This hipster showed us infinitely cool back in 1848, which is totally 0K 😉

Science geek jokes aside *, learning has three aspects. The tuition, the practise, and the assessment. Measurement is not simply to verify competence, but it’s vital to correcting and enhancing understanding.

hipsterMetrics
Athletes seeking peak performance are being joined by all and sundry seeking motivation for exercise, in usage of metrics. Simple weight and repetitions, or distance and times logged, or biometrics such as heart rate (to keep inside a safe envelope of effort). Recently heartrate variability (HRV) sensing has been adopted to inform the decision of whether to train today. Or sleep in. To explain: fight & flight is from the sympathetic nervous system causing endocrine outputs such as adrenalin (epinephrine). It’s a survival response arising in the reptilian depths of our brain, around 6 times faster than rational thought process in the cortex. DON’T STEP ON THAT SNAKE ………………………………………………… no, wait up – it’s just a stick. Heightened arousal has already set off neuroransmitter and hormone cascades however. Chemical affect upon the heart ticker has a delay in effecting increase, which means that the beat-to-beat changes are subtle but steady. Rest & digest parasympathetic ying balances autonomic control of yang‘s panic, and is entirely effected by the vagus nerve. This electrical moderation of rate took time to formulate, but works near instantaneously. This means that beat-beat (R-R, or NN) intervals change markedly. Reporting on R-R through an HRV check is being suggested by coaches, to ensure the exercise activities are undertaken with the right mindset, mindfully.

HRV training uses biofeedback to display this measure of autonomic balance (or Vagal tone) in realtime, and seeks to amplify your increases in rate with the in-breath – a natural observation known as Respiratory Sinus Arrhythmia. Gevirtz and Lehrer provide many journal articles and video explanations, and a few months ago ‘Treating the mind to improve the heart‘ appeared in Frontiers in Psychology journal announcing studies underway at a US Veteran’s Affairs medical centre. The simplicity of the measure means it’s already quantified, thus a useful assessment. Neurofeedback training adds a level of complexity, by selecting EEG leads on the scalp to quantify, and visually report focus in regions of the brain responsible for control – such as sensorimotor for chronic pain. The history of training by reward for helpful brainwaves goes back to Sherman’s meditating cats in ’65. This is the second aspect, a practise.

Finally, the didactic beginning: tuition. Educational courses in mindfulness abound, this is a no-brainer!

Practicalities. HRV is supported by many cheststraps which very accurately measure the electrical R-R interval, and upload this to smartphone apps capable of Bluetooth LE e.g. Polar H7 and Zephyr HxM. Rather than BLE, Garmin uses Ant+ wireless as does 60Beat – SweetBeat for iOS interfaces on both these protocols. iThlete have a simple sensor to detect blood pulsing in the finger,  in a medical rather than sports context and this has been validated against the gold standard of ECG as a tool for developing countries.

* Zero degrees Kelvin (0°K) is very cold – the theoretical absolute minimum.

The butterfly emblem is frequently chosen by carefree souls, which suits my care-less persona also! My attention has flitted to continued controversy over two chronic pain studies – PACE for chronic fatigue, and Auckland University’s Stroke and Applied Neurosciences report: ‘Daytime napping associated with increased symptom severity in fibromyalgia syndrome’. Blogs and commentaries frequently generate traffic by highlighting controversy (but not mine, of course). Digging out the truth is easier by discarding any opinionated article which doesn’t link the original study for scrutiny, since both were published in open publicly accessible forums. If it matters, it’s usually in PublicLibraryofScience or the like. If hidden behind the commercial barrier of a medical journal, then it was probably just an extension of Pfarma’s marketing (if the statement by past editor of the unimpeachable British Medical Journal is to be believed). The late, great Dr Dave Sackett tickled my humours with his Clinical Trial Organisation HARLOT (How to Achieve positive Results without actually Lying to Overcome the Truth).

Linked study PACE was of very high quality. UK govt sponsored and large enough to be powerfully conclusive, it randomised sufferers from chronic fatigue into four arms:- standard medical care alone, or in combination with either of Cognitive-Based Therapy (CBT), Graded Exercise Therapy (GET), or Adaptive Pacing Therapy (APT). The outcome published in The Lancet in 2011 showed improvements in fatigue and physical functioning scores for CBT and GET, but not APT. An outraged patient community expressed alarm that doctors would prescribe exercise to reverse lack of physical condition resulting from illness. A planned followup investigation this year re-ignited the furore, explaining that CBT and GET mediate changed belief and citing a Belgian study “…the role of beliefs in chronic fatigue syndrome and fibromyalgia, which suggested that fear and avoidance of movement were associated with poorer outcomes.” Criticisms include the PACE protocol’s broad inclusion criteria, that their participant’s syndrome wasn’t real CFS are quite ironic given the difficulties experienced by anyone seeking validation for their own sero-negative invisible illness. Emotive catastrophisation reflects the shame felt at being stricken to bed – when the reality uncovered by another Belgian team is that CFS suffferers were hitherto over-achievers. This study isn’t published for the public, but I’m grateful for someone breaching Elsevier© copyright. It also seems free from bias.

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All the evidence is clearly presented in the links, so I won’t insult by advising what you ought to think of it all. Complaints will have to be made to the 640 who presented their results. However, the failure of APT bears editorialising. It was a program delivered by experienced Occupational Therapists per PaceTrial.org published manuals . APT wisely directs diarising of activity and subsequent post-exertional malaise to establish baselines of safe achievement, thus the salient lesson of ‘you play, you pay’ is documented in order to inform self-management. Advice is given on the need to inform work, family or friends on limited capacity to give of oneself. Diaphragm breathing exercises are explained with the importance of control over fight/flight responses. How could this not improve wellbeing? The answer awaits further analysis, but clearly deficient is any strategy for activity which may increase the envelope of energy. The therapist manual requires joint devising with the client of goals and aims  in CBT and GET only, and instructs not to motivate for an improvement in function in APT. Emphasis on self-compassion  without guidance for rehabilitation will leave patients stuck where they are. Mindfulness of the condition without movement to actively re-engage with the world, is analogous to theory without the practical. <continues Mar 2018>

Onto psychologist Alice Theadom and her survey. The implication is of causality between resting up and worsening symptoms, under the heading of Results: “Daytime napping was significantly associated with increased pain, depression, anxiety, fatigue, memory difficulties and sleep problems.” Worsened relationship with one’s boss too, I’d reckon. If the order of words was changed, one would presume that fibromites suffering worsened symptoms take more naps. But in each presentation of facts uncovered, the order is naps -> bad outcome. Briefly consider the impact to sleep, and the difference reported by nappers being an average of 17 minutes less each night. Mmm ‘kay. When strong pain hits, hit the couch and make up for that lost quarter hour. Incidentally, table 4 shows that the use of opioids is as strong a predictor of likelihood to nap as is gender. That one’s overlooked in the text, and close behind come gabapentin and pregabalin for sending you to sleep.

mackey

How to Breathe

The mindfulness teachings of Jon Kabat-Zinn in his book ‘Full Catastrophe Living’ aren’t new. Among palliative counselor Stephen Levine’s books is ‘A Year To Live’, wherein he advises living each day as if it’s your last. If it’s not too late to learn to breathe for the dying (drawing upon his work with Elizabeth KĂŒbler-Ross), then offering to the healthy a soft-belly breathing meditation is all the more valuable. This idea recognises that grief, and tension are held in a guarded, rigid stomach. A simple check is to place a hand on your belly, and the other on the lower half of your chest. Looking down, inhale deeply through your nose. If the hands move apart, you’re a stomach breather … and the studies show, probably male.

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Our two choices for getting air in are rarely explained, but the implications of a tight tummy are that the diaphragm muscle can’t flatten down. This means a chest heave is required, to expand the lung cavity by lifting the ribs outwards. These muscles work against the cartilage joining the ribs to your sternum, flexing that which has become harder with aging. Voice teacher and opera singer Dominique Oyston suggests that women generally conform to societal expectations of first, a flat tummy, and second, having a petite voice that’s raised in pitch. This means pinching off your breath, instead of letting your voice boom out from deeper down (which scares off men who’re insecure about their masculinity!).

The acute pain of early stages of childbirth is countered by conscious, patterned breathing in antenatal classes. A clinical trial for those suffering the archetypal pain caused by fibromyalgia (Zautra and Davis et al) reported in Pain 2010 that slower, deeper breathing reduced pain intensity due to external stimuli, suggesting in explanation an enhanced parasympathetic nervous system tone – overcoming fight/flight of the sympathetic response.

Much like medicating is not just a matter of forcing up hormone or neurotransmitter level, better breathing is not a simple matter of getting more oxygen through to tissues. A trial of 40 sessions in a diver’s hyperbaric chamber to allow normally toxic 100% oxygen delivery as treatment for fibromyalgia used SPECT imaging to determine areas of the brain where activity was changed by the therapy. The magenta section is the Anterior Cingulate cortex (ACC), previously showing less activity than is considered normal, had become enhanced after the 8 week course. This is the area where emotions lead to regulation of heartrate and registering pain (the greatest improvement was in the Brodmann Area 24, for those into neural mapping). The authors concluded the therapy induced neuroplasticity, proposing the effect as due to suppressed glial auto-immune response reducing neuroinflammation. The oxygen overdose’s reasoning can be described as triggering anti-oxidant pathways.

image002 - CopyDelivered by way of a more practical channel, EEGs after an 8 week Breathworks mindfulness course showed changes in the same ACC as pictured in the inset, increasing activity before administration of a painful stimuli. The ability to prepare oneself for suffering isn’t an easy skill to grasp. The course’s first task focuses meditation on a single point, observing one’s breathing.This interoception of bodily sensation is processed by spindle neurons, a type restricted to only two brain regions – the cognitive-emotional area of the insular cortex and the ACC. Lessons progress onto body scans, creating patterns associating feelings and senses, so as to effect mindful recollection for self-control (as discussed previously).

Handling pain better doesn’t make the pain go, straight away. However these regions interface to the endocrine system, and the hypothalamus-pituitary-adrenal (HPA axis) glands release old friends adrenalin, cortisol, and immune system regulator prolactin. If big changes need to be made, it’s best to start at the top – instead of swallowing chemicals in the hope of a quicker fix.

Soften the belly to receive the breath, to receive sensation, to experience life in the body,

Soften the muscles that have held the fear for so long. (Levine, 1997)

 

6

The smarter way to a 6-pack

Working the obliquus muscles by crunching won’t help back strength anyway. For more, read http://www.yogajournal.com/article/practice-section/forget-six-pack-abs/

Thoughtlessness

After a lecture by Tibetan Khenpo, Tsultrim Lodro, a question was asked by an upset Buddhist about the appropriation of mindfulness teachings by the military – specifically the use of breathing techniques by snipers. His answer was that soldiers in battle are suffering as much as anyone who’s in need of compassionate skills. The intro to Clint Eastwood’s American Sniper delves into taking of a life as an impossible decision for another mortal to make. Iraq veteran Garett Reppenhagen is a fine example of those who squeeze the trigger and the burden they carry as a result.  His Holiness the Dalai Lama is concerned that mindfulness used for a performance advantage has failed to adopt the fundamental truth of ‘drenpa’, or literally – memory. In ‘Beyond Religion’, it’s “the ability to gather oneself mentally and thereby recall one’s core values and motivation”.
The Western cherry-pick of this single-pointed focused practice but neglect of greater understanding requires a deeper examination of mindfulness, presented here as a reflection on July anniversaries of civilian aircraft downed by the military. MH-17 over the Ukraine being a repeat of an event lost from our memories. On July 3rd in 1988 a Ticonderoga class cruiser, still today the most advanced warship in the US fleet, fired missiles at Iranian airbus flight 655 killing all 290 onboard. Identify Friend or Foe civilan aircraft radar squawks were ignored by combat system operators who tracked the takeoff (on a commercial schedule), acquired the target, and the Commanding Officer approved the warfare officer’s request to engage.

Crew members monitor radar screens in the combat information center aboard the guided missile cruiser USS VINCENNES (CG-49).

Crew members monitor radar screens in the combat information center aboard the guided missile cruiser USS VINCENNES (CG-49).

Mindful techniques require introspection, using the stillness of a calm mind to examine within. CAPT Rogers, with his degree in Psychology should have been able to reflect upon his feelings of anticipating being celebrated as war heroes on the morrow, American Independence Day. This delusion of being under threat could hardly receive adequate attention in that heated moment (imagine “stand down from Action Stations, Skip’s gone to meditate”!), but rather needs longterm cultivation of self-awareness as a practice. Recognition of unhelpful emotional states whilst observing bodily senses assists in overcoming instinct or temptation. The fight & flight response which results from amygdala hijack of the rational higher brain is an evolutionary necessity which becomes catastrophic when in command of a warship. An agitated sympathetic nervous system is clearly manifest in vital signs of accelerated breathing and pounding heart, however monitoring of self by looking within is an acquired skill. Vidyamala Burch’s coursebook ”Mindfulness for Health’ describes misattribution of arousal as “because thoughts, physical sensations, and emotions are all intimately connected.” Freud  misled psychologists by proposing that id and super-ego are discrete entities balancing instinctive and moral behavior, and physicians take the disconnect even further. Responsibilities end with referral for psych treatment. Mind-body interventions are considered to be a type of approach that falls under the umbrella of complimentary and alternative medicine (CAM), which also includes manipulative therapies and herbal products. Repeat, CAM supporters theorise that mind, body and behaviour are all interconnected, and incorporate strategies that are thought to improve psychological and physical well-being, and aims to allow patients to take an active role in etheir treatment. This is considered ‘alternative’?

William James 1884 article in ‘Mind’ laid the groundwork for what’s now groundbreaking discoveries in interoception, or reciprocal bodily & emotive interplay. It’s still early days, while psychiatrists grapple with implications of anxious rats having had irritable bowels. A reprint of med student textbooks will have to wait awhile yet, but Eastern philosophies are ahead of the science here. Mindfulness as defined today relies upon non-judgemental attention to the present moment, which is good. Further teachings * from His Holiness the Dalai Lama introduce an emphasis on remembering, holding in mind an awareness of oneself: “Mindfulness is the ability to gather oneself mentally and thereby recall one’s core values and motivation…. With such recollection we are less likely to indulge our bad habits and more likely to refrain from harmful deeds” .  Recalling insights obtained from meditation is the only way to form new memories, otherwise the same old patterns of behavior will result in a life of Groundhog Day replays. The pragmatic psychologist remains value-free but to do so is an ‘ethical dementia’, to quote Buddhist monk Alan Wallace. Selectively deciding which of those among our clutter of feelings are wholesome takes judgement, based on a set of values. Accept the whole, simply being what it is. Recognise the good, and nurture it. In this way self-esteem is protected, and being attentive to emotions will notice those leading to dire consequences. The ancient Pali word sati means recollection, holding in mind. Being mindful.

*Beyond Religion pg 109

Previous blog postings on mindful meditation had focused on the science, but the complexities of innate immunity and autonomic response may be so overwhelming that the wise approach would be to simply try for yourself.  On the other hand, eastern spirituality provides explanations of health benefits which are heavily laden with Sanskrit language – probably equally offputting. A key learning is the concept of impermanence, the notion that All Things Must Pass (borrowing from Timothy Leary’s LSD inspired interpretation of Tao philosophy). Change, as an all-encompassing and irresistible force, and often unwelcome predicament creates a sense of loss if it won’t pass. The difficulty is managing the change, in order to avoid a worsening due to remorse or seeking of retribution. The Buddha wrote of the second arrow of anguish compounding the suffering of pain. The business world relies upon change as a path to growth, so has embraced mindfulness as a management of the inevitable. Individuals however, too often associate Buddhist notions such as impermanence with religious dogma rather than a philosophic understanding.

A middle way, between medical science and faithful belief is to be desired. At an International Yoga Day gathering, surgeon Ranjit Rao promoted “the higher echelons of Yoga, culminating into meditation. The ability to bring the sympathetic nervous system under control by reducing adrenal hormones is a great boon…”, and anyone who practices sufficient self-control to write a blog every single day on holistic approaches has my respect immediately*. Professor Jayashri Kulkarni, President-elect of the International Association of Women’s Mental Health said that “Finding individual mental peace through the practices of yoga and mindfulness can restore balance in physical and mental health“. Many other bridges can be found, and I found works from Arogyadhama to be eye-opening.  But there’s one language which crosses all cultures.$worship

Money speaks most persuasively throughout history, dwarfing the thousands of years that Ayurvedic therapies have been evolving. Researchers from the UK’s Bangor University reviewed the health economic justifications and issues in the medical journal of Mindfulness this year. The obvious bonus arising from a group session as compared with personal psychotherapy is a monetary one, due to economies of scale. The quandary arises in testing the benefit of a public health initiative delivered to groups of participants, whereas testing the efficacy of an  intervention has always focused on an individual’s complaint. Cost-effectiveness reports for health funding are typically consequent to successful trials of a therapy conducted under rigorous research protocols such as blinding of assessors. For a medication, this is easy – commitment to take a pill bears no burden. But to undertake 8 weeks of intense  focus requires a degree of commitment from a patient who’d presume the therapy to have merit, and thus reported outcomes may be biased.

Even more complex is compliance with medicine’s gold standard test – the Randomised Control Trial (RCT). The control or comparator group is either standard care or a placebo/sham treatment, but neither conform to our requirements. There is unfortunately no standard in care for fibromites (just as well for courts workload, else judging from social media narratives then 100% of their time would be booked by medical malpractice litigants for whom nothing is being done!), although consensus opinion endorses a multi-disciplinary approach.  And duping the controls with a fake course of unhelpful training is a nonsense too. A Cochrane review in April evaluating RCT attempts for mind and body therapies reports a standardised mean difference in Quality of Life score of 0.43 for psychotherapy, and a corrected figure for Mindfulness Based Stress Reduction (MBSR) of 0.39 (corresponding to an improvement of 9.5  points on a scale of 100). Another previous meta-analysis on MBSR for fibromyalgia by Lauche & Schmidt et al calculated score of 0.35 for QoL is very much in accord.  These results are significant, but insufficient.

One avenue for better results is the means of delivery – an individual therapy session vs group. Jon Kabat-Zinn’s MBSR launch a quarter of a century ago with publication of ‘Full Catastrophe Living’ has been adapted in this manner as Mindfulness Based Cognitive Therapy. Doctors reporting good results such as Craig Hassed, or Unlearn Your Pain’s Howard Schubiner may have benefitted from their clinical credibility when transforming client thinking. The timescale for achieving results also deserves further study – yogis put in years to attain insight, whereas a pharmacy can plaster over problems in a quick transaction. Understanding progress through diaries is to be encouraged, and biofeedback also holds promise. This could be respiratory testing (breathing.com offers some simple tools) or heartrate monitoring in order to understand autonomic nervous system balance between fight&flight and rest&digest. Your opinions and experiences are sought, as this solution continues to evolve.

* Admirable achievement even before considering he also authored ‘Meditation and Martini: the subtle cocktail of balance’

 

The Oz equivalent to the US FDA is the TGA, and their advisories provide both patient and doctor with assurances of drug safety. Ours can be searched at http://www.ebs.tga.gov.au to find that they consider the evidence for cardiovascular risk in Celebrex/celecoxib as being wholly provided by the report ‘Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study’. This is a trial conducted by the manufacturer Pharmacia – five doctors were employees and Fred Silverstein MD was a consultant, hence another employee, but a contracted one. CLASS ran for 27 months, but only the first 6 were written up. Any heart attacks or strokes 48 hours after stopping the drug were excluded, so if chestpain led to dropping out of the trial then any subsequent event was deemed to be irrelevant. Even if fatal. Flimsy, verging on dodgy grounds – so some detail is provided here for your discerning evaluation.

Steroids such as Prednisone are awesome, but awful in longterm usage. Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) for pain relief, a second generation inhibitor of COX-2 (_coxib)  inflammatory prostaglandins with less stomach risk than COX-1 inhibitors of prostaglandins (so far, seemingly so good). COX-2 is a driver of the PEG2 level controlling your hypothalamus’ setting of core temp – last flu bout, you noted fever came with pain? And the hypothalamus initiates inflammatory cascades via the HPA axis: churning out cortisol, adrenalin… oh dear. Some prostaglandins encourage herpes virus – to which everyone will have had exposure by the age of three. It’s everywhere. The likeness between fibromyalgia and viral-induced chronic fatigue hasn’t been overlooked by surgeon Skip Pridgen, who’s patented combo of celecoxib and an anti-viral is claimed to have commercial prospects for treating FM. But it’s also associated with a 37% increase in heart attacks and strokes – as Wikipedia would tell you.

Their citation is the 2013 Lancet article by the CNT collaboration (including Cochrane group’s usual suspects Bombardier * and Tugwell), systematically reviewing trials for adverse events associated with NSAIDs, which are fortunately rare during the monitored period. Especially since the inclusion criteria for arthritic participants precludes existing cardiovascular disease – hardly representative of real patient’s co-morbidities! The breakdown in a supplementary report shows that in fact 200mg has an indeterminate risk, but volunteers testing 400 should be nervous, and those on 800mg must be wondering about misplaced trust and whether insurance is paid up. A similar result during a trial of pain relief for colorectal cancer on 2,000 patients caused the safety committee to terminate, even though the elevated risk for those on only 200mg was non-significant. The Forest plot shown is named for its ability to show with confidence the wood amongst the trees, aggregating many trial results and weighting the risk according to their studies’ reliability.
celebrexOK
Vioxx, or rofecoxib COX-2 inhibitor scandal of FDA corruption and pharma coverup of heart attacks during trials was summarized by the court trial statement of “malicious, oppressive, and outrageous” conduct. Every suspicion of misconduct was confirmed. Complicit medical journals, doctors recruiting patients for ‘seeding’ of the market, and off-label promotion accompanied by false claims resulted in a settlement of $4.85bn. It’s equally easy to be fearful of Celebrex, even though Pfizer’s fight against patent expiry has conviction. Of its merit and benefit, not just the criminal convictions 😉

Along with CNT, the Safety of NSAID group meta-analysis of 25 studies found that higher dosages doubled the lower dose’s slightly increased risk of a heart attack. But declines to define where the dose cutoff lies.  The International NSAID Consensus Group think it’s good for those without elevated cardiovascular risk or with hypotension (likely to be evident in fibromyalgia and CFS). The cheque-red (sic) history of disdain for truth and ethical behavior exposed by court evidence demonstrates the need for systemic overhaul, because the truth is suppressed by industry.

Pfizer bought celecoxib via Monsanto’s drug subsidiary Pharmacia&Upjohn along with patent rights and their falsified trial data – since internal memos described “cherry-picking” of only the favourable results (mentioned in the opening paragraph). The new owner’s marketing efforts have been formidable, but accounts department was tardy in paying bills – the drug’s original discoverer Brigham Young University only recovered royalties from Pfizer through a half $bn court settlement. Anaesthetics Professor Scott Reuben was jailed for fabricating celecoxib trial results, coincidental with his promotion of combo therapy with Lyrica or Neurontin (No! Really?) Pfizer’s sponsorship of the studies doesn’t appear in hospital financial records however, raising the possibility that funding was paid directly to the fraudster. Interestingly, only one man was responsible for complete fabrication of studies. None of his team’s research careers were affected.

A 2002 BMJ article addressed fear of ulcers, independently reviewing studies on 15,000 participants. It was co-authored by Pfizer associate director of R&D. And omitted to collate adverse events of a cardiovascular nature ie those likely to kill you, since ”… While it is important to evaluate this concern, this was not possible here as the celecoxib trials we included did not report outcomes comparable with those assessed in Vioxx Gastrointestinal Outcomes Research.”

Meantime, the jury’s out. If pain relief affords you better Quality of Life, then individual decision making would be far easier if evidence wasn’t provided by dishonest researchers. Longterm study registered as NCT00447759 includes cardiovascular risk in the ‘Standard Care versus Celecoxib Outcome Trial’, without mentioning that Pfizer invested $43m (it’s a note within a press release, but no sponsors logo appears alongside nine of those for collaborating universities) – rather it’s claimed to be “an academic, investigator-initiated study, requested by the European Medicines Agency (EMEA) and sponsored by the University of Dundee.” The website states that “The study commenced in January 2008 and is expected to run until at least 2012”. Also concluding soon is NCT00346216, tracking some 20,000 patients over 7 years by Pfizer sponsored researchers, who’re reticent to declare conflicts of interest in their article on ‘Rationale, design, and governance of Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen’ (PRECISION) – other than having signed an undertaking to avoid commercial relationships during the conduct of the trial.

Coincidental report: ‘Celecoxib, but not rofecoxib or naproxen, attenuates cardiac hypertrophy and fibrosis‘, co-authored with Pfizer staff and published in 2010  is certainly promising, since this re-modelling is a leading cause of heart failure. These two studies could be win-win for Pfarma’s master puppeteer, and shareholders seem likely to be Celebr-ating. Pfizer’s statin Lipitor, being the highest grossing drug of all time, means that commercial interests are inexorably intertwined with every conference-attending cardiovascular expert’s research funding, but the secrecy is disturbing … (to be continued).

2017 update: PRECISION reported to ACR a couple of months ago, and SCOT trial was published. It’s safe enough.

* Claire Bombardier reported consultancies for Abbott, Amgen, AstraZeneca, Bayer Inc., Biogen Idec, Bristol-MyersSquibb, Hoffmann-La Roche, Merck(Schering Plough Canada), Pfizer and UCB Canada Inc., and is a member of an advisory board for Janssen (Merck & Company Inc.), Combinatorx Incorporated, Schering Plough, Pfizer, and Takeda Canada and holds research grants from Abbott Laboratories, Bristol-Myers Squibb Canada, Janssen, Hoffman La-Roche, Pfizer, Schering Canada and UCB… as listed  at doi:10.1093/rheumatology/kes032. The disclosure of conflicts-of-interest in the Lancet  the year following has only three consultancies listed. Near enough’s, good enough.

New Romantics FB3 actually wrote this about Thatcher-era Britain so the soundtrack doesn’t warrant linking, but the title suffices to illustrate a theme. In the mid-60s Canadian cystic fibrosis patients were entered onto a tracking registry, and other countries followed suit. The US foundation extracted outcome reports and used it to rank treatment centers, and the UK NHS mandates recording of all clinic attendance thus facilitating cross-country reporting. The best practice evidence revealed in this way is certainly less biased than any Cochrane review, since it’s also completely non-selective.
A more commercially oriented registry has been built at the for-profit PLM described here a few months ago. An FAQ encourages sufferers to ‘donate their data’ towards finding a cure, and this raises the intriguing idea of their vested interest overriding concerns about case confidentiality.

It’s not such a new idea. Grand rounds are a tradition in teaching hospitals, and case studies or series present de-identified but intimate details for elucidation of a condition. They’re win-win situations. Research institutions can also bend privacy rules to their own means – such as through ‘opt-off’ implied consent. Registries.org.au shows the benefit of, and reliance upon full capture of clinical care outcomes for quality monitoring.
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On the other hand, requests to the Director of Grants at NHMRC for the identities of reviewers approving research funding applications (in order to scrutinize for conflicts-of-interest) are denied – using as disclaimer “confidentiality of applications and that (sic) all personal information is dealt with in accordance with our obligations under the Privacy Act”. Their oxymoronic Principles of Peer Review of articles 2 “All stages of peer review are transparent” and 6 “Participants respect that confidentiality is important to the fairness and robustness of peer review” contradiction is exposed when a falsified report is challenged, posted in detail here. For anyone wishing to draw on a correlation between mental health and chronic pain, for all eternity, that study can be cited. The artificial construct of epidemic mental illness results in inadequate treatment available to those genuinely suffering, and a pill-popping panacea instead of fruitful therapy.

Similarly secret, we are invariably blinded to identities of the peers for a peer-reviewed journal. The commercial imperatives of publishing have been exposed by luminaries such as the BMJ editor, who, following a quarter of a century as chief executive wrote in open-source PLoS: ‘Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies’. Studies on the peer review process also show this form of governance is a fallacy. It seems to have been lost that the purpose of research is to improve outcomes, and that the data belongs to the patient rather than their drug dealer. Ownership has underpinned the ethical guideline of ‘beneficence’ instituted after Nuremberg, and accountability was promised by the institution when informed consent is granted by study participants.  That consent can’t be withdrawn posthumously if it doesn’t work out as expected.
Militant united voices can redress the present disempowered situation, only tolerated out of the individual patient’s desperation to obtain effective treatment for which they’re handsomely rewarding their service provider. That’s my dream. The reality is that a petition to draw the attention of our Health Minister, raised on the forum representing a (conservatively) estimated 600,000 fibromites managed only a few thousand signatures. As to whether meekness, or ignorance of commercially driven bias is to blame I’d suggest the former. Even if ‘doctor’ no longer translates from the Latin ‘teacher’, their authority is nonetheless unassailable.

Why don’t we do it in the road?

Paul McCartney wrote this song watching monkeys in Rishikesh, wondering what’s holding us back from doing it anywhere & with anyone. Near-same DNA also drives us to procreate or perish, a larger tribe being protective against predators. Compare the Emperor penguin, whose solitary annual egg is so precious that the male nurses it for the Antarctic winter. Now that’s hardcore toughguy! Can you imagine SAS or Special Forces taking on 2 months duty at 20 below, round the clock? Whether our species is better off breeding or brooding is best explained by Butters in the International Women’s Day episode screened in Oz yesterday and linked as a clip. These 8-year old boys are our best hope for future men moving on from our neanderthal roots.procreate

Hunting tigers to the brink of extinction has successfully risk managed our perishing, but we haven’t kept pace by evolving. Jon Kabat-Zinn wrote in ‘Full Catastrophe Living’ “But the flight-or-fight reaction kicks in even when there is no life-threatening situation facing us. It is sufficient for us just to feel threatened.”  The monkey brain reacts by releasing catecholamines such as adrenalin in order to to enhance survival – quickening the heart and vasoconstricting peripheral blood vessels. Hopefully the higher brain cortex can override the chemical flood with some rational control, delivered electrically through the parasympathetic nervous system. The degree of balance in this response is measured by HeartRate Variability studies of the fine-tuning control that can be achieved.

The value to an organisation of equanimity over impulse is promoted by neurologist Alan Watkins with his advice to HR on calm leadership. A subjugated ‘rest & digest’ parasympathetic system is called dysautonomia, and the fibro & CFS patient communities are passionate advocates of A/Prof Chris O’Callaghan with his Tilt Table Testing at the Austin’s Blood Pressure Clinic. Explaining the process when giving a diagnosis doesn’t often lead to resolving the internalisation of stress, which blocks autonomic responses. Carrying the muscular tension inside soon limits depth of breathing, favouring rib expansion over the more relaxed soft-belly diaphragm. Flexing your rib cartilage gets difficult with age, and it hurts. Luckily there’s instructions on how to breathe at the site breathing.com, and it’s never too late to learn. Psychoendoneuroimmunologists understand the impact of carrying around allostatic load, unfortunately noone can understand their bridging of four disciplines. Certainly not the GP, nor the patient with their expectation that there’s gotta be a pill to fix this. I hope South Park will explain this in one of their inimitable parables for me. Meanwhile, here’s a contemporary take:

This post’s theme is more cleverly conveyed by Zvyagintsev in ‘Leviathan’, where the human condition is literally spelt out for you. Putin thinks the film’s about himself, but of course he would.

2014© Medscape staff surveyed physicians on ethical issues, finding less than half confessed to a weakness for a freebie. That’s encouraging to drug reps, since influencing just a few Key Opinion Leaders pays dividends. So long as the flock all think alike, this being exemplified by a disclosure. The practitioner failing to practice what he preaches!drugreps
Dr Justin Coleman boldly challenged pharma thru his official position with Royal Aust College of GPs, fronting a well-publicised ‘no reps’ in the surgery campaign which raised ire among his fellows. Seriously, who’d ever believe wealthy physicians could be bought with a Bic? A humour-laden registrar tutoring session blogged recently under ‘Uncertain Dealings’ raises doubts. “Thus, when a patient complains of a painful lower back, my eventual diagnosis, after a thorough history and examination, is ‘low back pain’…. And, as for assuming my intervention of massage or gabapentin directly causes the pain’s eventual resolution, well
call me Dr Doubt!” Bon mots over a patient suffering pain aside, this is revealing. Gabapentin is an anti-convulsant for epilepsy, which happens to also fix everything – if Pfizer’s offlabel marketing is to be believed. Fines for such of $430m in 2004, $142m in 2010, and $615m (including $325m class settlement) in 2014 were just incidental costs alongside their promotional budget. The best evidence from Cochrane states that less than half of those with postherpetic neuralgia or diabetic neuropathy will obtain pain relief. So uncertainty over cause leads to a stab (glad he didn’t become a surgeon) that the pain originates from damaged nerves, and an indirect consequence of a hundred Pfizer Aust pain presentations to doctors in the previous 6 months just happens to be a prescription for Neurontin. And a little rub down there, in case of a herniated disc perhaps.

There’s been 6 studies into gabapentin for nociceptive pain, ie hurting without malfunctioning nerves, and all the results were suppressed by the company. They weren’t published, because they were negative. This disturbed Kaye Dickerson sufficiently to inspire a 57 page dissertation on the gabapentin, with a few hundred pages of supporting appendices.
The white knight * can offer no other assistance, and how did this come to pass? A letter from Pfizer Aust in 2003 prefaces the corporate strategy – avoid offlabel fines by investing in more approval trials. Dawn Carroll was recruited by Pfizer in ’07 and co-authored an updated Cochrane review in ’10, which was surprisingly favourable to their products gabapentin and pregabalin for chronic pain. All up, she’s published 50 articles with the Pain & Palliative Support group of Cochrane’s Editorial boardmember Prof Andrew Moore. Moore’s 2014 article for Jnl of the American Medical Association, ‘Antiepileptic Drugs for Neuropathic Pain and Fibromyalgia’ confirms that marketing-based medicine penetrates everywhere: “The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain and the National Institute for Health and Care Excellence recommend gabapentin and pregabalin as first-line treatments for neuropathic pain. These results support the recommendations.”

The future holds little promise, since a check of registered ANZ Clinical Trials of gabapentin for bad backs tells us Pfizer is comparing gabapentin against pregabalin for sciatica – which won’t offer us much of a choice (they’re related drugs having identical mechanisms). The obvious difference is that pregabalin is more expensive – the fine for offlabel promotional bribery was double that of its stablemate, at $USD2.3bn

I’d ridiculed medicine’s adoption of the caduceus previously. Perpetually going in circles makes the ouroboros – the snake eating itself, a more appropriate motif.

*Justin claimed in a memo that his example was an ironic motif, because he campaigns against industry influence on prescribers such as for gabapentin.  I value his opinion on popular culture as an illustrative means, and intend to  incorporate same next month. But perhaps the somewhat more socially critical Southpark, than the sagely Gandalf.

30,000 fibromites subscribe to PatientsLikeMe (PLM), submitting medical history, medications prescribed and a subjective pain & fatigue score. Site FAQ is unashamed in disclosing that information is for sale, the loss of privacy being traded against useful efficacy reports on interventions.  Epidemiological comparisons between climatically alike countries Canada/Baltic states and Australia/NZ wasn’t of as much interest as was extracting timeframe from first symptoms to the patient’s obtaining a diagnosis of FM. Although India’s supremacy isn’t statistically significant (Mann-Whitney non-parametric test is around the median, rather than averages) at reducing doctor-shopping in order to find an enlightened one, this issue is nonetheless worth visiting. Which is where the past few months went!india

First observation was that doctors aren’t quite so other worldly as in the West, and as a service provider they’re relatively cheap. Few bucks for a consultation, which can easily be circumvented since pharmacies don’t require a script. The GP competes with doctors of Ayurvedic medicine using traditional methods, regulated and funded by Govt. The most famous advocate, Deepak Chopra is currently undertaking clinical trials into efficacy across 6 Universities (including Harvard). Practitioners questioned on therapy’s mechanisms seemed well informed. Fabricated pharmaceutical trial reports in Hyderabad is a recent cloud of infamy over the 1000 generic drugs suspended by the European Drug Agency, but scientific research has been less creatively and more rigorously innovative. An excellent appraisal of other’s studies on active therapies for fibromyalgia out of Delhi ‘Autonomic nervous system profile in fibromyalgia patients and its modulation by exercise: a mini review’ was sufficiently impressive to warrant linking of an excerpt under Downloads.

A second observation is that meditation and yogic thought were embraced by a disproportionate number of foreigners. Rishikesh is the usual destination, but an interest in Iyengar yoga led down the coast through Pune (BKS’s hometown) to Goa (more than just a beach!). The Himalayan Iyengar school relocates here for the winter, running Yoga retreats like bootcamps. Although the practice includes props used to support chronic ailment sufferers in position, the 4 hours were intense. Describing their teaching that “
 all myalgias can be fixed by hanging upside down” as lacking evidence base is an understatement, but the idea of tackling dysautonomia by increasing pressure upon baroreceptors could indeed have merit. At a nondescript studio in Koregaon Park, Pune the class concluded with assessment of disposition and dietary recommendations. This picked up lifestyle behaviors that preceded contraction of FM, and was quite in accordance with science (© Elsevier). Yoga is described as India’s gift to the world, and local surgeon Dr Ranjit Rao shares his insights “Chronic pain conditions such as …, and fibromyalgia are often better managed with a holistic approach that includes yoga as well as other modalities.” His book ‘Meditation & Martini‘ attempts to bridge the gulf between advocates of pharmacotherapy and self-healing.
Gooders*, but is it effective? A query on PLM which ranks all interventions by patient’s score puts yoga third, behind LowDose Naltrexone and D-Ribose (mitochondrial fuel supply). Surprisingly, theCochraneLibrary.org has very little to contribute. Of 34 conditions treated by yoga reviewed systematically, ranging from epilepsy to dementia there’s no report on benefit in musulo-skeletal conditions (bar Prof Wieland’s in-progress evaluation of the literature for chronic lower-back pain). Rheumatology has focused overmuch upon lifelong dependence on palliative drugs at the expense of multi-disciplinary therapy, but another excerpt scanned this time from ‘Yoga for Arthritis‘ out of Swami Vivekananda Yoga press in Bangalore is rather more inclusively enlightened.

* Naval slang, translated: ‘Good as’ can be expected, in an otherwise hopeless situation. Actually, I’ve always had a healthy respect for India.