[COGlory]

Sorry for the potentially insensitive question, but I really am wondering about this:

>One side effect I should mention: many report extreme anxiety. However, I was starting an anxiety medication for the first time (something I should have done 20 years ago, but alas ...) and so those effects were muted or hidden to me.

I would have imagined that most people with CF already had extreme anxiety - wondering when the infection that is going to end one's life will arrive. Is it really possible that Trikafta is causing noticeably worse anxiety?

[junon]

Just an anecdote.

My best friend died of CF just a few years ago. He talked candidly about his eventual death, to the extent it was uncomfortable at first (but we ended up being to the level of making jokes about it, which I think was a positive thing for both of us).

He changed his WhatsApp status to a coffin and skull-and-bones emoji right before he went, just as a joke.

He didn't live with a shred of anxiety - least anxious person I've ever met. Dude was down for anything and everything, and could have probably fought off a bear despite being comically short and concerningly skinny. Easily one of the most kind and relaxed souls I've ever met.

[bdcravens]

Most of us, especially adults, are pretty much settled in with the state of our condition - we've had it our entire lives. Anecdotal, but many CF patients (including in online communities I'm a part of) have reported a lot of increased anxiety.

[mason55]

> I would have imagined that most people with CF already had extreme anxiety - wondering when the infection that is going to end one's life will arrive. Is it really possible that Trikafta is causing noticeably worse anxiety?

There's a discussion of this in the article. Essentially, a bunch of people have said that they started experiencing extreme anxiety when they started Trikafta, and that stopping or lowering the dose helped immensely. However, clinicians have said that there's no actual evidence that the Trikafta is causal.

So it seems to be a bit of an open question and I'm sure an emotional one on both sides.

[ipaddr]

Clinicians are always a day late and a dollar short. The evidence comes from these people reporting. These clinicians need a 50 million dollar grant to get that proof.

[TechnicalVault]

If you've ever had to organise a scientific study you'll understand why. Privacy and ethics are important but they make recruitment of a large and representative sample for any medical study a nightmare. First you'll need to run your protocol past an ethics board and do back and forth until it's agreed. Once you have that done you'll send out an invite (often blind) in hopes of getting people who fit your study aims and you will get who you get. There are often costs associated with this.

So now you have some willing participants you have to screen your initial group to filter it down to people who actually meet your recruiting criteria and consent them for your study. Finally you actually get to gather your data, if you need people to come in for sampling and have to cover their expenses.

Next you'll look at your data and realise there's some confounding effect which reduces your powers to infer anything (e.g. somehow you overrecruited a particular group and they turn out to do something which correlates with the thing you're studying). You'll cry a little and realise you need to recruit more people to have any statistical power to draw a conclusion.

tldr; medical and scientific studies are hard if you want them to actually have any validity.

[AdamN]

It seems like we really need to move forward to 'indefinite/active studies'. I believe some researchers are trying to get onto this pattern but of course there are major privacy/quality of care concerns.

By 'indefinite/active studies' I mean that the studies never stop - data just keeps going back into the system as a flywheel of the drug distribution process. I take a second-generation drug for CML (leukemia) and none of my health data goes back into research unless my doctor decides to elevate my data into a paper or something (which I don't think has happened yet).

[markus92]

These kind of platform trials are getting more common luckily! Famous example is the COVID Recovery trial.

[pas]

wouldn't this side-effect become visible in Phase4 data? (and there should be at least some hints of this in the previous ones)

so, what I'm trying to say is that for this particular drug we "just need to wait", no?

[matthewtse]

(I left a previous comment as a similar sufferer of a lifelong genetic disease that was cured by a breakthrough medicine: https://news.ycombinator.com/item?id=37541222)

Funnily enough, although in practical terms my life is infinitely better than it was before the drug in, I would rate my anxiety as higher than it was before.

A lot more options open in the world, a lot more to hope/pine for, a lot more to lose. Back in the days when my expected future was to just hang out in bed, there wasn't much else to do than to just chill and read a book.

[therein]

Just an anecdotal experience so doesn't necessarily mean anything but the only person I knew that had CF had absolutely no anxiety from his condition.

If anything he was a very mature guy for his age, having realized he has limited time but of course I wouldn't know the internal struggles he might have kept from us.

[vkou]

People generally get acclimated to the situation they are in.

If you have anxiety over money, for instance, you'd probably still have it, regardless of whether you had $15,000 in your bank account, or $15,000,000.

[fnordpiglet]

I grew up with a lot of money insecurity, was homeless for a while and started my career with nothing - one change of clothes and a floor to sleep on. I’ve since done very well for myself and have a considerable amount of net worth at this point and a lucrative forward for as long as I want to keep working at it.

I’ve lost most of my money anxiety, but it took a lot of purposeful work inside myself to achieve that including years of daily meditation and intentional study of Buddhism. Before that my money anxiety was unbearable. It didn’t matter how little or how much I had, because it wasn’t about money in truth. It was a fear of losing control and other things like self worth and identity issues as a result of my earlier life. As I learned to let go of the self and my identity and live life as it is rather than what I’m afraid it might be I’ve lost my fears, not just about money but all of them. In my experience lack of money instigated my anxieties but once they started it didn’t matter how little or much I had.

That said it drove me to get more and more, and I enjoy having more than when I had none. But even if I lost it all I would be ok now.

[TotalCrackpot]

That's interesting - does your career require any formal education? Or were you able to develop some crucial skill on your own? Can you share what is your career about and where you started and where are you now? For example - do you hire employees or are you a landlord now, or are you an employee?

[fnordpiglet]

No, I’m a software engineer. I barely graduated high school because I was too busy smoking pot and programming at a time when you needed a degree to get a good job so didn’t have much opportunities despite being pretty skilled at programming. I got a job at Netscape tho as one of the first tech companies that didn’t look at credentials before skill. I did well there and did my own companies. But before I had nothing and move to California with $5 and a change of clothes, slept on the floor of someone I randomly met on irc (I was lucky it didn’t turn out worse than it did don’t try this at home!) until I found a job. Anyway, after Netscape and my startups I became a quant on Wall Street, finished my cs degree, and have had a successful career since. Now I’m the top IC at a late stage startup.

[TotalCrackpot]

I don't really see how you become a quant on Wall Street before you finish the CS degree, they I think look at credentials a lot, can you at least give the name of the prop shop that hired you without a formal education? Did you have any good results in algorithmic competitions or math competitions in high school? And how did you learn programming without an actual computer? Did your parents buy you a computer when you were young?

[fnordpiglet]

A lot of quants didn’t go to college. On my team at a top trading desk at a top bank we had about 15 people, 4 of which never went to college. I actually got an internship due to a person on the desk having worked for me prior and went full time then finished my degree, so was already in school. But many folks took an alternate route. They were usually well experienced when they were hired. But in an arms race where what you can do is more important than nominal credentials a degree simply makes it easier.

No, I was a total loser in high school. I barely graduated and had awful test scores and did no extracurricular activities other than smoke pot.

My grandparents bought me a computer when I was young, I think because my mom saw how much I was interested in them. It was a c64, but had no storage devices so I had to type in programs from scratch each time which was a tall order for a 6yo, but I did it anyway. At some point someone gave me a 486dx2 board that was an extra and I built my first Linux box running 0.96. My schools also had an internet connection and I could get dialup access to some sunos boxes and some NeXT boxes in the library when I was in high school. One of my greatest wishes growing up was to have enough money to have the best monitor since my monitors were always garbage. My house now has nice TVs and monitors everywhere LOL, but they’ll never hold a candle to my first VGA monochrome monitor I delivered papers for a year to buy.

[currymj]

early 2000s was a different time also. nerd career paths hadn’t yet become prestigious and formalized.

there were no middle schoolers optimizing their resumes for how to get a Jane Street internship in 8 years bc Jane Street was only a few years old. same for a lot of other firms.

[dan-robertson]

Some shops care more than others. Going to a target school also matters a lot more for interns/new grads than for more experienced hires.

[pfannkuchen]

You might even have more with 15M! It’s much harder to replace if you lose it.

[cbeach]

On the subject of correlation/causation, I once took a drug called Accutane to cure my teenage acne. Listed side effects included: "Mental health issues depression, psychosis, aggressive behaviour and suicide ideation and attempts"

Accutane was the best medicine I ever took. It resolved my acne (permanently) in a matter of weeks. I felt elated afterwards and never experienced mental side effects.

However, prior to the drug, I'd experienced several of the listed side effects, due to the acne itself and its devasting effect on my self-esteem.

For many teenagers suffering from serious acne, they'd also have mental side effects due to the skin disorder, meaning there would be a strong correlation between Accutane use and people suffering mental episodes. And if the wonder drug didn't cure the acne, as promised, I can imagine that failure might push some acne sufferers over the edge.

So, Accutane itself could be harmless, but the circumstances of its use might suggest causal link to mental side effects which are not causal at all.

[dan-robertson]

Yeah a lot of the side effects you listed sound a bit like they could be within normal expectations for teenagers, or just slightly heightened. Reminds me of an SSRI that happened to also massively reduce caffeine metabolisation without anyone noticing, and loads of the known side effects were really just effects of caffeine overdose – insomnia, jitters, headaches, etc.

[ipaddr]

It takes a lot including many suicides to get that side effect listed. You are lucky it didn't reach that point for you. With a little more time or repeated usage it probably would have got you as well.