It seems just yesterday that I was casting a skeptical eye on yet another dubious acupuncture study. OK, it wasn't just yesterday, but it was less than two weeks ago when I discussed why a study that purported to show that acupuncture worked as well as drug therapy for hot flashes due to breast cancer therapy-induced menopause. Unfortunately, these days these sorts of dubious studies seem to be popping up fast and furious like Whac-A-Mole, so much so that I can't always keep up with them. So it is again, although this time it's acupressure, not acupuncture. Unfortunately, this time it's an experiment on children as well. Why woo-meisters insist on subjecting children to their woo, I don't know, but they do:
An adhesive bead placed at a pressure point between the eyebrows reduced anxiety by 9% during the preoperative waiting period whereas anxiety continued to rise 2% for children who got sham acupressure (P=0.012), reported Shu-Ming Wang, M.D., of Yale, and colleagues in the September issue of Anesthesia & Analgesia.
However, the randomized trial showed acupressure had no effect on the need for intraprocedural propofol (Diprivan) or the depth of sedation.
Steve Novella's not going to be happy about this. The lead author of the study is Shu-Ming Wang, MD in the Department of Anesthesiology at Yale School of Medicine. I feel his pain. I'm lucky in that I have not seen much woo in my particular institution thus far. I can only imagine how irritating it would be to be at an institution that not only produces studies like this one but has earned a prominent place in my Academic Woo Aggregator, largely thanks to its most famous woo-meister, Dr. David Katz. I don't see him on this article, but I see his influence permeating even departments that should know better.
But my sympathy has lead me to digress.
Let's get get back to the topic at hand. First, note how little the purported effect was. Second, note that an objective measure did not change, namely the amount of sedation required (more on that later). But you won't hear that in the credulous article I found about the study:
Acupuncture has been shown to relieve anxiety in adults before surgery, but acupressure -- a noninvasive stimulation technique -- is likely to be more appealing to children than a technique involving needles, the researchers noted.
These findings are likely to be clinically important since excessive preoperative anxiety contributes to operative delays and heightens the pain response, commented Zeev N. Kain, M.D., of the University of California Irvine and a coauthor on the study.
Yes, it's all there: Claims that acupuncture definitely works, and a claim that a very small effect is "clinically significant." For example, later in the article, Dr. Kain claims that a 10% reduction of anxiety is significant in adults and then extrapolates from that that therefore an 11% reduction must be significant in children based on--no evidence.
But let's get to the paper itself, entitled Extra-1 Acupressure for Children Undergoing Anesthesia. Looking at the paper itself, I find a lot of holes. Being the old fart that I am, I can't help but liken the number of holes in this study to the number of holes it takes to fill the Albert Hall. Yes, my friends, it's that bad. Let's look at their hypothesis first:
We examined whether acupressure in the Extra-1 (Yin-Tang) point would result in decreased preprocedural anxiety and reduced intraprocedural propofol requirements in a group of children undergoing endoscopic procedures.
What I find interesting is that there's no discussion at all of why they think that. Why? There's no physiological mechanism discussed, no potential reason discussed, not even a speculation. Why this particular point? It's just a spot between the eyes. There's no plausible mechanism or reason to suspect that it would work. Yes, they do cite some papers claiming that acupuncture and acupressure "work" for adults, but neglect to mention that the totality of evidence is at best equivocal. But they give no reason for us to think that sticking a bead on one area of the head would somehow magically decrease postoperative anxiety.
So, how, specifically was this study done? Fifty two children were randomized to either acupressure a the Extra-1 point or "sham" acupressure defined thusly:
- Ex-1 Group. Intervention applied at the Extra-1 acupoint, which is located in the midpoint between the eyebrows.
- Sham Group. Intervention applied above the lateral border of the left eyebrow. This widely used sham point was selected as it has the same dermatomal distribution as Extra-1 and does not result in any reported clinical effects.
Wow! It sounds all science-y, doesn't it? They even used the term "dermatomal distribution"! Very nice. There are a couple of problems revealed in the methods, here directly quoted:
- In order to prevent any possible bias, all participants were informed that the aim of this study was to determine "which acupoint on the forehead is more effective in reducing preoperative anxiety."
- The acupuncturist (SMW) applied acupressure beads to the two intervention groups based on a random computer-generated assignment.
The first point is a almost as though authors decided to try to gin up a placebo effect as much as they can. I would have said that the study was to test whether acupressure works. It's a subtle but important difference. The second part tells you something very, very important, namely that the person giving the treatment was not blinded to the experimental group. Dr. Wang is an acupuncturist who presumably believes in the efficacy of acupuncture and acupressure. It's not unreasonable to wonder if through body language he telegraphed which group each child was in. If the effect observed had been large, one might argue that that couldn't account for such a large effect, but the effect reported is small, only 11%. Add the two together, and I worry very much about the validity of the reported results of this study. Further add that it is unclear whether any of the other treatment staff was blinded. Again, when the reported difference is so small, such issues become very important.
Finally, one part of this paper that is very important and that I might not have noticed if someone in a certain discussion forum hadn't mentioned it was the method used to monitor anaesthesia. True, it wasn't the primary endpoint, but it is important. It turns out that the Bispectral Index (BIS), the method of monitoring patients, is an EEG-linked system that produces a score between 0-100, with 0 representing no brain activity and 100 representing an awake patient. The target was 40 to 60, and, it should be noted, a BIS less than 60 is generally considered adequately anaesthetized for endoscopic procedures. It turns out that BIS is not nearly as well accepted as is implied in this manuscript and has several limitations, such as variation with different anaesthetic agents, a proprietary closed system where the practitioner can't be sure how the BIS is calculated, difficulty correlating with depth of anaesthesia, and inapplicability in some special patient populations.
However, the biggest, most glaring weakness of this paper is that, although the self-reported anxiety scores were 11% lower in the "true acupressure" group than in the sham, there was no difference in the amount of Propofol sedative necessary to maintaint a BIS between 40-60. Indeed, it's rather amusing to watch the authors try to rationalize this observation away as being insignificant:
Lack of group differences with regard to intraprocedural propofol consumption should be viewed in light of three previous studies. In a study of adult patients, Maranets and Kain noted that only higher trait anxiety (but not state anxiety) resulted in higher propofol requirements for maintenance of anesthesia. Thus it is not surprising that in this study reduction of preprocedural state anxiety did not result in reduced intraprocedural propofol requirements. Further, it is possible that intraprocedural effects of acupressure were suppressed by propofol general anesthesia. Indeed, a previous functional magnetic resonance imaging study by our laboratory indicated that acupuncture-induced blood oxygen level dependent signals were suppressed by propofol general anesthesia.25 A similar observation was seen using an auditory evoked index monitor. Lu et al. noted that electroacupuncture enhances the sedative effect of propofol in a target plasma concentration of 1.5 !g/mL but not at 2.0 !g/mL.
That's right. Propofol kept acupressure from working, so the same amount of propofol needed was the same between groups. Funny how that worked out so that its effect perfectly did that, isn't it? Ain't always the way it works out in these studies? It's also funny how the authors dance around how small the effect supposedly observed was, a mere 11%, an effect that could easily be random chance and/or due to lack of blinding of practitioners, and that there is no standard for what is considered clinically significant in children.
This study is yet another example of putting a lot of effort to have all the trappings of science to study a question that, at its heart, is in essence magic. Remember, acupressure is based on prescientific and mystical concepts of how the body works through some unmeasurable "life force" that flows through certain "meridians." Moreover, like most "positive" studies of woo, it demonstrated a small effect that's at the edge of significance. I will, however, admit that comments after the Medscape article did give me a chuckle:
Interesting but not real Chinese medicine. Personalization, comprehensiveness and strategy are foundational to classical Chinese medicine. This study says something obvious to anyone at beginners- level of Chinese medicine. This lowest common denominator technique applied generically only hints at the much greater value of real acupressure and acupuncture. Get someone in there who really practices Chinese medicine based on classical principles to design these studies.
The problem is, "real" practitioners of Chinese medicine generally design studies even worse than this one or don't do studies at all. After all, they believe acupuncture works. What more do they need? Even more amusing:
No real practitioner would design or do a study like this, as it was not structured to be to any real or appropriate treatment. There was NO design to do any anesthesia/sedation, so any outcome there would not be expected. Even the point used would not be on the top of the list for this procedure. The anxiety reducing point that was used (Yintang)is only one point in a complete breakfast.... and would never be used alone. There are more appropriate points that could be used for the desired effect that this study was looking for. This was a poorly designed study, and even then it produced results. I understand that some of the philosophy of this study would be a cheap and easy way anybody, even not trained as was stated in the article, to reduce anxiety in kids in an invasive procedure. There are ways to do that. as most practitioners would know.
In other words, the investigators picked the wrong magic points or didn't use enough magic points! But even more hilariously, he's claiming that even a "crappy" study from an acupuncture standpoint produced "results." Yes, it did: Questionable results that are probably not real.
Just like nearly every study of unscientific "complementary and alternative medicine" therapies. Given that this was a study in which the subjects were children, one question remains to me: How on earth did this study get through the Yale IRB?
Shu-Ming Wang, Sandra Escalera, Eric C. Lin, Inna Maranets, Zeev N. Kain (2008). Extra-1 Acupressure for Children Undergoing Anesthesia Anesthesia & Analgesia, 107 (3), 811-816 DOI: 10.1213/ane.0b013e3181804441
Personally, for studies like this I'd always like to see a wider variety of conditions, so that you'd have:
a) experimental group
b) placebo group
c) no treatment group
d) nice-relaxing-massage group
e) cup-of-cocoa-and-a-nice-chat group.
Because, even on the tiny chance that acupressure or whatever woo *does* have a minor effect, I'd be pretty damn amazed if it managed better than d) or e).
And here we were worried that you might have had a bad reaction to the flu shot...
My first thought upon reading this was "Don't these people know what error bars look like?" and my second was "OMG... I think I know that guy!"
Now, I don't know how common a name Shu-Ming Wang is, nor what percentage of Shu-Ming Wangs practice acupuncture, but it is possible this guy used to live in my home city! My first job here was at a very woo-ey health food grocery and herbal supplement store, and I remember a regular customer named Shu-Ming Wang (usually paid by check, so I saw his name a lot) who was an acupuncturist and also some kind of naturopathic doctor.
Really nice guy... but a True Believer and a CAM evangelist.
"How on earth did this study get through the Yale IRB?"
Like most IRBs, the one at Yale that "reviewed" this study didn't bother to evaluate its "scientific merits," despite the clear regulatory requirement to do so.
Actually, the IRB is charged to examine protection of human subjects. Most institutions have two committees, a scientific review board, which examines the scientific merit of the proposal, and an institutional review board, which examines human subject protections and ethics. Maybe I should have asked how this got through the SRB.
This study like so many other poorly designed CAM studies I recently learned about in "Snake Oil Science" relies once again on the placebo effect to make marginal improvements on patient well being. As always though there aren't enough variables covered let alone the idea proposed that the placebo effect may be responsible.
I enjoy reading these articles debunking acupuncture studies and it's efficacy, and my reason is this: It's amusing at this time period to try to examine acupuncture scientifically within the usual clinical drug study modalities. I work every week in detailed drug studies that go to unbelievable lengths in time, (years) energy, paperwork, testing ect to eventually find that perhaps Avastin has a 2.5% more safe effective outcome (not causing strokes)compared to Lucentis. This costs how much money? And how many studies have I participated in that revealed nothing much? Many.
And then I work toward an Acupuncture degree the other half of the week, witnessing amazing outcomes in people physically, emotionally and spiritually. I've been an patient of acupuncture for 14 years for real
reasons and outcomes, paying dearly now for an education that I'm certain can heal and help people manage their lives better. And you know what often creates the most significant changes in people? That invisible thing called energy, attention,intention, care, listening and touch.
Is that Woo? For a scientist maybe. But does that scientist "love" his children?
Is it possible to enroll people into a legitimate study to measure "comfort", or "love"? Can you measure that? You can't measure how a few (precisely placed) needles down the back can very often see a patient leaving an acupuncture treatment and falling into the deepest sleep they've had in months.. And you can't measure how they "feel so much more grounded and peaceful in general" after an acupuncture treatment.
This is an amusing issue to me while having a foot in both the clinical world and the "Woo" world. These clinical studies are perfectly square trying to encompass a river. No wonder they say nothing in the end.
Clearly Les whilst you claim to have a foot in the clinical trial world you don't have your head there.
Does being nice to your patients have non-specific effects that are welcomed by all involved? Yes it does. That's why you need properly designed clinical trials to separate out the effects of treatment from the non-specific effects of being nice to people and taking an interest in them.
PS. Don't make love to your patients I think even acupunturists might frown on that.
NM, You are correct! My head is not in clinical trials as they are often the most dehumanizing interactions created by man. I performed 3 of them just today, putting a patient through hell just to get "test results".
And please note, I DON"T "need properly designed clinical trials" to know anything.. YOU DO!
NM, You are correct! My head is not in clinical trials as they are often the most dehumanizing interactions created by man. I performed 3 of them just today, putting patients through hell just to get "test results".
And please note, I DON"T "need properly designed clinical trials" to know anything about nice...Clearly, YOU DO.
NM, You are correct! My head is not in clinical trials (who says it should be) as they are often the most dehumanizing interactions created by man. I performed 3 of them just today, putting patients through hell just to get "test results".
And please note, I DON"T "need properly designed clinical trials" to know anything about nice...Clearly, YOU DO.
I appreciate your witty approach to reviewing published research. Our system for validating empirical evidence may be far from perfect -- but it's the best thing we've found so far. Keep on separating the 'Truth' from the 'Woo'.
If you are making interactions with clinical trials patients into "the most dehumanzing interactions created by man" then I'm clearly not the problem.
Good work on the quadruple post though.
Please reveal your medical/research experience (years, professional expertise, focus ect)relating specifically to patient care. Maybe then we can really talk in depth.
So, to sum up: another study that was poorly designed, and in such a way as to skew the results toward favorable outcomes for acup*ure, fails to demonstrate any significant clinical benefit from acu*ure after corrections for design flaws. Am I missing anything? ;-)
I doubt that very much Les. My qualifications to discuss this topic far exceed any reasonable hurdle you might dream up. The point is that you do not require any of the criteria you list in order to discuss this topic. Anybody has the right to. When it comes to RCTs I value the opinion of patients, doctors, my postman and my grandmother.
You call RCTs "the most dehumanzing interactions created by man", which is a ridiculous statement, and then insist on qualifications in an anonymous setting when somebody calls you out on it.
RCTs are not dehumanizing unless somebody makes them that way. They are society's attempt (and that includes patients) to make healthcare better. They are at their core a marriage between both scientific and humanistic ideals.
Interesting how you refer to people ast RCT's.. very interesting choice of words as you still do not speak of your professional experience.
Are RCT's humans?
My statement about some clincial study requirements being "the most dehumanizing interactions" still remains firm.
DM, if you had any real experience in performing studies, you would understand how difficult and oftentimes dehumanizing the practices are. Clearly you have no experience at all.
Strict protocols determine exactly what (bigger companies) glean in information from a patient and it's often very taxing on them (see an often dehumanizing experience that patients accept for the sake of study)
Clearly you don't have experience with this aspect of research. And frankly the more you talk, the more you show your lack of experience and also become diagnosible by acupuncture standards. Your words and energy are already on the board and taken in. Would you like me to tell you about yourself?
DM, you und
Clearly you do not understand or have ever received Acupuncture. Acupuncture is not a new "woo woo " technique. It has been used for at least 2000 years and kept the ancient Chinese well and healthy for years. Do you understand what the decline of it was and why it fell out of favor? Not due to the idea that it does not work. It was purely political. When the Communist took over they banned Acupuncture. It was only practiced in the remote areas of China. THAT was how the techniques were preserved! Believe it or not it was banned because the communist wanted to copy western medicine. NOW China is returning to acupuncture. I am currently in school for a Graduate degree in Acupuncture. Yes I have a undergrad degree in Nursing and have been a nurse for close to 30 years. I have seen a lot of good and I have seen some pretty silly treatments take place purely because of money. Acupuncture, when done by a qualified acupuncturist is not only effective but is life changing.
My suggestion before you use your power as a writer is to DO YOUR research! This is the sort of writing that misleading and poor at best. You have no facts or basis in this article. The least you could have done is get a series of treatments from a good and qualified Acupuncturist.
Oh and Acupressure though not always as effective is a great technigue to use on childern who are afraid of needles. You eventually work up to useing needles.
Oh dear, yet more integrative baloney from Yale: see it here http://dcscience.net/?p=247 . And the usual pathetic defence from 'Les'. I fear that it is Les who has not done the research. Read Barker Bausell's book, or indeed just read Orac.
The fact of the matter is that present day acupuncture is something propagated by Mao-tse Tung for nationalist propaganda reasons, and to avoid spending too much on proper medicine for the peasants). He is on record as saying he didn't really think that it worked himself. Unfortunately after Nixon's visit to China, James Reston was hoodwinked my Mao's propaganda and spread it to the West.
For many sorts of Chinese Medicine the tests simply have not been done. Acupuncture is different. Some quite good trials have appeared in the last ten years or so. The result is quite clear. Acupuncture cannot be distinguished from sham acupuncture (either retractable non-penetrating needles, or real penetrations on the "wrong" places). It is now very well established that (a) the alleged mystical principles of acupuncture are pure hokum and (b) acupuncture is no more than a theatrical placebo
Clearly you do not understand or have ever received Acupuncture. Acupuncture is not a new "woo woo " technique. It has been used for at least 2000 years and kept the ancient Chinese well and healthy for years. Do you understand what the decline of it was and why it fell out of favor? Not due to the idea that it does not work. It was purely political. When the Communist took over they banned Acupuncture
Actually, I find it rather amusing to hear MPM telling me to "do my research" while he/she uses the tired old "appeal to ancient wisdom" BS argument along with appeal to anecdotes to justify acupuncture. As Dr. Colquhoun pointed out, MPM doesn't even know history. Mao promoted traditional Chinese medicine to keep the peasants happy without having to spend any money. Another assault on my poor beleaguered irony meter.
An old friend of mine has a rare disease called benign metastasizing leiomyoma (BML). In BML, uterine fibroids metastasize to other parts of the body, such as the heart, spine and lungs. BML is so rare that they don't really know the best way to treat it. My daughter and husband's cardiologist is Steve Nissen, and at my request he arranged for my friend to see a team of doctors at the Cleveland Clinic who had previous experience with BML. Unfortunately, my friend did not take advantage of this opportunity (even while continuing to complain that her doctors do not know what they are doing).
Recently, she told me that she had gone to an acupuncturist who promised that she would be able to help her with the pain she is having.
I'm not sure what the moral of this story is, except that people with serious illnesses don't always make the best decisions and there is not that much you can do about it.
Gah, ScienceBlogs ate my comment!
Anyone considering acupuncture should really read this blog entry by a Science-Based Medicine blog contributor and infectious diseases doc-- it's about how an acupuncturist's improperly-sterilized needles infected his patients with MSRA.
Is there any research to prove that the so cold gold standard of " western science" ( which is still an infant compare to eastern science) , the double blind random controlled studies are any more effective than any other form of studies? Or, are we just assuming they are because they they are so expensive, laborious and of course suit well the Drug industry?
Western medicine would be great if it wasn't for all the side effects. If you try hitting a small needle with a big hammer, you are likely to break the needle ( but at least its not sticking out any more , right?).
But didn't the truly best working "natural" medicines (such as making teas from the raw versions of active ingredients and whatnot, before technology got involved) also have side effects?
The line between a good medicine and poison is a fine one, even for modern products, because to have any effect the stuff has to be strong and able to mess around with your body chemistry, doesn't it? Even old traditional texts have a "strong medicine = must be very very careful with it" feel.
That is why you want to make sure that your medicine is backed by 2000 years of human trials, not just 7-10 years of testing on rats and humans(treated as rats).
nbs said "which is still an infant compare to eastern science)"
Please define "eastern science".
Does it include the work done by the three Japanese researchers who just won a Nobel Prize in physics? See:
2,000 years of human trials? What were the results? What happens if I take cohorts of people with the same disease and treat them with modern scientific medicine, or with eastern woo?
I did not confuse humans with RCTs. You made that up. That's a cheap trick known as a straw man argument. It is not 'interesting', it is boring and predictable.
My qualifications as they pertain to all stages of RCTs, as I have already clearly stated, are far in excess of anything you might be able to dream up as a hurdle. You on the other hand seem to not be able to tell the difference between superiority trials and equivalence trials despite giving the impression that you are a trials assistant for what sounds like a statin equivalence or non-inferiority trial (and then complaining about a small difference). And yet again 'qualifications' are irrelevant to the discussion at hand.
Once again, RCTs are not dehumanizing unless you make them that way. Your typical clinical trial is not.
If you don't like working in clinical trials I would suggest that you get a new job. You are clearly unsuitable because you are unplugged from any scientific way of thinking.
This is the kicker for me (I quote) "And frankly the more you talk, the more you show your lack of experience and also become diagnosible by acupuncture standards. Your words and energy are already on the board and taken in. Would you like me to tell you about yourself? "
We'll ignore the misuse of the concept of 'energy' as it's just another garden-variety altmed handwaving reality-avoidance technique.
Am I to take it that you think accupuncture can be used as a method of clairvoyance now? This must be great. You can now diagnose without ever having to meet a person or know anything at all about them. Now that's dehumanizing.
You don't even need the needles. Which, I think, is the point that Prof Colquhoun and Orac have been demonstrating all along.
The idea that 2 people can have the same disease is at the root of the problem. Just because we share the same virus or bacteria does not mean we will respond the same way. Although, we could have similar symptoms.
Treating a bacteria (trying to kill it...) is not the same as treating a person into health.
Oh for heavens sake. Despite what one may wish to believe, we are not particularly unique individuals. Many people can catch the same thing, whatever else is going on in their lives. You can do everything "right" and still get cancer. A bacterial infection is just that. If you want to change your life for the better, go for it, but no health guarantees, okay?
getting far off topic nbs said "Treating a bacteria (trying to kill it...) is not the same as treating a person into health."
So how does your vaulted "eastern medicine" treat bacterial infections, and what it the general outcome? For a specific example what is the general cure rate for "eastern medicine" for syphilis compared to antibiotics?
Could you also define what you mean by "eastern medicine"? Does it include the statin developed in Japan that I just took for my high cholesterol? Is it something that has changed with the input of new data, or has it stagnated?
I've been an patient of acupuncture for 14 years for real reasons and outcomes, paying dearly now for an education that I'm certain can heal and help people manage their lives better.
Why are you so certain, when apparently acupuncture hasn't managed to heal you in 14 years? Either you've had one problem for 14 years, and acupuncture hasn't healed it, or you've just had a series of problems for 14 years, in which case acupuncture isn't helping you manage your life better.
"I've been a patient for 14 years" doesn't exactly make me want to rush out and sign up for acupuncture.
And you know what often creates the most significant changes in people? That invisible thing called energy, attention,intention, care, listening and touch.
These are all different things. For example, it is possible to pay attention to someone without caring for them - the sniper is paying attention to his intended victim. Totally deaf people, despite their inability to listen, are as far as I can tell as capable of care, attention, touch, and intentions as anyone else, and similarly for people without a sense of touch. I also note that energy is sometimes visible, when it sends off photons.
Is that Woo? For a scientist maybe.
No. Woo is about the lack of experimental evidence backing up the claims of any particular treatment. For example, the ability of energy, in forms like electricity, heat and kinetic, to kill has been proven perfectly adequately to all the scientists I know.
I agree with some others that study referred to initially does not appear valid. "German Acupuncture Trials (GERAC) for chronic low back plain. Randomized, multicenter, blinded, parallel-group trial with 3 groups."
For a start, the nature of the sham acupuncture in this study was challenged 'because it works better than multimodal conventional therapy used in routine care'. (In 'Sham Acupuncture was not a placebo'). How do they decide what actually is sham acupuncture?
It's not easy to know what going there but these studies are not clear enough to arrive at definitive conclusions for or against acupuncture.
Actually, the studies are pretty darned clear: Acupuncture is no better than placebo. It doesn't matter where you stick the needles. And sham acupuncture "works" as well as acupuncture. I'd say the conclusions are pretty darned close to definitive.
I always hate to see scientifically-minded folks behaving like creationists. Yes, I know, acupuncture (or acupressure) studies have produced equivocal results, depending on the particular use they have been put to (not surprising - even if it IS useful, it is undoubtedly not useful for all the many ills people try to use it for).
But the complaints about this study seem like they are born of evangelism, not skepticism. It had a statistically significant effect, but the effect size wasn't great enough for you? That is pretty subjective. And your later comment that that small effect "a mere 11%, an effect that could easily be random chance" suggests you dont understand how statistics work - they gave you a p value (0.012), which means the same thing if the effect is 11% or 100% - that is just silly to invoke effect size here.
So, does acupuncture work? I don't know, but am skeptical. I would like to see a large meta-analysis that is well structured, but in the meantime, I have to say that railing against reasonable studies (compared to most in the literature) doesnt shed much light.