>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?

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.

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.

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

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).

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.

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.

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.

Also at that time, as you say, there wasn’t a broad cultural awareness of the money to be made in quantitative fields. In fact this was the era of Revenge Of the Nerds movies and glorification of the idiot jock getting a business degree and the passionate nerd being the butt of the joke. You really only went my route if you were a total fuck up loser. Now the social view of things has completely pivoted.

I would say interestingly the middle school kids optimizing their resume only make it so far in industry. They’re never really passionate about what they’re doing they’re just laddering. At some point they shift to management or product or something. At the top firms though the people who really make the money and whose opinion has ultimate power are the fuck up losers who live and breathe their passion and would do it for free if that’s all there was.

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.

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.

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.

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.

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.

He would take his enzymes, do the vibrating jacket treatment. He graduated and got a full time offer from a nice company. As he was relocating, he picked up some infection and passed away in a few weeks. None of us expected it. This was months before I heard of the approval of Trikafta.

This seems like a no-brainer way to treat obesity, by restricting or blocking such enzymes. Obviously the downside is diarrhea and other malabsorption symptoms, but obese people have too much nutrition. Blocking absorption seems easier than dieting, as no willpower required. You shit out the undigested food.

If you eat a tub of ice cream as dinner, you're going to have a bad time.

Source: have CF.

So I just wanted to say: it was an impactful piece of writing, enough so that I remembered it quite clearly after a single read these few months ago.

Interesting. I'm an uncle to a family member with CF (and I'm a carrier) and one of their long battles has actually been weight. To the point of doing things like downing olive oil to try and keep up the weight. They've eventually had to take the fairly drastic measure of getting a feeding tube installed. Getting enough calories in just hasn't been possible until the feeding tube.

My personal situation is probably pretty unique, in that I have CF as well, but had a double lung tx many years ago. A couple years ago my transplant team (actually it may have been the CF people.. fuzzy memory) asked me if I was interested in getting on Trikafta and after thinking it over for about 30 seconds I told them I'd probably pass. It seemed like it wouldn't have any beneficial effect on my lungs, as they no longer "have CF", and that I assumed it would just make extra weight for my decently healthy but still under par lungs to have to drag around. They didn't disagree.

Hearing about any kind of advancement is huge. I can't even begin to understand what you've gone through, but am so happy to hear there is a new medicine to help with such a cruel disease and that it's made a world of difference to you. Sometimes it feels like medical science is still in the dark ages and I get saddened that we haven't got flying cars or Dr. Beverly Crusher can't wave some device over me and fix all the ailments I now have. Other days I hear about these kinds of advancements and it makes me smile!