Cysteine proteases are named after their reaction mechanism, which involves a key cysteine residue within the enzyme. It doesn't have anything to do with the amino acids in the cleaved proteins.
The problem is that N-acetylcysteine tastes and smells awful (like farts/rotten eggs) and often causes nausea and vomiting as a side effect.
The vast majority of people use acetaminophen in a safe way, and acetaminophen doesn't really have many side effects by itself, so you'd make life more unpleasant for a large number of people in order to prevent a tiny number of acute poisonings.
Probably if this were implemented, most acetaminophen users would switch to e.g. ibuprofen which is less acutely toxic in overdose but has much more chronic toxicity (to the stomach and the kidneys) when used over a long period of time, even at a normal dose. I'd wager this change might even be a net negative on the whole.
Experiences may vary; I’ve tasted and smelled NAC.
The smell is reminescent of a high-potency cannabis strain. (Sulfur-containing molecules.)
The taste is very acidic and a bit astringent.
Generally the smell and taste of something isn’t a concern with medication. I don’t think acetaminophen tastes great.
I’ve never encountered or seen the digestive issues that are often mentioned. I’ve seen other side effects which were noticeable – mast cell and histamine related I believe, kind of weird ones, like psoriasis kind of drying out a bit and the skin on the lips “refreshing” itself. (Really!) Subtle side effects and hard to put into words without making them seem bigger and weirder than they are, but NAC can nonetheless be a sort of histamine and mast cell “flusher”, so to speak and as it seems. Beneficial in the long run imo ime, but tricky to package universally.
Still, NAC is also tragically unknown and unused! There’s tons of fascinating literature on it. They fried rats’ brains with methamphetamine and fixed them with NAC; Brutal study, intriguing results on very significant mechanisms.
I take NAC to help with hangovers, I used to get smashing headaches and people would recommend random Korean and japanese 'hangover supplements', I was obviously very skeptical and googled every ingredient to check it is safe. The ones that worked had NAC or gluthanione. Looked into it and bought some and always take it when I drink or have panadol. Have not noticed any other subjective effects
Nausea or vomitting is rare, I imagine if it were common those hangover cure sellers would go out of business
Interesting!, thanks! NAC is all over the place; I didn’t know about this application.
And yeah I was 100% skeptical too!
Now I’m more sceptical of the kinda “nothing is known, nothing is knowable” angle, you know? There is so much knowledge, actionable, often unread, often unused.
(Have to mention it, if useful: Na—R-ALA (alpha lipoic acid) and ambroxol are kind of in the same vein. Ambroxol is strangely a sort of bromine counterpart to NAC and its sulfur atom. Sold as a mucolytic but is… alllll over the place. Funny
how mucus, mucous membranes, the nervous system, and oxidation/redox stuff is all so adjacent it seems.
I have no idea why but after a severe period of stress, I happened to take Na-R-ALA as sometimes do and 60mg of ambroxol as mucolytic cough syrup. For a cough. And… the feeling was like in the movies where they stab someone with a giant syringe to revive them. Trainspotting or Pulp Fiction or whatever. I felt like I gasp-crawled out of a pit inside myself. It makes no sense. It was… a very distinct experience. And it didn’t seem like an airway clearance thing, more like my nervous system was refreshed.
So I hit the books. And it turns out ambroxol crosses the blood-brain barrier and is an antioxidant, and affects ion balance in neurons, and there are studies indicating it helps with… Parkinson’s and fibromyalgia (!!!). And those papers are pretty interesting and appear to be constructed on solid molecular biological premises.
That's interesting I took r-ALA before, cannot recall dosage but felt nothing of that sort or subjective/psychoactive at all. Several people I know report acute changes too when taking lion's mane but I don't
As a detail, I clearly experience the better bioavailability of Na-R-ALA. Often marketed as “stabilized”. As well as what I believe is the increased bioavailability of Na-R-ALA dissolved in water.
The main point I wanted to make is that it occurred to me when reading your comment that I know myself to be somewhat “oxidatively burdened”, if that’s a term? I have mild psoriasis, which is known to use oxidative and redox capacity in the immune system’s activation in the rash. (afaik immune cells “fire bullets” of oxidization at perceived intruders.) There are other stressors in my life which are also inherently oxidising in the molecular biology of it. I’d bet a nice bottle of Oban that that is a factor in the sense of relief.
There's a myriad of other ones as well, they all have similar UIs, with the primary goals being to never hide any important info from the user, and to let the user take important actions quickly. That naturally leads to high density. Nevertheless it needs to be reasonably intuitive, since doctors and nurses tend to not be very tech-savvy, which leads to some interesting design constraints.
I worked as an EMR consultant for a few years, helping teach medical staff to use these things. The thing that struck me was that while some of the UIs look "outdated" by web standards, the software often did a great of taking medical staff through their daily workflows. I feel like a lot of websites do the opposite - they look nice, but using them is a pain.
(Conversely, most staff hated new EMRs, because it enforced doing things the hospital wants its staff to do for liability and billing, but the staff doesn't want to do - for example, asking Maternity nurses to talk to new mothers about smoking cessation.)
My mom builds EMR workflows for a major hospital and my father and sister are doctors (both very tech savvy--my sister has a computational bio background for her Bachelor's prior to her MD).
None of them have anything good to say about Epic.
They are infamous for being trash and difficult to use though. There's an entire field of "EMR consultants". It's also why there's a EMR startup on hacker news every other week.
The outcome can vary wildly, even in the same EMR software, depending on the implementing team. I worked a place where it was the implementation team's first time, but they listened heavily to requests from different departments. The most common request was to reduce the number of different views and screens, compared to the old custom software that was being replaced. Resizable fonts without having to change screen resolutions was another one.Staff also wanted to keep the rest as much the same as possible, but add a few little things here and there..
The new EMR software was highly configurable, so lots of this happened. Staff teams signed off on it, and had training from the implementation team.
Fewer screens? Check! …Wellll, sorta: some very long scrolling views…which didn't play nice with mousewheels. It would seem like the page randomly and mysteriously stoppe scrolling, then suddenly scroll normally. There were lots of weird data entry errors, from all staff, regardless of prior reputation for accuracy. They were just getting used to new software, right? Nope. I tracked this down to the dropdown lists scattered on the long scrolling pages. As a page scrolled, random lists ate scroll events, changed the list item to either the first or last item, then permitted scrolling to continue.
Fonts worked mostly great…except some of the typefaces follow the should-be-criminal design of allowing various characters to to look identical. Font sizing worked as expected. I think Pre-cert desk liked Candara, for the way numbers stood out.
Notes fields…these were our downfall, sometimes multiple times per day. Anything put into them was inserted as raw text into SQL:
Patient said xxxxxxx -- ESR
…or…
something-something 'quoted thing'
…would mean the database locked up, no exams savable or queryable, no patient intake, no checkout until I.T. admin could fix it. The implementation team was gone, and non-responsive, so sticky notes with a list of forbidden characters seemed to be everywhere.
I believe some contracts for referrals were lost, due to delays and errors. Some staff quit, after months of no fixes. But I later heard from one of the most affected staffers that the same EMR software was installed at our biggest competitor, and no issues at all.
Reading about this process always makes me wonder: in a particular round, was an elector allowed to choose someone who had already been chosen in a previous round? And if yes, to what extent was this done in practice?
Depending on this detail, the character of this election process changes completely, since if repeats are allowed, it could easily degenerate into an oligarchy of ~50 people consistently choosing candidates from among their ranks.
Eh, there will be a lot they don't agree on, but they could very easily agree on lots of stuff that's detrimental to the populace, i.e. mainly agree on who gets the spoils of exploiting the government. That's plenty to incentivize them to limit their competition to just each other.
No, they could not agree on who gets the 'spoils of exploiting the government', because (a) the whole concept is mostly fictional narrativizing, and (b) neither one person getting something, nor everyone splitting something equally, is something fifty important people can agree on, and the exact percentage split could be bickered over for a decade.
To be clear, I meant to say "mainly disagree on who gets the spoils" etc, but didn't notice until too late. (that might sound like a lame excuse, but I agree it obviously doesn't make sense as written.) We seem to be in vague agreement on that mechanic. But I think it's pretty plausible that an oligarchy would agree on keeping access to the pie, even as they fight over the size of their slices. Which, in the original context of designing a voting system, is a very relevant concern.
It wasn't clear at all to me that the peg doesn't need to overlap the holes perfectly, I was almost ready to give up at lvl 2! Thank you for the solution
It's definitely widely used in Germany, where I work. I don't know how common it is in the US, though.
I often think about what makes medicine so different from aviation and your other examples, culture-wise. It's not like there's no safety culture at all in medicine, but clearly these kinds of structures are deployed to a much lower extent.
One major reason might be the far larger diversity of possible situations in medicine. It's possible to make a checklist for surgical safety because every surgery is similar, same to how every plane flight is similar. But if I think about, for example, harm due to adverse effects from medications, or missed abnormal values in blood tests, it feels very difficult to create a checklist to prevent those that would be specific enough to be useful, but also general enough to capture all important situations these might arise in.
In this sense, I think certain “low-hanging fruit” of safety culture improvements have already been captured in medicine. Apart from surgical safety, I can think of check lists for chemotherapy administration, for blood transfusions, for management of a severe allergic reaction, and other specific individual things. Pointing and vocalizing is also done in surgery, albeit in a less formal way. “Two sets of eyes” policies exist in e.g. pathology for more certainty in diagnosis of cancer.
Nevertheless there is clearly room to improve, as evidenced by the continuing occurrence of “never events” such as retained foreign bodies in surgery. There are certainly economic factors at play here as well: unlike in the free market, in the medical system there is often very little economic incentive for quality, and the same principle I mentioned before — of the immense diversity of possible situations — makes top-down regulation very tricky.
Maybe part of it is also that the potential harm from a retained foreign body is much lower than the potential harm from a plane crash. And maybe medical care is so much more common than plane flights that by base rate alone, mistakes in the former will be much more common. Yet I still think there is much that can be done, and I am unsure what exactly is preventing that from happening.
> One major reason might be the far larger diversity of possible situations in medicine
Yes but the major is the number of deaths. An incompetent surgeon can kill at most one person at a time. Besides, variance in surgery is much higher than in aviation.
Once drugs lose patent protection, it's difficult for them to gain approval for new indications, because drug approval procedures are extremely expensive and there's no patent holder left for whom it would make economic sense to spend all that money.
So in cases like valproate for migraine, those drugs usually stay off-label long term. That makes them unattractive for doctors to prescribe, since they assume more liability if something goes wrong, and insurance companies are less likely to cover the drugs.
The way information about off-label uses gets communicated is basically the same way as elsewhere in science: through scientific papers, conferences, textbooks, and the like. A doctor who discovers that their migraine patient does well on valproate might publish this as a case report. If there are many such reports, someone might do a randomized trial. Once there are many randomized trials, meta-analyses can be performed, and eventually, the information will end up in textbooks and medical school curricula.
It takes a certain amount of agency for a doctor to stay up to date on the latest research; while medical boards tend to have certification requirements for CME (continuing medical education), these are usually quite lax, and a truly lazy doctor can probably just live their years without really learning anything new.
At the same time, reading all new research that comes out is basically impossible, and even just trying to do this would risk always following the latest fads that later evidence might show to, in fact, be harmful. Every doctor needs to find their own middle ground here, and you as a patient must find a doctor that suits your own preferences.
> Once drugs lose patent protection, it's difficult for them to gain approval for new indications, because drug approval procedures are extremely expensive and there's no patent holder left for whom it would make economic sense to spend all that money.
This is precisely why I think a gov't run research effort is the right way to handle this. You don't want to grant a new patent on the existing drug just because of new use of it. That would prevent the generics being used for the original purpose. So if the bigPharma company that created it for original purposes does not want to spend money researching alternate uses, then allow the gov't direct the research in the name of keeping its citizens healthy.
Unfortunately, that doesn't really stand up as a great solution with using the current administration as an example of what happens when you get anti-science mindsets in charge of things. It also helps to have a gov't that is empathetic for its citizens which does not always happen.
Yes, in fact, most of the types of research I mentioned, where random people at hospitals do small trials on existing medications, is going to be partially government funded.
But care must be taken to avoid the tulip subsidies problem [1]: the barriers to drug approval are regulatory, not natural. If a drug regulatory agency sets high requirements for approval and another governmental agency must do expensive work to satisfy these requirements, there is a risk that costs go out of control without any real benefit.
Instead, my favoured solution would be to significantly relax regulatory requirements in cases like this where a drug has already been proven to be safe both in the original approval trials and in years of real-world use, such that when trials and meta-analyses exist that suffice to convince the medical establishment of a drug's safety and efficacy for a new indication, these would also be enough for the drug to gain approval for that indication.
I wonder if some sort of coalition of compounding pharmacists might be up for making and retaining a repository. They at least make some money by helping would-be patients take these drugs, right? So even if it's nothing like Big Pharma money, I can't really think of anybody who'd have a better chance to benefit from promoting off-label use cases for out of patent drugs than them.
If Mozilla really is as shady about user data as some people think they've become, someone's about to be pretty confused about why they suddenly have hundreds of nearly-identical screenshots of this HN page on their servers
> Prof. Dr. Melanie Volkamer is a full professor at KIT in the Department of Economics and Management. She leads the SECUSO research group.