeeding trillions of times a day.
Again, this is true for spaghetti code. It is a mistake to think "spaghetti = broken". Spaghetti = hard to understand/maintain.
Won’t let me respond to you directly, but I haven’t failed to note that. I’ve never seen someone say anything positive about the reliability of spaghetti code.
> if there was ever something you'd want to redesign from the ground up, it's us.
Well god wrote all the code in like 7 days for this dump, so what did you expect? Quality?
Though I sometimes equate end times with "I'll get around to fixing that bug one day" as every supposed date of end times never comes. god really is a programmer.
Similar experience for me. I was in the worst pain of my life, suffering from a herniated disk and sciatica. I got an epidural steroid injection and the pain completely went away. I felt like I could run through walls, fortunately I didn't test that hypothesis. The relief lasted for about a week and then the pain started to come back but it was never as bad as it was before the injection. Fortunately steroid do more than just relive pain for herniated disks, they actually stimulate healing as well. But the doctor told me in no uncertain terms that this wasn't something I could do again anytime soon, it's a one-off.
Anecdotally supported advice: keep that core strengthened!
I was tweaking my back every 4-6 months (like Nearly bed ridden for a week each time for 2 years, then Last summer I started doing an hour yoga class once a week and haven’t had any problems since!
I'm asthmatic and every now and then have to do a 1-week course of Prednisone.
It really is quite amazing how it makes you feel superhuman ... but oh dear, the crash the other side is horrible.
I remember reading the side effects the first time I took it and was shocked - but it's essentially the "nuclear" option when it comes to inflammation and honestly, still one of the best things we have.
Random aside - I wish I had a tough love doctor that would tell it to me like it is, and pay close enough attention to refuse to let me do things.
I don’t even really use the term “my doctor”, I just see a doctor when I need to. I’m 30 and live in a large city, and I’ve rarely seen the same doctor more than a couple times in a row. I go in for a physical roughly once a year, and the doctor will sit and talk with me for 10 minutes or so. But otherwise if I need something checked out in between I often get seen by a PA or whatever doctor in the practice is free. I’ve never really felt encouraged by the same doctor to see them repeatedly, or to email them personally if I have a medical question like I know some people do. So when I move to a different neighborhood or something, I just end up seeing a different doctor next time.
Am I just getting bad doctors? How do you find this type of buddy doctor that becomes a long term relationship and really cares about you personally, like I hear about other people seeming to have.
It is critical to get a primary care physician you bond with, or at least can build some rapport with. My late father was a cardiovascular and thoracic surgeon, but then decided to go back to school (while teaching) to get his boards in internal medicine. He had two motivations: one was not to be the Old Surgeon that has to have his privileges revoked, and the other was his evolving relationship with the world, largely facilitated by SSRIs. His journey from surgery to internist over many years gave him what I think was a pretty good insight into the human condition.
As an internist and primary care physician, he had one patient who presented with back pain and was loaded on opiates, wanting refills plus more dope. He talked with her for almost an hour (a unique privilege most don't have in today's healthcare system, and likely none will going forward) and ended up sending her home with an SSRI and a note to check back in a little while. A few weeks later she was calling the clinic's owner raving about how she felt so much better, her back didn't hurt anymore, etc. I'm not writing that to say SSRIs > opiates, just to say in her situation he correctly identified her pain was due to depression. You don't get there unless you have rapport with your doc and the time to talk with them.
The point is that you have to find a doc you like and one that can spend time with you. Unfortunately I don't know of a good way of doing that. I'd hook you up but my dad passed some years ago. I'd love to hear people's ideas on finding someone like him — I need a doc, too.
That can be very difficult. Increasingly, physicians employ a staff of PAs and/or nurse practitioners who handle cases. Those staff seem to move around more frequently than physicians, so even if I keep going to the same office, the staff may have almost entirely changed.
This, coupled with the fact that, as an American, my ability to see a particular doctor (or even supporting staff) is highly dependent on whom I am employed with at any given time.
If you switch jobs regularly, you will likely end up on multiple insurance plans, each with their own set of participating medical professionals. Sometimes there is overlap, often there is not.
I'm going to disagree with all the other commenters so far. You are only going to find a tough love doctor if you're really, really lucky. Having a long relationship with a doctor might help with continuity of care, but the truth is there is no doctor that is going to be more invested in you than YOU.
In fact, I would recommend going to MORE doctors if you have concerns. That's why you get second and third opinions for important medical decisions.
I have high cholesterol. My father had a heart attack around 40. His father died of a heart attack. I told all my past doctors this and I have never gotten "tough love". Maybe because I have a young looking face and I'm rail thin. Maybe because I know my family history so they assume I know the risks. I put off statins in favor of trying diet and exercise unsuccessfully until I met a doctor that finally DID more forcefully suggest a statin. I should have started taking them way sooner.
A doctor is not where to find tough love or to find a friend. A doctor is where you go for expert opinions and recommendations. Inform yourself and be responsible for your own health.
> Am I just getting bad doctors? How do you find this type of buddy doctor that becomes a long term relationship and really cares about you personally, like I hear about other people seeming to have.
Doc here:
Stay in one place, go to the same guy repeatedly over time, and ideally, be really candid with them, and send them your family members. When I see half (or more) of a household, it's an entirely different dynamic. You can't buy the sort of relationship that comes of seeing someone's kids grow up, and then treating that kid. That kid is like... 5% blood relative to the doc at that point. He will never be "just a patient." Or when you treat someone and their mother - that's a different level of candor right there, because that person trusts me with their mother - that right there suggests I can be more open with them, because they won't immediately blame/hate me for news they don't like.
Time is the key, though. A lot of patients, if they get "tough love", turn around and go to a different doc. Especially the ones that say they just want to hear it straight - they are trying to convince themselves, I think. So getting to "tough love" is something that's built up over time, in both directions. (Also, studies suggest that it's somewhere between "not effective" and "actively harmful" when it comes to positively changing patient's health-related behavior, so it's not a super high priority.)
Bonus points if you go to someone that only takes cash. For a once or twice a year visit, it's not that much money (compared to, say, one month of most prescription meds), but it means they don't have to hustle you through an 8-minute visit to keep their lights on. You can only get so much of a connection with someone that's forced to hustle you out of the door - it's jarring and kind of upsetting to everyone involved, on both sides of the interaction. (When I was in training I was told pretty candidly I'd make a fantastic attending one day, if I learned to actually hustle patients fast enough to be able to afford keeping an office open. ... You can imagine, I structured my career towards cash patients only. I don't like being inaccessible to folk, but I hate it less than I hate giving people half-assed help when they're in need.)
Another good element is going to a physician that you're community-bound to in some way other than a strict transaction. Your kid's little league coach will have an entirely different relationship to you than "random doctor." That's becoming less common these days, unfortunately - with the way reimbursement is swinging, I don't know of many docs that still have time for much in the way of community activities. They exist, but they're a lot rarer than they used to be.
As someone who has glaucoma (diagnosed at the young age of 25, unfortunately, but thankfully with almost no vision loss) and also has a need for corticosteroids due to other issues... yes, this is a very fine line I sometimes have to walk. Corticosteroids exacerbate eye pressure problems that come with glaucoma, which could counter the effects of my glaucoma medications.
I had anaphylaxis after accidentally eating something with peanuts in it and went to the hospital. I was given* Decadron (brand name dexamethasone) among other things, eventually I was fine and went home later that evening.
The next day I got out of bed and pretty much fell over. I could barely stand up. Wife took me to the hospital again, it turns out I had a reaction to dexamethasone.
Definitely not something to play around with.
*I don't recall if it was a pill or an injection. Probably injected, since I had trouble swallowing.
All true, but the trade-offs here are clear. This drug is being looked at for patients who are in the hospital on oxygen or a ventilator. At that point side effects aren't very relevant since their odds of dying are somewhere between 25-40%. Anything that significantly reduces those odds is going to be worth it.
Not sure what side effects you experienced with Dexamethasone, but I can speak about my experience with Prednisone, which is a drug in the same family (glucocorticoids [1]). I was prescribed Prednisone in order to fight off a severe allergic reaction to something that was never identified (this is not an unusual scenario). It worked wonders. I would say it's at 100 to 1000 more potent than benadryl. Now, once you get on Prednisone, you become dependent. You can't just quit cold turkey. You need to taper off. I didn't know that if you try to accelerate the tapering you might experience some surprises. I was just very enthusiastic to reduce my dose. I ended up with some excruciating joint pains in the Emergency Room (or A&E, as this was happening in London). After some MRI, they concluded I have nothing, gave me an ibuprofen and discharged me. This was not a fun experience (except for seeing how many drunk people visit the ER on a weekday night in London).
While modern medicine was not able to tell me what happened with me, I created this little mental model: Prednisone was keeping my immune system in check. Without enough of it, the immune system went haywire, and I was experiencing something akin to severe acute rheumatic arthritis. Once I upped my dose, this went away. I was then very disciplined with my tapering, and eventually, after 3 more months, I got off of Prednisone. Five days from now I'll be 2 years Prednisone free.
I can speak to both. But, for me, Prednisone was the hardest to break; I took Prednisone for more than 10 years with very high doses first and slowly tampering off. It saved my life and, yes, it worked wonders. On very high doses I was on the top of the world—euphoria. But once the tampering started, that’s when the negative side effects came: sleepless, agitation, restlessness, depression, mood swings, and much more. My doctor mentioned that with its benefits she could list a side effect from A to Z. You have one year one me, but I too get to celebrate being Prednisone free.
I'm surprised that medical studies seem to happen in silos. The severity of adverse effect is well known in China during the 2003 SARS period. Dexamethasone is cheap probably due to the mass production of the drug in China in the early noughties. Before isolating the coronavirus of SARS corticosteroid drug abuse led to serious problems where patients had their lives saved but eventually disabled.
The chinese lead scientist in SARS/Covid19 is known for saving lives with these drugs (super high dose and cocktail drugs) but also warned their serious effect after the treatment. There was a huge debate of stop using them all together in favour of traditional chinese medicine (which is equally biased). Of course they save lives but you are at risk of huge comprises of the human body.
Corticosteroids are strongly contraindicated for topical application to the face, because of the risk of glaucoma.
Systemic (that is, oral/intravenous for full-body effect) corticosteroid use doesn't usually have this specific side effect.
The side-effects of corticosteroids are generally No Fun Whatosever (I speak both as a former pharmacist and as someone who has needed them on occasion) but they're the go-to treatment for some very unpleasant inflammatory conditions. But you should remember that they're immune system depressants and should never be used without medical supervision.
(Side effects range from glaucoma leading to blindness -- for misuse of topical creams on the face -- through to sudden death -- for abrupt withdrawl from prolonged systemic doses.)
Not to be over-speculative, but I think OP is probably referring to the rebound effects of corticosteroids which have been documented recently as related to skin conditions [1].
The "a skin rash I still struggle with until today" is probably skin thinning, too. Powerful steroids can permanently reduce the thickness of the skin, revealing capillaries in thin-skinned places like the face. It can look like a permanent sunburn.
While I do believe they should not have announced it in public, but this could be useful. Steroids are immunosuppressants and end up neutering the immune system. Severe cases for Corona virus ended up due to hyperactive immune system (based on various reports). Taking a steroid is good for short term when you have an auto immune disease or inflammation, swelling, but it hurts the body's capacity to fight other infections. I had RA and was given a steroid for a week. No pain whatsover, i could run, and go about my day normally. Side effects: I could not sleep, and the moment i stopped taking them, the pain returned.
Could work in short term but this seems more like a stop gap than any cure/medicine which works against the virus. This is something which would taper your immune system down so you wont have adverse effects. The potential side-effects are huge.
They aren't claiming that this cures the virus. It's purely to treat the cytokine storm that causes most covid deaths. This is for people who are already hospitalised and receiving oxygen, with the most dramatic results for those on ventilators. At that point the mortality rate is high enough that the risks of side effects are worthwhile.
The only thing this comment should used as evidence of is that taking prescription medication without a prescription - especially a steroid of all things - is idiotic. The layman has absolutely no way to tell what a small or minuscule dose actually is.
Your post needs to mention that this is for use in SEVERE COVID-19 patients; those on oxygenation and ventilation. At that level, side-effects from the steroidal pale in comparison to DYING from COVID-19.
Is this true? I have taken the strongest steroids topical, oral and by injection (undiagnosed DH) and never had any side effects except small time relieve of my symptoms that could have been fixed by a strict diet
For systemic inflammation problems (including uveitis, joint pain, and intermittent brain fog), have you experimented with probiotics, especially acidophilus (including L-92), as well as cutting gluten and other potential allergens from your diet?
The problem is that there is little more than a press announcement at this point. There are no data. There is no paper. There are no details to consider.
We've seen this movie before, and it's gone badly (remdesivir, hydroxychloroquine). Safe and effective drugs require copious details, and you'll find none of them here.
This is a very well-respected, well-known multi-arm trial 10x the size of US govt (NIAID) studies. It's 6x larger than Dr. Fauci's remdesivir study. It's highlighting a cheap, generic drug; nothing like Remdesivir.
It would be unethical to delay this announcement, especially when most hospitals are already supplied with the treatment.
We haven't seen this movie before, this is much more promising with much larger sample sizes. PLUS, this EXACT study (RECOVERY) found that HCQ was not effective for severe patients. While I believe in peer review and publication, these are Oxford University researchers using sample size of over 2000 COVID patients in the treatment arm, so it's FAR beyond "this movie before" where HCQ studies with a couple dozen patients were hyping far beyond the statistical merit.
It's simply not that effective, it has a very small treatment effect and isn't a great tool, but it's certainly much more justifiable than hydroxychloroquine, which took much of the oxygen out of the room when POTUS and the GOP hyped it FAR beyond its statistically shown merits.
As far as I can tell it is extremely common to give steroids (and dexamethasone is among the default choices) in those cases already. I can't quite tell but it doesn't sounds like it was compared to other steroids so I would hold judgement before we hear more.
At any rate, hype over initial briefly reported findings is rarely useful.
Edit: I was checking how common was it to give corticosteroids before the trial (pretty common as I suspected) but it's almost amusing that the WHO was recommending not to use it[0]. I wonder if this will be yet another miss for them.
> Edit: I was checking how common was it to give corticosteroids before the trial (pretty common as I suspected) but it's almost amusing that the WHO was recommending not to use it[0]. I wonder if this will be yet another miss for them.
So what you're saying here is that you blame the WHO for not recommending something before there was evidence for it, because now there is a study indicating effectiveness and they should have known that before the study was performed?
No, what I was saying is "I wonder if this will be yet another miss for them."
>they should have known that before the study was performed
I don't even think that's necessarily true given how common the use of corticosteroids both with COVID and in comparable situations.
It was just something that amused me and now I regret including it in my comment as it seems to distract from the main bit of information I was conveying.
"“Corticosteroid treatment should not be used for the treatment of COVID-19 -induced lung injury or shock outside of a clinical trial,” the commentary concludes."
So they're saying: don't use it until there is sufficient evidence that it works. That's not a "miss for them". It's a prudent and conservative recommendation, which is exactly the kind of recommendation they should be making.
> it's almost amusing that the WHO was recommending not to use it
Why is everyone picking on the WHO constantly? It's like it's a reflex at this point, as far as I can tell designed to shift "blame" off of... other parties who got lots of stuff wrong.
In this case you're spinning really hard. The WHO guidance you're quoting, quoted in the article you link, was really mild: "“Given lack of effectiveness and possible harm, routine corticosteroids should be avoided
unless they are indicated for another reason,” WHO authors wrote." Is that really unreasonable? In January they didn't have evidence of effectiveness, and drugs have side effects. Sounds like correct reasoning to me. Do you actually disagree?
And in any case that quote is from a document in January, the current version (from March, also linked from the article) is here, and makes a bunch of complicated points about steroid use, citing contemporary research which was inconsistent about effect: https://www.who.int/docs/default-source/coronaviruse/clinica...
Because they've made multiple avoidable bad calls.
>In this case you're spinning really hard.
'WHO was recommending not to use it' is a quick summary of statements like "routine corticosteroids should be avoided
unless they are indicated for another reason,”. How is this not a recommendation against it and 'spinning really hard'?
At any rate, I didn't dig into that part much (WHO recommendations are much much less important than medical trials), I just found it interesting enough to mention.
Note that those recommendations are made for medical professionals, and in fact that recommendation does not conflict with this study. For people with mild symptoms (not requiring oxygen nor ventilation) it doesn't change the mortality risk, so indeed it shouldn't be used as a routine drug for everyone who is COVID-19 positive. In fact, knowledge of SARS and MERS indicated that corticosteroids could be harmful, so it was absolutely the right call to make: if they aren't indicated for a certain reason, don't use them routinely for most patients.
It all comes down to politics. Some people want covid to be the "fault" of someone else. The WHO is a good target, because they did indeed have some really bad communication work in the early days of the infection:
1. They stated, more assertively than they probably should, that they believed the virus was contained in Wuhan and not spreading in the community (that's the "no human-to-human transmission" quote that gets taken out of context).
2. Their statements that people should not try to acquire PPE masks were poorly phrased and seemed to imply that masks don't work (obviously they do).
3. There was that one incident, not related to the outbreak really, where a WHO official hung up the phone rather than take questions about Taiwan (for geopolitical reasons, Taiwan is not a member of the WHO). This led to a thousand "WHO is in China's pocket" takes.
I mean, just in general the WHO has not comported themselves well here. There's been plenty of routine incompetence to complain about, and frankly they haven't really don't much to help.
But the political vitriol you hear about them is 100% blame shifting. Most of the people yelling loudest about the WHO failing to give good advice about this dangerous disease tend to argue in other contexts that the disease isn't so dangerous, we shouldn't be forced to wear masks, the economic damage is too great, liberty is at stake, etc...
Honestly I don't think it's true to say it's about politics. The WHO tweet from 14 January was very misleading and no doubt caused things to get worse:
> Preliminary investigations conducted by the Chinese authorities have found no clear evidence of human-to-human transmission of the novel #coronavirus (2019-nCoV) identified in #Wuhan, #China🇨🇳.
As far as the WHO was aware, and at the time of posting, that tweet was entirely accurate.
They're not the CIA. They don't have an adversarial spy arm. They rely enormously on member nations' self-reporting, and they rely on those reports being honest. That clear evidence came later on doesn't mean the WHO had clear evidence at the time.
(And, as the saying goes, absence of evidence isn't evidence of absence. Nothing in that tweet says "it can't spread"; it says "we can't solidly confirm it has been yet".)
Consider this imaginary scenario. Imagine a dead body is found in the street in front of your house. The dead person has multiple stab wounds, and there is a knife 20 feet away from the body.
Imagine you inform the police, but they come 2 hours later, and announce that they'll investigate the death. Then 2 days later they come and announce that they had no evidence that this was a murder. They also announced that staying in and locking your doors had shown to not stop serial killers and was counter productive.
Do you want such an investigative agency?
I would prefer if the police said something like this within 1 hours of arriving at the crime scene "the stab wound and a bloody knife indicate that this might be a murder. In order to stay safe, the residents should stay in, take precautions and lock their doors"
In case you didn't get what I referred to, there is no reason to doubt via a SARS like virus with respiratory sickness may be transmitted via air. Their default reaction should have been to assume the worst. Further, saying that travel restrictions do not stop a disease is a stupid statement to make. Specially when we see South Korea, Taiwan, Vietnam, Hong Kong, NZ etc exterminate the virus.
WHO is to blame as much as individual governments.
> Van Kerkhove added, however, that human-to-human transmission would not be surprising given the WHO’s experience with SARS, MERS and other respiratory pathogens.
> Van Kerkhove’s message was not lost on reporters. The Telegraph in Britain headlined its article on the news conference: “WHO refuses to rule out human-to-human spread in China’s mystery coronavirus outbreak.”
Within a week (Jan 20) they'd confirmed the human-to-human transmission, too.
Why was this their fault? As far as everyone was aware all the cases came from a food market, and a few days later when it was clear it was H2H they said it was.
There were some people in local Chinese government that had preliminary indications that it might have transmitted H2H, but that data propagated in under a week after the tweet and it's not the WHO job to run an intelligence agency.
But it's NOT misleading. It's correct. They (both the Chinese health care folks and the WHO thought) that all the cases were from that one market and that it wasn't spreading in the community. That's what "human-to-human transmission" means in context. (They were wrong, obviously, but that was a sincerely held belief given the evidence at the time.)
The misleading bit is to try to insist that what the WHO "meant" was something more akin to "it's not contagious, you can't catch it". NO ONE thinks a respiratory virus isn't contagious. The WHO quite clearly did not mean that. And yet we still have this argument months later because people like you steadfastly refuse to assume good faith (and bad writing) on the part of the WHO.
That, sorry, is politics. The WHO isn't your tribe, so they have to be skewered as enemies instead of interpreted as (however confuddled) people just trying to do their job under extreme time pressure and with limited information.
By the time of the tweet, it was pretty well established that there was at least familial spread (aka human to human) in Wuhan. Everyone raised at eyebrow at the tweet because it goes against all observations on the spread, even from official Chinese reports.
The WHO is clearly a very conservative and cautious organization. They won't do anything without really good studies and evidence. In this pandemic, though, this staunch stance gives a perception counter to lot of common sense and comes off as inaction.
> Van Kerkhove added, however, that human-to-human transmission would not be surprising given the WHO’s experience with SARS, MERS and other respiratory pathogens.
> Van Kerkhove’s message was not lost on reporters. The Telegraph in Britain headlined its article on the news conference: “WHO refuses to rule out human-to-human spread in China’s mystery coronavirus outbreak.”
It only took a few more days for the evidence to emerge to the WHO's satisfaction, too. Widespread attempts to justify American officials' inaction in February/March based off the Jan 14 tweet are disingenuous.
> Jan. 19 WHO tweet: “An animal source seems the most likely primary source of this novel #coronavirus (2019-nCoV) outbreak, with some limited human-to-human transmission occurring between close contacts.”
> Jan. 20 WHO tweet: “It is now very clear from the latest information that there is at least some human-to-human transmission of #nCoV2019. Infections among health care workers strengthen the evidence for this.” At the time, there were only 222 confirmed cases in the world, including four deaths.
If it was a foodborne disease that came from a food market, there could have been perceived familial spread that was really just delayed onset and not H2H.
I was personally of the opinion that it was H2H at the time, but taking a few more days and having a complete confirmation was absolutely the right thing to do, given how we wasted that time anyways. There would have been no real upside and many downsides to such a decision for everyone.
> By the time of the tweet, it was pretty well established that there was at least familial spread
That's going to need a cite.
But again, you're trying to ding them on a technicality about wording (you've just moved the goalposts from the usual "they said it wasn't contagious!" line) instead of applying what to most folks seems like the obvious interpretation.
There was legitimate concern early on that misuse of masks by the general public, along with behaviour changes caused by a false sense of security, might have a net negative effect. There's now data that this is not the case, so the recommendation has changed, but the concern wasn't crazy on the absence of data.
The potshot upthread wasn't about "giving the WHO any authority" though, it was taking an unrelated subject (corticosteroids for covid), digging an out-of-context statement, and trying to smear the WHO.
That part is politics. Talk about what they actually did wrong, don't drag them in here where they aren't relevant.
Because they are a political organization first and a medical organization second, and not a particularly effective political group either, combining the worst of bureaucracy with questionable alliance and motives.
> Because they are a political organization first and a medical organization second, and not a particularly effective political group either, combining the worst of bureaucracy with questionable alliance and motives.
Please expand with some sources if you can, because I keep hearing this as a particular political talking point, but have never seen any real backing to these claims.
Steroids are extremely double edged. If it actually is a miracle cure, it’s definitely going to be something that should be administered by doctors, not random patients.
I've seen small observational studies with positive results about other IL-6 and TNF-a inhibitors, like Remicade.
I have a particular interest in this because of Crohn's Disease - might the disease be making me high risk, and might my treatment (Entyvio, which operates differently from Remicade and its kin) help offset that anyway?
Now that the "hydroxychloroquine is dangerous" research has been retracted, does HCQ count as a 3rd treatment? Or did we never get confirmation that it was effective?
Edit: what's with the downvotes? Go look at my post history, I'm not some Russian astroturfing bot. And I got a lot of informative replies, which is why I asked in the first place.
To be even more precise, ineffective in hospitalized patients. UMN has done another study for "outpatient" (that is, not hospitalized) treatment and sent the results for review.
I'm not expecting any different results than from this one, but we'll know soon enough.
The RECOVERY study is also studying azithromycin, a drug commonly administered with HCQ when used against this disease. It would be ironic if that one proves to be effective (study is still ongoing).
I have been following both the UMN study and this Recovery Trial. I realize, in between whether HCQ prevents SARS-CoV2 and whether the same helps severe hospitalized cases, we have another question of whether it works as early treatment. The first question seem to have been well answered by Dr Boulware's team. The third one seem to also have been definitively been answered by the Recovery team. However, as yet, other than people taking sides in what has now become something of a religious war, I am yet to come across a study that definitively answers this question of whether HCQ can work when given as early treatment. Most of the Covid-19 related literature that is so far accessible seem to be of a very poor quality. But, still, I am hoping we will have properly conducted and sufficiently powered randomized control trials in due course that should answer most of these questions as well as find out a good way out of this quagmire.
It's not even clear that we don't have evidence. The study was retracted because the authors did not want to provide more details on where/how they obtained their data. Probably because they were contractually obligated not to use the data in the way that they did (they made some vague statements to that effect).
Others studies by one of the authors (Sapan Desai) whose company Surgisphere is supposed to be behind the alleged fraud are being scrutinised and even his credentials are under question now - https://www.theguardian.com/world/2020/jun/10/surgisphere-sa...
Are you referring to the retracted Lancet study or the just-breaking-news about the Oxford Recovery Trial where they were using lethal dosages of the drug? [1]
This seems to be the response to every trial that shows chloroquine and friends to be ineffective, though. "Well, of course there was no positive effect, the dose was too low." "Well, of course there was no positive effect, the dose was too high". "Well, of course there was no positive effect, you didn't tape a halibut to the patient's head". "No, not a cooked one, you fools, a live one!"
At a certain point, it's possibly worth considering that there may be no there there.
I've noticed on Derek Lowe's blog that there seems to be a definite hydroxychloroquine brigade that doesn't exist for any other purported therapy. And as you noticed, this brigade will pick apart HCQ studies for not doing X for a bajillion different varieties of X. (Not simultaneously dosing with zinc and/or azithromycin is the one that tends to be mocked the hardest on the blogs).
Before any of the studies came out, I was reading anecdotes specifically stating, "this only works with zinc". Which is not that hard to believe, from a biochemical perspective.
Apparently most or all of the studies do not include zinc. Hooray.
Here is a preprint that shows HCQ plus Zinc is effective.
My knowledge on this matter comes only from watching a few YouTube videos. From that it has seemed all along that the treatment required is HCQ + Zinc. Zinc is what stops viral replication and HCQ helps get Zinc into the cells.
So why are so many trials not using Zinc.
There may actually be a study which says what you claim, but what you've linked is a HCQ shill site, and tracing links I was not able to find a link to an actual study.
Again, there may actually be a study which says what you've claimed. I'm not anti-HCQ, I'm anti-propaganda-posing-as-science.
I'd not start dropping HCQ like candy. Beyond the retracted COVID study, it is established that there are risks associated with HCQ usage. use can lead to cardiomyopathy, prolong QT interval and trigger arrhythmia.
source: drop chloroquine cardiomyopathy into pubmed or google scholar.
I agree with you that "dangerous" isn't binary. To be clear, the medical literature I was referencing are focused on medical grade HCQ. I apologize that I was glib in my "like candy" comment. I'm reacting strongly to this topic because the current level of pop-culture medical expertise, partiuclary around HCQ and also vaccines, is concerning to me.
We've been dosing people with hydroxychloroquine for malaria for years so it would be very surprising if it suddenly turned dangerous. It's pretty clear at this point from a number of randomized trials that giving it to people who have developed Covid-19 isn't particularly useful. It's still possible that it might be useful prophylacticly, there's been some promising non-RCT studies coming out of India and at least one RCT underway, but I'm not sure I'd bet on it.
EDIT: And to be clear the Indian studies suggested you wanted to be taking it for weeks before first exposure to SARS-2.
Just because something is a useful medicine that's been given for a while doesn't mean it can't also have serious side effects, some of which could conceivably exacerbate Sars-CoV-2.
Or not, there's no evidence that it does. But a lot of medicines are "dangerous", including Plaquenil, particularly if applied for the wrong circumstance or given to people with contraindications.
> Or did we never get confirmation that it was effective?
The reverse, there's confirmation it's ineffective. It may not be dangerous (I don't know) but it's no longer allowed as treatment in the US as the evidence has shown it's not useful.
Can we stop talking about this and move on yet?
It was only ever really of interest because Trump was flailing about for anything to make it look like he had a plan earlier in the year.
No, there was interest because this was used in South Korea. Then, trump said a thing, everyone lost their minds, studies were rushed, the press lied about intermediate statistically-insignificant results, and it was a complete embarrassment to the medical community. The politicization of a medicine has been one of the stupidest things I’ve ever seen in my lifetime.
> The politicization of a medicine has been one of the stupidest things I’ve ever seen in my lifetime.
This seems to have been going on since Wakefield and the anti-vaxers; and one of the big reasons for rejecting chloroquine was exactly that it was being promoted by a whole infrastructure of dodgy quack websites. Which is undoubtedly where Trump got the idea from.
It may not be dangerous (I don't know) but it's no longer allowed as treatment in the US
This is not true. It is still allowed as a treatment, and there are still studies going on using it in the US. The FDA emergency approval has been removed, which is more of a technical status. You can no longer acquire it from the government stockpile, and it is no longer recommended.
Fair enough, as a non-American I presumed the withdrawal of approval meant something stronger than a recommendation.
Regardless, the point stands, evidence of efficacy is lacking, evidence of lack of efficacy appears to be coming in, this whole thing has turned into a political canard and is likely distracting from real progress.
All the early studies that indicated some effectiveness were basically garbage. The french study that caused most hype was flawed in multiple ways. The fact that a study showing its ineffectiveness was retracted is not evidence of the opposite.
Chloroquine (not hydroxy, good old chloro) is used in Central Asia. Death rate is pretty low (less than 10 per million), if you trust official media source of the countries in the region.
> Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).
> it was done against standard of care (so it can mean a lot of things)
This looks like a technical phrase, and the parenthesis suggests that its meaning or implications should maybe be obvious, but they aren't to me! Do you mind elaborating?
"Standard of care" basically means "whatever the current protocol to treat the disease is" (normally it means "the accepted treatment", but there isn't one yet), which can mean just trying to keep the fever down, supplementation of fluids, but also administration of drugs (with the exception of the one tested, of course).
As you can imagine, it is quite variable in what it means, because it varies across countries and occasionally even hospitals (I'm sure the RECOVERY people have taken this into account, though).
It is different from a placebo study because in that case your control is something you know is inert and "does nothing".
The title is click-bait. This and other steroids have been used by doctors against COVID-19 from the beginning. So have blood thinners, and plenty of other medications, and even radiation. From what has been gathered so far, COVID leads to an attack on the endothelial layer of your blood vessels that is responsible for clotting. That causes potentially permanent damage and if immunity doesn't last long, also potentially accumulating cardiovascular, pulmonary, and renal damage. From there COVID or the body's immune response can hit multiple organs at different times turning your life into a flimsy house of cards. Medicines for one organ can kill another (blood thinner targeting a clot in your body can and does cause a stroke, or some other issue). Just like a little push of the gas pedal or the breaks. The driver's (your doctor's) skill is far more important than a single medicine at this point.
> Assuming that when it goes through peer review it stands — and these are well-established researchers — it’s a huge breakthrough, a major breakthrough,” said Dr. Sam Parnia, a pulmonologist and associate professor of medicine at the Grossman School of Medicine at New York University.
Dex is an important part of a first aid kit for high altitude mountaineering as it's somewhat unpredictable who will be afflicted by various issues related to altitude or when.
Haven't seen the movie but it is one of the drugs prescribed for altitude sickness. Or rather, one of the ones often carried for use in life-threatening cases.
This is good news, but it doesn't change anything from a public health perspective, because:
> Of those who are admitted, most also recover but some may need oxygen or mechanical ventilation.
> And these are the high-risk patients dexamethasone appears to help.
At best this might take a little bit of pressure off the healthcare system in the treatment of the most severe cases. As others pointed, steroids are powerful/dangerous stuff so they won't be using this except in the most advanced cases.
I’m not sure if the low-dose dexamethasone treatment really is that “dangerous”, frankly. Steroids do have side-effects, but this drug is quite well-known and used frequently. Under medical supervision, and especially if the dosage is low, it seems likely it will be safe.
Definitely not nothing. My point is that this treatment, however effective, isn't effective early enough in the disease's progression such that it allows us to reduce public health response measures by any significant amount, whereas a treatment that was very effective at an earlier stage of the disease would.
Oh, yeah, definitely. Such a treatment would be a game changer, and this one is not. Still, in the absence of such a treatment, this is very nice to have.
I had idiopathic acute pericarditis several years ago with two months of anti inflammatories keeping it in check, but ultimately 3 days of low dose dexamethasone finished the job. My case was thought to be autoimmune - similar to the cytokine storm spoken of with COVID-19. Very effective and potent steroid.
It's possible there are more than 300,000 cases, since not everyone with the virus gets tested, so you can't assume 40,000/300,000 is the true death rate. There are likely many with milder symptoms who do not get tested and recover without going to the hospital, so the true death rate is lower than the confirmed deaths/confirmed cases figure.
The best estimate, based on New York data, puts the death rate at 1.4% [1]
The number of cases in the UK is likely to be underestimated by a factor of 10 because it only takes into account cases confirmed by testing, and not everyone is tested, especially not mild/asymptomatic cases. This is consistent with several other studies in various places.
There is no "death rate" metric. There is CFR (case fatality rate) and IFR (infection fatality rate). We know that there are many more infections than known cases, and serological studies point to total IFR <1%, with massive stratifications by age (<50 having extremely few fatalities, and >50 having increasing IFR every age bracket).
This drug may be a hammer, and a better tool is desirable. But finally, a hammer that may work! I am hopeful this will move us faster along the direction of normalizing.
Isn't administration of (potent) steroids the standard treatment for autoimmune reactions - what seems to happen on the extreme cases of COVID - already?
I only knew of Dexamethasone as cancer treatment. Which intuitively makes me wanna question how good of an idea this is. That said, my knowledge on medicine outside the sheer basics is practically none... I mean correct me if I'm wrong here but aren't cancer treatment drugs prone to cause severe side effects in general?
Dexamethasone is not cancer specific. It is used in cancer treatment but mostly to reduce swelling and the effects of tumors. It doesn't have the side effects of chemo. It has its own set of problems it brings with the benefits.
I know of Dexamethasone as an anti-emetic for chemotherapy. It doesn't treat cancer but treats one side-effect of chemotherapy. It seems to be so helpful such that it enables some forms of chemotherapy not possible before.
It seems weird to use a corticosteroid as an anti-emetic but I have seen with my own eyes that it is helpful.
> A total of 2104 patients were randomised to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomised to usual care alone. Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).
Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75]; p=0.14).
Based on these results, 1 death would be prevented by treatment of around 8 ventilated patients or around 25 patients requiring oxygen alone.
Given the public health importance of these results, we are now working to publish the full details as soon as possible.
Can we please stop these histrionic comments.... that was a bad human mistake, and your comment reads like you are screaming on top of your lungs to throw all the results away.
But, does it invalidate the results of this trial at all?
If these results hold (by other studies), cutting death rates by 1/3rd is a huge positive result...
> This is the RECOVERY trial. They have already likely killed patients through gross incompetence
That could be used as the dictionary definition of histrionical. "They" meaning an entire study group killed people? Well, no, actually a single doctor MIGHT have, during a single incident. You've over dramatised reality to the point of absurdity, thus histrionical.
The person responsible for the initial error is quoted in today's article. I singled him out in my comment. It takes more than one researcher to ignore a protocol calling for a dosage 3x in excess of that used by any other study, then paper over the fact that this happened.
>Well, no, actually a single doctor MIGHT have, during a single incident.
You'll find that I used the word "likely", indicating a lack of absolute certitude. This is a statistically reasonable statement based on their dismal HCQ results.
Please stick to material critique of the informational content conveyed.
UK covid handlig/research is full of grossly incompetent things. First they went for herd immunity because their flawed models predicted that it'll be okay, then they backtracked the last moment.
Then they announced that their vaccine will be ready by fall when every other respected scientist said that it'll take a year. Something if off to me with the UK academic standards in medicine.
I don’t follow British corona policy closely, but as far as I can tell, the they in those sentences, in most cases, were politicians (that also _had_ to make choices based on very much incomplete information, but that’s a different subject). You can’t blame UK academic standards for that.
The herd immunity thing was the UK’s admittedly shambolic government; scientists and the medical profession immediately raised concerns. And I don’t think anyone’s saying the Oxford candidate vaccine will actually be available and approved for mass use this year?
That assumes everything goes well, which is a big if, but seems possible. The fact we've had no bad news so far despite the advanced trials is good news.
Theirs is AZD1222, fka ChAdOx1 nCoV-19. It has goofy delivery dates for multiple markets.
We've had no bad news because it's a simple design that bets on robust immune response doing the job. It's in contractors' interest to push ferocious timetables regardless of whether this vaccine strategy is viable: if it isn't, payouts are still secured prior to evidence of this coming to light, so they don't get stuck holding the bag. If it is, they're getting to market by next flu season.
>a simple design that bets on robust immune response doing the job.
That means greater surveillance time, because so little has been established about activity thresholds that might be deemed properly immunizing. Greater reliance on strong immune response than more complex designs means greater uncertainty with respect to each step of the trials, including projecting general population results from challenge trial results.
So the bad news can't come as fast as it might for other designs. So far, the main worry has been poor activity in monkey challenge testing. But that's not enough to call "bad news" yet. https://doi.org/10.1101/2020.05.13.093195
There's no downside to proceeding with manufacturing at full speed provided the financing is secured, yes. That's what I was getting at. "Produced at no-profit" still comes with significant opportunities for contractors and liabilities if they haven't been paid yet. It would be a nightmare for a public-private partnership to fall apart with manufacturing costs left uncovered because a vaccine platform has fallen out of favor. At the scale of multinationals, even issues like brexit having been pseudo-postponed until the end of 2020 right before all of this stuff hit might have something to do with how they're trying to structure delivery timetables. It's hard to say how any particular firm structures multiple deals with billion dollar pricetags.
That's deliveries of a vaccine which may never be usable. Is there any indication that it'll actually be _approved_ by then?
Manufacture of this promising candidate in advance of full trials and approval probably isn't the craziest thing to do, but my understanding was that there was a significant risk that it would never be approved, never mind by October.
I'm in the Phase 2/3 trial for the Oxford vaccine. They really are doing everything possible to have it ready ASAP (as early as October) if they can. They are reviewing trial results in real time and have scaled the trial to many cities in the UK. They quiz us on exposure and test us for COVID weekly. But they are also clear that the vaccine might not work at all or that it might take longer to find out.
One big issue is that the rate of the virus is the community is dropping quickly in the UK. We are down to less than 1 in ~1,700 having it. So with a trial size of 10-20k people, you can see that the whole trial hangs on a single digit number of people who will be exposed, hence the constant testing to flag those people.
To increase the chances of getting a result, they have stood up a new wing of the trial in Brazil where the virus is more prevalent now.
- Shared personnel are hot on the heels of a deeply dubious result and attempted damage control that has involved an outlandish claim of misrepresentation in an interview.
- This has all the right smells so far to expect further questionable research practices.
- A press release was prioritized over a preprint, even though the authors absolutely know that readily-available drugs will be taken up as primary treatment methods as soon as this news meme spreads. They have given the research community zero time to double-check.
- Wildly sensationalist claims made to the press.
>They might have made that mistake.
This wasn't a simple mistake. Look at ice9's exploration on twitter (see [2]). The whole thing's quite damning.
While this mistake by one person may have happened, you cannot really use that to dismiss the whole trial.
Be aware that FranceSoir is not a reputable source, you could liken it to the UK's Daily Mail. And Covexit also looks like a French conspiracist website set up by Pr Raoult's fans.
Sources matter in this debate because populists across the world (and especially in France with controversial Pr. Raoult) are championing hydroxychloroquine with inexplicable passion.
It fits their conspiracist view that the truth about cheap, easily accessible treatments has been hidden so that big pharma could sell more expensive drugs (the news about dexamethasone destroys that argument)
Much like for climate change deniers, you always see the same few rogue scientists and news outlets, and I could immediately spot which side your comment was on just by looking at the links.
They were first to this scandal precisely because they are conspiracists. A website with a name like covexit is nothing I would normally link. ice9, who has been a very solid twitter-lit-reviewer on repurposing candidates for quite a while, started the discussion in the anglosphere via primary sources and these tertiary sources. That better sources hadn't covered the topic yet is unfortunate, but time waits for no one and their claims are independently verifiable.
I reviewed covexit's apologia for Raoult, including his absurd response to RECOVERY's HCQ news, before making any post with the link mentioned. The 2020-06-15 paste was imported straight from one of my social accounts. Friends there already have context spread across many months from me re: topics like HCQ and Raoult.
Today's BBC article on dex is spreading like wildfire, exactly like the HCQ meme did. It has great potential to inflict damage. Better sources had to wait.
>I could immediately spot which side your comment was on just by looking at the links.
You presume too much. I work on web archival and synthetic biology. I'm not a fanboy of celebrity doctors/medical research cranks.
Please read [2], understand it, and see if you still have a need to reply.
If this cuts deaths by 1/3rd, isn't that totally sufficient to end all lockdowns and border restrictions immediately? The death rate looks basically like the annual flu with this drug, particularly when we consider that it will just be one bad season then fairly minor from then on, when much of the population gets natural immunity.
> It cut the risk of death by a third for patients on ventilators. For those on oxygen, it cut deaths by a fifth.
That's the optimistic way of phrasing it. Let's look at the reality. From the article:
> For patients on ventilators, it cut the risk of death from 40% to 28%.
> For patients needing oxygen, it cut the risk of death from 25% to 20%
28% of patients on vents (1 in 4!) still died. 20% of patients on oxygen (1 in 5!) still died.
Another thing: this is not going to help anyone who isn't in the hospital. You could still drop dead of a heart attack or stroke while at home with a "mild" case of the virus. It could happen even if you're asymptomatic. And the people who the drug does help are still at risk for significant, possibly lifelong complications.
> The death rate looks basically like the annual flu with this drug
No, it doesn't.
> particularly when we consider that it will just be one bad season then fairly minor from then on
"One bad season" will be 1-2 million dead from the virus here in America, plus more people who die as the healthcare is overwhelmed and ceases to function.
Please stop pretending this isn't a serious disease.
Essentially, dex is usable for treating the sickest of the sick patients — those who are closest to becoming the unlucky 1% who die. If every patient who reaches that stage received it, we could potentially see the death rate drop, maybe to around .6%. Still higher than the flu by a lot. And, if every hospital is overrun with runaway infections, not everyone could even get their dex.
It's baffling that you are comparing the death rate that happened DURING A LONG LOCKDOWN with a non-lockdown annual flu death rate.. and acting like if we can drop the numbers a bit it's the same thing.
Your logic is essentially saying the lockdown did nothing to reduce deaths/infection.
That estimate wasn't particularly well-received, and the facts on the ground make it look especially dubious. NYC has has 17k deaths, for instance, mostly in April and early May. If you assume that _everyone_ in NYC has been infected, that would be an IFR of 0.2%. An antibody survey in late April found a prevalence of about 25% in New York City, which, assuming it's accurate (huge assumption, obviously) would indicate a rate of about 0.8%.
Of course not, any estimate of this number is going to be controversial because it implies that someone messed up. The "reception" from one side in an ongoing debate means precisely nothing to me.
> An antibody survey in late April found a prevalence of about 25% in New York City, which, assuming it's accurate (huge assumption, obviously)
Yes, fairly big assumption. I wonder if the seropositive numbers have changed since then?
> NYC has...
NYC has/had a lot of uncommon things that you don't mention:
- Filthy subway system with horrible ventilation that is used by almost everyone many times a week.
- Large proportion of residents living in apartment buildings with shared HVAC.
- Public health protocols which were extremely quick to hospitalize and then intubate patients (even those without positive PCR tests).
- A directive from the state government which forced nursing homes to accept COVID-positive patients.
I’m a little frustrated that all the doctors seemed to have gotten this wrong. Using steroids was completely missed and ignored as a treatment for severe patients, as I understand dexamethasone was only shown to help people on oxygen or ventilators. It seems everybody was focused on covid being a respiratory disease, when in fact it looks like it’s actually circulatory.
It was not missed. The recommendations during the first wave were to avoid corticosteroids because they were thought to be nefarious in this case. At least in Europe.
Now we switched to the opposite. Behold, medical statistics the 8th world's marvel!
It takes time to understand diseases, basically. This thing has been circulating for less than a year, and the West has only taken it seriously for a handful of months.
No, it wasn't missed. What happened was that doctors thought that steroids would suppress the immune system, and that is not what they wanted at the time. My wife is asthmatic, and she was warned not to use her daily inhaler because it was a steroid.
Now, the belief is that the cytokine storm is what we want to avoid, and by suppressing the immune system, we can avoid it. So the original conclusion was completely wrong, but that's what happens when you have a new virus. Everyone thought this was a respiratory disease, but now it's looking more like a blood disease.
Corticosteroids were recommended to reduce the body’s overreaction.
What I am wondering about is whatever happened to Ivermectin, that was so promising back in April. MERCK makes Stromectol since the 70s. Clears the entire infection in 48 hours!
Given that it was discovered in the 1950's, I don't think you're going to see a patent on the versions currently being used in clinic. Now,if someone creates a more bio-available/active functionalized variant of it, fine that might get patented. But I doubt it would have much of an impact on the suggested COVID19 treatment (and would likely be years away from market)
You can actually get patent protection on things like dosage and indications. But it's much weaker than for composition-of-matter patents and often courts rule in favor of challengers.
It would be like attempting to patent testosterone. I'm going to boldly claim that it couldn't happen. Maybe a big PR campaign could cause everyone to switch to a new version which is very expensive and has no different properties, but this drug's going nowhere.
The drug was hyper-effective. An unbelievably tiny quantity can remove any inflammation (eye, skin, hair skin rash, etc...). But the fall out and side-effects are no joke even for seemingly super minuscule doses. It was a horror story for me with horrible eye inflammation, small inflammations in different parts of the body and a skin rash I still struggle with until today. Mind you I took small localized doses and not an injection. I wasn't aware that it can travel through your skin, get into your blood and make a mess.
I think the research will need to specify potential side-effects and their probabilities. It's trade-off at the end of the day.
PS: Do not ever think of trying it without medical advice and doctor supervision.
[1]: https://en.wikipedia.org/wiki/Dexamethasone#Adverse_effects