Excluding opium, (which the Creator himself seems to prescribe… as if it were foreseen that wherever there is hunger to be fed there must also be a pain to be soothed) … I firmly believe that if the whole materia medica [medical drugs], as now used, could be sunk to the bottom of the sea, it would be all the better for mankind,—and all the worse for the fishes. Harvard Medical School dean, 1860

This is a man who hadn’t experienced the wonder of penicillin, or appreciated commercialization of aspirin for quick and easy pain relief, so the quote from Oliver Wendell Holmes Sr is merely quirky. The opioids have become contentious today, as though dictated by fashion, but dissent on the merit of miraculous pills is a constant. Psychiatrist and pharmacovigilante David Healy wrote with exasperation on the irresponsible prescription of meds for mental health, using images of hanging victims to drive home their accompanied risk of suicidality. After an outcry his next post ‘Spectre of Dissent’ used pictures of self-immolation, such as a Buddhist monk protesting the Vietnam war, in order to emphasise the seriousness of medication harm, legally, by doctor’s orders.

Movie ‘The Constant Gardener’, based on actual events.

In 1996 Pfizer rushed researchers to trial their experimental antibiotic Trovan at a meningitis outbreak in Nigeria. Ethical approvals were forged, and the drug trial comparator was only administered at 1/3rd the standard dose. Similar numbers of recipients of Trovan died as those in the (undertreated) control group, and the FDA approved the drug for adults although not for children. Within one year, over 100 cases of acute liver failure led to withdrawal of any approval. The Nigerian govt was given $75m to settle the case. The horror/thriller plot of the film, described by its author thus: “by comparison with the reality, my story [is] as tame as a holiday postcard“, stemmed from Pfizer’s damage control by discrediting the Nigerian prosecutor – done in collusion with the US ambassador. Considering that the corpse shown hanging had their genitals cut off and stuffed in its mouth as an inducement to keep quiet, wow.

This was a human rights abuse. “Happens all the time” was the response of Monash’s School of Public Health biostatistics Professor to my concern at another atrocity. Billion dollar fines have been about as worthless as a tax on criminality. A cost of doing business. Trump’s appointee to head up the FDA, Scott Gottlieb, was universally acclaimed as a good choice. But his ‘user-pays’ concept of charging pharma for their time, $905m for reviews  in 2017, has been accompanied by a threefold drop in rejections since 2010.

Does fast-tracking approvals carry a greater risk?

Undoubtedly, yes. But that must be weighed against the harm of delay. A dozen years are easily lost between the translational research breakthrough, through safety and then comparative benefit studies, before availability to the public. The question of risk vs benefit becomes a moot point though, when regulators are not sufficiently independent from industry influence. The Drug Utilisation SubCommittee reports to PBS on the subsidies for the market, the consumer patients testing ground. It’s chaired by a Professor who’s taken Pfizer sponsorship for a study, and writes on the benefit of branded over generic, but omits mentioning the commercial conflict of interest. Double standards are rife.

State AMA President doesn’t advertise, eh?

Under AHPRA rules, testimonials are banned: no reviews, or views on a service provider. Head of Victorian AMA, Dr Julian Rait knows it’s OK for a review on a third party website that he does not control – Google reviews clearly aren’t promotional. They can be brutal. Sharing experience is very much in the public interest, and Rait’s recent reply to my memo on open disclosure (‘Duty of Candour’) was appropriately candid. Telstra’s HealthEngine is an alternative service however it is indeed an advertising & booking service, since negative reviews are edited out.
The non-response on this matter from AHPRA chair Dr Joanna Flynn (an aide stating that “All registered medical practitioners are expected to abide by the [Good practice] code)” is merely wishful. And they endorse HealthEngine’s censorship, ostensibly to remove clinical performance ratings, but in effect encouraging a smokescreen for shoddy conduct.

In the UK there’s a statutory Duty of Candour – when a medical error is made, a conciliatory conference is enforceable. It affords a learning opportunity for the contrite doctor, although apologies are non-prejudicial i.e. not an admission of guilt. Our regulatory body in Oz maintains exclusivity on registered practitioners – no public ratings, and all complaints dealt with behind the scenes. An incredible dismissal of an AHPRA complaint and then an expert physician making contentious, unsubstantiated on-air comments led to my testing procedural rigour through such a complaint. Again, dismissed as it was “reasonable for the Prof to proffer an opinion“.  Except that this wasn’t a personal, but a professional, opinion that was disparaging to complementary medicine.

Perhaps medicine will one day be called before a Royal Commission, so as to expose the kickbacks paid to advisors, much as financial services has been. I’m overwhelmed by the ‘smoke and mirrors’, and am off to do a ‘snow job’ myself. A real one, as an honorary ski patroller, at the mountain retreat of Mt Stirling. I’ll return after contemplation of humanity’s evils. Geoff

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Important: This article may arouse emotions including despair. If afflicted with intolerable, chronic pain then I suggest discussing these issues with your support network.

'No future', the anthem for fans of Johnny Rotten

‘No future’, the anthem for Johnny Rotten/John Lydon fans.

Fibromyalgia (FM) pioneer Prof Fred Wolfe looked up the endgame result for 8,000 fibromites and 10,000 osteoarthritis sufferers over a period of up to 35 years. Neither condition showed increased mortality overall, but for those 15 with FM who succumbed to suicide this risk was treble the national average.  His report is similar to one in Denmark reporting a six-fold increased risk, and not unlike the outcomes found from tracking registry CFIDS for Chronic Fatigue. Some insights can be found from a survey on symptoms of pain and Quality of Life which shows medical professionals failing to validate their illness to be the major determinant of poor subjective score.

Women’s Healthy Aging Project (WHAP) has tracked a cohort of 440 in Melbourne for 25 years to study disease impact on Quality Affected Life-Years. Although musculoskeletal has been included in scope (above the red line), requests for any available research rheumatologist to partake have been unfruitful.

Govt priorities

Aussie Govt priorities: cancer, heart, neuro, mental, lung, diabetes, injury, and lastly arthritic.

Leaving aside the prioritised ranking of #8 (a Dutch burden report puts it up at #1, and cancer as #8), this is remarkable since Monash homes the Cochrane evidence base for musculoskeletal. Their collation of clinical guidelines by 700 active health care professionals, researchers and consumer representatives is a task shared with Ottawa, however the Canadian Govt recently pulled funding to Tugwell’s team. Although this group claims to be inclusive of FM, there’s no reviews of treatment efficacy published. Those are instead posted on the Pain, Palliative, and Supportive Care (PaPaS) group site, where 16 interventions are evaluated. Repeat – there’s no consideration given to treating FM syndrome, but focus is wholly upon symptomatic pain relief. In perpetuity, which makes the FM meds market rather attractive and trial sponsorship good business sense.

A challenge was issued to PaPaS editorial manager Prof Andrew Moore re the inclusion of a Pfizer employee, Dawn Carroll, in a 2009 ‘independent’ review of Pfizer products Lyrica and Neurontin (considered as helpful: “For gabapentin and pregabalin only we found reasonably good second tier evidence for efficacy” in the latest version). His reply was thoughtful and extensive, particularly in regard to their recent policy decision to segregate FM from neuropathic pain. This decision isolating distinct conditions is at odds with our TGA & PBS approvals for Lyrica/pregabalin for neuralgia but not FM – despite being the most commonly prescribed treatment. Further insanity is shown in the single approved med for FM, the SNRI (anti-depressant) milnacipran not actually being distributed in Australia.

But I can’t help but be troubled by their letter to the BMJ dismissing Dr Des Spence’s criticism of Cymbalta (and he’s someone who’s also skeptical of Lyrica’s benefit). Prof Moore reveals that he’s paid as a consultant by Eli-Lilly, the manufacturer of Cymbalta. Examination of publications reveals that Robert A Moore is the same person – the moniker varies depending on whether writing as an independent or apologist for a drug company.

Hope comes from bold rheumatologists who offer scrip for Disease Modifying Anti-Rheumatic Drugs in FM, and patient communities who share their experiences. Over 100,000 fibromite subscribers to one site donate their data in hopes of cure or remission. 1.6% are on a DMARD (including the aggressive biological agents). There’s no formal trials ever run on these drugs suitability, this is instead totally circumventing a broken system. For other solutions, see here.

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’

 

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.

Prestigious journal The Lancet Vol 359 Issue 9315 page 1442 uses a historical example to remind us to critically judge the Doctor’s ℞. In 1745 the Royal Physician recommended tobacco smoke enemas for victims of drowning during immersion therapy sessions – their being conducted as a treatment for mania. The modified bellows were subsequently provided at stations alongside the Thames river by The Institution for Affording Immediate Relief to Persons Apparently Dead. In an 1840 Kennisgeving (Notice) the Mayor of Rotterdam exalts those responsible for a successful resuscitation by rectal fumigation with a tabaksrookklisteer, after which the practice declined – since it was determined that nicotine was toxic.
I’m not sure that I can do this comedic material justice. If your health practitioner holds you underwater too long, they’re equipped to blow poison up your anus and that’ll restore life? klisteertabak There’s no reports of rectal tobacco usage on Antipodean shores for the countless victims of drowning during the settling of the colony. And it’s not known whether British Tobacco influenced medical adoption of the toxic weed as a cure-all. Nor do we descendants of convicts know whether inappropriate inducements are behind current prescriber’s choices. Lacking an equivalent of the US Sunshine Act for open payment disclosure between pharma and researchers, sponsorship remains cloaked in secrecy. Likewise it hasn’t been deemed necessary to copy America’s Office of Research Integrity, seemingly more prudent to deal with misconduct offline.

Medicine Australia’s Transparency Working Group was unable to reach consensus on a roadmap to setting something up in around abouts a coupla years. Health Ministerial policy is strictly hands-off, shown in a Feb 2014 reply to concerns of specific misconduct “[ahem]…. The Department is supporting an industry-led implementation advisory group that is guiding work to strengthen self-regulation including through the design and development of shared communication systems and a common complaints mechanism“. That’s a relief! I was worried that this matter was being managed by the cleaners because none of the TWG members endorsed the Transparency Model, and the Discussion Paper hasn’t been heard of since the month previous when the TWG was disbanded. And while reform languishes under whichever carpet it was swept, we must trust in our antidepressants as truly beneficial. There’s nothing to prove otherwise – death certificates do not have provision for medication regimes. Similarly so long as any medical procedure wasn’t in the previous 24 hours, the Coroner needn’t be told about that either. The offer proposed (and subsequently accepted) in Edition 18 of Medicine Australia’s (MA) voluntary Code of Conduct submission to the ACCC, being for reports disclosing consultancy payments from Aug 2016 means the clock for direct kickbacks has only two years left to run. That’s real self-regulated progress. Although the loophole exempting payments to researchers via an institution requires that we add to our lexicon “Trust me, I’m a Vice-Chancellor”.
MA Education Event reports disclose that healthy funding is indeed available, to specialists. Amongst Pfizer’s 1490 payments in the last reporting year was over a million dollars spend in sending 34 rheumatologists to conferences in the US and Europe, and 1-day pain management seminars locally. How apt that their Immunology Business Manager’s qualification is commercial pilot with a marketing degree! I’m unaware as to whether pregabalin was promoted, but can’t imagine any material presented had been sourced locally (there being almost* no fibromyalgia research conducted in Australia). ProPublica ‘Dollars for Docs’ 2012 scrutiny of Pfizer’s global corporate citizenship showed just $USD2.8m for travel alongside $USD144.2m for research. These ex gratia payments recognise that our Aussie rheumies are more world weary than world class. I nonetheless trust that that one day we’ll convulse with laughter at the arcane and archaic ℞ of anti-convulsants Lyrica and Neurontin for an autoimmune disorder.
* A survey in 2012 of seven Monash outpatients using pregabalin found diminished anxiety. Higher levels of trust also, no doubt.

A rhetorical question posed by the bard leads Prof Muhammad Yunus (no, not the Nobel Laureate – this guy was merely responsible for the pioneering 1982 study of fibromyalgia) to muse: “…anything that is not currently viewed as a disease is viewed as predominantly or exclusively psychological and benign and is not taken seriously by the health care providers”. For fibro’s status to be promoted from a syndrome to a disease requires an understanding of causality. That would allow treatment of cause, rather than merely alleviating symptoms.20090221_whats-in-a-name_poster_img

Wherever symptoms outweigh evidence from signs the patient is relegated to a diagnostic dumping ground of functional somatic syndromes. Somatization disorder sufferers are characterized by pain and headaches resulting from distress. The recent version of Diag & Stats Manual of Mental Disorders (DSM-5) has grouped these along with hypochondriacs into the category Somatic Symptom Disorder. Other simplifications result in broadening the size of the SSD patient market sixfold over DSM-IV criteria (Rief et al 2011). Thankfully it advises that many individuals with fibromyalgia would not satisfy the criterion necessary to diagnose somatic symptom disorder (ie any one of either: Disproportionate and persistent thoughts about the seriousness of one’s symptoms, Persistently high level of anxiety about health or symptoms, or Excessive time and energy devoted to these symptoms or health concerns.©) Otherwise anyone on disability benefits, or income protection insurance could be critically judged by their practitioner as catastrophising. But of course, fibromites have rheumatology specialists managing their treatment, otherwise secondary care escalation would be straight to psychiatrists and everyone would be on anti-depressants [cue hollow laughter].

How much of fibro is in your head remains enigmatic, just as much so as attempting to explain specificity due to exact locations of the 18 tender points in the 1990 ACR criteria (this week I’m bagging psychs, not rheumys since I need help in understanding enthesopathy!). The selectivity of the blood brain barrier means that the hormone and neurotransmitter levels that matter won’t ever be measured in blood serum. Not that this affects the presumption of a dysregulated hypothalamus-pituitary-adrenal axis , and hypothesized low levels of serotonin (in) or cortisol (out) aren’t seen as necessary to be monitored in order to be prescribed a serotonin reuptake inhibitor. The anti-depressant drug mechanism relies upon lifting the use-by time for the chemical to come in for recycling and thus ensures plenty of serotonin. Blind trust & guesswork are valuable skills in applying neuroendocrinology theories to each individual, and the patients & research consultants to pharma have these attributes respectively ….  in spades ♠

Naval exercises in training for battle involves scenarios whereby the ability to fight is reduced, so then priority shifts to preservation of the vessel. The CO called this ‘move’, but as it’s my blog I can call it fleeing to refuge *. If immobilized, all focus is redirected onto staying afloat. Fibromyalgia is considered a dysfunction of the ‘fight or flight’ autonomic nervous system, the symptoms testing ones strength and endurance much like my military example.

blowfishA Patient Reported Outcome site drugs.com ranks consumer opinions of generic treatments. The highest rated treatment for fibromyalgia with more than just a few believers is guaifenesin protocol. Promoted by Dr Paul Amand, it’s based on a cough mixture and restricted dietary exposures. The only controlled investigation of effectiveness found no benefit during a yearlong double-blind trial, although they were unconcerned about alleviating any discomfort due to snot and sicca – secondary Sjogren’s. An Eli-Lilly advisory board member Prof Bennett assures us of no medical basis for any of the claims (regardless of its history as a muscle relaxant). Alternative medicine provides hope of refuge, but empirical evidence should be sought before fleeing the healthcare system. Ask on a patient forum …… and then flee.
The first dozen treatments are all off-label and appear ahead of the three US FDA approved medications. These two SNRI anti-depressants and an anti-convulsant have been re-tested for effectiveness in 5 trials each, and the Cochrane Collaboration concluded in review that the two SNRIs “provided a small incremental benefit over placebo in reducing pain”, and no effect on fatigue or sleep. Pregabalin gave “small benefit over placebo in reducing pain, fatigue and sleep problems”, and only 11% more participants reported much improvement. Life-preserving dependence upon pain relievers offers the sufferer little more than help to stay afloat.
A few patient advocates have taken up the fight to resolve FM. This blog adds to their voices.

* The RAN mission is to ‘Fight and win at sea’. Glad their intent isn’t to get a draw, or do it up the rivers. Contrast the Indian Navy: ‘Hit first, hit hard, and keep hitting’.  When the Oz and US Navy’s still had their heads down on Somali piracy doing Hazard Risk and Cost Benefit Analyses, the Indian ships went in pursuit. Successfully, without the need to make movies about it.