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Thread: homeopathy, the placebo effect, and mainstream medicine.

  1. #31
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    I don't understand how a placebo can work if you know it's a placebo, though. Man, our brains are weird.

    CJSF
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  2. #32
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    Quote Originally Posted by CJSF View Post
    I don't understand how a placebo can work if you know it's a placebo, though. Man, our brains are weird.

    CJSF
    I think this may be due to mainly 'knowing' it at a conscious level. Maybe the subconscious just goes 'haay, doctors! White coats! Druuugs..this thing sure gonna work'....
    Formerly Frog march.

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    Quote Originally Posted by grant hutchison View Post
    Asthma, again, a good placebo responder, with objectively measurable changes in airway reactivity resulting from placebo administration.

    At what point did you work out your puffer was empty? Had you already had some good placebo responses before you realized?

    Grant Hutchison
    Oh, there's never any doubt when it's empty. You always shake it before taking a puff. You can hear the aerosol slush back and forth. No aerosol, no meds. But I use it anyway (because I can never seem to keep from losing a working one).

    I should clarify: I can always seem too get the teensiest hiss out of it. That lets me pretend I'm getting something out of it - but there's just no way there's any meds in it. Hearing a 'ts' is not enough to get aerosol in my mouth, let alone medicine in my lungs.

  4. #34
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    Quote Originally Posted by grant hutchison View Post
    Benedetti performed really complicated clinical trials in which he compared the effect of real drug which the patient knew to be real drug, with real drug administered without the patient's knowledge, with real drug the patient was told was inactive, with inactive substance the patient was told was inactive, with inactive substance the patient was told was real drug ... and so on.
    If you receive a real analgesic drug which you know to be an analgesic and in which you have confidence, it'll work better than if you receive the same drug but no-one tells you you're receiving it. In a model using dental pain, just knowing you're getting a good drug is worth the equivalent of 8mg of morphine in extra analgesic effect. That's a huge and clinically extremely relevant effect
    Dear Grant, thank you for this illuminating comment. It seems the placebo effect sits at a nebulous interface between psychology and physiology.

    There is a vast self-help literature relating to placebo medicine spawned by books such as The Power of Positive Thinking, which gets regarded with some disdain by narrowly scientific attitudes and yet has important lessons.

    An interesting book with implications for the psychology of the placebo effect is The Healing Power of Faith, Science Explores Medicine's Last Great Frontier by Harold G Koenig MD, head of the Duke University’s Center for the Study of Religion/Spirituality and Health. As a medico in the 1950s, Koenig explains he was surprised to see his scientific medical colleagues regard phenomena such as 'spontaneous remission' with indifference, so he studied such events and found the common factor was faith and determination. Attitude really is central to health. The placebo effect is part of a range of proofs of the interaction of mind and body in ways that can be usefully harnessed for health and wellbeing.

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    Quote Originally Posted by grant hutchison View Post
    preparations labelled as being expensive work better than the same drug marked as being cheap and generic
    Is this true even when we know about this and have chosen a cheap generic product over the expensive branded one (and having sufficient chemistry education to know they are identical)?

    In other words, are we rational cheapskates doomed to suffer from less effective medication?

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    Quote Originally Posted by CJSF View Post
    I don't understand how a placebo can work if you know it's a placebo, though. Man, our brains are weird.

    CJSF
    Did you know the Jiminy Cricket is right too? If you force a smile, you start to feel better and you can test the feeling with hormones.
    The body does tell the brain through posture as well as through activity. It may be called weird but it's real.
    sicut vis videre esto
    When we realize that patterns don't exist in the universe, they are a template that we hold to the universe to make sense of it, it all makes a lot more sense.
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    Forcing a smile can give me a headache.
    Formerly Frog march.

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  8. #38
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    Quote Originally Posted by Mudskipper View Post
    Forcing a smile can give me a headache.
    Well if you believe it, it will work!��
    sicut vis videre esto
    When we realize that patterns don't exist in the universe, they are a template that we hold to the universe to make sense of it, it all makes a lot more sense.
    Originally Posted by Ken G

  9. #39
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    Quote Originally Posted by grant hutchison View Post
    Allopathic?

    Grant Hutchison
    yes, it's that eve and I don't have to drive, I don' even have to cook, so my words may get blurred, but it's all in good spirit. Cheers
    sicut vis videre esto
    When we realize that patterns don't exist in the universe, they are a template that we hold to the universe to make sense of it, it all makes a lot more sense.
    Originally Posted by Ken G

  10. #40
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    Quote Originally Posted by profloater View Post
    Well if you believe it, it will work!��
    well I suppose it's not really forcing a smile; sometimes I just can't stop it! And if it goes on too long, I suppose I get a scalp headache.
    Formerly Frog march.

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  11. #41
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    Quote Originally Posted by Strange View Post
    Is this true even when we know about this and have chosen a cheap generic product over the expensive branded one (and having sufficient chemistry education to know they are identical)?

    In other words, are we rational cheapskates doomed to suffer from less effective medication?
    It would be interesting to try to come up with an experiment to check that one. While you can randomize people to receive the expensive or generic packaging, you can't randomize them to choose the expensive or generic packaging. You'd need some sort of cohort study, of the kind used to study lifestyle risks and industrial diseases.

    Grant Hutchison
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  12. #42
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    Quote Originally Posted by Robert Tulip View Post
    An interesting book with implications for the psychology of the placebo effect is The Healing Power of Faith, Science Explores Medicine's Last Great Frontier by Harold G Koenig MD, head of the Duke University’s Center for the Study of Religion/Spirituality and Health. As a medico in the 1950s, Koenig explains he was surprised to see his scientific medical colleagues regard phenomena such as 'spontaneous remission' with indifference, so he studied such events and found the common factor was faith and determination. Attitude really is central to health. The placebo effect is part of a range of proofs of the interaction of mind and body in ways that can be usefully harnessed for health and wellbeing.
    Koenig's book is interesting, but I felt it suffered from sampling errors (IIRC, there's no mention of those alcoholics who reject the "12-step" approach because of its spiritual component), and a certain confusion of correlation with causation (does being active in a religion make you more likely to follow doctor's instructions, or does being more likely to follow instructions make you more likely to adopt a religion?).

    Grant Hutchison
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  13. #43
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    Quote Originally Posted by Strange View Post
    Is this true even when we know about this and have chosen a cheap generic product over the expensive branded one (and having sufficient chemistry education to know they are identical)?

    In other words, are we rational cheapskates doomed to suffer from less effective medication?
    I would just like to let you know that generics are not necessarily identical. Prime example is the IV antibiotic Zosyn which has EDTA to improve solubility, whereas some generics do not contain the EDTA. I would guess that subtle changes, such as surfactants, preservatives, or antioxidants might have more profound differences than we realize as some of these can affect cell intake, endocrine disruption, metabolism etc. Otherwise, why use them in the first place.
    The moment an instant lasted forever, we were destined for the leading edge of eternity.

  14. #44
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    Quote Originally Posted by Copernicus View Post
    I would just like to let you know that generics are not necessarily identical. Prime example is the IV antibiotic Zosyn which has EDTA to improve solubility, whereas some generics do not contain the EDTA. I would guess that subtle changes, such as surfactants, preservatives, or antioxidants might have more profound differences than we realize as some of these can affect cell intake, endocrine disruption, metabolism etc. Otherwise, why use them in the first place.
    Manufacturers of generic drugs are required to demonstrate bioequivalance before the drug is licenced - although the excipients may vary between the branded and generic versions, the actual circulating levels of the active pharmacologic ingredient must be shown to match, both in terms of peak level and area-under-curve.
    So while patients who have reactions to the excipients (such as allergy) may find that generic preparations are not interchangeable, they are interchangeable in terms of drug delivery to the tissues.

    Grant Hutchison
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    Quote Originally Posted by grant hutchison View Post
    Manufacturers of generic drugs are required to demonstrate bioequivalance before the drug is licenced - although the excipients may vary between the branded and generic versions, the actual circulating levels of the active pharmacologic ingredient must be shown to match, both in terms of peak level and area-under-curve.
    So while patients who have reactions to the excipients (such as allergy) may find that generic preparations are not interchangeable, they are interchangeable in terms of drug delivery to the tissues.

    Grant Hutchison
    I really don't think it addresses cellular uptake. Just to the cell or virus, human or pathogen
    The moment an instant lasted forever, we were destined for the leading edge of eternity.

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    Quote Originally Posted by Copernicus View Post
    I really don't think it addresses cellular uptake. Just to the cell or virus, human or pathogen
    So you're hypothesizing a pharmacological interaction at the tissue level between the drug and the pharmacologically inactive excipients?

    Grant Hutchison
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    I have been reading "telomeres" and research shows just having happy friends lengthens your telomeres, the end bits of your DNA, and thus extends your healthy life. Just reading the book has made me feel better! Relevant? I think so. So it is!
    sicut vis videre esto
    When we realize that patterns don't exist in the universe, they are a template that we hold to the universe to make sense of it, it all makes a lot more sense.
    Originally Posted by Ken G

  18. #48
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    Quote Originally Posted by grant hutchison View Post
    So you're hypothesizing a pharmacological interaction at the tissue level between the drug and the pharmacologically inactive excipients?

    Grant Hutchison
    't underestimate the power of the Chemistry. I believe you are an ER doctor, so you must be incredibly smart. Many times they are a step or two above a regular doctors ability. But don't underestimate the complexity of chemistry. I have tried curcumin, which they say isn't absorbed well through the stomach. Traditionally it is used with pepper, oils and other spices. So some places have added piperine and it is supposed to improve absorption some great about, maybe 20 times. Great, so I've tried it, but I still don't feel any different. I figure it is a long term thing. Another company complexes it with some phosphatidylserine or phosphatidylcholine which are some type of food grade lecithin or derivative. Supposed to really increase the absorption. Well these are very similar to the phospholipid layer of the cell walls. Somehow I am very sensitive to anything with choline, or lecithin, or anything that increases acetylcholine. Huge muscle spasm side affects. To me it is not much different than an anti-muscle relaxer. My only point, is just because we have studies about placebo affects. Your best bet as a clinician, in my humble opinion, go the extra mile when a patient says something, but don't be naive either about some peoples ability to be manipulative.
    The moment an instant lasted forever, we were destined for the leading edge of eternity.

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    Quote Originally Posted by grant hutchison View Post
    So you're hypothesizing a pharmacological interaction at the tissue level between the drug and the pharmacologically inactive excipients?

    Grant Hutchison
    I should mention that getting stuff into cells is a whole new field of medicine. http://www.sciencedirect.com/science...69409X16301314
    The moment an instant lasted forever, we were destined for the leading edge of eternity.

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    Quote Originally Posted by Copernicus View Post
    't underestimate the power of the Chemistry.
    I don't. But we do actually have evidence from clinical trials, comparing the action of various bioequivalent preparations, using different excipients, showing that they don't just produce the same drug levels, but the same physiological effects. In terms of drug action, generic and branded drugs are equivalent. In terms of idiosyncratic reactions to individual excipients, they aren't.
    (Curcumin as dietary supplement has been subjected to multiple studies, at costs measured in hundreds of millions of dollars, which show it has almost zero bioavailability and no clinical effect, so I guess I'm not particularly surprised that you don't notice an effect even when you try different preparations.)

    Quote Originally Posted by Copernicus View Post
    I should mention that getting stuff into cells is a whole new field of medicine. http://www.sciencedirect.com/science...69409X16301314
    That's about getting stuff into cells using other cells as the vehicle. That's certainly new.

    Grant Hutchison
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    Quote Originally Posted by grant hutchison View Post
    I don't. But we do actually have evidence from clinical trials, comparing the action of various bioequivalent preparations, using different excipients, showing that they don't just produce the same drug levels, but the same physiological effects. In terms of drug action, generic and branded drugs are equivalent. In terms of idiosyncratic reactions to individual excipients, they aren't.
    (Curcumin as dietary supplement has been subjected to multiple studies, at costs measured in hundreds of millions of dollars, which show it has almost zero bioavailability and no clinical effect, so I guess I'm not particularly surprised that you don't notice an effect even when you try different preparations.)

    That's about getting stuff into cells using other cells as the vehicle. That's certainly new.

    Grant Hutchison
    This is from wikipedia. Though excipients were at one time assumed to be "inactive" ingredients, it is now understood that they can sometimes be "a key determinant of dosage form performance";[1]:1 in other words, their effects on pharmacodynamics and pharmacokinetics, although usually negligible, cannot be known to be negligible without empirical confirmation and sometimes are important. For that reason, in basic research and clinical trials they are sometimes included in the control substances in order to minimize confounding, reflecting that otherwise, the absence of the active ingredient would not be the only variable involved, because absence of excipient cannot always be assumed not to be a variable. Such studies are called excipient-controlled or vehicle-controlled studies.

    https://en.wikipedia.org/wiki/Excipient

    Don't underestimate the ability of a Pfizer to use confounding factors to make their stuff hard to duplicate. Its just business.
    The moment an instant lasted forever, we were destined for the leading edge of eternity.

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    Quote Originally Posted by Copernicus View Post
    This is from wikipedia. Though excipients were at one time assumed to be "inactive" ingredients, it is now understood that they can sometimes be "a key determinant of dosage form performance";[1]:1 in other words, their effects on pharmacodynamics and pharmacokinetics, although usually negligible, cannot be known to be negligible without empirical confirmation and sometimes are important. For that reason, in basic research and clinical trials they are sometimes included in the control substances in order to minimize confounding, reflecting that otherwise, the absence of the active ingredient would not be the only variable involved, because absence of excipient cannot always be assumed not to be a variable. Such studies are called excipient-controlled or vehicle-controlled studies.

    https://en.wikipedia.org/wiki/Excipient
    Yes. Which is why we run the sort of studies I already mentioned:
    Quote Originally Posted by grant hutchison View Post
    But we do actually have evidence from clinical trials, comparing the action of various bioequivalent preparations, using different excipients, showing that they don't just produce the same drug levels, but the same physiological effects.
    If an excipient turns out to be an active pharmacological ingredient, then it's (by definition) not an excipient, and it needs to be part of the generic product in order to reproduce its effect.

    Grant Hutchison
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    Quote Originally Posted by grant hutchison View Post
    Koenig's book is interesting, but I felt it suffered from sampling errors (IIRC, there's no mention of those alcoholics who reject the "12-step" approach because of its spiritual component), and a certain confusion of correlation with causation (does being active in a religion make you more likely to follow doctor's instructions, or does being more likely to follow instructions make you more likely to adopt a religion?).

    Grant Hutchison
    A review of Koenig's book is available on the internet, by David Grinstead. He makes the following comments:

    "Twelve step programs, depending heavily on personal religious experience to achieve and preserve sobriety, are highly successful. Compared to purely secular treatment, after a year into recovery, those in religious-based recovery programs were almost eight times more likely to report abstinence.

    Duke University’s Center for the Study of Religion/Spirituality and Health studies have produced these findings:
    • The deeper a person’s religious faith, the less likely he or she is to be crippled by depression during and after hospitalization for physical illness.
    • People with strong religious faith are less likely to suffer depression from stressful life events, and if they do, they are more likely to recover from depression than those who are less religious.
    • People with strong faith who suffer from physical illness have significantly better health outcomes than less religious people.
    • Religious people live longer... are both physically healthier into later life and live longer than their non-religious counterparts.
    • People who attend church regularly are hospitalized much less often than people who never or rarely participate in religious services.

    This book is about hard scientific data and facts that focus on the impact of traditional religious faith and practice on physical health and emotional well-being. It does not contain anything of specific spiritual guidance or pastoral advice."
    The relevance of these findings to the placebo effect is that they show that psychology and social interaction are essential to healing. Absent a hopeful vision of results that is reinforced by positive thinking and peer support, chemical healing alone is weaker in efficacy. The pharmaceutical industry has incentive to encourage focus on drug treatment, although sustained health requires social support networks. The placebo effect appears to rely on the neurology of social interaction.

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    Again, we need to know the population(s) studied, before we can assess the risk of sampling errors and confounding variables in those results.

    Duke's results come from the USA, but are not reproduced in more secular European countries. And there is actually a negative correlation, on a country by country basis, between prevalence of religious observance and average longevity.

    So we should perhaps step away entirely from the topic of religion, and look at access to public health and social integration.

    Grant Hutchison
    Last edited by grant hutchison; 2017-Dec-26 at 02:07 AM.
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    Quote Originally Posted by grant hutchison View Post
    Again, we need to know the population(s) studied, before we can assess the risk of sampling errors and confounding variables in those results.

    Duke's results come from the USA, but are not reproduced in more secular European countries. And there is actually a negative correlation, on a country by country basis, between prevalence of religious observance and average longevity.

    So we should perhaps step away entirely from the topic of religion, and look at access to public health and social integration.

    Grant Hutchison
    While we don't really know true meaning, I think it is important to feel like we know true meaning. And this is healthy, but not right. If this is wrong, I don't want to be right. This may be related to the placebo affect. I feel as though we need to feel like we are okay with what we are. A little unease is always needed as well. So, while medicine, access, and all that are important, validating peoples feelings is important too, giving them confidence in the system is important, but being skeptical has its place is well. There is no one easy formula.
    The moment an instant lasted forever, we were destined for the leading edge of eternity.

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    the question of overcoming skepticism in order to enjoy a placebo effect is interesting to me. I find I deliberately invest belief in certain people in order to convince myself , I guess that's confirmation bias.
    sicut vis videre esto
    When we realize that patterns don't exist in the universe, they are a template that we hold to the universe to make sense of it, it all makes a lot more sense.
    Originally Posted by Ken G

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    Then there's the idea of deliberately keeping yourself ignorant to avoid nocebo effects. I was lead author on a study many years ago which looked at what people actually wanted to know about their planned surgery. What they were interested in was landmarks in the recovery process; what they generally didn't want was to be told about was all possible adverse events. But the legal concept of "informed consent" has steadily driven forward the idea that everyone must be told every possible bad thing that could happen to them, whether they want to hear it or not. Just before I retired the General Medical Council in the UK removed all possible wiggle room for surgeons and anaesthetists by setting out in detail all the bad things we had to say to patients before they had their surgery, even if they didn't want to know.
    So we're being set up to deliver a powerful nocebo effect.
    The delivery of modern medicine has also removed an important aspect of the placebo effect from anaesthetic practice. It used to be that an anaesthetist would see his/her patient the night before surgery, and spend some time winning their confidence. Nowadays, patients increasingly pass through "pre-assessment" clinics well in advance of surgery, where they see someone who almost certainly won't be giving their anaesthetic on the day. This has advantages in picking up potential problems early, when there's still time to get new tests or to alter medication and avoid cancelling surgery at short notice. The disadvantage comes from the fact that the pre-assessment anaesthetist is unable to formulate a specific anaesthetic plan with the patient, and ends up having to talk in vague generalities about "Your anaesthetist on the day may want to do this or that". At best it leaves the patient with a feeling of unease; at worst it gives the patient a perception that the two anaesthetists disagree with each other about the best plan.
    So we're being set up to deliver a very poor placebo effect.

    Grant Hutchison
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    Quote Originally Posted by grant hutchison View Post
    So we're being set up to deliver a powerful nocebo effect.
    This is regrettable, and a greater "attornistic (solistic?)" society brings such things. How noticeable are the nocebo effects due to such liability notice "procedures"? Are the night before surgery visits a newer counter-measure approach to the warnings?

    I would guess that astrology would fit with this thread nicer than we would wish, but it might explain its perpetual popularity.
    We know time flies, we just can't see its wings.

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    Quote Originally Posted by George View Post
    This is regrettable, and a greater "attornistic (solistic?)" society brings such things. How noticeable are the nocebo effects due to such liability notice "procedures"?
    Research into this topic is relatively new, and a lot of it involves research ethics rather than clinical ethics. Much of it unfortunately resides behind paywalls. But here's a quite striking early example from Silvestri et al. (2003):
    During the first phase of the study patients received atenolol 50mg ... , 32 patients were blinded on the drug given (group A), 32 were informed on the drug given but not on its side effects (group B) and 32 took [the drug] after being informed on its side effects on erectile function (group C). After 3 months the incidence of erectile dysfunction was 3.1% in the group A, 15.6% in group B and 31.2% in group C.
    So being told about the side effect increased the chance of experiencing it 10-fold.
    You can find a few more references on this topic in a more recent editorial by Wells.

    So we have a couple of conflicting directives here. As physicians we must respect the autonomy of our patients, and therefore provide them with full information to make their own decisions. But we also have primum non nocere ("first do no harm"), which was part of my "Hippocratic Oath" even though Hippocrates never said it. So having respected the patient's autonomy by telling him about the danger of erectile impotence that comes with the beta blocker, do I then tell him that this information is potentially harmful, and he'd be better off not thinking about it? Or do I withhold the information on the grounds that the knowledge is itself more harmful than the drug?
    Back in the days when physicians and patients were treated like grown-ups, I used to get to the end of the stuff I thought the patient really needed to know, and then I'd fix them with a level gaze and would say: "That's the end of my usual story. I can tell you more about the dangers of this surgery and anaesthesia, and I am very willing to do so. Is there anything else you want me to talk about?" Usually they'd so No, and sometimes they'd say Yes. And we'd take it from there. And a lot of how that went would depend on how well I had established a relationship of trust and honesty in the foregoing fifteen minutes or so.
    To me, you can't legislate this stuff - it's about the personal relationship between two people, one of whom is putting their life and well-being into the hands of another. (But then, I'm a dinosaur.)

    Quote Originally Posted by George View Post
    Are the night before surgery visits a newer counter-measure approach to the warnings?
    Quite the reverse. We used to get patients in the night before surgery, and in the midst of various blood tests and x-rays and paperwork I could have a leisurely chat, taking as long as we both needed. But that was a patient occupying a hospital bed when they had nothing wrong with them. That's expensive. So the new model is an outpatient visit to the preassessment clinic, followed by a "same-day admission" on the morning of surgery. So instead of going to see the patient, in later life I would just sit down in my office in the afternoon and look through a checklist and a set of blood tests, and any action that the preassessment doctors had taken in response to the checklist and blood results. So I would have a patient perfectly prepared for surgery, except that I wouldn't see them until the morning of surgery - often not until the moment they arrived in the operating room. This is not conducive to the sort of therapeutic consultation that both of us would probably have preferred.

    OK. So why wasn't I seeing my own patients in the preassessment clinic? Because it takes less time to preassess a patient than it does to conduct their surgery, and if I was sitting about in a preassessment clinic, I'd have my feet up a lot of the time if I was only seeing those patients I'd eventually anaesthetize. So from my employers' point of view I should be in the operating theatre giving anaesthetics, while a colleague spends a day in the preassessment clinic blasting through ten operating lists' worth of patients.

    Grant Hutchison
    Blog

    Note:
    During life, we all develop attitudes and strategies to make our interactions with others more pleasant and useful. If I mention mine here, those comments can apply only to myself, my experiences and my situation. Such remarks cannot and should not be construed as dismissing, denigrating, devaluing or criticizing any different attitudes and strategies that other people have evolved as a result of their different situation and different experiences.

  30. #60
    Join Date
    Jun 2004
    Location
    Lugano, Switzerland
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    7,137
    Quote Originally Posted by profloater View Post
    Did you know the Jiminy Cricket is right too? If you force a smile, you start to feel better and you can test the feeling with hormones.
    The body does tell the brain through posture as well as through activity. It may be called weird but it's real.
    I wonder about the influence of positive thinking and a positive attitude.

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