It's good that they mentioned the severe toxicity of paracetamol in overdose. It does kill many people, and it's not a pleasant death. It also accounts for many organ transplants.
It would have been nice if they'd said that, taken carefully and with no over dose, paracetamol is a very safe and very effective medication. It's very cheap. (At least here in the UK, I found it bafflingly expensive in the US.)
Cultural note: In the UK most medication is dispensed in blister packs. You can buy paracetamol off the shelf but you can only get limited quantities. Most shops will only sell you 16 tablets (at 500 g each) or 32 if you buy it from a person. You can get 100 if you see a pharmacist and persuade them you need them, but that'll be a struggle in most places. You can get large amounts if you have a prescription. 16 tablets at 500 g each would cost around £0.20 (for budget pills). Blister packs was an effective suicide control measure, reducing the number of pills taken and the number of overdoses attempted. Reduced quantities of pills sold had an initial success in reducing suicide rates, but number have since risen. Pills in the homes of old people are especially dangerous. This is because they're not locked away, and young children visiting sometimes take the pills. And also because suicide rates among old people are depressingly high.
Brand-name Tylenol is relatively expensive, but generic acetaminophen/paracetamol is dirt cheap in the US. Here are 200 tablets of 500 mg each for $4.00, i.e. $0.02 per tablet: http://www.walmart.com/ip/Equate-Extra-Strength-Value-Pack-A...
In Switzerland, I _can't_ buy more than ~2  packages with 16 pills (500mg acetaminophen/paracetamol) at a time without a prescription from my doctor. And the biggest package size is 100, but that always needs a prescription. Also, you can only buy it at a pharmacy anyway.
: it depends a bit on the pharmacy/pharmacist, sometimes you can get away with 3, but they start asking questions and propose you just come back again when you used up the 2 packages they are willing to sell to you.
paracetamol is nasty stuff - dying from it is not pleasant, and it's surprisingly easy to do.
The only cases I'm aware of where purchase numbers are limited for OTC drugs is when separate laws targeting drug precursors impact them, which is why you can't buy large numbers of pseudoephedrine tablets at once (they can be used to manufacture meth).
The FDA does seem to be reducing the maximum dosage of each tablet, though: from 2014 the maximum will be 325mg, so the 500mg tablets linked above will be phased out. But that change seems aimed at reducing accidental liver damage from excessive "normal" use, rather than aimed at reducing suicides from deliberate overdoses.
There are exceptions (but I'm not sure if they're from the Law Enforcement side, or the FDA). For example, you can't buy Sudafed (whose active ingredient, pseudoephederine(?), is used to make meth) without severe restrictions: not more than a pack a day, need a valid ID, etc.
Do you (or anyone else) have some concrete data for incidence rate of fatal overdoses in the U.S.? I'm curious if it's really all that common.
This is not true. It's about preventing impulsive suicides, not premeditated ones. If a depressed person is having an episode and all they have in their house is 16 pills, then it removes the opportunity: maybe by the time they've make it to the shops and buy more, the moment will have passed, and a life would be saved.
It's been shown time and time again that you can reduce absolute suicide rates by removing opportunities like this. If I remember correctly, there was something similar involving gas ovens, though I can't find the reference now. Guns, bridges, etc. are all similar too.
When it comes down to it, if someone's determined enough to kill themselves, they will, but the truth is most people aren't and doing things like only selling small quantities of pills really can prevent suicides.
About gas ovens: There's less carbon monoxide in modern gas delivery. (http://io9.com/5959303/why-have-people-stopped-committing-su...)
>The switch from coal gas to natural gas also had one unexpected effect. During the ‘50s and ‘60s, about half of the suicides in Britain were by coal gas. By the ‘70s, when the transition to natural gas was complete, the number of gas suicides had dropped to zero and the overall suicide rate was down a third. Even the suicidal appreciate convenience. If it's too much trouble, as Dorothy Parker said, "You might as well live."
Also, regarding my above post (which I can't edit now), I didn't mean to imply that "just" 16 pills was even remotely safe because I'm sure it's not (I'm not a doctor) but the general point stands...
Death from paracetamol overdose is by liver failure, and that takes a week or so to happen, but after the first 24 hours there's not much you can do to prevent it apart from liver transplant.
Paracetamol overdose is a small number of liver transplants in the UK, but a significant number of the 'super urgent' transplants.
Is the attempted-suicide overdose rate in decline? That seems to be the main question as to whether the law helped.
A few days before this, my family had tried to have her sectioned as mentally ill (she was suicidal from post-natal depression). They psychiatrists kept her in for observation for 48 hours, then released her. 24 hours later she was dead, and her child an orphan.
All the law did was slow her down for maybe 15 minutes in her suicide attempt.
Secondly, one cannot prevent one from committing suicide, but making it harder will give people time to reconsider their planned suicide.
I still think that 10 packs of Paracetamol, if I had them in my home, would last me not for a year, but easily for the rest of my life. But maybe I am still too young and healthy to judge that.
Oh, and I guess you can get really remote in the UK. There's plenty of remote islands (with affordable housing: http://www.npr.org/templates/story/story.php?storyId=4866217)
He could get it added to a prescription, which makes getting the quantity easy but it then becomes more expensive. (Unless he qualifies for free 'scripts.)
Or you could just haggle with a pharmacist.
But, yes, it's an added hassle at a time when you very much don't need the extra hassle.
There are very few places that come close to feeling remote, certainly. And it's only getting more crowded =/
I can't imagine how hard it would to control be if she was taking painkillers on an as-needed basis for a long time. People with dementia are often surprisingly clever and resourceful, considering the disease.
It is amazing that someone could drink that much water, without a restroom bream or just not feeling thirsty anymore. But I can imagine overdrinking over a course of days in response to feeling dryness, and not realizing that she is overdoing it.
You may feel better about this if you take some Tylenol ;-)
I don't see how there's anything wrong with selling brand-name drugs next to generics. In fact people that believe brand name drugs are more effective will have a better response to the more expensive drug because of the placebo effect. If anything, they're getting a better response to the same dose of the same drug than the rest of us plebs that know better than to pay a multiple of the cost of the generic.
Care to explain why?
I buy Tylenol branded acetaminophen. Granted, I only buy one bottle every three years or so, but I'm perfectly fine spending a few dollars more. While acetaminophen is acetaminophen, when I buy Tylenol, I'm buying into their quality control and the experience that has come with that company, over many years. It's worth a few dollars to me to make sure that I'm getting what I'm buying and nothing more.
Do explain how brand loyalty is "embarrassing" to humanity.
Medicine is a relatively good place for paranoia though, and for feeling safe. Most brand loyalty is even sillier. Don't get me started about designer clothing.
This makes no sense to me. If I have a good experience with a company, then any subsequent experience is far more likely to be good than a random selection?
The entire point behind brands is consistent experience.
Brand loyalty is broader and can potentially be justified.
Something like ADHD medication can make a difference. One of the most difficult months I've had has been a month where I tried the generic and the side effects were way worse than the brand name at same dosage.
The moral, for me, is to be very cautious with generics. I believe most of them are fine (I would never pay full price for Tylenol :), but the more critical the medication is to me, the more research I will do on the generic.
The FDA recently pulled a 300mg generic bupropion generic because the extended release formation produced nowhere near what the branded medication did.
Most generics are equivalent to the branded medication, but there are exceptions out there.
if so, you're a liar. the generic patches undergo thousands of tests before a doctor ever has one prescribed.
sorry to burst your anecdotal evidence bubble. but you are fabricating things.
'Anecdotal evidence bubbles' are fascinating. Try posting links to research about the placebo effect instead of resorting to name calling.
But in my mind the generics are just as good as name brand, albeit sometimes different. I guess I'd be just as likely to react poorly to the inactive ingredients in the name brand and might find a generic better in some cases.
In addition, some of the details of the chemicals (such as I guess the angles of the molecules) may be different, because the generic manufacturer imperfectly reverse engineers the process used to make the drug.
Clinical trials to validate the generic are less strict.
Those are "dynamite plots", a favorite of scientists, but the statisticians I know prefer to use boxplots or dotplots instead.
As the submitted article notes, responding to the press releases by the study authors,
"This all raises more questions than it answers. This study was small. The headlines are grandiose. The way people pass moral judgements is not necessarily indicative of their level of existential anxiety."
Indeed. This is an intriguing issue to study, and well worth some further studies by other investigators to see if the results will be replicated in other study populations, but the author of the submitted article was correct to have a headline with an open-ended question rather than a definitive statement about Tylenol. On my part, because I take different over-the-counter pain relief medications when I need any of those, I'm curious if this result would be replicated for aspirin or for ibuprofen. That the pain of stubbing a toe and the pain of rejection in love might have some of the same brain mechanisms is suggested by our use of the word "pain" for both phenomena. But that requires further study. (I'm sure there are many studies already on that issue, but I'm not deeply familiar with the research literature on that topic.) That pain (of either kind) might motivate action and thus dulling pain might reduce motivation for some actions is also plausible, and also has surely been investigated before, but perhaps there are still some very basic facts about that issue yet to be discovered. As so often happens after a new study is published, the most firm conclusion is "further research is needed."
It's interesting to compare ourselves: a population of pill poppers at the slightest twinge, to those in other parts of the world who simply don't. Perhaps it affords us some extra (or different) mental space in an intangible way.
Reducing inflammation tends to reduce anxiety, so the effects would definitely be similar. That said, tylenol also binds to the cannabinoid receptors, albeit weakly, so that may have something to do with the effect there.
1. This study has precisely no meaning until it has been replicated, preferably with a larger set of experimental subjects.
2. Science is not one study making ten claims, it is ten studies making one claim. This study falls into the former category.
3. The study describes, it doesn't try to explain. Science requires a testable explanation, one that can be generalized and potentially falsified by independent laboratories. If the study had offered a possible, testable explanation, it would have crossed the threshold of science.
4. It's important to say that psychological studies are virtually never replicated. One reason is that the original studies tend to maker nebulous claims that are difficult to quantify (like this study does). Another is that psychological studies tend not to be accompanied by the original study data, to a greater extent than studies in scientific disciplines. A third reason is that psychological journals tend to reject replication papers, especially those that don't confirm the original study's findings.
2. Apparently the first study isn't science. I didn't realize that science was a catch-22 situation.
3. This is so absurd that I feel like I'm being trolled. They have a testable hypothesis: that acetaminophen/paracetamol has a side effect of X.
4. See https://yourlogicalfallacyis.com/
Nothing in science has meaning before replication. Look at cold fusion for a classic example where this rule was ignored. Of course, you may be speaking of the prevailing standards in psychology, in which case you're right -- but then psychology isn't a science.
> 2. Apparently the first study isn't science.
That's correct -- it isn't.
> I didn't realize that science was a catch-22 situation.
Only if you can't replicate any studies. That's psychology's problem, but not science's problem. In science, studies are replicated regularly, and no one takes a study seriously if it hasn't been replicated, especially where human health is concerned.
> They have a testable hypothesis: that acetaminophen/paracetamol has a side effect of X.
That is not an explanation, it's a description. Science requires testable explanations. The paper doesn't presume to explain its results.
If I say "the night sky is full of little points of light", that's certainly testable -- someone else can go outside the tent and confirm it, but it's just a description -- not a basis for science, which requires that someone have the nerve to suggest an explanation for what has been described.
But if I say "those points of light are actually thermonuclear furnaces like our sun, at greater distances", I have offered a testable, falsifiable explanation. That's science.
If someone correlated a specific biochemical action in individual neurons with later very specific behavior, that might count as science, but that would be neuroscience, not psychology. Psychology doesn't try to analytically connect specific physical causes to effects -- it's satisfied to describe outcomes without pretending to know why they are so.
> See https://yourlogicalfallacyis.com/
The fallacy is yours, not mine. You appear to think one study making ten claims constitutes science. In fact, science is ten studies making one claim.
Actually, two labs reported achieving cold fusion before the results were published, and another also claimed to replicate the findings. See http://www.its.caltech.edu/~dg/fusion_art.html for a comprehensive, well-written examination of this.
The Bayesian approach to assessing the validity of scientific claims, which is quite popular these days, implies that every scientific study has some meaning before replication. However, it requires reasonable priors. Most people who are not in the field won't have reasonable priors, and most people who aren't scientists won't be used to thinking this way at all.
In this case, my prior for this study being true is probably higher than yours because I remember its predecessor (which you can read too at http://dept.wofford.edu/neuroscience/NeuroSeminar/psfSpring2...). It's apparently neuroscience and not psychology by your definition because it has neuroimaging data that links the effects to the behavior of specific neurons, even though it was published in the same journal.
Generally, I suggest you devote more time to studying the history and philosophy of science before making pronouncements about it :).
Yes, but they were all false and later proven false. A replication doesn't mean two or more labs making the same mistakes. There's a bit more to it than that.
> Generally, I suggest you devote more time to studying the history and philosophy of science before making pronouncements about it ...
I have. Science requires testable, falsifiable theories. Psychology doesn't have any of those. This is not remotely controversial.
Quote: "Simply, to be scientific, a theory must predict at least some observation potentially refutable by observation."
> It's apparently neuroscience and not psychology by your definition because it has neuroimaging data that links the effects to the behavior of specific neurons, even though it was published in the same journal.
The measurements were apparently neuroscience, but the claims that followed certainly weren't. It's not uncommon to see an apparently scientific measurement, followed by conjectures that aren't in any way supported by the measurements.
Science proceeds by theories either supported or refuted by empirical evidence. Psychology proceeds by votes.
> Yes, but they were all false and later proven false. A replication doesn't mean two or more labs making the same mistakes. There's a bit more to it than that.
The article I linked to (which was written by David Goodstein, a professor of physics at Caltech and definitely not a crackpot) discusses the situation surrounding cold fusion in a great amount of detail, and illuminates the difference between proof and scientific consensus. If you believe the account, no one ever proved that the experimenters were not observing what they claimed to observe. Instead, the main problem was that the effects were not consistent, that they seemed to good to be true, and that there was no physical explanation at the time they were "discovered."
> > Generally, I suggest you devote more time to studying the history and philosophy of science before making pronouncements about it ...
> I have. Science requires testable, falsifiable theories. Psychology doesn't have any of those. This is not remotely controversial.
> Quote: "Simply, to be scientific, a theory must predict at least some observation potentially refutable by observation."
The statement you cite is preceded by the phrase "In falsificationism..." As the article notes further down, "Naïve falsificationism is an unsuccessful attempt to prescribe a rationally unavoidable method for science."
As for psychology not having testable, falsifiable theories, that's probably true for some definitions of "psychology," but it's a huge discipline, and there are some rigorous psychophysics papers out there that test real hypotheses. (I'm a neuroscientist, not a psychologist, but I'd be happy to send you some of my favorites.)
> The measurements were apparently neuroscience, but the claims that followed certainly weren't. It's not uncommon to see an apparently scientific measurement, followed by conjectures that aren't in any way supported by the measurements.
I agree to this to a limited extent. The claim that everyone cares about is that Tylenol has a psychoactive effect, and showing that brain activity changes when Tylenol is administered definitely supports that claim. Trying to draw connections between brain activity and pain is much harder.
> Science proceeds by theories either supported or refuted by empirical evidence. Psychology proceeds by votes.
Both hard sciences and psychology proceed by votes. This is demonstrated by the cold fusion article, and it's also one of the main theses of Thomas Kuhn's Structure of Scientific Revolutions. Why do you hate psychology so much?
> In fact, science is ten studies making one claim.
If it is a fact, can you provide a source for this definition? I've never heard it before, and it contradicts everything that I've encountered to date.
And I do know people who would use this definition: every single person I know who is a scientist.
I think it's a rather pithy distillation of the process of gaining scientific consensus. The source would be: "learn what the process of science is about, how it works and about the philosophy of science and this quote becomes a rather obvious truism"
A single study is to science what a single TDD test case is to software engineering. Despite what crappy news outlets tell you.
All that said, lutusp is being pretty negative about this study for no obvious reason. Someone needs to do the exploratory work at the beginning and this is interesting work, whether you call it science or the start of science. The rest seems like complaining about the press being the press.
And your evidence is that we're having this debate?
Do you mean the idea that science must craft and then test theories? That's not at all controversial, and every legitimate science is defined by its theories. Without the Standard Model, physics isn't science. Without the theories of evolution, genetics and cell biology, biology is not science. Without theories about geological processes and plate tectonics, geology is not science.
How could we determine whether a field is or is not a science unless the determination was based on its tested, defining theories? We know astrology is not a science because its theories fail when tested. Are you saying that astrology would become a science by not having testable theories?
> When people operating on a different definition of science encounter your definition ...
Not only is this not my definition, it has been expressed in a number of legal decisions that, for example, keep Creationism out of public school classrooms. The reason? Creationism's theories fail when tested.
>> In fact, science is ten studies making one claim.
> If it is a fact, can you provide a source for this definition?
My source is the practice of science. Einstein's relativity theory, as pretty as it was on paper, was not accepted until the corpus of evidence for it was overwhelming, in dozens of confirmations (this required experimental work until the mid-1960s). Plate tectonics was not accepted until the field evidence became overwhelming. Examples abound. All on need do is read some science history to discover that one publication means nothing.
> These are the things that one will naturally wonder about in the context of contempt, even if the contempt is accidental.
Science doesn't care about contempt, it cares about evidence. Contempt is completely irrelevant to the process, and every scientist knows this.
No it doesn't.
Science aims to characterise phenomena. Normally, this just means describing the outcomes of a repeatable scenario – pretty much what redcircle stated.
It may seem like science can explain some phenomena but that's really only because multiple observable levels below the surface phenomena have been fully characterised. But for any phenomena, if you dwell down through all of the characterised layers, there's always a point at which science can only probabilistically describe what happens, it can't explain why.
> No it doesn't.
Name a legitimate science that is not defined by its testable explanations. Physics has the Standard Model. Biology has evolution, genetics and cell biology, all well-tested theories.
We know astrology is not a science because its theories fail when tested. Is your argument that astrology would become a science by not having testable theories?
Without testing, without evidence, a scientific idea has no standing. It's not science until there is empirical evidence in support of an idea (or that falsifies the idea). Without empirical confirmation or falsification, it's philosophy, not science.
> Normally, this just means describing the outcomes of a repeatable scenario
Every time I go outside at night, there are these little points of light in the sky. I don't know what they are, but they're the same every time I look. So ... I just became a scientist. Yes?
Contrast that description with a proposed, testable explanation -- that those points of light are thermonuclear furnaces like our sun but at a greater distance. We can test this idea, possibly falsify it. Falsifiability is a requirement for science, but one cannot falsify a description -- for that, we need a proposed explanation.
> ... there's always a point at which science can only probabilistically describe what happens, it can't explain why.
That's not science, it's philosophy. Science requires a collision between falsifiable explanations and empirical evidence.
The study is not impressive. Most studies aren't, and exploratory, early-stage studies rarely can be. It's OK that early studies of a phenomenon are not impressive, but the tests do seem to be extremely narrow. The claims should be equally reserved and narrow. I certainly wouldn't start invoking morality, judgment, or other abstractions of the human psyche (as did the author of this article) from such a small and contrived set of experiments.
Yes, but a longitudinal examination of psychology publications shows that, compared to mainstream science, psychology studies are rarely anything but "early-stage studies". Almost none of them is ever successfully replicated, nor is an effort made to replicate them, compared to other fields.
> I certainly wouldn't start invoking morality, judgment, or other abstractions of the human psyche (as did the author of this article) from such a small and contrived set of experiments.
I of course agree, but then it's a psychology study, where such hand-waving claims are commonplace.
If the the first study on any question is completely meaningless, there'd be no motivation to try to replicate it.
Regarding #2, it depends what you mean by "making a claim". A study could test a single hypothesis, validate the hypothesis, and then list 10 things that arguably could follow from that hypothesis. For example, after timing the transit of Mercury and validating relativity, a paper could then in its conclusion list other likely consequences of relativity.
I think a lot of your statements about "science is ..." are confounding a single study with the entire body of scientific progress. Science requires replication and science requires theoretical explanations. That doesn't mean that a single study always has to provide its own replication (it can't!) or theoretical explanation. An experiment that dis-confirms a theory doesn't have to provide an alternative theory in order to be part of science; the theory may come later.
Not to a scientist. Without replication, a single study is conjecture, interesting but weightless. Are you not aware that an unreplicated study is a standing joke among scientists? Why do you think the gag science journal is named the "Journal of Irreproducibe Results"? Scientists find the name funny because (a) it's an inside joke and (b) it's a truth about science that member of the public just don't get.
> That doesn't mean that a single study always has to provide its own replication
Then it's a good thing I never said that. But a single study has no standing until and unless a disinterested, independent laboratory succeeds in replicating it.
This issue is so critical to the future of psychology that, after a series of scandals about replication and credibility, a well-known figure in the field has made an emergency call to create replication circles among psychologists to (a) replicate each other's studies, and thereby try to (b) restore public confidence in the field. He says without a replication program, "I see a train wreck looming."
Quote: "For all these reasons, right or wrong, your field is now the poster child for doubts about the integrity of psychological research. Your problem is not with the few people who have actively challenged the validity of some priming results. It is with the much larger population of colleagues who in the past accepted your surprising results as facts when they were published. ... My reason for writing this letter is that I see a train wreck looming."
To see the importance of replication, all you need to do is read the scientific literature.
And yes, I'm familiar with the JIR. I was introduced to it about 35 years ago by my high school's astronomy teacher, Mr. Norm Sperling, now the editor and publisher.
I wouldn't take any major actions based on a single study, other than trying to replicate or counter it, but that doesn't mean it has "no meaning". You have legitimate criticisms of the study, but you wrap them in overly-broad generalizations about what is and isn't science.
You remind me of an old friend who had such a strict definition of "science" that he claimed that in 4 years as an undergraduate at Caltech, he'd only met one "scientist".
So is Prof. Kahneman a scientist?
Quite often an explanation for a hypothesis is found long after the hypothesis itself has been proven correct. Eg: "puerperal fever is a contagious disease (and washing hands helps prevent its transmission)" has been establishd long before the germ theory of disease was even formed.
Yes, and science requires microscopes and telescopes. But science isn't defined by microscopes and telescopes, it's defined by what scientists do with them. By themselves, these individual elements aren't science, because they don't lead to a falsifiable proposed explanation, the single essential element in the definition of science.
> Quite often an explanation for a hypothesis is found long after the hypothesis itself has been proven correct ...
A hypothesis cannot be "proven correct". That's reserved to theories -- explanations that generalize observations and predict their relevance to phenomena not yet examined.
> "puerperal fever is a contagious disease (and washing hands helps prevent its transmission)" has been establishd long before the germ theory of disease was even formed.
Yes, and shaking a dried gourd over a cold sufferer will cure his cold. Isn't that science? -- it always works! If I visit 1000 cold sufferers and shake my gourd over them, every single one of them will get better if I shake the gourd long enough. So is my procedure science? No, it is not -- because I have not tried to explain why my method works, nor have I considered alternative explanations for my result.
The dried gourd example, and a thousand other examples of sloppy thinking, show that testable, falsifiable explanations are a requirement for science.
Why would one replicate it if it has no meaning? Might as well try a new experiment.
Thomas Insel, the sitting chair of the NIMH, disagrees with you. In his Scientific American article "Faulty Circuits" (http://www.scientificamerican.com/article.cfm?id=faulty-circ...), he says:
"In most areas of medicine, doctors have historically tried to glean something about the underlying cause of a patient’s illness before figuring out a treatment that addresses the source of the problem. When it came to mental or behavioral disorders in the past, however, no physical cause was detectable so the problem was long assumed by doctors to be solely “mental,” and psychological therapies followed suit.
Today scientific approaches based on modern biology, neuroscience and genomics are replacing nearly a century of purely psychological theories, yielding new approaches to the treatment of mental illnesses."
I draw your attention to the phrase "scientific approaches based on modern biology, neuroscience and genomics are replacing nearly a century of purely psychological theories ..."
Science requires empirically testable, falsifiable theories. Psychology doesn't have empirically testable, falsifiable theories. End of story.
I suppose it's all too intuitive, though. Even slight, unnoticeable changes in consciousness - to the point that even you don't notice - may in-fact be detectable on paper. I hope this leads to more research into the mental changes for other drugs classified as "non-psychoactive" (who doesn't love more data? :). Anyways, to end off by inserting some colloquialism into my thoughts here...
Trippy study, mannnnn.
A noteworthy risk however is that you'll make false connections -- ie. garlic is good for fight off HIV.
... also great to read about the mental implications of priming. I'll be more punitive/forgiving depending on the unrelated thought I had minutes earlier...
Well, it kind of fits the definition (except psychoactive drugs have their primary effect in the brain)
I've suffered from what doctors call "pain syndrome" for years. Many different parts of my body are painful at any one time. It is years since I had a pain-free day.
I never accepted that I had pain syndrome, even when doped up simultaneously on codeine, paracetamol, tramadol and diclofenac. And still in pain. Finally I was moved onto morphine, but I still cannot sleep at night because of the pain.
However, I think that my pain problems were exacerbated by (at the very least) paracetamol (max dose daily for 2 years). It is well known that sulphur compounds (NAC specifically) are required for the detoxification of the byproducts of paracetamol. Long term use of paracetamol will lead to sulphur depletion in many people. And it seems this depleted sulphur is compensated by the body taking sulphur from other places (joints, cartilage), thus causing further pains.
Trying to get an answer from doctors and pharamacists about why taking sulphur reduces my pain more than the above concoctions of "pain-killers" got me nowhere, so the above is my explanation for why the more paracetamol I took the worse my pain problems got.
It's been a bad 5 to 10 years. My opinion is that "pain syndrome" was almost certainly not my problem. My pains were all skeletal/joint pains, except for pains that would suddenly appear in my left hand or right calf, even when doing nothing. Those latter two I could explain as being neuropathic, but after being in so much pain from my back, coccyx, hips and shoulder, I think my pain registration system was out of whack. And I wouldn't be surprised to discover that all the different "pain killers" I was taking were in fact contributing to further problems.
Currently I am just on morphine, but must tie myself to the bed at night to stop myself turning over in my sleep. If I lie on my sides, the pain will build (even through morphine) until it wakes me up. By that stage turning on my back will not reduce the pain and I cannot get back to sleep. Taking a sulphur supplement (NAC, or MSM) seems to be as effective as morphine (neither alone or together is really satisfactory though).
What has been so appalling in my case, has been the difficult of getting doctors to look at the individual problems properly in early stages (so a dearth of scans/treatments), until it got to the point where they were saying "you have pain syndrome". Most of the treatments that have had any success are those that I have insisted they do even when they have said they won't work. Some major treatments I have had to insist they don't do (cutting nerves??).
I'm finally getting a scan this week on my hips, after asking for this for almost 2 years. Hopefully it will show what I expect it to show, and they can treat it with steroids.
I shoulda stuck with psychology after all! This sounds fun! Who thinks of this stuff?
I don't know how you could sit through this film without already being disturbed.
Some studies have demonstrated liver enzymes raise significantly on a typical extra-strength dose of acetaminophen, called paracetamol in Europe. This could be indicative of low-level damage, for casual users (it's frequently prescribed for minor pain)
A quick and simple hack is to take it along with N-acetylcysteine, usually given for coughing.
Personally, to play it safe, when I have to take more than half a gram of paracetamol, or when I have to take it for more than 2 days in a row, I add n-acetylcysteine with it.
Cheap, and without side effets at low doses. (BTW, it's used IV in the ER as the antidote for tylenol overdosing)
Since this seems not to have happened, does anyone know if there's some side-effect of taking N-acetylcysteine alongside paracetamol/acetaminophen as standard? Or was it just a question of price?
For other things, like perception, drug effects, etc., it seems less likely that this is actually a problem, because there's no reason to believe the neural pathways that acetaminophen operates over are different between any two humans.
If you really need to detect effects that are so small they are meaningless for almost any practical purpose, then you might need thousands of people in the study.
You can try to manipulate your power in a variety of ways through the sample selection process (which can ultimately modify your external validity). The major variable that most people manipulate is simply the size of the sample (i.e., the number of people). You need a sample of a large enough size such that you could even hope to detect the effect you expect to see.
Ultimately, one can say, "This study had 80% power to detect an effect size of 30%."
Search for "We recruited"
You can intuit this by imagining 10000 studies, each of which had a P-value of 0.99. Seeing 10000 negative studies and no positive studies, you'd be convinced that there was no real effect, intuitively. But multiplying 0.99 10000 times yields a P-value of 2.2 x 10^(-44), a result of impressive significance.
To combine studies, many people use inverse variance weighted meta-analysis, e.g., https://en.wikipedia.org/wiki/Inverse-variance_weighting
To combine p-values, what we really want is the CDF of the product of p1 and p2 in the distribution formed by the product of uniform random variables. Mathematica can compute this; the general formula is (p1p2)(1-log(p1p2)), and for the two p-values in question this yields p = 0.0019 (which is close to what I said initially, but only because I made a calculation error; .02*.01 = 0.0002). Thanks for pointing out the mistake in my reasoning! I learned something.
That actually makes quite a bit of sense...
These days everyone has an opinion on everything, combined with a very judgmental tone - and at the same time living extremely purposeless and egocentric lifes.
Aspirin can be harmful to the stomach lining; aspirin can be fatal to people under 12; aspirin has a number of risky side effects; aspirin can be very dangerous for some people with under-lying conditions.
I think cocaine and opium has a longer history too.
The point of this story is whether Tylenol IS safer, and that's mostly contingent on the person (and studies showing its own inherent risks).
Among the NSAIDs, aspirin is the strongest anti-coagulant, and the anti-coagulation effect can last for weeks. While small doses of ASS are beneficial for people who are at risk for thrombosis, they significantly raise the risk of eg. brain haemorrage.
You could of course take something like ibuprofen, which affects coagulation less. But all NSAIDs attack your stomach, so after some time you'll have to start taking something like pantoprazol to "protect" your stomach...
AFAIK, paracetamol doesn't affect blood clotting and it doesn't attack your stomach. It's dangerous if you take doses of more than 3 gram per day, and you really shouldn't take it if your liver is failing. Alcohol can also cause severe side effects when taking paracetamol.
There is no "perfect drug". If there was a drug that would only have positive effects on our body, evolution would have made our bodies produce that substance on their own.