Thursday 29 July 2010

What do we do about placebo?

ResearchBlogging.org
Body in Mind recently featured a piece on the ‘Moral Dilemma of Offering a Known Placebo’ in which Neil O’Connell talks about how the ‘placebo effect … in part rests on the effects of expectation, belief in the treatment and possibly a re-evaluation by the patient of their symptoms’. He was referring to treatments like acupuncture, electrotherapy and so on, and calls them ‘magic kisses’ because they work in a similar fashion to the ‘Mummy will kiss it better’ treatment I’ve given to my kids when they were younger.  The dilemma lies in the fact that placebo is simply an inert, inactive ‘intervention’ given as if it was active - inevitably requiring deception on the part of the practitioner, and what this can do to things like trust and informed choice by the patient.

So much of what we do as clinicians, particularly physical and occupational therapies, has a limited evidence base.  At the same time, some of the ‘active ingredients’ that have been identified in ‘placebo’ are the very things we are taught to develop – like active listening, instilling positive expectations, helping people re-evaluate their situation.  It’s incredibly difficult to disentangle the ‘active’ from the inactive components of the treatment.

Like Neil, I have concerns about encouraging, even inadvertently, any belief in a mystical, magical ingredient – chi anyone?  I also have concerns about any intervention that suggests the need for an ongoing relationship with a clinician – six-weekly ‘adjustments’ sir?  Or interventions that leave the power (or locus of control to be pedantic) with a gadget or device or substance that someone else needs to operate – three monthly infusions madam?

Dan Moerman’s view of health interventions suggests that every treatment inevitably contains culturally-based elements.  These are the result of an interaction between the person seeking treatment, the social environment in which they live, the treatment setting, the ritual associated with the treatment process, and the interpersonal relationship with the practitioner – everything we do in any healthcare encounter will influence the ‘healing’ or ‘meaning response’ of the patient.

Along with the placebo effect (meaning response), we sometimes forget the nocebo effect – the ill effects that people develop as a result of receiving an inactive treatment.  Take a look at any of the randomised, double-blinded, placebo controlled studies, and in a good one, you’ll see listed all the side effects that people developed when receiving the active treatment – and if you look carefully, you’ll also see the side effects that people developed when receiving the inactive treatment.  It’s entirely likely that along with our very effective, evidence-based treatments, some people will also either fail to respond, or will develop side effects that negate the positive effects of the intervention.

So what on earth do we do about this placebo thing?

Putting my ‘patient’ hat on for a moment, and remember that we are ALL patients at some point in our lives, I know that I want honesty from the practitioner I’m seeing.  I want to choose whether I have a certain treatment – or not.  And I want to know my options.  I’d like to be told about both the side effects and the hopefully positive effects of the treatment.  I want to know the evidence-base for the treatments I get (and if I don’t get told, you can bet, like many of our patients, I’ll be onto the internet and into the journals quick as a flash to find out!)

I don’t want to have a long-term relationship with a practitioner who will want to see me every six weeks or three months, and I don’t want chi (or woo).  I’m not into magic, superstition or intuition.

I’m inevitably going bring all my socially-shaped judgements and beliefs and prejudices into the treatment setting, and I know this is going to influence the outcome.

I’m likely to decide on a particular practitioner on the basis of word of mouth (reputation), what I’ve read from the literature (call that advertising if you will), and I’ll probably decide to return (or not) depending on his or her interpersonal skills – and because I too am influenced by the superficial – I’ll probably be influenced by the decor in his or her rooms and the cost of the treatment!

You see, we’re all influenced by these meaning responses.

So… what to do about placebo?  I, like Neil, hope that as the evidence accumulates, I will throw out the treatments that don’t have solid support from well-constructed RCT’s.  I will be mindful of my reputation and hope to have one that means I’m recognised by my adherence to an evidence-based approach to pain management.  I also hope I’ll always focus on helping people to help themselves, so I don’t inadvertently foster dependence on me.  I won’t be incorporating woo, chi or crystals (at least, not on the basis of current evidence!)  I won’t be using gadgets except as part of helping someone develop their own skills.  If I ask someone to come back after a bit of a break, it will be only to review how they’re going with their own goals, and to help them re-jig their plan for the future.

And I will try to recognise that some people will come to see me and will not ‘get better’ – not because of my approach, but because they have come into treatment with their own beliefs and expectations, their own ‘meaning response’ might interfere with what I’m doing.  Above all, I hope I’ll be honest about what I’m doing and be prepared to change my approach on the basis of science.

That darned placebo – whatever do we do about it? Learn more I hope!

Moerman DE (2002). The meaning response and the ethics of avoiding placebos. Evaluation & the health professions, 25 (4), 399-409 PMID: 12449083
Moerman, D., (2003). Doctors and patients: The role of clinicians in the placebo effect. Advances in Mind-Body Medicine. Vol.19(1), pp. 14-22.
Moerman, D., (2003). “Placebo” versus “meaning”: The case for a change in our use of language. Prevention & Treatment. Vol.6(1), pp. No Pagination Specified

Comments
9 Responses to “What do we do about placebo?”
  1. MM says:

    It appears your approach to providing a placebo treatment is to place yourself in the shoes of the patient, and then provide service in conformity with your own expectations. And you appear to be typical of doctors: trained to make decisions as scientists, disdainful of superstition, and desirous to personally weigh the possible consequences of various courses of action.

    While you and I may not like woo, many patients clearly do. Some people look to doctors or other experts not for information and choices, but answers.

    Why not provide treatment based on the patient’s preferences, not your own? You could provide each patient, prior to being diagnosed or treated, with information regarding the placebo effect and ask whether they would like placebo-like treatments to be incorporated where appropriate.

    Recognizing the limits of medical understanding the and the real effects of placebo treatments doesn’t mean you need to take advantage of patients by seeing them three times a week. As noted in the Mind and Body article, you can suggest relatively inexpensive acts that are otherwise beneficial to a patient–taking a vitamin, eating green leafy vegetables, walking 30 min. a day–even if there is no evidence these acts will help the specific problem at issue.

    Give patients information and let them decide–even on the issue of whether they should be given further information. The alternative may be that patients without adequate information will simply seek out expensive placebo treatments on their own.

      Reply
  2. Ronny says:

    Placebo/nocebo is of no serious clinical value or significance, and lying to patients is never acceptable (perhaps with a tiny handful of short term exceptions, like when dealing with a parent who is strongly suspected of abusing their child, or patients who are tipping over into psychosis and need hospitalising).

    (Of course, this effect should always be controlled for in formal studies. But beyond that, meh.)

      Reply
  3. Bernadette Murray says:

    I chuckled when you admitted that the decor might play a role in your perception of a practitioner.
    Seriously though, I really started thinking about the ethics of the nocebo effect particularly when I caught
    myself mentally entertaining the thought of forwarding an email to a friend with graphic pictures of a particularly
    ghastly outcome from a repetitive behavior. I did not take this action because of course this is manipulation –trying to influence my friend to stop a behavior that I have ever so helpfully identified as being inimical to her health and well-being. And that frankly –TRUTH now–I find irritating and annoying.

    The stupidest use of nocebo IMHO are those chain-mail emails that have magical benefits if only one forwards to the certain stipulated number of recipients; otherwise if one breaks the chain, whamm-o the curse is upon thee.

    Slightly more subtle, in the past I have had a doctor use the “if you do not take this medicine as prescribed, you
    could die” exhortation. I would have preferred a candid tempered discussion of limits of knowledge about the consequences of not treating the condition. Since I did not die when I stopped the taking medication and my test results came back within normal ranges, I unfortunately came to harbor some cognitive beliefs about doctors in my early twenties such as “doctors lie and exaggerate to ensure patient compliance ” and “doctors always minimize how painful a procedure really is so you will agree that the benefit surely outweighs such modest discomfort.” ha!

    I did not think doctors were EVIL or malicious. Seemed to me that they were rationalizing that the end justifies the mean (and they did not believe that they could present evidence to me and expect me to make a rational decision ) so they needed to employ some extreme emotional motivation.

    Fortunately, I have had many more encounters and opportunities to interact with doctors and I realize that those human beings, many of whom have discarded the white coat and are willing to share evidence and discuss options, are not homogeneous in their orientations.

    I have also come to realize that many alternative remedies are marketed in a weird kind of nocebo-fashion as non-existing illnesses are invoked so that the “remedies” can alleviate or cure them. ” A Toxic system filled with free radicals is the underlying cause of all illness….sip on acai juice while experiencing the health benefits of chelation therapy combined with a colonic.” Yup time to exorcize that demon “toxicity”

    Coming back to what you are saying so well in your post: the problem with placebos is the Dumbo’s magic feather conundrum. Dumbo can fly without the feather, and we as patients actually generate our own neurotransmitters which modulate our own systems. I really like your emphasis on interacting with your patients so that they can fly on their own (metaphorically speaking of course ;-)

      Reply
  4. Neil O'Connell says:

    Great post Bronnie (thanks for the mention) and I couldn’t agree more. I think patient choice is a difficult concept here because it is very difficult for patients to access or distinguish good health information. There is so much misdirection, anecdote and outright fraud out there and when you are in desperate need you become vulnerable to the peddlers of false hope. I guess it boils down to “keep what works, keep the care and dump the magic”.

      Reply
  5. ian stevens says:

    Its a difficult issue, ethically prqctically and economically (for both private providers and patients) in many ways. However, positively if we can enhance meaning ,facilitate a persons own process of restitution and understand what may move a person towards this state than this has to be a good thing? Spaces and places where treament takes place for example have been studied by the Rheumatologist Esther Sternberg. Often complex cases of distress and disabilty are shunted into stark clnical rooms with rushed appointments (this was my experience of several pain clinics).
    I fully endorse pain managment , enhancing self efficacy and minimising disability. However in Neils terms a few ‘kisses’ probably will not go amiss. A good narrative which looks at a patients journey dealing occupational therapy following an elbow fracture and secondary neurogenic pain is the Sociologist Ann Oakley’s Fracture. The response Ann obtained through the enhanced treatment effect cultivated by the acupuncturist (environment ,demenour , care ) was in stark contrast to the orthopaedic clinic . People often seek care, reasurance and an ‘individualised’ approach –this is often lacking in many protocol led clinics.
    I disagree with the post that suggest placebo and nocebo are of no clinical importance. For many people nocebo is a feature of many health care interactions and according to Benedetti may have strong negative physiological consequencies. As biomechancial explanations of pain are dominant many people are told or interpret the results of tests,scans etc in often maladpative ways ….you have the spine of a 70 year old often leads to catastrophisation and disability for example.
    I think for some people ‘chi’ used as a metaphorical explanation is not too bad… metaphors used wisely may indeed enchance meaning and downregulate threat. I suggest tai chi and use the principles all the time–it does not mean that I think chi,prana etc are ‘real’ but perhaps these metaphors may improve a persons self image /intereoception (especially if they learn to do things themself) .The danger perhaps is if these things are relied upon too much …..’Peddlars of false hope’ …yes a big problem and it is easy for those in the scientific medicla community to sit on a pedastal casting stones on CAM etc when many interventions offered by the medical profession offer little and in many cases are iatrogenic. I would have no problem suggesting certain ‘woo’ therapies offered by some caring people I know over and above an interventional pain clinc or rheumatology clinic for example . Allowing a stressed out person with often complex social issues a little respite seems fine in some circumstances . It may be a better use of resources than the mri/ct multiple health professional pharmacology route which tends to be a frequent occurrence.
    Sometimes I just think we live in a overly medicalised culture and placebo treatments will just evolve to meet the demands of the population seeking care and attention!

Yep!

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Brainstem, spinal cord images hidden in Michelangelo’s Sistine Chapel fresco

Acupuncture Pseudoscience in the NEJM

Here is the conclusion quoted from a recent New England Journal of Medicine (NEJM) review article on acupuncture for back pain:

As noted above, the most recent wellpowered clinical trials of acupuncture for chronic low back pain showed that sham acupuncture was as effective as real acupuncture. The simplest explanation of such findings is that the specific therapeutic effects of acupuncture, if present, are small, whereas its clinically relevant benefits are mostly attributable to contextual and psychosocial factors, such as patients’ beliefs and expectations, attention from the acupuncturist, and highly focused, spatially directed attention on the part of the patient.

Translation – acupuncture does not work. Why, then, are the same authors in the same paper recommending that acupuncture be used for chronic low back pain? This is the insanity of the bizarro world of CAM (complementary and alternative medicine).

Let’s break down their conclusions a bit. They have reviewed the clinical evidence, as I and others have done before, and found that when real acupuncture is compared to various forms of sham acupuncture (the acupuncture version of a placebo) there is no difference. As I have written many times before – it doesn’t matter where you stick the needles, or even if you stick the needles. Since acupuncture consists of sticking needles in acupuncture points, the only reasonable conclusion from this evidence is that there is no specific effect from acupuncture – acupuncture does not work.

The phrase, “contextual and psychosocial factors, such as patients’ beliefs and expectations, attention from the acupuncturist, and highly focused, spatially directed attention on the part of the patient.” is a fancy way of saying “placebo effects.” In other words, there are some non-specific subjective benefits to getting attention from a practitioner. There is this assumption, however, that these benefits are real and worthwhile. However, they are likely to be illusory – an artifact of observation and reporting, not a real improvement in the patient’s condition. In real science-based medicine, that is the underlying assumption – placebo effects are largely illusory – a variable to be controlled for.

But there has been recent controversy over the role of the placebo effect in ethical and evidence-based practice. This is, in my opinion, largely a back door attempt to justify CAM treatments that do not work. The claim is that placebo effects are real and useful. But a systematic review of the placebo effect in clinical trials concluded:

We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed.

In other words – for any objective outcome, there is no important placebo effect. For outcomes that are subjectively reported by patients, there is a highly variable placebo effect. It is plausible that the expectation of benefit could result in the release of dopamine and endorphins and produce a physiological decrease in pain, for example, in a subset of people, and there is some evidence for this. But this is, at best, a transient symptomatic effect – not therapeutic.

Such effects are also non-specific – meaning they do not derive from the intervention itself, but from the therapeutic ritual surrounding the intervention. Even treatments that do not work may therefore provide these non-specific benefits. My opinion is that the non-specific benefits of the ritual of treatment should be combined with an actually effective treatment, not magic pretending to be medicine. There are many reasons for this. One is the ethics of patient autonomy and informed consent – giving a fake treatment to a patient violates the patient’s rights, in my opinion.

Further, there is potential downstream harm from convincing patients that fake magical treatments are effective, because of placebo effects. Then using obscure language to hide the fact that the treatment actually does not work. This distorts the public’s view of medicine, and of what works, and sets them up to be victims of fake treatments when their ailment is not subjective or self-limiting. In other words – refer them to an acupuncturists when they have back pain and they may rely upon acupuncture, or some other non-scientific intervention, when they have a more serious illness.

The authors of this article recommend:

He has specifically requested a referral for acupuncture, and we would suggest a course of 10 to 12 treatments over a period of 8 weeks from a licensed acupuncturist or a physician trained in medical acupuncture.

This contradicts their own conclusions. Why is training in acupuncture necessary? That training largely consists of identifying acupuncture points, knowing which points to use on an individual patient, and knowing the technique of needle insertion – but none of these things matter. The sham ritual is all that matters – you can literally fake it and get the same response. I bet a 10 minute video is all that is necessary. In fact I bet even that is not necessary – you could probably fake it well enough to get a maximum placebo effect without any prior demonstration.

What the authors of this article have done is something that is increasingly common in CAM (when it is trying to infiltrate academia and peer-reviewed journals like the NEJM) – reviewing the evidence, admitting that the CAM treatment does not work, then making an elaborate and misleading appeal to placebo effects, and ending with a recommendation to use the treatment that does not work. Specifically, they not only recommend using the treatment, but in its fullest magical form, complete with all the disproven claims (that is what “medical acupuncture” is). It’s a bait and switch con game, nothing more. Come for the placebo effect, then be treated with magical nonsense.

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Acupuncture does have beneficial effects with some people. I have recently stuck some needles randomly about my knee that has been hurting intermittently for a year or so and it felt great afterwards (a case study of one!). We know that something happens but no-one knows exactly what. Stick needles anywhere and there's an effect. Well, the brain is probably going to do something in response to this tissue 'invasion' and maybe in certain cases it prioritises away from the pain hence the relief. Some talk about endogenous opioids, adenosine and DNIC. Perhaps they all have a role. Certainly expectation, belief and understanding will have a part to play as in any treatment. Modulation of pain is complex and the notion of local effects is out-dated. Multidimensional responses are more likely (Thacker & Gifford, 2002).

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Friday 23 July 2010

Champagne fizzles out if served with a splash

Champagne being poured into a glassNot the best way to pour champagne.Carlos Alvarez / iStockphoto

If you want to enjoy champagne to the full, pour it out as you would a beer.

Sommeliers and connoisseurs may find the suggestion hard to swallow, but the evidence published in the Journal of Agricultural and Food Chemistry1 seems irrefutable. Pouring champagne into a tilted glass helps it to retain the dissolved gas that is vital for the gustatory experience, say Gérard Liger-Belair and his colleagues at the University of Reims in France.

The French team compared the amount of dissolved carbon dioxide in a fresh flute of champagne poured the traditional way — splashing it into a vertical glass — with that after pouring along the inside of a tilted glass, as one does with beer to avoid giving it too much frothy 'head'. The researchers found that champagne served chilled (at 4 °C) contains about twice as much dissolved CO2 using the beer-like method.

A typical 75-cubic-centimetre bottle of champagne contains five litres of dissolved CO2. When uncorked, the release of pressure means that the liquid becomes supersaturated with the gas, which then begins to escape as bubbles. These contribute to the pleasure of drinking champagne in several ways: they give it a lively appearance, release aromas (the 'nose'), produce the stimulating oral sensation of collapsing bubbles, and create sharp tang owing to the conversion of CO2 to carbonic acid inside the mouth.

"CO2 has a strong effect on the sensory experience and flavour of champagne," says Susan Ebeler, an analytical chemist and oenologist at the University of California, Davis. "Flavour is a multisensory experience, including aroma, taste, colour, mouth-feel and even auditory cues. CO2 can affect many of these senses."

Cold comfort

The slower a glass of bubbly releases its CO2, the longer it remains vivacious. Yet it turns out that most CO2 is lost not through bubbles bursting but by simple diffusion across the liquid surface. That is why flutes are used in the first place: the narrow neck reduces the surface area from which gas can escape.

The correct way to pour champagneTilting the glass helps to keep more carbon dioxide in solution.Gérard Liger-Belair / American Chemical Society

Pouring has a big influence on the gas content, both because the 'tongue' of liquid falling from the bottle to the glass exposes a large surface area and because turbulence and entrapment of air bubbles as the liquid hits the glass can speed up diffusion of CO2 out of solution.

The beer-pouring action should cut CO2 loss on both counts: the column of flowing liquid is less exposed to air, and the gentler impact reduces turbulence. Liger-Belair and his colleagues have confirmed this, using a standard method for measuring dissolved CO2 concentrations (based on the activity of the enzyme carbonic anhydrase, which reacts with carbonic acid), and using a method called thermography, which provides snapshots of CO2 levels in air based on how strongly it absorbs infrared radiation.

The researchers also show that both to maximize CO2 retention and to obtain the full benefits of the beer-pouring technique, the champagne must be chilled. When served at close to room temperature (18 °C), champagne served by the beer technique loses about two and a half times more CO2 than when chilled — almost as much as it loses when served in the traditional way at room temperature.

Liger-Belair and his team show that increased gas loss from warm champagne is mostly a result of two factors. First, the colder liquid is more viscous, and so gas-leaking turbulence is dampened more quickly. Second, CO2 molecules diffuse slowler in cold water, and so are unable to reach the surface as quickly.

Will champagne lovers be persuaded to alter their ways? "Champagne is a universe full of traditions," says Liger–Belair, who has worked as a consultant for the research department of Moët & Chandon. "But maybe champagne and science can mix to offer a better way of tasting," he says. He has at least one convert already. "Based on this paper, I probably will pour using the beer-like method now," says Ebeler. 

  • References

    1. Liger–Belair, G. et al. J. Agric. Food Chem. advance online publication doi:10.1021/jf101239w (2010).

Absolutely vital advice!

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Pregabalin and Transcutaneous Electrical Nerve Stimulation for Postherpetic Neuralgia Treatment

Check out this website I found at pdfs.journals.lww.com

Perhaps this synergy will help other conditions that involve neuropathic pain, e.g. back pain that has a NP component. Understanding the TENS parameters will allow us to determine potential mechanisms and hence other ways of facilitating these processes and pathways.

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Thursday 22 July 2010

Serotonin cell discoveries mean rethink of depression

IF YOU thought depression was caused by low serotonin levels, think again. It looks as if the brain chemistry of a depressed person is much more complex, with mounting evidence suggesting that too much serotonin in some brain regions is to blame.

If correct, it might explain some of the negative side-effects associated with selective serotonin re-uptake inhibitors (SSRIs), antidepressants like Prozac which increase the amount of the neurotransmitter serotonin in some parts of the brain.

The traditional view of depression was largely based on the observation that SSRIs boost mood- although why they do so is unknown. "Because antidepressants increase serotonin in some parts of the brain, people assumed that depression must be the result of low serotonin levels," says Christopher Lowry of the University of Boulder in Colorado. But the discovery of multiple types of serotonin-releasing neurons in the brain, along with high levels of serotonin recorded in people with depression, is prompting a rethink.

"What's more likely is that there are subgroups of serotonin neurons that are overactive in depressed patients, rather than underactive as we have all been assuming," says Lowry.

It's likely there are groups of serotonin neurons that are overactive, not underactive as assumed

One of the first clues that something might be amiss with the traditional theory came three years ago, when Murray Esler at the Baker Heart Research Institute in Melbourne, Australia, and colleagues found that the level of serotonin in the brains of people with panic disorder was four times higher than in healthy volunteers (Stress, DOI: 10.1080/10253890701300904), and in depressed people who were not receiving treatment it was two times higher than in volunteers (Archives of General Psychiatry, vol 65, p 38). They also showed that long-term use of SSRIs in people with depression and panic disorder seemed to decrease serotonin levels through an as yet unidentified mechanism.

Now, in studies of rats and mice, Lowry has found that there are multiple types of serotonin neurons that can be independently regulated. He presented his results at the Forum of European Neuroscience in Amsterdam, the Netherlands, last week.

This fits well with findings from other groups that there are two types of serotonin receptor in the amygdala, a brain region linked to emotion and anxiety: 5-HT2A receptors that inhibit anxiety, and 5-HT2C receptors that promote it. The roles of the receptors were identified by injecting drugs that either stimulated or inhibited each receptor and observing the animals' behavioural response.

Together, the findings might mean that while high levels of serotonin in some brain regions like the prefrontal cortex can lead to improved mood, high serotonin in other regions could have negative effects.

Evidence for this idea comes from Gina Forster at the University of South Dakota in Vermillion and colleagues, who injected a stress-related molecule into the brains of rats and found that it triggered two phases of serotonin release. An initial wave of serotonin appeared to increase fear-like behaviour in the rats, while a second wave decreased this behaviour, possibly because it activated a brain region called the medial prefrontal cortex, which is associated with calming of fears (Neuroscience, vol 141, p 1047).

The new findings have implications for how SSRI drugs work. In the long-term, SSRIs do tend to have a calming effect, although more research is needed to understand how they do this.

However, in the short-term some people taking SSRIs report feeling increased anxiety. This is "almost certainly due to the activation of one of these groups of serotonin neurons", says Lowry. The suicidal thoughts some people taking SSRIs claim to experience may also be linked to boosting serotonin, as suicide is thought to be associated with increased impulsivity. "It may be that certain types of SSRI are affecting these impulsivity circuits in the brain," says Lowry.

Learning more about these different groups of serotonin neurons could lead to better treatments for depression and anxiety disorders. "It might be possible to design very specific drugs that can turn on or off specific groups of neurons that are deregulated in anxiety or depression," says Lowry.

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Oh Pharmaceuticals. .

Thu Jul 22 18:48:44 BST 2010 by nigel

lol we've (kind of) known about this since 1997: http://www3.interscience.wiley.com/journal/119148194/abstract

-the intro's gives a good overview of how wavy the whole low-seretonin theory was 13 YEARS AGO

..but someone's gotta sell their SSRIs haha

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Structural brain alterations in patients with irritable bowel syndrome discovered

Brain training needed for IBS?

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Coffee perks up memory and balance in geriatric animals

This is great news, coffee may not be the stimulant we thought but it can help with memory!

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Monday 19 July 2010

Flat-shoe pain? Blame the high heels, study says

'Cuddle chemical' eases symptoms of schizophrenia

NASAL sprays containing the hormone oxytocin, nicknamed the "cuddle chemical"Movie Camera because it helps mothers bond with their babies, have helped people with schizophrenia.

Although the 15 participants used the sprays for three weeks only, most reported measurable improvements in their symptoms in this the first trial to test oxytocin in schizophrenia. "It's proof of concept that there's therapeutic potential here," says David Feifel at the University of California in San Diego, head of the team running the trial.

Most participants reported measurable improvements in the first ever trial to test oxytocin in schizophrenia

Each participant received oxytocin or a placebo for three weeks, then the opposite treatment for three weeks with a week break in between.

On the basis of two standard tests for schizophrenia, taken before and after each block of treatment, participants averaged improvements of around 8 per cent when taking the oxytocin compared with the placebo (Biological Psychiatry, DOI: 10.1016/j.biopsych.2010.04.039).

The effects didn't kick in until the final week, suggesting that it takes a while for the hormone to begin acting. "Standard antipsychotic drugs increase their efficacy several weeks later too, so oxytocin fits that profile," says Feifel.

Feifel thinks that oxytocin is dampening down the excessive production of the neurotransmitter dopamine, which can trigger schizophrenic symptoms such as hallucinations. He says the rationale for treating people came from his own team's studies showing that oxytocin could relieve a form of psychosis in mice, and research showing that people who sniffed nasal sprays of oxytocin became more trusting, which could ease paranoia symptoms in schizophrenia.

Feifel is seeking approval from the US National Institutes of Health for a larger trial testing oxytocin at a range of doses, and over a longer time.

"This work provides compelling data on the utility of oxytocin as a treatment for schizophrenia," says Heather Caldwell of Kent State University in Ohio, co-author of a study in 2008 showing that "knockout" mice unable to make oxytocin were more prone to a form of psychosis.

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Compelling?

Fri Jul 16 14:47:13 BST 2010 by Allan Brewer

Actually I wouldn't say "8% improvement" was "compelling data".

Compelling?

Fri Jul 16 21:44:34 BST 2010 by allenallen

Yes, one wonders.... 8% fewer voices in their heads or were the voices 8% nicer in tone?

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The mind is the body - tumor suppression by enriched environment

This is a really nice piece of work providing mechanisms that could underpin the beneficial effects of an enriched environment. Understanding how we can create such environments for treatment and advising patients how to do so themselves to optimise their rehabilitation programmes that is so very important.

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Depression and dulled vision

A group have found that those suffering depression have an altered contrast perception and therefore 'see' the world around them as duller. The team speculate that the neurotransmitters involved in vision may have an emotive function. Click here

Astrocytes & sleep

As we find out more and more about the immune system and everyday function, it becomes pertinent that we develop a practical understanding of how we can work with this wonderful body system to benefit patients. This study looked at the way in which astrocytes influence neurons and how they affect sleep through action upon adenosine. Click here

Tuesday 13 July 2010

Exercise and the brain

As a physiotherapist with a background in neuroscience I am particularly interested in the effects of the exercises I prescribe upon the brain. Fortunately there is some excellent research that tells us about some of the responses and changes that occur in this wonderful organ when we engage in exercise. Understanding this can help us to make better decisions about being or becoming active and also to explain why we can feel different when we cannot exercise due to injury or another reason.

We know that exercise is important for cardiovascular health and reducing the risk of diseases such as diabetes, but less is commonly known about the beneficial effects upon the brain. In fact, knowing more about these responses could spur some individuals to taking on exercise or increasing activity levels.

Due to the release of certain neurotransmitters, neurotrophins and other factors in response to exercise, we see growth and repair of new brain cells (neurons), changes in neuron efficiency and the development of new blood vessels in the brain. What does this mean? It means that our mood is better, we can learn more effectively, reduce the effects of ageing, sharpen up our concentration levels, remember more and have an overall better experience of living. It’s a no brainer.

Mind your Immune System

Preventing CRPS after wrist fracture

NHS 'to undergo radical overhaul'

By Nick Triggle
Health reporter, BBC News
Health Secretary Andrew Lansley

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Health Secretary Andrew Lansley: "GPs will lead a bottom up design of services"

The NHS in England is to undergo a major restructuring in one of the biggest shake-ups in its history, the government has announced.

Hospitals are to be moved out of the NHS to create a "vibrant" industry of social enterprises under the proposals.

And, as expected, GPs are to take charge of much of the budget.

The move will lead to the abolition of all 10 strategic health authorities and the 152 management bodies known as primary care trusts.

THE KEY CHANGES

Continue reading the main story
  • GPs - Asked to get together in groups to take on responsibility for spending much of the NHS budget
  • Hospitals - Encouraged to move outside the NHS to become "vibrant" industry of social enterprises
  • Patients - More information and choice, including ability to register with any GP they want to
  • Managers - Strategic health authorities and primary care trusts face the axe

The new structure will be held accountable by an independent NHS board which would be free from political interference, the government said.

Meanwhile, responsibility for public health will be passed to local authorities.

In many ways, the plans outlined in a White Paper go further than expected. The coalition agreement had promised no top-down reorganisations.

But Health Secretary Andrew Lansley said he had decided to go further than first envisaged to rid the health service of "unnecessary" bureaucracy.

He said the proposals would be challenging and turn the NHS "upside down" but in doing so help reduce management costs by nearly a half within four years.

He added: "The government's ambition is for health outcomes - and quality services - that are among the best in the world."

'Experiment'

The GP move had long been championed by Mr Lansley - and in recent months the British Medical Association had indicated it was willing to work with him on the idea.

The plans mean GPs working in groups will be in charge of a vast collection of hospital, mental health and community services - although specialist services and dentistry will not fall under their remit.

ANALYSIS

Continue reading the main story

It had been clear for some time that Andrew Lansley was planning big changes.

But it is a mark of how far-reaching the White Paper actually is that many experts are still shocked by the scale of the proposals.

At a time when the NHS is having to find savings of up to £20bn by 2014, the proposals are being seen as a huge gamble for the service itself and the health secretary personally.

At the heart of the plans are GPs. They, Mr Lansley believes, are better placed than managers to make decisions about services.

Buffeted by years of criticism over what have been perceived as excessive pay rises, GPs now find themselves in the curious position of being given the keys to the NHS safe.

The question on everyone's lips now is: Can they spend it wisely?

Under the new system, the independent board will sit above as many as 500 consortiums of GPs to set standards and hold the groups to account.

Another key aspect of the changes involves giving patients more information and choice. To achieve this, a new body, HealthWatch, will be set up to compile data on performance, while GP boundaries will be abolished to allow patients to register with any doctor they want.

Mr Lansley also announced he expected all NHS trusts, which run hospitals and mental health units, to get foundation status by 2013.

He also said he would be relaxing the rules which cap the amount of income a trust can make outside the NHS, opening the door to them seeing more private patients.

He said this would allow them to innovate and widen the scope of what they did, but he also admitted it would mean those which were not financially viable could go under.

The government will now consult on its plans before rolling them out over the next three years.

Shadow Health Secretary Andy Burnham

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Shadow Health Secretary Andy Burnham: "reorganisation is last thing the NHS needs"

Professor Chris Ham, chief executive of the King's Fund think-tank, said: "It is a very radical programme. We have never seen anything like this since the inception of the NHS in 1948."

But he said the moves were not without risk, pointing out some GPs would not have the skills to manage the budget.

Shadow health secretary Andy Burnham went further, describing the changes as a "political experiment".

"It is a huge gamble with a NHS that is working well for patients."

There was a mixed reaction from NHS staff. Unison said the changes could lead to "chaos", but the BMA said they could benefit patients and it was looking forward to working with ministers.

Katherine Murphy, of the Patients Association, called for more clarity over how and what information would be provided to patients.

"We need more details," she added.

Posted via email from Specialist Pain Physio

Low vitamin D levels associated with cognitive decline

Vitamin D levels associated with Parkinson's disease risk

Monday 12 July 2010

Early Alzheimer's identification method discovered

Antibody cuts brain damage in strokes

THE discovery of an antibody that binds to certain brain receptors could reduce the side effects of a common stroke drug and buy additional time in which to use it.

The preferred treatment for ischaemic stroke, in which a blood clot cuts off the blood supply to brain tissue, is a drug called rtPA, which dissolves the clot. However, that drug has to be given within the first few of hours of a stroke, otherwise the risks of treatment outweigh the benefits. Dissolving the clot can lead to a sudden rise in blood pressure, increasing the chance that a blood vessel will rupture and bleed into the brain.

Only 5 to 10 per cent of people who suffer a stroke make it to hospital early enough to be treated with rtPA, says Denis Vivien of the University of Caen Basse-Normandie in France. The rest are given drugs that do not destroy the initial clot but reduce the chance of further clots forming.

One reason for a delay in administering rtPA is that a brain scan must be carried out to determine the nature of the stroke. People with haemorrhagic stroke, in which a blood vessel in the brain bursts, should not receive rtPA as it increases the risk of bleeding.

Now a startling discovery by Vivien has put a different perspective on this relatively simple picture: rtPA is actually released by brain cells. "This was completely unexpected," he says.

In small quantities, rtPA binds to brain-cell receptors for a chemical called NMDA. This triggers a short-lived influx of calcium, enhancing learning and memory. But damaged neurons release rtPA in large quantities, and this can cause neighbouring neurons to die. High levels of rtPA can also damage the blood-brain barrier, which may explain why the drug sometimes triggers dangerous bleeding.

Vivien has also developed an antibody that could overcome these problems. It stops rtPA from binding to the NMDA receptors, blocking its negative effects. When mice were injected with the antibody on its own or in combination with rtPA, the amount of brain damage resulting from a stroke was reduced by up to 70 per cent - both when the antibody was given immediately after the stroke and 6 hours later. Three months later, these mice also showed significantly less disability.

"With the antibody, we completely prevent the deleterious effect of rtPA and we can increase the time window during which it can be given," says Vivien, who presented his results at the Forum of European Neuroscience in Amsterdam, the Netherlands, this week. If the results are replicated in humans, this might mean that the antibody could be given on its own, even before a stroke sufferer reaches hospital. The antibody could also make it safer to administer rtPA for a much longer period, vastly increasing the number of people who could benefit from it.

What's more, because the antibody blocks the effects of the rtPA being released by damaged brain cells, the treatment might benefit people who have had a haemorrhagic stroke. "We can postulate that maybe all stroke patients could benefit," says Vivien, who is now working with a pharmaceutical company to take the antibody into clinical trials.

We suggest that maybe all stroke patients could benefit from receiving this antibody

Resting brain activity shows up damage

Studying brain activity at rest could help assess the extent of damage caused by strokes.

Imaging techniques can highlight large areas of damage, but disabilities seen in people who have had a stroke suggest that more brain regions have been affected than are picked up by scans.

To better pinpoint damage, Maurizio Corbetta of Washington University in St Louis, Missouri, used functional MRI to scan the brains of 23 stroke patients. He measured resting state activity in networks of neurons involved in controlling arm movements and directing visual attention. He then correlated these patterns with the extent of each person's disabilities.

Corbetta found that the coordination between these networks was disrupted in those who have had strokes compared to healthy individuals, even though the regions themselves showed no obvious structural damage.

"For the first time we can assess the damage to brain networks in areas that otherwise appear normal on a scan," says Corbetta, who presented his results at the Forum of European Neuroscience in Amsterdam, the Netherlands, this week. He now plans to see whether this activity can be used to predict how well people will recover from a stroke.

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Have your say

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"rtpa" Versus "tpa"

Thu Jul 08 16:35:52 BST 2010 by Eric Kvaalen

Most of the places in this article where it says rtPA it should say tPA, which stands for "tissue plasminogen activator". The r of "rtPA" stands for "recombinant", so this refers to tPAs which are made artificially using recombinant technology. In other words, rtPAs are "drugs", whereas tPA is the natural protein produced by our cells.

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Brain Re-training To Decrease Pain

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