7 ms·

There seems to be an assumption underlying medicine that things must be true at the population level for them to also be true at the individual level. I think m

There seems to be an assumption underlying medicine that things must be true at the population level for them to also be true at the individual level. I think medicine is picking its populations wrong. Example: the skeptical doctor in the article notes that "strep infection is extremely common in children, accounting for as many as a third of all sore throats—but you don’t see droves of kids with abnormal behavior crowding emergency departments and psychiatric clinics in late winter and early spring." But what if a more complex chain of events, or a genetic or immunological abnormality, is necessary to go from strep -> psychiatric episode? Meaning that there might be a very small sub-population of children for whom strep has a chance of causing these symptoms. I also see this thinking erroneously applied to other psychiatric disorders like depression. Antidepressants seem to help some people, and not help some other people. Averaged over the entire population, they appear to have a mild positive effect. But there could easily be multiple causes of depressive symptoms, based on genetics, diet, behavior, drug use, and past trauma. Why do we take it as a given that antidepressants should help all of these sub-populations equally? To take it to an extreme, there are many causes of blindness. Giving vitamin A to someone who lost his eyes in a car crash will clearly not help, even though vitamin A can "cure" blindness in some people. If we ran a double blind trial of vitamin A as a cure for blindness, it would almost certainly fail at the population level because blindness caused by vitamin A deficiency is a very small sub-population of all blind people.

nappy 5y ago
This is a well understood concept in medicine, and a central part of the drug approval process.
- Pyramus 5y ago
  Yes and no. Yes, obviously the drug development process is very complex and a lot of thought goes into interactions at the N=1 level. However, we are hardly at the point where drugs are developed for individuals, based on their genetic makeup. The best we can do (with exceptions) is design drugs for women/men, and this is a very recent development. In addition, per definition, a drug can only be effective/safe at the population level. To make a very simple example, we think caffeine sensitivity has two distinct high/low genotypes. As a result, all recommendations of caffeine consumption will either be too high or too low.
- AnthonBerg 5y ago
  It can be witnessed as a central part of the drug approval process, certainly. However, sometimes the lack of this perspective can also be noticed during the interpretation of scientific results. The perspective is not consistently part of the discourse.
jdthedisciple 5y ago
I agree with you and I'd even go as far as to say the same applies to novel vaccines or mRNA gene therapies: Yes, those may be effective for most people, but for others with certain preconditions, these may prove to be detrimental. In fact, we have seen this happen, such as increasing numbers of myocarditis in young males after getting their biontech shot. Point being, a little scepticism and reluctance in taking new stuff like that is always warranted and noone should be ostracised for that.
- joshuaissac 5y ago
  mRNA vaccines are not gene therapies. https://www.genomicseducation.hee.nhs.uk/blog/why-mrna-vaccines-arent-gene-therapies/ https://www.genomicseducation.hee.nhs.uk/blog/why-mrna-vacci...
  - jdthedisciple 5y ago
    Depending on the definition, they are or aren't. There seems to be a disagreement. https://www.google.com/amp/s/www.swfinstitute.org/news/83947/covid-mrna-vaccines-are-a-form-of-gene-therapy/amp https://www.google.com/amp/s/www.swfinstitute.org/news/83947...
    - creativenolo 5y ago
      The NHS article states "The mRNA from the vaccines does not enter the cell nucleus or interact with the DNA at all, so it does not constitute gene therapy." The article you have posted explains what gene therapy is confidently, but it doesn't explain, or reference particularly well, why an mRNA would be considered gene therapy or why it would alter genes.
      - AnthonBerg 5y ago
        We should strive to take jthedisciple’s comments at face value, and literally. From there we will arrive at a charitable interpretation. Here is an example where Harvard Stem Cell Institute discusses mRNA therapy as gene therapy: https://hsci.harvard.edu/translation/what-are-drugs-4-gene-therapies https://hsci.harvard.edu/translation/what-are-drugs-4-gene-t... The Wikipedia entry on gene therapy discusses mRNA therapy under the Non-viral section: https://en.wikipedia.org/wiki/Gene_therapy https://en.wikipedia.org/wiki/Gene_therapy – “BioNTech, Moderna Therapeutics and CureVac focus on delivery of mRNA payloads, which are necessarily non-viral delivery problems.” Indeed the mRNA vaccines carry a genetic payload – a segment of viral genome which is modified using a genetic perspective and from a position of genomic understanding. mRNA is a temporary and deliberately non-permanent message carrier substrate; Here too, humanity’s employment of such facts can be interpreted as scientific knowledge of the matters of the genes. If we choose to call mRNA vaccines gene therapy – which they are less clearly than other techniques – then it is certainly the better gene therapy for purposefully avoiding permanent alteration of the genome in the subject to be treated.
viraptor 5y ago
> Why do we take it as a given that antidepressants should help all of these sub-populations equally? Do we? Antidepressants are a whole class of things. We've got a few options, which indicates we don't expect equal effects. Same with painkillers. Same with statins. Same with migraine medication. These work for the similar problems but depending on the person you will use different one. Sometimes you'll even just cycle through them if you don't see the effect of the previous one. I think you're starting with a wrong assumption there.
- midjji 5y ago
  We dont, but we act like we do - Most doctors will try SSRI first despite most knowing they only work for about a third and most doctors will refuse to treat depression using non SSRI antidepressant medication.
  - nradov 5y ago
    Doctors usually try SSRIs first because they are inexpensive, well tolerated in most patients, and often effective. If the patient doesn't respond then most doctors are willing to try alternatives.
    - atatatat 5y ago
      In my experience, the patient can seem content because their outbursts of whatever kind have decreased in regularity, and they're more neutral on...everything. It also seems to disconnect them from some portion of mental model creation (as in, learning and understanding day to day inputs), lowering overall executive function, causing some to slowly spiral into disorganization, perhaps bad habits, perhaps general nihilistic tendencies, without realizing it — especially those who have been prescribed these and have nobody to objectively weigh how the med is striking them, and assist with coming to the correct dosage.
    - midjji 5y ago
      SSRI have severe sideffects, but mostly of the kind that doctors strangely seem to think of as harmless, such as the well known and quite common loss of sexual interest, which kills quite a few relationships. Even worse there is growing evidence that it occasionally causes a permanent reduction or loss of sex drive. The group who self identify as asexual have almost all been prescribed SSRI as young teens, and this might well be causation, not correlation. After all, if you got SSRI as a kid and then never felt your sex drive before it was permanently lost, how would you know? SSRI are almost mostly ineffective, with roughly 70% not responding at all. They were however heavily marketed as the patented, and very expensive prosac for decades and more importantly while they occasionally treat depression, they feel bad to use and are never used recreationally, and thus avoided the moralizing around drugs. Not to say the marketing wasn't needed, people were highly sceptical of using chemicals to treat depression, especially as people occasionally melted from serotonin storm before they figured out dosages and cross interactions. Doctors are restrictive in which alternatives they try, not because they are afraid of side effects, but because off label use requires personal responsibility, and is often against policy one way or other. Good alternative treatments include hallucinogens, in particular ketamine and peyote in large single dose treatments when not taken in a clinical setting but with friends. These have long been avoided despite good evidence they work astonishingly well for depression. This is partly because of the war on drugs propaganda and moralizing, but mostly because these hallucinogens cannot be patented, meaning its not worth the price for the large manufacturers to do the marketing to overcome the anti drugs propaganda. Its not random chance that they are currently trying chiral variants, partial ingredients and various anti hallucinogens and treatment schedule combinations of these, despite all evidence so far indicating its all worse than the well studied plain unpatentable medicine. Another example is Amphetamines which in typical doses prescribed to children with adhd treat the primary observable downside of depression i.e. low energy, low focus, loss of work, reduced activity, etc. Unsurprisingly, the subgroup of depressives which respond well to exercise roughly a third, respond very well to treatment with amphetamines. As anyone who ever considered maybe working out, but not really wanting to, and then took amphetamines will tell you. With amphetamines, its almost certainly not a direct treatment of the depression, rather it facilitates changing habits in such a way that a common pathway out of depression is more likely to be taken. They have a significantly increased likelihood of suicides compared to hallucinogens, but the effect is comparable to that of SSRI. The main sideeffect of therapeutic/low doses of amphetamines is weight loss, a mostly desired outcome. So excluding people with easily tested for heart problems and trivial to identify anorectics, why not try it... Well its war on drugs propaganda again... Doctors have a nasty habit of thinking they should make the judgement regarding the tradeoff between various treatment, instead of presenting the options to the patient and letting them decide. But the real problem is idiotic moralizing around "drugs :O".
klmr 5y ago
> There seems to be an assumption underlying medicine that things must be true at the population level for them to also be true at the individual level. That really isn’t true: medicine as a field does not have this assumption, and rare disease research is a thing (and it’s commonly acknowledged that “rare diseases”, taken together, aren’t rare at all). In fact, rare disease research is providing acute clinical diagnosis and sometimes cures for highly individual cases. Personalised medicine is probably the fastest growing subfield in medical research. Your example of antidepressants underlines this: it’s in fact widely acknowledged that, while antidepressants on average only have a very mild effect, they can be very effective (or, conversely, not effective at all) for an individual, and they are actively prescribed with this in mind. Contrary to what you’ve claimed, no expert assumes that antidepressants have a uniform effect across subpopulations. However, treating each disease as a completely individual case just isn’t feasible at scale, and is usually also not appropriate. So the first anamnesis will always focus on common diseases, and rightly so.

nappy 5y ago

This is a well understood concept in medicine, and a central part of the drug approval process.

Pyramus 5y ago
Yes and no. Yes, obviously the drug development process is very complex and a lot of thought goes into interactions at the N=1 level. However, we are hardly at the point where drugs are developed for individuals, based on their genetic makeup. The best we can do (with exceptions) is design drugs for women/men, and this is a very recent development. In addition, per definition, a drug can only be effective/safe at the population level. To make a very simple example, we think caffeine sensitivity has two distinct high/low genotypes. As a result, all recommendations of caffeine consumption will either be too high or too low.
AnthonBerg 5y ago
It can be witnessed as a central part of the drug approval process, certainly. However, sometimes the lack of this perspective can also be noticed during the interpretation of scientific results. The perspective is not consistently part of the discourse.

jdthedisciple 5y ago

I agree with you and I'd even go as far as to say the same applies to novel vaccines or mRNA gene therapies: Yes, those may be effective for most people, but for others with certain preconditions, these may prove to be detrimental. In fact, we have seen this happen, such as increasing numbers of myocarditis in young males after getting their biontech shot. Point being, a little scepticism and reluctance in taking new stuff like that is always warranted and noone should be ostracised for that.

joshuaissac 5y ago
mRNA vaccines are not gene therapies. https://www.genomicseducation.hee.nhs.uk/blog/why-mrna-vaccines-arent-gene-therapies/ https://www.genomicseducation.hee.nhs.uk/blog/why-mrna-vacci...
- jdthedisciple 5y ago
  Depending on the definition, they are or aren't. There seems to be a disagreement. https://www.google.com/amp/s/www.swfinstitute.org/news/83947/covid-mrna-vaccines-are-a-form-of-gene-therapy/amp https://www.google.com/amp/s/www.swfinstitute.org/news/83947...
  - creativenolo 5y ago
    The NHS article states "The mRNA from the vaccines does not enter the cell nucleus or interact with the DNA at all, so it does not constitute gene therapy." The article you have posted explains what gene therapy is confidently, but it doesn't explain, or reference particularly well, why an mRNA would be considered gene therapy or why it would alter genes.
    - AnthonBerg 5y ago
      We should strive to take jthedisciple’s comments at face value, and literally. From there we will arrive at a charitable interpretation. Here is an example where Harvard Stem Cell Institute discusses mRNA therapy as gene therapy: https://hsci.harvard.edu/translation/what-are-drugs-4-gene-therapies https://hsci.harvard.edu/translation/what-are-drugs-4-gene-t... The Wikipedia entry on gene therapy discusses mRNA therapy under the Non-viral section: https://en.wikipedia.org/wiki/Gene_therapy https://en.wikipedia.org/wiki/Gene_therapy – “BioNTech, Moderna Therapeutics and CureVac focus on delivery of mRNA payloads, which are necessarily non-viral delivery problems.” Indeed the mRNA vaccines carry a genetic payload – a segment of viral genome which is modified using a genetic perspective and from a position of genomic understanding. mRNA is a temporary and deliberately non-permanent message carrier substrate; Here too, humanity’s employment of such facts can be interpreted as scientific knowledge of the matters of the genes. If we choose to call mRNA vaccines gene therapy – which they are less clearly than other techniques – then it is certainly the better gene therapy for purposefully avoiding permanent alteration of the genome in the subject to be treated.

viraptor 5y ago

> Why do we take it as a given that antidepressants should help all of these sub-populations equally? Do we? Antidepressants are a whole class of things. We've got a few options, which indicates we don't expect equal effects. Same with painkillers. Same with statins. Same with migraine medication. These work for the similar problems but depending on the person you will use different one. Sometimes you'll even just cycle through them if you don't see the effect of the previous one. I think you're starting with a wrong assumption there.

midjji 5y ago
We dont, but we act like we do - Most doctors will try SSRI first despite most knowing they only work for about a third and most doctors will refuse to treat depression using non SSRI antidepressant medication.
- nradov 5y ago
  Doctors usually try SSRIs first because they are inexpensive, well tolerated in most patients, and often effective. If the patient doesn't respond then most doctors are willing to try alternatives.
  - atatatat 5y ago
    In my experience, the patient can seem content because their outbursts of whatever kind have decreased in regularity, and they're more neutral on...everything. It also seems to disconnect them from some portion of mental model creation (as in, learning and understanding day to day inputs), lowering overall executive function, causing some to slowly spiral into disorganization, perhaps bad habits, perhaps general nihilistic tendencies, without realizing it — especially those who have been prescribed these and have nobody to objectively weigh how the med is striking them, and assist with coming to the correct dosage.
  - midjji 5y ago
    SSRI have severe sideffects, but mostly of the kind that doctors strangely seem to think of as harmless, such as the well known and quite common loss of sexual interest, which kills quite a few relationships. Even worse there is growing evidence that it occasionally causes a permanent reduction or loss of sex drive. The group who self identify as asexual have almost all been prescribed SSRI as young teens, and this might well be causation, not correlation. After all, if you got SSRI as a kid and then never felt your sex drive before it was permanently lost, how would you know? SSRI are almost mostly ineffective, with roughly 70% not responding at all. They were however heavily marketed as the patented, and very expensive prosac for decades and more importantly while they occasionally treat depression, they feel bad to use and are never used recreationally, and thus avoided the moralizing around drugs. Not to say the marketing wasn't needed, people were highly sceptical of using chemicals to treat depression, especially as people occasionally melted from serotonin storm before they figured out dosages and cross interactions. Doctors are restrictive in which alternatives they try, not because they are afraid of side effects, but because off label use requires personal responsibility, and is often against policy one way or other. Good alternative treatments include hallucinogens, in particular ketamine and peyote in large single dose treatments when not taken in a clinical setting but with friends. These have long been avoided despite good evidence they work astonishingly well for depression. This is partly because of the war on drugs propaganda and moralizing, but mostly because these hallucinogens cannot be patented, meaning its not worth the price for the large manufacturers to do the marketing to overcome the anti drugs propaganda. Its not random chance that they are currently trying chiral variants, partial ingredients and various anti hallucinogens and treatment schedule combinations of these, despite all evidence so far indicating its all worse than the well studied plain unpatentable medicine. Another example is Amphetamines which in typical doses prescribed to children with adhd treat the primary observable downside of depression i.e. low energy, low focus, loss of work, reduced activity, etc. Unsurprisingly, the subgroup of depressives which respond well to exercise roughly a third, respond very well to treatment with amphetamines. As anyone who ever considered maybe working out, but not really wanting to, and then took amphetamines will tell you. With amphetamines, its almost certainly not a direct treatment of the depression, rather it facilitates changing habits in such a way that a common pathway out of depression is more likely to be taken. They have a significantly increased likelihood of suicides compared to hallucinogens, but the effect is comparable to that of SSRI. The main sideeffect of therapeutic/low doses of amphetamines is weight loss, a mostly desired outcome. So excluding people with easily tested for heart problems and trivial to identify anorectics, why not try it... Well its war on drugs propaganda again... Doctors have a nasty habit of thinking they should make the judgement regarding the tradeoff between various treatment, instead of presenting the options to the patient and letting them decide. But the real problem is idiotic moralizing around "drugs :O".

klmr 5y ago

> There seems to be an assumption underlying medicine that things must be true at the population level for them to also be true at the individual level. That really isn’t true: medicine as a field does not have this assumption, and rare disease research is a thing (and it’s commonly acknowledged that “rare diseases”, taken together, aren’t rare at all). In fact, rare disease research is providing acute clinical diagnosis and sometimes cures for highly individual cases. Personalised medicine is probably the fastest growing subfield in medical research. Your example of antidepressants underlines this: it’s in fact widely acknowledged that, while antidepressants on average only have a very mild effect, they can be very effective (or, conversely, not effective at all) for an individual, and they are actively prescribed with this in mind. Contrary to what you’ve claimed, no expert assumes that antidepressants have a uniform effect across subpopulations. However, treating each disease as a completely individual case just isn’t feasible at scale, and is usually also not appropriate. So the first anamnesis will always focus on common diseases, and rightly so.