Metamizole is an amazing drug, I'm always grateful that I work and live in an area where it is available.
But it is not a miracle drug. Metamizole-induced agranulocytosis absolutely exists, and the insidious thing is that you don't know in advance if you will get it or not. You're trading common but avoidable side effects (ibuprofen, APAP/paracetamol) for rare but unavoidable ones (metamizole).
I've seen patients with severe side effects of all three classes of non-opioid painkillers (severe GI bleeds from ibuprofen-induced ulcers; acute liver failure from APAP overdose; metamizole-induced neutropenic fever). None of them seemed very pleasant. But if I had to choose, I'd still use APAP first line because it's the only one where you can avoid the severe side effect with certainty, by simply staying under the recommended maximum intake.
Sorry if this is too specific/personal, but I've been wondering, why does the treatment timeline include antibiotics (dalbavancin)? Does dalbavancin have any suspected antitumor effects, or was it simply to treat complications of surgery / catheter infections?
(edit: actually now that I checked the treatment timeline again it seems to be gone now. It was there 2 weeks ago!)
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.
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.
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.
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.
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.
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.
I feel like you could do even better than chilies/ginger for replicating the burn. The burn from chilies feels completely different than the burn from alcohol, because ethanol is much more volatile than capsaicin. Plausibly, using a more volatile TRPV1 agonist such as allyl isothiocyanate (from horseradish/mustard) would produce an even closer effect.
I wish there was a version of this for proportional fonts as well. I never use monospace fonts for coding anymore if I can avoid it, but I'm still in search of the “perfect” proportional coding font.
> I’ve always liked blogging about calendrical things, but I don’t remember doing anything on the Metonic cycle before. If I had written faster, I could’ve published it on Friday the 13th. Too bad.
On the other hand, you published it during a full moon. That's at least slightly appropriate given the subject matter :)
The “invisible symbols” are necessary to correctly represent human language. For instance, one of the most infamous Unicode control characters — the right-to-left override — is required to correctly encode mixed Latin and Hebrew text [1], which are both scripts that you mentioned. Besides, ASCII has control characters as well.
The “colorful icons” are not part of Unicode. Emoji are just characters like any other. There is a convention that applications should display them as little coloured images, but this convention has evolved on its own.
If you say that Unicode is too expansive, you would have to make a decision to exclude certain types of human communication from being encodable. In my opinion, including everything without discrimination is much preferable here.
But it is not a miracle drug. Metamizole-induced agranulocytosis absolutely exists, and the insidious thing is that you don't know in advance if you will get it or not. You're trading common but avoidable side effects (ibuprofen, APAP/paracetamol) for rare but unavoidable ones (metamizole).
I've seen patients with severe side effects of all three classes of non-opioid painkillers (severe GI bleeds from ibuprofen-induced ulcers; acute liver failure from APAP overdose; metamizole-induced neutropenic fever). None of them seemed very pleasant. But if I had to choose, I'd still use APAP first line because it's the only one where you can avoid the severe side effect with certainty, by simply staying under the recommended maximum intake.