The Nonlinear Library: LessWrong LW - Do you believe in hundred dollar bills lying on the ground? Consider humming by Elizabeth
May 16, 2024
09:30
Link to original article
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Do you believe in hundred dollar bills lying on the ground? Consider humming, published by Elizabeth on May 16, 2024 on LessWrong.
Introduction
[Reminder: I am an internet weirdo with no medical credentials]
A few months ago, I published some crude estimates of the power of nitric oxide nasal spray to hasten recovery from illness, and speculated about what it could do prophylactically. While working on that piece a nice man on Twitter alerted me to the fact that humming produces lots of nasal nitric oxide. This post is my very crude model of what kind of anti-viral gains we could expect from humming.
I've encoded my model at Guesstimate. The results are pretty favorable (average estimated impact of 66% reduction in severity of illness), but extremely sensitive to my made-up numbers. Efficacy estimates go from ~0 to ~95%, depending on how you feel about publication bias, what percent of Enovid's impact can be credited to nitric oxide, and humming's relative effect. Given how
made up speculative some of these numbers are, I strongly encourage you to
make up speculate some numbers of your own and test them out in the guesstimate model.
If you want to know how nitric oxide reduces disease, check out my original post.
Math
Estimating the impact of Enovid
I originally estimated the (unadjusted) efficacy of nitric oxide nasal sprays after diagnosis at 90% overall reduction in illness, killing ~50% of viral particles per application. Enovid has three mechanisms of action. Of the papers I looked at in that post, one mentioned two of the three (including nitric oxide) a second mechanism but not the third, and the other only mentioned nitric oxide.
So how much of theat estimated efficacy is due to nitric oxide alone? I don't know, so I put a term in the guesstimate with a very wide range. I set the lower bound to (one of three mechanisms) to 1 (if all effect was due to NO).
There's also the question of how accurate the studies I read are. There are only two, they're fairly small, and they're both funded by Enovid's manufacturer. One might reasonably guess that their numbers are an overestimate. I put another fudge factor in for publication bias, ranging from 0.01 (spray is useless) to 1 (published estimate is accurate).
How much nitric oxide does Enovid release?
This RCT registration uses a nitric oxide nasal spray (and mentions no other mechanisms). They don't give a brand name but it's funded by the company that produces Enovid. In this study, each application delivers 0.56 mL of nitric oxide releasing solution (NORS) (this is the same dose you get from commercial Enovid), which delivers "0.11ppm [NO]*hrs".
There's a few things that confusing phrase could mean:
The solution keeps producing 0.11ppm NO for several hours (very unlikely).
The application produces 0.88ppm NO almost immediately (0.11*8, where 8 hours is the inter-application interval), which quickly reacts to form some other molecule. This is my guess, and what I'll use going forward. It won't turn out to matter much.
Some weirder thing.
How much nitric oxide does humming move into the nose?
Here we have much more solid numbers. NO concentration is easy to measure. Individuals vary of course, but on average humming increases NO concentration in the nose by 15x-20x. Given baseline levels of (on average) 0.14ppm in women and 0.18ppm in men, this works out to a 1.96-3.42 ppm increase. More than twice what Enovid manages.
The dominant model is that the new NO in the nose is borrowed from the sinuses rather than being newly generated. Even if this is true I don't think it matters; sinus concentrations are 100x higher than the nose's and replenish quickly.
Estimating the impact of humming
As far as I can find, there are no published studies on humming as an antimicrobial intervention. There is lots of circumstantial evid...
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Do you believe in hundred dollar bills lying on the ground? Consider humming, published by Elizabeth on May 16, 2024 on LessWrong.
Introduction
[Reminder: I am an internet weirdo with no medical credentials]
A few months ago, I published some crude estimates of the power of nitric oxide nasal spray to hasten recovery from illness, and speculated about what it could do prophylactically. While working on that piece a nice man on Twitter alerted me to the fact that humming produces lots of nasal nitric oxide. This post is my very crude model of what kind of anti-viral gains we could expect from humming.
I've encoded my model at Guesstimate. The results are pretty favorable (average estimated impact of 66% reduction in severity of illness), but extremely sensitive to my made-up numbers. Efficacy estimates go from ~0 to ~95%, depending on how you feel about publication bias, what percent of Enovid's impact can be credited to nitric oxide, and humming's relative effect. Given how
made up speculative some of these numbers are, I strongly encourage you to
make up speculate some numbers of your own and test them out in the guesstimate model.
If you want to know how nitric oxide reduces disease, check out my original post.
Math
Estimating the impact of Enovid
I originally estimated the (unadjusted) efficacy of nitric oxide nasal sprays after diagnosis at 90% overall reduction in illness, killing ~50% of viral particles per application. Enovid has three mechanisms of action. Of the papers I looked at in that post, one mentioned two of the three (including nitric oxide) a second mechanism but not the third, and the other only mentioned nitric oxide.
So how much of theat estimated efficacy is due to nitric oxide alone? I don't know, so I put a term in the guesstimate with a very wide range. I set the lower bound to (one of three mechanisms) to 1 (if all effect was due to NO).
There's also the question of how accurate the studies I read are. There are only two, they're fairly small, and they're both funded by Enovid's manufacturer. One might reasonably guess that their numbers are an overestimate. I put another fudge factor in for publication bias, ranging from 0.01 (spray is useless) to 1 (published estimate is accurate).
How much nitric oxide does Enovid release?
This RCT registration uses a nitric oxide nasal spray (and mentions no other mechanisms). They don't give a brand name but it's funded by the company that produces Enovid. In this study, each application delivers 0.56 mL of nitric oxide releasing solution (NORS) (this is the same dose you get from commercial Enovid), which delivers "0.11ppm [NO]*hrs".
There's a few things that confusing phrase could mean:
The solution keeps producing 0.11ppm NO for several hours (very unlikely).
The application produces 0.88ppm NO almost immediately (0.11*8, where 8 hours is the inter-application interval), which quickly reacts to form some other molecule. This is my guess, and what I'll use going forward. It won't turn out to matter much.
Some weirder thing.
How much nitric oxide does humming move into the nose?
Here we have much more solid numbers. NO concentration is easy to measure. Individuals vary of course, but on average humming increases NO concentration in the nose by 15x-20x. Given baseline levels of (on average) 0.14ppm in women and 0.18ppm in men, this works out to a 1.96-3.42 ppm increase. More than twice what Enovid manages.
The dominant model is that the new NO in the nose is borrowed from the sinuses rather than being newly generated. Even if this is true I don't think it matters; sinus concentrations are 100x higher than the nose's and replenish quickly.
Estimating the impact of humming
As far as I can find, there are no published studies on humming as an antimicrobial intervention. There is lots of circumstantial evid...