I can’t breathe… oxygen makes me sick

Antioxidants are good, right? Wrong! According to Cochrane, a statistical trainsmash of the results from all relevant clinical trials found that beta-carotene, vitamin E, and higher doses of vitamin A increase mortality. Some countries aren’t govt funded to license that link, so in brief: a collate of 78 studies with 297,000 participants determined that antioxidants caused harm. One might think that this made marketing of such products a little awkward, but its publication in 2012 hardly sent shockwaves around the world – indeed the report is one of many similar findings. Free radicals in advertising? Sure they can stay, although Trump may want to lock them up.

Thanks Ron, now for the weather....

Thanks Ron, now for the weather….

A little science (sorry), oxygen oxidates – that’s what makes metals rust. Stable oxygen or O2 does the opposite, it ‘reduces’ one electron at a time, becoming more oxidative in reactive species (ROS) superoxide ->hydrogen peroxide->hydroxyl. These free radicals are biologically toxic – the immune system uses such ROS to kill invading microorganisms. Lipid peroxidation is the process of cell membrane destruction by radicals (and this can be a programmed termination), so the body relies on antioxidant enzymes to keep this in moderation. The danger of hydrogen peroxide’s potent reactivity is shown by its use as rocket fuel, and in torpedoes – where there’s no air to burn in any conventional engine. A leak was responsible for the explosion that sank the nuclear submarine Kursk. We’ve been designed to run on rocket fuel, and no supplements can stop this.

In 1956 Professor Denham Harman argued in the Journal of Gerontology that breathing oxygen caused free radicals to prosper, ultimately leading to death. You can’t read that without a subscription, sorry again. In interview he explained: “I was sitting there reading. All of a sudden the phrase ‘free radicals’ crossed my mind. You know just ‘out the blue’. I’m sure you’ve had the same experience…. And it was apocryphal, it just was born of thin air! No one … everyone accepts it and no one has a clue to the source!“. Aside from the decade spent getting the idea to take root, this theory became mantra but has recently come under challenge, such as the article ‘The free-radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan‘. I’m really, very sorry again, but this important research on whether oxygen is a good thing is also copyright. It’s only relevant to the cave salamander (Proteus anguinus) and the naked mole rat (Heterocephalus glaber) anyway, since these clever critters live up to 8 times longer than is typical, thriving under high oxidative stress in the absence of protective antioxidants – levels about 70 times lower. Perhaps exposure to advertising is proving fatal to our species? On the other hand 28 scientists collaborate in speculating that Harman’s thought bubble was a blunder, questioning accepted dogma that the longer you breathe air the closer you come to death.

Novak undergoes HBOT

Novak undergoes HBOT (photo courtesy of HyperMed)

I published a report on the efficacy of hyperbaric oxygen (HBOT) for neuralgia – the pain arising from damaged nerves. Anyone clipping a pulse oximeter to their finger nailbed knows that their O2 saturation is ~98%, nearly perfect due to uptake by haemoglobin (making blood red). HBOT in a compression chamber also floods the plasma with dissolved oxygen, and ROS increases exponentially.  Explaining the seemingly contradictory harm from oxidative stress was avoided by citing arguments about preconditioning – HBOT kickstarts natural responses. Speit calls it adaptive protection, and Deneke describes a rebound effect, whereas Thom considers the brief exposure in HBOT as minimal harm risk from ROS (a natural process anyway). One HBOT benefit is after traumatic brain injury – the vasoconstrictive effect of oxygen reduces cerebral fluid hence intracranial pressure, without compromising perfusion. Hypoxic neurons die, whereas if you overdose on oxygen then temporary convulsions are the worst that can happen. Another Cochrane review   discusses the consequence of such therapy – the authors raise moral issues of how much improvement justifies keeping alive (potentially) severely brain-damaged peoples. HBOT for Multiple Sclerosis is commonplace in the UK, but poor quality of clinical trial evidence raises the question over exploitation of vulnerable people clutching at straws. It’s also an interesting therapy for connective tissue disorders, and although benefit for sporting injury has been disproven , world #1 Novak Djokovic relies upon the treatment. Most centres (6000) are in China and Russia, with 306 in Mexico as reported in the ‘Physiology and Medicine of Hyperbaric Oxygen Therapy’ chapter contributed by Gerbino & Hampson, 2006. Medicine discredits much of their available research as evidence, either due to perceived bias or translation difficulties.

Quod me nutrit, me destruit (what nourishes me destroys me)

Quod me nutrit, me destruit (what nourishes me destroys me)

Oxygen builds you up, knocks you down, and builds you up again. The recent publication ‘Dual effect of oxidative stress on leukemia cancer induction and treatment’ informs us that ROS induce cancer, but that’s also how the cytotoxic chemo drugs destroy malignancies “…. only a thin line separates the beneficial level and deleterious level of ROS“. The mitochondria engine powering your cells maintains this fine balance, enough antioxidants to create the ROS and then eventually break them down to water.
Six times nominated for a Nobel Prize, Harman also published a paper linking polyunsaturated fats to cancer risk. Perhaps best not to eat avocado, nuts, seeds, fish, or leafy greens, and find air with less oxygen – such as in a high density city? Nutritionists are now rethinking fats, as I wrote elsewhere, meantime take it easy on the antioxidants.

Author Geoff’s lifespan is still 40 years short of Harman’s achievement, and I do take a supplement: CoQ10. It’s complex.

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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.

Hope comes from bold rheumatologists who offer scrip for Disease Modifying Anti-Rheumatic Drugs in FM, and patient communities who share their experiences. 65,000 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 totally circumventing a broken system. For other solutions, see here.

Gagging

Endemic corruption within medical research is of no concern to government, since the issues previously raised have been put to Health Ministers and even to PM Turnbull. Without a response. Few have the integrity to whistleblow, due to lack of both regulatory authority and legal protection. After all, there’d be no shortage of backfill for your position upon dismissal from the increasing numbers of vulnerable foreign workers on tenure of a temporary visa. The blue bar charted shows post-docs, paid the same as a burger-flipper while Australia trains them in our wily ways. Employment Minister Eric Abetz denied existence of this scam in correspondence of 16th Sep ’15, despite a University advising “The Department of Immigration and Border Protection has limited the value of the living assistance which can be provided by the University to subclass 402 – research stream visa holders. The maximum contribution by the University to living expenses is approximately $34,000 per annum (at October 2012); this amount may alter on an annual basis.

402

Report BR0169

This matter has been raised with Immigration Minister Peter Dutton several times, but the office has never responded. Wouldn’t he be concerned about history judging him harshly, should the truth ever come out regarding misconduct? Uhh, no. Already looking at a pension of 1/6th of a million dollars annually, that means his CV needn’t be without a fault or three. Even if it’s already blemished by his  previous portfolio as Health Minister resulting in his poll ‘win’ from Australian Doctor magazine as being the worst performer in its 35 year history. No remorse at that failure either – last months confrontation with doctors of Lady Cilento childrens hospital showed his contempt for human rights also.
Your vote comes with no guarantee of governance, as there’s no accountability for policy made up on the fly. President of the amoral AMA turned politician, Dr Brendan Nelson, surprised both the Air Force and Defence Materiel by purchasing $7bn in Super Hornets from ex-parliamentary colleague Andrew Peacock, then a Boeing salesman. “It just flawed me … there was no independent analysis,” recalls AVM Peter Criss, a retired Air Commander of Australia. John Howard approved the suggestion in 2006 without seeking expert opinion, and far from showing remorse for events as they’ve unfolded is instead reveling in regularly being voted Australia’s best PM by Murdoch press conducted polls. That’s despite being outed as a liar regarding ‘children overboard’ by Admiral (rtd) Ritchie, onetime Chief of Navy.

The first planes were delivered in 2010, but six years later we’re still investing heavily in a future around the Joint Strike Fighters (JSF). That’s a project we’d supported by pre-purchasing 100, but both the budget and time were wasted during the cocaine-fuelled ‘nought-ies’ (the era which led to the GFC). Both aircraft are already outclassed by the Russian SU-30 & 35s purchased by five SE-Asian neighbours. “This thing [Super Hornet] will not survive in a fight now in our region,” says Criss. While the JSF struggles to achieve operational readiness, the SU ‘Flanker’ continues to evolve.

Photo courtesy LAC/W (RAAF) Kim Eager Sarah McLeod from the Ducati team with Dr Brendan Nelson. Minister for Defence Dr Brendan Nelson launched the Defence Motorcycle Awareness Campaign at the Sutton Road DriverTraining Centre, ACT near Queanbeyan on the 4th August, 2006.

Photo courtesy LAC/w (RAAF) Kim Eager
Sarah McLeod with ‘Top Gun’ Dr Brendan Nelson on the 4th August, 2006.

If Brendan ‘need for speed’ Nelson didn’t know what he was doing (he dropped out of his economics degree), nor do we know what they’re thinking. There’s a Senate inquiry into the JSF concluding in May 2016, but a previous report is pertinent “… the arguments are of a highly technical nature and much of the data necessary to form an understanding of the performance of the JSF is classified and not available for public scrutiny“.  The quid pro quo of political understandings with business here doesn’t work so well strategically however. Regardless of commitments to JSF, or however many M1A1 battle tanks Howard purchased, it’s been made crystal clear that our new “best friends” are Japan. Regional instability as a consequence of South China Sea conflict won’t be America’s problem, even if they are the trigger.

The secrecy that allows medical research to fester is the cause of the problem here, too. Any misconduct in national affairs remains secret, and public servants intending to whistleblow should pay heed to Sn 70(2) of the Crimes Act, 1914: A person who, having been a Commonwealth officer, publishes or communicates, without lawful authority or excuse (proof whereof shall lie upon him), any fact or document which came to his knowledge, or into his possession, by virtue of his office, and which, at the time when he ceased to be a Commonwealth officer, it was his duty not to disclose, shall be guilty of an offence.
 Penalty: Imprisonment for two years.

The USA, on the other hand, rewards with a payment up to 10% of the public monies recovered.

Changed thinking about the mind

In 1994 rheumatologist Elliot Pellman chaired the NFL’s council on Mild Traumatic Brain Injury (TBI – there is NO ‘Mild’ in this issue). “Concussions are part of the profession, an occupational risk,” … a football player is “like a steelworker who goes up 100 stories, or a soldier. Veterans clear more quickly than rookies…They can unscramble their brains a little faster, maybe because they’re not afraid after being dinged“.

“There’s going to be some controversy about you going back to play.”  Pellman personally sent a concussed Wayne Chrebet back onto the field soon after he had been knocked unconscious by a hit, reportedly telling him, “This is very important for your career.” Days later, Wayne is sluggish and his head aches. In 2005 Pellman et al published their seventh study in the official journal of the Congress of Neurosurgeons, concluding: “Return to play does not involve a significant risk of a second injury either in the same game or during the season.” And remember that the identities of the physician peers who reviewed and approved this nonsensical article are kept secret.

This may be perplexing to non-US residents. The opening of 2012 Southpark episode ‘Sarcastaball’ explains why taking a massive hit is a game tradition, using the naivete of kids.

0Forensic pathologist Dr Bennet Omalu’s investigations from 2002-’09 are documented in the book by Jeanne Marie Laskas, ‘Concussion’ (and now a Ridley Scott film). An outsider to medicine despite attaining eight degrees,  his strongly principled clash with the industry is a repeat of the tobacco deception. Right down to the NFL sharing the same law firm, Covington & Burling! US Congress questions were the turning point for transparency over subsequent years, and not the medicos. NFL boss Roger Goodell still thinks the concussion protocol just needs tweaking.

Self-regulation failed again.

It was only a month ago that the National Institutes of Neurological Disorders & Stroke, and of Biomedical Imaging & Bioengineering defined the ‘neuropathological criteria for the diagnosis of chronic traumatic encephalopathy‘ (CTE). Mostly unintelligible to layfolk, it’s nonetheless of sufficient importance to be published in a public journal. Like boxing, CTE is estimated in about a quarter of gridiron players, and is manifest in mental disturbances – but the tau tangles are invisible to imaging, until staining of brain slices post-mortem. Higher risk is posed to the spectrum of disease from Alzheimers to Parkinsons, and the month prior funds were allocated to research on diagnostic tests in the living. Although the NFL contributed nothing, the Players Union did. Professor Stern’s lab website is linked, and the urgency of guidelines for safer ages to start playing football fires discussion of their work, since the myelin sheath on neurons improves protection after the age of 14. Demyelination diseases include MS, so research implications go far beyond these elite professionals turning violent. Omalu also found CTE in a TBI war veteran who suicided, hence the penny has dropped regarding ‘Walking Wounded’.

I clashed with our Ski Patrol MO, then a Resident at Box Hill hospital, over management of a teenager who’d bounced off a tree. His mother’s concern was that the subdued manner was totally opposite to his usual bouncing off walls. A doctor trumps a paramedic, and I was chastised for trying to turn him into a victim. She sent them home, saying “Don’t worry about vomiting, he’s likely to be carsick“. Next day I rang the family – he slept for 21 hours.

How can this come to pass? I suspect the teaching in a medical degree that anything above the ears is the province of psych, must be addressed first. Holistic medicine is the only sensible way to treat.

 

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/

 

 

‘The Strange Case of Dr Jekyll and Mr Hyde’ was an 1886 novel written to contrast public and private lives of a reputable gentleman. Duplicity is a constant failing, but often what’s revealed is just an iceberg’s tip above massive issues. Thanks to the only mandatory Pfarma reporting in Oz, Medicine Australia’s Education Events, we know that Pfizer spent an average of $12k on each of the 23 rheumatologists they recently sent to European and American conferences EULAR and ACR. The full reports give an insight into specialist’s lives outside the surgery, as $43.3m was spent on them in the 6 months to Sept 2015. Worse still in 2010 pharmaceutical companies reported $637m expenditure on research, but nobody knows who received the money *. There is monumental potential for conflict-of-interest as the scope of new-gen bio-agents increases (monoclonal antibody drugs, hereafter referred to as the  _mab drugs).

Tony Abbott recovers after finishing Pfarma-sponsored 'Pollie Pedal' in 2013

Tony Abbott recovers after finishing Pfarma-sponsored ‘Pollie Pedal’ in 2013

Amgen sponsored 799 events in the last 6 months. Focusing in more closely, we really can’t be sure just how safe is their anti-inflammatory _mab for arthritis, Enbrel. Regulatory authority TGA advises physicians under Adverse Effects: “In placebo-controlled trials, no increase in the incidence of serious infections (fatal, life-threatening, or requiring hospitalisation or intravenous antibiotics) was observed“. Uhuhh.

Allegations it caused Eagles frontman Glenn Frey’s death due to pneumonia can’t be verified. In the latest EULAR journal ‘Annals of Rheumatic Diseases’ Winthrop & Smolen et al suggest it’s a good idea to track outcomes of _mabs. ‘Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases’ reveals the shortcoming that “no consistent OI [Opportunistic Infection] definition was identified across [368] studies“. Hence a list of OIs was drawn up, topped by the pathogen responsible for pneumonia. The best evidence for their recommendations was the publicly accessible meta-analysis by Kourbeti, Ziakas, & Mylonakis which put the odds of infections 1.8 times higher for _mab recipients than controls (usually patients on frontline med, methotrexate)  in Rheumatoid Arthritis (RA) trials – a small but significant risk. But note that RA doubles that risk over healthy comparators already.

That’s short term though, a trial median of around 6 months for the drug to prove its worth. Aust Rheumatology Association’s Rachelle Buchbinder established the ARAD tracking database a decade ago to determine _mab safety. It’s paid for by Pfizer, BMS and AbbVie. The few reports published in journals thus far inform us of customer satisfaction such as subjective Quality of Life surveys, and that no increased risk of cancer occurs, and that herpes/shingles virus infection rates are 1.7 times higher. Specifically for Enbrel, this result came after a median of 3 years followup. So the longterm prognosis is much like the brief studies would indicate. A worsening, but hardly deadly. Glenn’s manager wisely declares he has taken legal advice to limit his accusation.

This drug inhibits TNF, a cytokine messenger that augments our innate immunity system. As understanding of the molecular basis of many diseases improves, an inflammatory aspect is a recurring theme. The prospects for treatment with anti-TNF therapy look promising, but for the fact that the body needs to be regulated by internal controls. And not shareholders, salesfolk, or Jekyll. Interestingly, a trial for Enbrel in Alzheimers found that TNF levels rose. Feedback systems are adaptive.

Future studies could well heed the EULAR belief that their “… list of infections should be considered potential indicators of alterations in host immunity, and that this list and the associated case definitions should be used to standardise reporting of OIs in future biologic and other disease modifying antirheumatic drug clinical trials“. It’d also be helpful if an outcome tracking registry reported on all OIs, instead of the trickle of data from ARAD. But unease over industry manipulation of research is fuelled by the doctors themselves. When a weakened version of the US Sunshine Act for disclosing contents of the unmarked envelope was being considered by the Aust Competition and Consumer Commission, the AMA submission sought a deferral: “A twelve month delay in implementing the ACCC’s condition would allow health practitioners to think about and plan for their ongoing relationships with pharmaceutical companies.”

Gap payments cover the weekender, the kid's schooling ....

Gap payments

EULAR 2016 is in London. The UK has an Office of Research Integrity, let’s hope some fresher ideas than creative accounting are brought home.

* Source: College of Psychiatry submission to the ACCC. They’re concerned: “Clinical research should be included in the transparency model. All payments above the threshold that are made to individual researchers, or research institutions, including hospitals, should be publicly reported. This would better enable doctors and other health professionals to interpret the research outcomes while taking into account their funding sources.”

Rage, rage against the dying of the light

… from ‘Do not go gentle into that good night’, Dylan Thomas

pfizer

staree

 

Before delving into the massive NHMRC research investment of public money  ($5.1m upfront) into Pfizer’s Lipitor that is STAREE, some preliminaries:

Few Australians would be unaware of the furore raised by Catalyst (The Heart of the Matter), and subsequent retraction by ABC management of the program. A couple of opinions on Dr Demasi’s journalism by Drs Briffa and Coleman, and their arguing in blog comments shows that even those in general agreement were discordant. Instead of ‘playing the ball’ and take on the well-orchestrated industry, I’ll ‘play the man’ and focus upon individual proponents of statin therapy. And their complicity. It’s a softer target due to a weakness in humanity – insatiable need for funding.
Heart Foundation CEO Jen Johns immediately warned that sales of statins would be harmed, and a month later they published a poll by their Rob Grenfell showing 10% had stopped the therapy. Their corruption is further detailed at this update, and is unsurprising given that the decade-long president is father of Pfizer’s lobbyist Andy Thirlwell. Even before the exposé aired, Prof Emily Banks had pointed the bone * thus: “It’s likely that if this program goes ahead, and it does the unwarranted undermining of statins, that there will be people who didn’t have to have a heart attack and didn’t have to die from a heart attack, who will die through reducing use of statins“. An expert in this field, having authored ‘Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality’, she’d be appreciative of Pfizer’s infamous blue pills for ED. Dr Grenfell concurs with a warning, “These results tell us that every man who is suffering from any degree of erectile dysfunction should be seeking medical assistance as early as possible“.

Grenfell and Tonkin et al wrote of the confusion in lipid management in May 2015 ‘Clinical Guidelines on Hyperlipidaemia: Recent Developments, Future Challenges and the Need for an Australian Review’ – considering the perspective of the American Heart Association “… the maximum tolerated dose of a statin be generally employed”, but their own concern is absence of an optimal target level: “Whilst the cost-benefit analysis of statin therapy is generally favourable, it is very sensitive to the absolute risk level of the patients selected for therapy”. Andrew Tonkin had already made his mind up in 2005 though, as chair of the Heart Foundation’s consensus Position Statement on Lipid Management a number of guidelines and criteria are given to prescribers. Along with a conflict-of-interest declaration. The same “provision of consulting services to Pfizer” should also have been disclosed in a JAMA report ‘Association of LDL Cholesterol…with Risk of Cardiovascular Events Among Patients Treated With Statins’, that was subsequently amended due to medico complaints to the journal.

Bias is a relevant fact in STAREE (STAtins for Reducing Events in the Elderly), but frequently missing. Monash colleague Sophia Zoungas should also have declared a 2007 Pfizer personal grant of $55k in articles such as ‘Treatment of Dyslipidemia and Cardiovascular Outcomes: The Journey So Far—Is This the End for Statins(?)’ advocating “the first [Randomised Controlled Trial] to determine the effects of statin therapy vs. placebo in an apparently healthy elderly cohort living independently” ie preventative Lipitor for the over 70s. This is not however, a trial designed to test a hypothesis. It’s an experiment on the elderly to see what happens. Lipitor is the hammer, let’s see if it nails aging! Extending of life is the outcome being investigated – meaning that if they’re wrong, then shortening of life may become apparent.  A successful trial is assured, since my previous example from this department shows an outcome can be invented with impunity. And worsened death rates ‘adjusted for’.

One example of deception is apparent already. In July ’14 Current Opinion in Cardiology neither professor mentions Pfizer’s backing, but offer panacea in claiming: “In a meta-analysis of observational studies, statin therapy was associated with reduction in risk of dementia, Alzheimer’s disease and mild cognitive impairment“. The cited references of Richardson et al (in response to the Lipitor label warning of additional risks, imposed by the FDA in 2012): “Published data do not suggest an adverse effect of statins on cognition.  The strength of available evidence is limited…” and a Cochrane review by McGuinness et al : “Demonstrated lack of benefit of statins compared with placebo on cognitive measures” actually contradict this claim! These issues were raised with Monash Chancellor Finkel, but the reply from his Director, Tony Calder abdicates responsibility: “The matters you allude to in your email are matters that are dealt with by University management therefore the Chancellor, as head of Council, will not be providing a response to your email.

Solving the problem of an aging population?

Solving the problem of an aging population?

Two years after Catalyst aired, a Med Jnl of Aust article advises that over the first eight months 61,000 have made up their own, negative opinion of the meds: “…changes in statin use occurred despite warnings in the Catalyst program that its content should not be taken as medical advice”. Co-author Sallie-Anne Pearson is noncommittal on consequence, having just published a study that concludes: “Deprescribing of statins may be indicated for some older people, because the evidence for benefit in primary prevention of cardiovascular disease is limited and there is an increased risk of side effects in old age.” Other, collaborative colleagues are more determined to restore Lipitor to its heyday position of the highest grossing drug. That popularity arose due to trial results on a surrogate outcome of LDL (Low Density Lipid) levels, without epidemiology data as to whether the drug improves survival rates in the community. We’re a trusting lot.

On the other hand the Brits stay true to form, by constant whinging about risks: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714436/ 😉

* Indigenous Australian’s forewarning of death as punishment