We’re all crazy now

PRO-logue. It’s telling that an identical German study to PRO-HEART was shutdown early. Comments by psychiatrist Andreas Ströhle and Nina Rieckmann from their Institute of Public Health : “Dr Angermann and colleagues reported that escitalopram did not reduce all-cause death or hospitalization… It is not clear why the authors expected that it would, as it does not reduce mild to moderate levels of depression… Rather, it adds to the mounting evidence that questions the risk-benefit ratio of prescribing antidepressants to patients with less than severe depression.”

Once upon a time, psychs drew a distinction between depression originating from within (endogenous) or that which arose due to circumstances (reactive). The former was treated by meds, but the market for anti-depressants has grown as the two-type concept has fallen out of favour. Pills manipulating neurotransmitter levels are a simple solution with scrip from your GP, one that doesn’t require psych expertise. The American Psychiatric Association aren’t blameless, since the criteria for mental illnesses is loosened with every release of the DSM. That manual has also expanded in order to inform practitioners of the complexity of the complex. But they have lost control in this non-infectious pandemic. Prof Peter Gotzsche is fanatical in advocating that prescriptions of such meds be reduced 50-fold, but for a less emotive perspective I suggest you follow psychiatrist Professor David Healy, or read his ‘Pharmageddon’.

Followon book to 'Deadly Medicines and Organised Crime'

Followon book to ‘Deadly Medicines and Organised Crime’

Earlier posts have complained at the fabricated conclusion that chronic pain is  manifestation of a mental illness. It was a researcher’s invented report that then conveniently led into a publicly funded trial for anti-depressants in osteoarthritis. It’s to the Royal Aust & NZ College of Psychiatry’s credit that their submission  against Medicine Aust code-of-misconduct application to regulatory authority ACCC was the only one to address perversion of research by industry. If they’re to be believed, academics are corrupted. And if Gotzsche is right, you can’t trust Patient Organisations for … “having done absolutely nothing to stop the blatant abuse of patients in industry-sponsored trials“, citing Dr Ben Goldacre’s book ‘Bad Pharma’ of 2012. It’s worse than that, as you’ll find out.

Heart Foundation Vic CEO Jennifer Johns has earlier come in for ridicule over statins, echoing her disgraced NSW President’s associations with the refined sugar industry. An Austin hospital cardiologist, in 2010 she funded her colleague David Hare and Baker IDI’s Prof Krum to trial  Lexapro as treatment for the depression that their heart failure patients are presumed to suffer, PRO-HEART. Also in this year the manufacturer’s promotion of such off-label usage cost them $USD313m in fines, with civil actions continuing. Such as 03-10395-NMG for wrongful dismissal of sales rep and whistleblower Chris Gobble, who complained to supervisors of “illegal kickbacks (i.e. paying doctors for no other reason than to induce them to prescribe Celexa and Lexapro)”. The marketing budget disclosed in the Confidential plan provided to the US Senate was $35m on speakers fees, and $36m on lunches. In one year. In one country.

The drug is also associated with hyponatremia, ie it worsens heart failure risk. None of the team answered this concern, but they were defended by the Heart Foundation’s Deidre Cope: “In regard to its Research Program, the Heart Foundation follows the NHMRC guidelines around disclosure of interest. The research funded by the Heart Foundation undergoes a rigorous peer review process involving assessment by independent, external reviewers. All funding decisions are scrutinised by an external committee to ensure that all aspects of the peer review process are consistent, transparent and ethical.” Affirming that they’re just as utterly corrupt as the NHMRC, as evidenced by Cicuttini and Wluka’s impunity.

The other half of the $820,000 raised by door-knockers and tin-shakers that PRO-HEART is costing was from Beyond Blue. No responses to approaches were provided at all. It’s too early to allege misconduct – the trial is running three years behind schedule, and a staffer thought late 2017 would see a report released. But it already stinks like something’s died. [Sep 2017 update: 2018 perhaps? BB CEO Georgie Harman states that she’s happy with the study progress – seven years after the first patient was enrolled in the 6month study]

There’s often a trite closing disclaimer in articles that if you suffer from depression, there’s phone support available at these numbers…… who’ll suggest medical advice. I’m more of the opinion that you think carefully, so have linked further material on happiness or absence thereof at http://themindfulgap.com.au/2016/02/05/the-blue-bird-and-the-black-dog/



Your life in their hands

An expression often applied to surgery, but physicians playing God is equally relevant to manipulation by mental health practitioners. Except that it’s Quality of Life that’s at stake. Institutions once committed difficult persons, but today medicating provides that confinement. Mostly beneficial in mental illness, mostly harmful otherwise.

So drawing the line for treatment carries grave responsibility. Complaints of this example of insitutional malpractice I detail here have however, been dismissed by  all governance authorities. In concluding that “Mental health is associated with changes in foot pain. Clinicians dealing with this population should consider the contribution of mental health in their management and treatment of foot pain” the connection is made – unless pain improves, it’s psych. The final page emphasizes the viewpoint, “the results from this current study suggest that foot pain could be related to mental health in the same manner as other chronic musculoskeletal conditions“. *
Except that the author’s data shows no significant association.
The report linked contains an untruth. Table 1 shows that mental health isn’t the factor – but rather it’s Vitality , or energy, which is determinant of recovery. The difference of 12 points equates to an increased likelihood of inability to work due to fatigue of over 60%, according to one validation of the SF-36 (Quality of Life) Vitality scale. Limitations of a self-report survey in judging someone to be suffering mental illness aside, this is a fabricated conclusion. And one which suits the purposes of the Professors in their subsequent trial of an anti-depressant in treating arthritis. This is no maverick opinion – Anita Wluka is musculoskeletal editor for BioMedCentral, and her department hosts the musculoskeletal group for the Cochrane Collaboration. It’s not a typo, else the ‘corresponding’ author would acknowledge the error. Nor did the editor of Arthritis Care & Research care to reply, indeed there appears to be no integrity underpinning the evidence base used by every doctor. The university ethics committee overseeing the study answered my challenge but only after four months had lapsed and I’d been suspended by the Dean, for causing distress to these academics by my complaints. Designated integrity advisor Prof Stephen Holdsworth hasn’t responded.

The misconduct isn’t confined to Monash either, Melbourne University obesity expert Joey ‘Mr Big’ Proietto contributed to the study, so their ethics committee was questioned. The only response was: “Due to the [Business Improvement Program] restructure which resulted in this office losing staff we are unable to reply to your request immediately. We will endeavour to respond as soon as possible. Thank you for your understanding“.

 The study was jointly funded by National Health and Medical Research Council and the Royal Aust College of Physicians. NHMRC Director of Grants Saraid Billiards isn’t fussed by misconduct within her alma mater: “we would anticipate that the institution would manage the allegation of research misconduct in accordance with Part B of the Code “. Rheumatology Assigner Academy and coincidentally co-author Prof Flavia Cicuttini could have taken this handpass, but perhaps too busy allocating funds and simultaneously consuming same? RACP “… has rigorous application, review and reporting procedures to ensure a fair and equitable process. …. but the College does not enter into correspondence regarding its decisions.”, according to research manager Laina De Winne. Spokesperson for federal Treasurer Hockey is concerned at budgetary drain, but “As this matter falls directly into the portfolio responsibilities of the Minister for Health the Hon Sussan Ley, Mr Hockey has asked me to refer this matter through to the Minister for her attention.” Joe’s been sent offshore, as our Govt does with many other children of refugees. Office of shadow Health Minister Cath King informs me that the complaint system is working: “Should you wish to pursue your concerns relating to potential conflicts of interest in the grants application process for NHMRC funding, I would encourage you to raise them with NHMRC directly .”

Evidence-based medicine Prof Paul Glasziou is overwhelmed by the extent of fraud: “Good luck with pursuing this. As I now focus on NON-drug interventions and the overall waste in research processes, I no longer get involved in individual problems in drugs research (as that would consume 10,000% of my time!)“. Adjunct Prof Ken Harvey of Medreach agrees, “As Paul Glasziou noted, it is difficult for those of us concerned about such matters to take up every case. The same, regrettably, applies to NH&MRC and University research and governance bodies although you certainly deserve a reply.” He suggested writing to the publishing journal editor, something attempted thrice without response. “Oh dear“, said Ken.

Members of the team are now collaborating with Mandana Nikpour and Andrew Tonkin on a trial of atorvastatin for arthritis, OAKS. Lipitor remains the world’s highest grossing drug on record, and Pfizer quite generous in granting early career kickstarts of $50-55,000. Mandy’s shy regarding her CardioVascularLipids grant, since it’s not declared in an article with Prof Rachelle Buchbinder ‘Should patients with systemic sclerosis-related pulmonary arterial hypertension be anticoagulated?’ (Internal Medicine Jnl of May 2013 ) even though Pfizer’s apixaban is suggested and a favourable result from her registered trial ACTRN12614000418673 will boost sales of their Eliquis. Again as with pregabalin/Lyrica trial PRECISE, NHMRC sponsored.

Arguably harmful except in the population who’ve already had a heart attack or angina, statins have one certain side effect. Fatigue. Which perpetuates the arthritic pain cycle, but Anita wasn’t going to tell you that. Pharmacology and rheumatology are bedfellows who’re profitable partners.

* Copyright © 2014 by the American College of Rheumatology


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

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.
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.

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.

A soundtrack may help to paint this picture – the link opens in another tab. Turn the volume way to the right. Dave Wayman’s songwriting for Shannon Bourne used by permission
What’s a Little Pain? I’m quite unable to describe the impact of suffering from fibromyalgia, but hope that the noise in your head will help whilst trying to educate carers about hypersensitivity.
It isn’t so easy to give rheumatology specialists an insight, due to their being the fount of all knowledge. Prof Fred Wolfe removed the following unabridged text from a posting to his blog on the grounds that “We will not publish insulting or crude comments”. Despite the topic being Empathy!
I’m so mad right now. Steaming, boiling, ranting, raving, wanting to kick, hit or punch something mad and I’m not apologising for it – Don’t read it if you don’t wanna know, I don’t give a damn.
My GP is moving after Christmas, so I guess since he thought it’s probably his last visit with me, why not tell me how he really feels about me.
Apparently in all his wisdom of treating me for one year of my Fibro journey, he felt justified to make the comment that I rely too much on medicine to fix the problems I have. That I don’t try other things, I just reach for medication and see if I can increase the dose to make myself feel better and that’s whats led me to where I am now. That he has done his best to try and get me off the medications and stop me relying on them but its my choice and as such I have to accept the side effects.
Give him one week. One god damned week where he doesn’t understand his body, where he has to try a hundred homeopathic remedies that all fail and leave him worse than before, where he reads so much about his condition he can’t think of anything else. Where his family don’t understand the strange things he does any more and laugh at him because he swears they will work, one day. Where a remedy works on day one, but doesn’t on day two for the very same problem. Where he has to throw thousands of his own money – a gvt pension – on a swing and a prayer because he’s so desperate for something to work. Where he has to turn to his GP to prescribe medication because the GP admittedly knows very little about his condition and can not help any other way. Where the illness makes him feel like a different person and the medication makes him feel worse in 20 other areas but fixes the one big ailment flaring that week. Where he can not socialise with anyone because his friends don’t understand and don’t want to – he can’t drink alcohol any more, he can’t party with them, can’t play sport, can’t join social clubs because of the exposure to noise, lights, sensation of any kind. Where he has to walk naked around the house for 5 days in a row because fabric is too painful to wear, sit on or lay on.
Damn him for thinking he knows anything about my life just because he sees me once a month. I don’t ask my physio for scripts because its not his job!! I don’t ask my GP to Dry Needle me cos it’s not his job!! So many things go wrong and there is so much to fit into an appointment every month, why would I tell him all the things I tried that didn’t work?? I’m there as a last resort, not a drive through takeaway. I’m there asking him for help with medication because that’s what he’s trained in – he has told me he knows little about Fibro, treats his share of patients with it, tries to keep up with the latest info, thats it. If it was 7 years ago and he was my naturopath, I probably wouldn’t ask him about diagnoses criteria for Sjorgens. If it was 5 years ago and he was my acupuncturist, I wouldn’t ask him to adjust my back. It’s now and he is my GP – isn’t it reasonable that I ask him for medication and not exercises for my Vertigo??
To even imply he tried to get me off medication is a joke – he said in my first appointment, as all dr’s do when they freak out at my medications, “oh you can’t have all these, we’ll have to wean you off some of these” and proceeded to put me on a new medication that very appointment!!
The crappy thing is that I ruminate heavily and I know that because of my mental health problems, these comments will stay with me a long time and the anger will turn into much more self destructive emotions.
However, I am very proud that I ignored him in the moment and continued on with the appointment as if he hadn’t just struck a red hot poker into the deep core of my being and planted a deep seed of paranoia and mistrust in me about what Dr’s are really thinking and if I will get the same attitude from everyone on my journey.

Neurotransmitter of the year 2014

An award largely forgotten after the glutamate debacle, when some restaurants decided you can’t have too much of a good thing. Serotonin may be too old for the game after half a century of tri-cyclic and SNRI usage, and quite frankly has put on an embarrassing amount of weight. Bad press due to misbehavior by lookalike pregabalin is likely to rule out GABA. AcetylCholine is a bit too vague-as to set hearts racing, but quietly achieves reduced inflammatory cytokines. Norepinephrine (common misspelling of Noradrenaline) has been fighting for sympathetic following with its edgy, flighty manner and dopamine will need more vigilance if it’s to retain the award. The thoughtful amongst you always expected this winner, but dopamine addicts can unclench your jaw and relax now. Smoko, perhaps?neuros

Besides aiding concentration, dopamine’s supporting role aka Prolactin Inhibitory Hormone breaks the pathway from leptin to inflammatory cytokine. Prolactin measures correlate with a bad prognosis in chronic Heart Failure, if the European Society of Cardiology is to be believed. Typical IL-6 levels in fibromites correspond to typical levels in New York Heart Association’s class II functionally limited. Diastolic HF in Chronic Fatigue is of concern to Miwa&Fujita, where ejection fraction is preserved but the ventricle muscle rebound is insufficient. The article in Healthcare for Women International where Leonard Jason found 20% of death certificates of CFS sufferers reported heart failure – at an age of 24 years less than the US national average will surely send chills, given the frequent syndrome coincidence of orthostatic intolerance with FM. And certainly a concern to fibromites, whose augmented prolactin response to Riedel’s or Malt & Ursin et al’s challenge test will send them to their prescribers for dopamine reuptake inhibitors (DRI). Pointless request however, they’re psycho-stimulants and perceived as likely to be abused – though you could have an opioid for pain instead! This reluctance is despite fatigue and concentration improvements from double-blind randomized clinical trials of the DRI methylphenidate for Chronic Fatigue Syndrome (Blockmans, van Houdenhove & Bobbaers or  Usón and Alecha). Pharmacotherapy solutions are actually quite a concern (doesn’t the MBBS degree cover iatrogenic issues at all?), for example amitriptyline. Despite already depleted CoQ10, fibromites are prescribed Endep which Prof Cordero has found exacerbates the problem*. CoQ10 is vital for heart muscle condition, and note that we haven’t yet considered CardioVascular Disease for which more unpleasant news was presented by Dana March of the CFInitiative this year. You’d have a coronary just thinking about it. All this risk in order to boost serotonin – neural levels of which can’t be ascertained, and serum levels don’t seem worth measuring!

Reader’s choice award for neurotranny of 2014 through your comments is eagerly awaited. But bear in mind that meddling via meds is dangerous.

*Oral treatment with amitriptyline induces coenzyme Q deficiency and oxidative stress in psychiatric patients

Didn’t ask for much. Apart from the linked letter, didn’t get anything. Perhaps I give too much background on mis-management of fibromyalgia by attaching evidence of conflicts of interest? Indifferent reply from the Hon Peter Dutton, Minister for Health …….care? (click to link).

My memo follows:

May 12th is marked as International Fibromyalgia Awareness day, shared with the ME/CFS campaigns. Fibro unfortunately has no national support group, nor any charitable foundation despite affecting between 6-800,000 Australians (predominately women). There are no studies underway in this country, nor is the prevalence known unless by extrapolation from overseas. On the other hand, Griffith University’s NCNED is committed to investigation of Chronic Fatigue. The disparity between the syndromes results from CFS being seen as attributable to a virus, thus specialist treatment is by referral to an immunologist. Whereas the obvious presentation of fibro being musculoskeletal pain resulted in ‘ownership’ by rheumatologists. Unfortunately it is disowned as being their problem – Profs Buchbinder and Roberts-Thomson being amongst those who deny that the disease belongs on the Australian Rheumatologists Association Database or of there being any need for a fibromyalgia register.

As I highlight to the Director of Monash’s Centre for Ethics in Medicine below, such indifference has resulted in failure to investigate the appropriateness of treatments. Pharma is frequently accused of commercial interest overriding patient welfare but  it’s obvious that this situation is unique in extending to misconduct – further explained at http://americannewsreport.com/nationalpainreport/drugs-fibromyalgia-good-8823155.html . The ‘Bad Medicine’ of greatest concern is pregabalin, marketed by Pfizer as Lyrica. In meta-analysis the NumberNeededtoTreat consistently exceeds the NumberNeededtoHarm, but research sponsorship suppresses any concern for the fact that this medication does more harm than good for fibromyalgia. And as the attached response by the office of Senator the Hon Fiona Nash advises, there’s no impetus to improve governance in research. I respectfully ask that consideration be given to a statement for May 12th which will provide encouragement to sufferers of this debilitating condition.

Yours sincerely, Geoff Kirwood

Mud slinging (Part 2)

May 12th is International Fibromyalgia Awareness Day. An event overlooked due to focus on the simultaneous campaign by ME/Chronic Fatigue syndrome’s National Association. Along with a supporting body, CFS sufferers are gaining understanding through research conducted at Griffith University by the National Centre for Neuroimmunology and Emerging Diseases (NCNED). FM is getting sweet FA in Australia however. Remarkable disparity in attention given that fibro is a greater problem …. tenfold so actually, and a consequence of good fortune in assignment of specialty, due to a perception that CFS emerges after a virus. This issue was raised with three wise professors with expertise in immunology. Rheumatologist Rachelle Buchbinder declined to answer what investigations her association could possibly undertake, and confirmed the exclusivity of their tracking database for “…drugs in the treatment of inflammatory arthritis so again you are correct that it does not include people who have fibromyalgia”. Peter Roberts-Thomson was unable to respond to the question as to whether rheumatologists should have responsibility for FM research, but justified selection of ‘well-characterised disorders’ for their autoimmune bloods bank to search for antibodies…. “Fibromyalgia could well have immunological pathology but to date no diagnostic autoantibodies have been described.” Sounds like the wise lawyer who only ever asks questions to which they already know the answers? And Geoffrey Littlejohn stayed mute.3monkeys
Dr Skip Pridgen of Alabama’s IMC seems to think FM is immune mediated, pulling in $USD 3.3m funding to evaluate an NSAID (non-steroidal anti-inflammatory) and anti-viral combo trial. No argument there from the neurologists, they’ve learnt the basics of post-herpetic neuralgia at school. The costing is all the greater since FDA guidelines do not recognize there being an unmet medical need for fibro, which could have justified an Expedited Program (I’ll concede that their last ruling was against a proposal for GHB – notorious as a date rape drug!). Of course, their CFS Guidelines for CFS/ME drug development drafted this month declares there being an unmet medical need. Given the stonewalling of FM research, what point can there possibly be in forming a national association here – since where would contributions be directed in order to achieve any good? Perhaps a question better answered by Prof Mark Hutchinson (Tall Poppy science Awardee 2010) at his Neuroimmunopharmacology lab in Adelaide Uni. Whose discovery that naloxone can suppress microglia activity in the brain and prevent proinflammatory cytokine release directly led to two successful trials of naltrexone for fibromyalgia at Stanford Uni. Approval remains roadblocked by the FDA however, giving Australia another chance to show initiative to the world. No, seriously… it happened once upon a time!

Bad medicine (Part 2)

Lyrica/pregabalin continued…… Integrity of research is maintained under an accord struck with journal publishers, whereby trial results will only ever be reported if the goal is declared upfront when the study is registered with a govt agency. This ensures inconclusive or negative results aren’t hidden in secrecy, and thus trial NCT00333866 in 2009 is open to scrutiny – a sponsor’s restrictive agreement on investigators publishing or discussing trial results notwithstanding. Under the leadership of Lynne Pauer (a Pfizer Director) 73 facilities worldwide randomly allocated fibro patients to either placebo control or else one of three dosages of pregabalin. 30% dropped out over the 14 weeks, and only the 450mg dosage yielded a statistically significant result in efficacy for pain. Paracetamol was allowed as a rescue therapy, surprisingly the amount needed for pain relief increased with higher dosages of pregabalin. Data from this and other trials was analysed by Oxford University who determined the Number Needed to Treat at 450mg to obtain one person benefiting by a moderate 30% reduction in pain intensity was eleven. On the other hand, worsening side-effects with increased dosage led a rheumy with a sense of humour to plot the Schwindel.

Pfizer has a patent thru’ to Dec 2018 on Lyrica however, and if all you have is a hammer then everything looks like a nail. American audiences are aware of their ad campaign which follows the “Here’s your answer, regardless of your problem” school of thought. Diabetic neuropathy? The ads announce “No worries”, although others are concerned about suicidality. And NonSignificant result study at 300mg dosing shows it’s every bit as good as placebo in reducing pain. whack-a-mole

Writing in the Medical Journal of Aust this year, rheumatologist Prof Rachelle Buchbinder complains that NationalHealth&MedicalResearchCouncil “funding is disproportionally low compared with the burden of these (musculoskeletal) conditions”. Her co-author Prof Chris Maher should impress then, in obtaining a $618,590 NHMRC grant for the PRECISE study trialing pregabalin as a treatment for sciatica. Coincidentally, The Age newspaper published on 24th July their promotional article against standard care claiming that: “This month the prestigious NEJM published a paper reporting that steroid injections are no more effective than a sham …”, but if you read Friedly and Jarvik et al’s report the placebo was lidocaine.  Yeah right, an anaesthetic is a sham control! Experts condemned the trial, writing: “This critical assessment shows that this study suffers from a challenging design, was premised on the exclusion of available high-quality literature, and had inadequate duration of follow-up for an interventional technique with poor assessment criteria and reporting.” Discouraging guided lumbar injections is pleasing to a Govt cutting health funding in 2015, since imaging is expensive. Pills can keep the pain at bay. 

PRECISE trial protocol cites Pfizer’s  Dr Zahava Gabriel on the cost-effectiveness for pregabalin, who previously participated in a team providing supposedly independent evidence with ‘A Systematic Review and Mixed Treatment Comparison of the Efficacy of Pharmacological Treatments for Fibromyalgia’ – whose conclusion “confirms the therapeutic efficacy of pregabalin”. The NHMRC’s funding submission includes the justification: “Currently there is limited, direct, high quality research to inform the use of pregabalin in the treatment of people with sciatica. A small prospective randomised trial of patients with chronic low back pain (n = 36), which included some patients with sciatica, suggested that pregabalin may produce a statistically significant reduction in back pain in the short term”. The cited pilot study by Romano & Mineo et al wasn’t placebo controlled – patients being allocated to consecutive periods on either pregabalin, an NSAID celecoxib, or both. The least improvement was shown by the pregabalin only group, so surely Maher’s colleague Prof Ric O’Day would endorse additional celecoxib therapy (especially after having served on Pfizer’s advisory committee)? Unless coming off-patent next year resulted in a commercial decision to dump Celebrex? A supposed risk of cox-2 inhibitors cardiovascular disease hasn’t been investigated, which makes Pfizer’s March 2014 contest against generic manufacturers in Court appear financially risky (tho’ rash judgements are rather clouded by memories of Vioxx corruption! 2015 update here suggests that 200mg is a safe dosage).

Money appears to be not a factor in NHMRC deliberations, otherwise $4.6bn in sales of Lyrica last year would have deemed that Pfizer themselves can reinvest to break a new market with backpain. Hopefully they’ll read other New England Jnl of Medicine articles before gifting in future. 

Regulatory compliance appears to have been taken to an all-time low within health research ….. obedience to industry! It also shows how hit and miss medicine is based on commerce rather than science – pregabalin having been developed as an anticonvulsant for epilepsy echoes Pfizer’s subsidiary Searle re-purposing of misoprostol (declared protective against ulcers by Dr Fred Silverstein & co) for inducing labour. A $70m birth injury litigation set a record, and spawned an industry for lawyers suing hospitals for off-label use of mistoprostol.