Okay, so ibuprofen impacts testicular function, acetaminophen/paracetamol causes muting of emotional response (along with the liver toxicity), many other painkillers are related to ibuprofen, and opiates are Right Out.
Is aspirin at least reasonably safe as long as the blood thinning isn't a problem?
I can’t take Ibuprofen (or any typical NSAIDS including aspirin) because of a medical condition, which has sucked over the last decade because acetaminophen really doesn’t help me at all when I’m excruciatingly sore for whatever reason.
In Oregon and Washington, where I’ve lived for pretty much my entire life, legal marijuana has been amazingly helpful, at least since I finally got around to trying it.
The various products out that are high in CBD and low in psychoactive ingredients have been really good at even my worst muscle aches and really painful, but not super serious, injuries like sprained ankles and such.
My surgeon after hip surgery even blessed the notion of using the opiates I was prescribed for as short as possible and then using high CBD edibles to cover the gap between excruciating post-op pain subsiding but still being in a lot of pain. In fact, he didn’t just bless the idea, he practically endorsed it as a “still emerging but very likely positive course of treatment” in his words.
I don’t use CBD like someone might (even if maybe they shouldn’t) pop ibuprofen, but it’s great to have an option between acetomenaphin and opiates.
>he didn’t just bless the idea, he practically endorsed it as a “still emerging but very likely positive course of treatment” in his words.
I love it! It's really sad and fucked up watching the federal government flail around trying to say otherwise. Meanwhile, they are getting all of their ducks in a row to ensure they can profit off of full on recreational legalization when that time comes. Between this issue and the healthcare issues it's terribly obvious the citizen's health and best interest is not first or maybe even second in order of importance to these people.
Actually, you don't get REM when you smoke. That's why you don't dream and it's why it comes back full-swing when you stop. I occasionally smoke and drink (alcohol also disturbs REM quite a bit), but I try and do it early in the day so I can get quality sleep.
I think kratom is helping me. I experience no psychotropic side effects, which is great. At some point, I'll stop kratom for a few months, see how my pain mgmt handles it.
I'll suggest you do your own research on it of course. I've known a few people, myself included, that have seen extraordinary results from taking it for various pain related to anything to do with joints (very split results on working or not, seems to do amazingly for some, and nothing for others). I didn't expect it to do anything, instead it saves me from taking pain killers every day (took my pain from a persistent 5 out of 10 to a 1 or 2 on most days, such that I never need pain killers; I take two each night).
I had to have hip arthroscopy because I had an impingement, leading to quite a bit of cartilage damage/labral tearing in the joint. They even had to reshape the end of the femur to remove the impingement. It's quite a recovery period of crutches, cane, etc. and the pain from the surgery was _supposed_ to be quite immense. Honestly, my hip hurt so bad for so long that even a day post-op it was less painful than it was when I went in. I only needed the opiates for a couple of days and used CBD once or twice a day for about a week- after that the pain was just a dull soreness.
Luckily, there was very little arthritis in the joint and three years post-op it's felt just fine and I've had no set backs whatsoever. Luckily I've not had to look into any type of long term pain management for anything.
1000 cases in the US, which means you're about 30x more likely to die in a car accident in any given year. Also, the syndrome isn't immediately lethal.
When people worry about infinitesimally small risks, it always makes me chuckle.
1000 cases in the US because there are no child friendly pain medications (sweet syrup and oral syringe) but by all means risk your child’s liver to prove us all wrong
In Europe, there's Aspirin-C and Upsarin, basically, pure aspirin with vitamin C, which eliminates the stomach lining issues [0]! I have no idea why this is not offered in America. Maybe, because there's no way to make money from patents and stuff!
> Maybe, because there's no way to make money from patents and stuff
That's definitely not the reason. The over the counter pain killer / pain management sections in CVS, Walgreens and Walmart are half filled with generic options.
No, it could be the reason. The patent/money issue is related to the initial FDA approval, which is very expensive (clinical trials).
If no one foots the bill for the testing, it won't spawn a FDA approved thing, right? And if it's not patentable, then it's not worth the effort to go through those hoops, because you won't be able to recoup the costs of doing the FDA approval steps because others could also bring generic versions to market right away, without a cool-down period, and at the same price.
If it is patentable, then it's worth it to make the drug and get it approved. You'll have 20 years to recoup the costs before generics can appear.
"infecting organism in dengue affects the platelets which are responsible for clotting (stopping bleeding) increasing the tendency of the person to bleed. Aspirin and Ibuprofen also have similar action. Both of them together could cause the person to bleed excessively pushing the patient into what is called the ‘Dengue Shock syndrome’. And once in this stage, medical treatment is needed in an emergency basis and hospitalization becomes necessary"
Infrequent, occasional use of opiates, for two or three days shouldn't be a problem. You do have to make a bit of an effort to get addicted to opiates, insofar as taking a pill a day for a couple of weeks constitutes effort.
According to the report, the transition from an initial prescription to chronic use begins very early on. Even a one-day opioid prescription carried a 6 percent risk of use at one year later and a 2.9 percent risk of use at three years later. The sharpest increases in the likelihood of long-term use came at five days after the initial prescription, with another spike seen at one month.
In all seriousness though, there is research being done and evidence to suggest that ketamine can be used for pain management. Most of it seems to be about using it synergistically with opioids, to reduce the amount of opioids required.
I think that all NSAIDs (like naproxen and ibuprofen) chew holes through your stomach lining, and a whole class of them were yanked from the market for causing heart attacks[1].
(But, yeah, naproxen seems to be one of the safest ones...)
All stomach effects are due to decreased prostaglandin levels. All NSAIDs function through inhibition of prostaglandin synthesis.
The exception is Tylenol/acetaminophen, as it doesn’t have an anti-inflammatory effect / doesn’t seem to act primarily on COX1/2. It’s currently popular to bandy about the theory that it targets spinal COX3.
https://en.wikipedia.org/wiki/Nonsteroidal_anti-inflammatory...: "NSAIDs cause a dual assault on the GI tract: the acidic molecules directly irritate the gastric mucosa, and inhibition of COX-1 and COX-2 reduces the levels of protective prostaglandins" (emphasis added)
Aspirin and many other nonsteroidal anti-inflammatory drugs (NSAIDs), (eg, ibuprofen, naproxen, indomethacin, and ketorolac) are carboxylic acids. Their pKa values range from 3.50 (aspirin) to 4.85 (ibuprofen). As such, they are not ionized at the acidic pH found in the gastric lumen and thus can be absorbed across the gastric mucosa. Once these drugs move from the acidic environment of the gastric lumen into the pH–neutral mucosa, the drugs ionize and are trapped temporarily in epithelial cells where it may damage these cells. How important is this effect? Calcium carbsalasate does not have this epithelium damaging topical effect, but causes the same ulcerative outcome[1].
This "topical" epithelial injury by many NSAIDs does not appear to be of prime importance in the pathogenesis of clinically important endpoints (symptomatic ulcers). The pathogenesis of symptomatic peptic ulcer disease caused by repeated exposure to NSAIDs is mainly a consequence of systemic (post-absorptive) inhibition of gastrointestinal mucosal cyclo-oxygenase (COX) activity. Even intravenous or intramuscular administration of aspirin or NSAIDs can cause gastric or duodenal ulcers in animals and humans [2].
PMIDs:
1 - 18242146 (“The incidence rate of peptic ulcer disease is similar in patients using low-dose effervescent calcium carbasalate compared with regular low-dose acetylsalicylic acid. This implicates that peptic ulcers seem to be related to systemic rather than to local effects of low-dose acetylsalicylic acid.”)
2 - 631484 (“These studies show that when the stomach is acidified by giving histamine intravenously or HCl intragastrically, intravenous aspirin produces large deep gastric ulcers.”)
Funny thing, naproxen is much kinder to your stomach than ibuprofen, but it's not generally used (and may be prescription-only?), in Australia at least. It does, however, carry a minutely increased risk of heart attack / stroke. I guess they'd rather give 1000 people ulcers than 1 more person die in a lawsuit-attracting fashion.
The regulators think, quite correctly, that people will generally take the dose on the bottle. If you only allow sales of Ibuprofen in 200mg pills and the bottle says “take two”, that’s what the vast majority of the public will do. If you allow sales of “ultra strength” 2000mg pills, a decent chunk of the population will take 2-4 grams because “ultra” must be better.
You can’t buy more than 2 packs of 200-250mg ibo in the UK at the time, and only one pack of anything higher, doses above 500mg require a prescription.
Prescription Ibo can be 2000-5000mg per pill so yes it does reduce the risk.
Naproxen (and Ibuprofen) can both cause kidney damage, particularly when you are physically active and/or not hydrating well (where hydrating well means getting enough sodium and glucose in addition to water). After experiencing kidney pain after taking naproxen on a hike and learning about this possible side-effect I am now very careful about naproxen use.
In case you were wondering: Cannabidiol (INN;[3] abbreviated as: CBD) is one of at least 113 active cannabinoids identified in cannabis.[4][5] It is a major phytocannabinoid, accounting for up to 40% of the plant's extract.
It’s worth noting that a legal version, extracted from Hemp (a form of Cannabis that has no psychoactive properties), is available via mail order anywhere in the U.S.
I've wondered about the efficacy of the hemp versions. A friend of mine was using CBD oil to alleviate his daughter's seizures, and had told me that the hemp based ones were ineffective, and that THC in a small dose had a complementary effect.
I'm not sure if that applies to everything CBD is good for, but does anyone know if it works mostly the same for body aches and the like?
I looked into the hemp based extract a while back and the conclusion I drew was that it was up for debate whether or not it was legal. Proponents cited a bunch of laws regarding industrial hemp while the DEA seemed to have another position entirely. Was this finally settled or is it still a bit gray?
Since vitamins and supplements are totally unregulated it could be that it doesn't actually contain any of the active ingredient it claims it does, thereby avoiding any legal issue.
I haven't heard that, either. I have heard that it has anti-inflammatory properties, which could indirectly reduce pain that arises from inflammation, such as arthritis. Here's one article describing it.
What I've read is that NSAIDs in reducing inflamantion, it can slow down the mobilization of immune cells that help clean up damaged tissues and promote new tissues.
Your comment intrigued me so I Googled and found this[1] article. Not sure what to think. The sample size in the study was even smaller than that in the original article.
I sometimes imagine, with horror, what would happen if after 500 years of progress, humanity were to realize that almost all cultural practices they painfully, one by one, undid, were all sensible to begin with for reasons that humanity didn't previously understand.
> I sometimes imagine, with horror, what would happen if after 500 years of progress, humanity were to realize that almost all cultural practices they painfully, one by one, undid, were all sensible to begin with for reasons that humanity didn't previously understand.
Especially since modern cultural change seems to have a tendency to be driven by the youngest politically-aware cohorts. Not a lot of time to acquire wisdom that might prevent that, if you're so young you haven't even collected enough knowledge yet.
“If the stars should appear one night in a thousand years, how would men believe and adore; and preserve for many generations the remembrance of the city of God”
You're just describing evolution. We almost assuredly don't practice most of the habits of whatever sludge we evolved from, regardless of how useful it is to sludge to continue such practices. And if we stop doing things, we will probably do so for reasons just as valid as why our ancestors started them.
>It might even explain why so many cultures had rites to male adulthood involving extreme pain.
Unless you believe that the rites were created to address the problem of "one day, there will be analgesics with antiandrogen effects, so we'll have a few centuries of practice at enduring extreme pain", then I don't see how there could be any connection.
> It might even explain why so many cultures had rites to male adulthood involving extreme pain.
Right. And a notable trend among those cultures is that they are all nearly extinct. So much for their fertility.
Of course this observation could biased due to my own ignorance. I only remember, like, 3 such cultures, and they were your typical African/Amazonian/Aboriginal tribes that still live in near-neolithic conditions.
Is there any industrialized culture that still follows such rituals?
When I think "painful initiation ritual", I think "glove made out of bullet ants" [1] not "organized sporting event in which everyone is wearing armor and hurting someone badly is grounds for stopping the game and rushing him/her to the hospital".
Even if you pick something like Boxing or similar contact sports where the goal is to intentionally hurt your opponent, it is still a far-cry from sticking your hand into a whiting mass of animals that have the most painful bite ever recorded.
Pedantic: it's a tree so it doesn't bite? But yeah, the gympie gympie [0] sounds horrible - potentially too horrible/long-lasting effects for a rite of passage? Luckily, it's in Australia!
You are absolutely correct. Pain is far more than a simple signaling mechanism to tell you to take your hand off the stove.
One of its more interesting applications is as a pathway to mystical experiences. In the Christian tradition for example one uses one's own pain to come into a kind of spiritual alignment with Christ's experience and in that way become closer to God.
I'm not particularly familiar with other spiritual traditions, but I'd be shocked if every single major one doesn't have some kind of mystical algetic praxis.
Where can I read about "dropping male fertility" as a medical thing? Just taking a blind guess, as someone who doesn't follow the medical field, I would suggest that increases in "infertility" are much more likely to be caused by the older age at which people are becoming interested in "fertilization" than environmental factors causing biological malfunctions. In other words, it's not that reproductive systems are breaking faster, it's just that people aren't using them until they're worse for wear.
Is the /d per day? If so that's well within what I've seen "normal" people take.
A regular Advil is 200mg. The usual dose is two pills, so 400mg. If your larger it's common to take three or four pills. Multiply by a dose ever six hours and it's quite easy to get to 3200mg per day.
Yup; after seeing my mom be recommended 3-4 pills every 6 hours as needed for knee pain, I sure don't bother with just 2 pills as a 200# male if I "need" ibuprofen. I either take 3, or I take nothing.
Fortunately I have no chronic issues, rarely need ibuprofen (in fact I'm paranoid about taking it for muscle aches as I've always felt it must harm muscle development, which seems to be catching traction as a theory), and generally avoid medications altogether, but it seems like if you're taking it, might as well take a dose that will do something.
TIL that my pain is weak and mild, even when I think I'm in a lot of pain. I'm well over 200 lbs (still), but 200mg of ibuprofen usually eradicates whatever pain I have. If it's reallybad pain, then I take 400mg.
TIL I have only experienced pain a few times in my life, and this apparently doesn't even include when I have had extensive dental work done as I don't let them give me any novocaine and don't mind them drilling into my teeth or cord packing my gums.
I am really hoping that it isn't just that you all are like, five years older than I am, and so I have to expect that I am going to just end up in pain a lot soon :/.
I think it depends on the person, a friend of mine would act out WWE type stunts: jumping on a trampoline full of tacks, getting hit with a chair in the head and bleeding all over... He says the pain tolerance has stayed with him through the years.
I've had two doctors suggest taking over 2000mg a day like it was nothing. One of them was a fellow hiker on the Appalachian Trail and suggested it as a daily regimen for regular joint pain (common for long-distance hikers). The other suggested it for aiding recovery from mild frostnip. (In both cases, I ended up only taking it for a few days.)
Unless you have stomach problems—NSAIDs are linked to ulcers—high doses of ibuprofen have not been thought of as terribly risky.
A nephrologist I went to a year or two ago explained to me that the danger of ibuprofen is total lifetime consumption. Once you approach 9lbs or so (surprisingly easy to hit if your habit is daily) your risk of kidney failure increases exponentially.
My nephrologists all say NSAIDs on long term use have a risk for acute kidney failure. They say Tylenol is safe in long term as long as liver is otherwise healthy and you stay under daily dosage limit.
Tylenol definitely accrues liver damage over time.
And your nephrologist is correct about NSAIDs. One of their direct effects is to reduce afferent blood flow to the kidney. Every time you take one you’re telling your kidney, “that amount of blood you think you need? Have a little less.” Blood flow to the kidney is extremely carefully regulated - this is never a good thing.
I've been prescribed up to 2400mg/d for a few weeks to deal with my knee. Not for the painkilling aspect (Because it wasn't painful), but for the anti-inflammatory.
Yeah, I have to say "Common drug X has negative side effects after sustained daily exposure to high dosages" is hardly surprising. The study says participants were given 1200mg per day for six weeks. For reference, a typical ibuprofen capsule in the US is 200mg.
I'm sure this result is useful for the medical community or men specifically dealing with hypogonadism, but it doesn't seem to have a great deal of relevance to the average consumer who uses ibuprofen for occasional pain relief.
> 1200mg per day for six weeks. For reference, a typical ibuprofen capsule in the US is 200mg.
Most people take 1-2 capsules (400mg), and the dosage documentation says no more than 8 per day (1600mg). The study seems to demonstrate people using the drug well within its over-the-counter maximum dosage. (When I tore up my knee as a teenager, my doctor prescribed it at about double that rate.)
If your doctor gives an Rx, they acknowledge that they're making a tradeoff and that it's the most applicable one for your overall health. I'm sure studies like this are helpful information for making such decisions, but this definitely doesn't seem to mean "taking ibuprofen will make you infertile".
For what it's worth, I've also been Rx'd large ibuprofen dosages for a period of weeks at various times, and I've had six mostly-non-defective kids so far. I don't think this study warrants any type of generalized panic...
I think I understand what you're saying, but anecdotal evidence isn't really the point here. The article is pointing toward a societal trend, not one that is likely to be observed on a case by case basis.
That said I do agree. All medications are a trade off of some sort. Usually the consequences aren't as bad as the effects of the drug, and I think this is no exception.
1200mg is only 2 capsules 3 times per day, less than the maximum recommended for over the counter use. However any pharmacist would tell you not to use it for more than a few days in a row without seeing a doctor.
That is actually the dose I use for my lower back pain and inflammation when it flares up - for a couple of days perhaps once or twice a year. Dates from a slipped disc about 20 years ago. Never serious enough for surgery, but still unpleasant.
Have you tried dropping the dose and interleaving with acetomenophin? I have been hearing recently that's an increasingly popular strategy, sharing the load between the kidneys and liver.
Because they work in different ways, that's what I'm fond of doing for myself and my children. Start with ibuprofen, then try a table of acetaminophen a couple of hours later.
If it's a really bad headache, start with one of each.
Here is a study[0] which directly contradicts that claim:
"Thus, the higher dose of ibuprofen (2400 mg per day) was not superior to either the dose of acetaminophen (4000 mg per day) or the lower dose of ibuprofen (1200 mg per day) for pain relief or improvement of function."
Have a source on that? When I was in college I had some bad inflammatory issues to the point where I couldn't even walk, but it only took 200mg once or twice a week to completely fix the issue. When I didn't take any at all it would get worse and worse until I couldn't even stand up, but as soon I took it I was completely fine in 20 min or so.
As much as possible, I believe we should all try to do everything in moderation. Never be too extreme in medicine, exercise, drinking, drugs, food, etc. Sometimes in life you can't avoid the situation, unfortunately.
A friend of mine had some good wisdom from her mom. If you have to take medication, take different ones, not always the same ones. If you eat premade food, buy different kinds, not always the same ones.
It's basically portfolio risk diversification. You increase the risk of having some negative effects, by virtue of trying more things, but you hugely decrease the risk of taking one thing excessively that does you a lot of harm in the future.
In the Pāli Canon of Theravada Buddhism, the term "Middle Way" was used in the Dhammacakkappavattana Sutta, which the Buddhist tradition regards to be the first teaching that the Buddha delivered after his awakening. In this sutta, the Buddha describes the Noble Eightfold Path as the middle way of moderation, between the extremes of sensual indulgence and self-mortification
Not a doctor / scientist. Can anyone tell me if this is a pilot study or reproduced results from other studies? Or in other words, should I take this as a fact yet?
This is from PNAS early edition, and has no citations yet (meaning nobody has used this work in subsequent studies). For the general topic, Google Scholar (https://scholar.google.com/) is excellent at finding journal articles on any topic (including testicular function as it relates to ibuprofen). At first glance, this doesn't appear to be reproduction of prior work either.
If you're asking if this is generalization to other healthy white men? It seems okay for a first shot. There is no fancy stats in this paper (they just use unpaired t-test to look for significance). They measured at two time points (+ the baseline condition) and both "real" (I don't really feel like including the Free T/LH ratio...) measurements that they found significantly different at minus 14 days remained significant (and same direction) at 44 days. The dose response curve seems particularly convincing to me.
It does seem that the particular study was centered around a single electrically stimulated exercise session. It would be difficult to try to guess what happens if combined with different (more sustained? more repeated?) exercise.
If you're asking if this is generalizable to any other group? No idea. Probably okay to generalize to all healthy men. But that's about it.
As for why this is so small? Looks like they just piggy backed on another study. Pretty reasonable use of resources.
A metric that may be useful: fragility index. How many positive results would need to be reversed to have the p-value exceed 0.05? Seems applicable for low-powered studies such as this one.
It isn't, but that's how you pitch for more research funding. I don't know anything about the economics of clinical studies or grant issuance, but I imagine it's hard to get the cash for a large sample up front so researchers go through this scaling process.
Not really. I mean in an ideal world yes, but right now we have no idea how many other people did a similar study, found no difference, and just didn't publish anything. Let alone accidental or purposeful p-hacking.
A p-value in a test statistic is the probability that the result of the test statistic could have been achieved through random data variations. A p-value is described in tandem with an alpha level, the minimum acceptable value to reject the null hypothesis in the test statistic.
In short: typical alpha is 0.05, so a p-value < 0.05 is considered "statistically significant" and the results are not attributable to random chance in a t-test. An unpaired t-test compares two populations, and a p-value below the alpha level indicates that differences are not due to random chance.
Take everything with a grain of salt, though. Low sample sizes dramatically change how test statistics produce results. P-value hacking is the practice of eliminating data from an experiment to produce statistically significant results or otherwise altering the data by adding buffers to ensure that a result confirms a belief a researcher has.
Given a statement and a sample with a mean and standard deviation, what is the probability that you manage to choose a sample with that mean and SD, assuming the statement is true?
For example, my statement is the average weight of chicken an american eats every month is 20 pounds and my sample gives me a mean of 16 and SD of 4. The p value is the probability of choosing a group of people who eat on average 16 pounds of chicken every month if the REAL mean is actually 20.
Edit to answer question: The p value doesn't "care" about the sample size - it is adjusted and remains accurate. And so if the p value if high for the sample in the study, that means it is a likely occurrence and the result is not very noteworthy.
It isn't. People talking about P values forget about p-hacking and selection bias. Any scientific study with less than 200 participants should be discarded and the failure to routinely do so has more to do with scientific laziness and the pro-profit incentive most journals have than anything else.
That's not entirely true and doesn't really convey the right message about p-values or study size. P-hacking and selection bias are definite concerns, but they're also concerns for studies with 200, or more, participants. Rather, we should put more of an emphasis on the statistical power of the study. We're not yet in the beautiful golden world of pre-registered studies, but even high-n studies can have huge disparities due to bad statistical power (eg: The Control Group is Out of Control).
I had to look up what you meant by pre-registered studies. In case anyone else wonders:
"Unlike traditional scientific publishing, in which manuscripts are peer reviewed only after studies have been completed, registered reports are reviewed before scientists collect data. If the scientific question and methods are deemed sound, the authors are then offered "in-principle acceptance" of their article, which virtually guarantees publication regardless of how the results turn out."
I'm essentially right. Studies with less than 200 people are essentially useless. It is more complicated than I originally let on, but not so much more complicated to muck up the takeaway. Most of our junk science has to do with these low population studies or with studies simultaneously studying high numbers of attributes.
Err, I don't quite agree with your description. The takeaway from your post was that low-n is worthless and high-n is ineffable, full stop. The size of the trial has very little to do with whether or not we are to believe the results insofar as it affects its statistical power. The fact that p-hacking and selection bias exist doesn't immediately imply that low-n studies are wrong. Those aren't problems unique to small sample size studies. For sure, statistical power isn't the catch-all thing to examine either--rather, pre-registration of studies would alleviate a great deal of falsities, but none of any of this has to do strictly with low sample size trials as your post implies.
Let's say the drug studied was a guaranteed 100% limb regenerative drug for amputees. Would you really require a 200 person study to prove that Examplinol successfully regenerates limbs? I hope the answer to that is "obviously not; it will be very clear whether or not it works with a low sample size." Of course, how would we change the study if it wasn't supposed to work in 100% of people? What if Sample Pharmaceuticals indicated that it only worked for 50% of people? Or 10%? Or 1%? Would it suffice to use 200 people each trial?
> Any scientific study with less than 200 participants should be discarded ...
Imagine you're investigating a drug for hair loss. You gather a group of 31 bald white men. 15 of them take a placebo and 16 take the experimental drug for 24 weeks. If, after 24 weeks, you find 1 of 15 controls with a full head of hair, and 14 of 16 test subjects with a full head of hair, is 31 too small a sample size?
Imagine you're investigating a drug for hair loss, like 20000 other researchers hellbent on achieving their goals. You gather a group of 31 bald white men. 15 of them take a placebo and 16 take the experimental drug for 24 weeks, but because your random allocation put more extra bald people in your non-control group you fixed it by balancing the two groups. Your counterpart that didn't have the same problem, uh, didn't make any adjustments. If, after 24 weeks, you find 1 of 15 controls with a full head of hair by some function you define, and 14 of 16 test subjects with a full head of hair again by some function that you define oh and we didn't adjust for anything but of course in the case where the drugs didn't do anything we did because the non-control group were all above average in both age and some other random things like testosterone levels. Is 31 too small a sample size?
31 is always too small of a sample size. These scientific studies are almost always bullshit and we all know it and we'd do something about it if we really cared but we don't because nobody is incentivized to fix it.
You had to introduce a lot of assumptions to invalidate the n=31. So let me lay it out in more detail.
I recruited 31 white men who self-report having no hair on at least 500cm^2 of their head. They all had hair as adolescents, and lost it gradually throughout their 20s or early 30s. They're all at least 37 now.
I then sort them into the two groups by assigning sequential IDs in random order. Those with an odd ID are in Group A, those with an even ID are in Group B.
I then give each participant in both groups a placebo for 24 weeks, having them check in every 2 weeks to measure hair growth, if any. At 24 weeks, I randomly assign two new courses of treatment to each group. I do this blindly, giving Group A pill X and Group B pill Y. Another 24 weeks (with check-ins every 2 weeks) and I find that Group A (taking pill X) all have full heads of hair. Well, except for Paul and Maury.
Meanwhile, Tom, in Group B (who took pill Y), is the only member of his group to have a full head of hair.
Statistically-speaking, my n=31 was a great sample size, and I'm also pretty sure Tom discovered he had sugar pills and stole the real stuff from Paul or Maury. :)
To address the possibility of seeing these results due to a confounding variable (like above average testosterone), this is about as likely as shuffling a deck of 31 cards, and all the red ones ending up in the front and all the black ones in the back. About 0.0000003%
Shit. I just rechecked my data, and it appears the "full-head-of-hair" group still had 482cm² of shiny scalp. I need to fire my measurement tech and issue a recall...
The point is though, that if enough people do the same study, and only the positive results are published, you're increasing the odds a lot of getting a positive result from someone. That's why companies often finance studies in their drugs. If enough people study their drugs, something which doesn't have a measureable effect, might have a measureable effect in some of these studies.
At which sample size this becomes reasonable is a good question though.
First, that's obviously not a rephrasing of what they said. They, very clearly, illustrated a valid case for a well-powered, low sample size study. They presuppose a case where 31 virtually identically-haired white men undergo a treatment and, voila, it works decidedly well.
Second, you're begging the question. You state that the drug doesn't work, yet have concocted a scenario in which it clearly and explicitly works. Even in your "cheatsy" example, 15 of the 16 people go from "bald" to "full head of hair." If the "full head of hair" metric is wrong it has nothing to do with the sample size, rather, we'll find this by examining how the study partitioned groups, pre-trial measurements and its claims to have calculated effectiveness over placebo (ie: actually reading the study).
Third, you've neglected statistical power (which is actually your argument here) for an incorrect statement about low-sample size bias. You state that the mechanism of action for this bias is a pre-partition between [truly bald, nearly haired] and then, given maybe a bit of luck, let good ol' father time take over and show, wow, the (useless) drug works! Maybe everyone experienced a 1.5x follicular density growth, but only because you've been able to presort the group do we see the non-placebo benefit more than the other... except this has nothing whatsoever to do specifically with sample size! If you can sort a trial with 31 people into 15 "truly bald" and 16 "near-haired" you bet you can sort a trial of 200 participants into 96 "truly balled" and 104 "nearly haired" or, heck, just don't even randomize your group selection at all! Or run the study 20 times and pick the successful one! Or any number of other tricks, which are real and meaningful and require someone to actually read the study to uncover instead of just looking at a clearly, very misunderstood, number.
The number of participants required to show an effect should be shown by power analysis. It depends a lot on the effect being investigated. An arbitrary number like 200 is not helpful.
This is also the cause of rotating advice for decades, eg “eggs are/good/bad/good/bad/good” which is s feedback loop between terrible science, predatory media, and a credulous public.
Is it callous of me not to worry about the testosterone levels of professional athletes? Because they seem to generally have enough. I worry more about people with RSI who often depend on overuse of anti-inflammatory meds and aren't demonstrably professionally masculine.
Professional athletes make for a good study population because they tend to keep records of their training/performance/injury status. Also their behavior influences painkiller consumption in the population at large through endorsements or just interviews on their fitness regimen. If you like sports and know your favorite athlete uses a certain class of product to deal with cramps, you're likely to recall that when you're in the drugstore looking to alleviate a similar problem.
No one is asking you to worry about professional athletes in specific. If the effect is demonstrated to be applicable to men in general, it would also affect the people you mentioned.
I'm suffering from Ankylosing Spondilytis (a non-cureable chronic disease similar to Artritis). Let me tell you, the side effects are the least of my concerns when I'm in chronic pain.
everything i read here refers to effects on testosterone levels. how does this relate to actual fertility (that can be measured in a semen analysis)? would lower testosterone levels affect count, motility, morphology, etc?
I've taken entirely too much Ibuprofen - I've had a lot of babies. Since the sample size of this study is 31 people, I say that my one case is significant and this study is bunk.
That's why you can't rely on a study of 31 people.
Is aspirin at least reasonably safe as long as the blood thinning isn't a problem?