OxyMoronic

Sport Integrity for dopes

A decade on, the Essendon drugs saga won’t go away – because it’s unresolved. Anti-doping ASADA are again fighting NewsCorp’s demand for release of documents under Freedom of Information. In 2019 the Administrative Appeals Tribunal refused disclosure under grounds of a confidentiality agreement. By taking action against 34 players, the AFL deems that culprits have received retribution. In 2013 the Medical Board fined the experiment’s architect Dr Willcourt (in absentia) $7000 for unprofessional conduct, essentially finding that there had been inadequate patient consultation regarding the Essendon supplements. AHPRA withdrew allegation 1D … ” that Dr Willcourt participated in the study and research program without ensuring that the program was approved by a Human Research Ethics Committee and/or acted in accordance with an approved research protocol.” VCAT had decided that since Dr Willcourt had already skipped the country, further sanction or conditions upon practising would result in a ‘mockery’ of such disciplinary action. Willcourt’s practice was just across Chapel st from HyperMed, and their meds are sourced from Nima Alavi’s Compounding around the corner – from which $80,000 worth of growth hormones and steroids were stolen by another artful dodger of AHPRA rules. But who brought the players to HyperMed for injection?

ABC 4Corners report ‘Whatever it Takes’ interviewed spokesperson Graeme Little at HyperMed, where he revealed that supposed villain Stephen Danks simply turned up on the doorstep. At the time, brother Paul Little was Essendon chairman, which weighs against sheer happenstance.

Paul Little, and below, brother Graeme Little

Players obey the coach, and James Hird obeys the orders of club Chairman. There’s hearsay that Hird met Danks at a Thai beach resort, but damned solid evidence the Little family are connected. Well connected. Paul now runs private terminal Melbourne Jet Base, which is also contracted for RAAF VIP aircraft, so used by PM Morrison in 2018 before official opening. In 2020 Paul was appointed to Morrison’s coronavirus economic taskforce, chaired by the CEO of Fortescue Mining (who’s been delaying Court over a quarantine breach). Best we not let this matter rest.

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Iatrogenic is the new Hippocratic

I’ve reprised an earlier post on hypocrisy in med research/experimentation, since reflecting on its value post-pandemic is important. Lives are at stake if we get this wrong.

The Undersea and Hyperbaric Medical Society is a key body of physicians who believe in the therapy, and is status reporting on clinical trials of hyperbaric oxygen (HBOT) in treating severe COVID-19. The rigour of a study by Gorenstein and Lee of New York Uni stands out and has progressed more quickly than another eight similar, however delayed by a restart after Institutional Ethics rejected an initial proposal for subject-own-controls ie measuring severity before & after then comparing with expected recovery rates. A Randomised control (RCT) was mandated, which may appear callous, in that half were denied adjunct HBOT but received standard care only.

The restart RCT has published a mid-term report, per Data and Safety Management, in order to warrant continuation. Although the fatality rate of the HBOT group was one third that of the control arm, the trial was stopped at the request of the US FDA. Why? An adverse event occurred, requiring investigation. A patient arrested in the ward shortly after the HBOT session, was resuscitated but then died. Wait on: they arrived at the chamber with sats of 66% (clip-on oximeter isn’t very accurate when this low, nonetheless hypoxia is indicated). Without bloods, hypoxemia is speculative, but care had already failed. The hospital’s failure in no way indicts the HBOT therapy as risky, and the current stymie by the regulator is actually causing harm (if the statistically significant interim results are to be believed).

Oxygen is cheap – it can be made at home for $2/hr, but without a pressurised chamber it’s benefit is limited to those with COPD and poor sats. Normal sats of 98% are at the limit of haemoglobin’s ability to bind oxygen, but increase the pressure and it dissolves into all tissues (especially the poorly perfused ulcerous diabetic ulcers, for which TGA/Medicare approve benefits).

There’s money in Drugs

On the flipside, snakeoil salesman Tobinick’s lobbyists have obtained funding for a maverick trial of Pfizer’s Enbrel/etanercept. That’s a company spending an avg of $3bn pa on advertising alone in the US, where such is allowed. If the market for this lucrative drug expands beyond rheumatology and into stroke etc, then its patent can be extended. Health Min Hunt tendered the project, reversing the principle of researchers competing for funding based on merit. Florey Institute at Austin Health won the business, unfortunately. They’ve been secretive. A reminder of their obligation to publish within two years of last data collection was answered by a sponsor with: “I do not anticipate we will have anything further to add to this or our previous responses to you…”

Tobinick sued a Yale neurologist for calling ‘lacks evidence’ on his Perispinal Etanercept dabblings in a post at Science Based Medicine. He lost, costs and all – $259,785, affirmed in Appeal. To date, after eight years, the only results presented are those dramatic YouTube videos. Vulnerable victims of traumatic brain injury or stroke, expecting such miracles, spend $45,000 for disappointing results. Governance should be protective, rather than raising unjustified hopes and fueling exploitation. Covert Pharma influence on politicians has been flagrant for a long time – the partnerships go back decades. Kieran Schneemann went from PM John Howard’s Chief of Staff to CEO of industry lobbyists Medicines Australia. Now Director of Govt Affairs at AstraZeneca (PM Scott Morrison’s awkwardly embarrassed new best friends), it’s doubtful that his intent is to redress their behaviour that incurred $USD543m in fines for government-contracting offences.

I felt no need to start writing afresh on this theme. There’s nothing new about this issue, it never goes away.

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Anti-antioxidants?

The Times newspaper shared this article under a tag of red wine’s possible blood pressure benefit (caveat: sufficient intake of the molecule for lowering BP requires 1,000 bottles/day). This line is less nonsensical… “by oxidising a protein called PKG1a in the blood vessel wall.” The free radical worm* turns.

The previous post considered hyperbaric oxygen therapy (HBOT) as destructive to viruses. Speculation attributing perplexing conditions to common herpes viruses eg h. simplex HSV or h. virus 6 in Alzheimer’s or hypothyroidism/Hashimotos is supported by the lab. Indestructability of HSV by the free radical hydrogen peroxide wasn’t long ago explained by discovery of catalase in the virus, perhaps only mitigated by increasing peroxide levels. Now consider this study of HBOT treating drug resistant bacterial infections where 3 weeks of the meds had failed.

Prior to meds, inflammation marker CRP (C-reactive protein, normal level<1) averaged 7.7, after meds 7.1, and after HBOT 0.8! The world faces a Superbug crisis, by virtue of our greed. Offshore manufacture of antibiotics in China and India creates free availability of drugs, and poor sanitation ie no toilets lets Antibiotic Microbial Resistance spread rapidly. Oxygen as a drug may eventually have to be used, eh? The running cost of an oxygen concentrator is ~7c per hour. Iran, Israel, and Turkey are researching the applications – unfettered by pharmaceutical industry control. Another microbe: the fungus, treated here at Alfred hospital and described in a glowing press release. Did you note that the idea came from a googling family member, not a medico?

Industrial cleaners tackling toxic contamination such as that left by meth labs, hoarding & rat infestation, etc use unattended free radical generators to bomb the bug: peroxide and hydroxyl. They’ll kill you, too… and yet your body’s processing of oxygen makes these, more so if an excess of oxygen is supplied. Needless to say, the Diving & Hyperbaric Medicine faculty of the College of Anaesthetists refuses to correspond on such matters. An investigative journalist’s report on their commercial allegiances gives a clue as to why meds are seen as the only answer.

*In Shakespearean times the ‘worm’ meant dragon. Apt analogy for fire-breathing monsters when one such oxidant is hydrogen peroxide (rocket fuel).

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Don’t go viral

Unable to garner any interest in a human-rights violation, explained previously at Framework or Façade?, I’ll retry … perhaps I’d been too flippant, which was my way of dealing with the shock 😦

Two atrocities

On the left is the SmART trial for Drug Conservation (DC), rather than fully-dosed AntiRetroviralTherapy (dotted line), for half of five thousand HIV+ recruited participants. It’s obvious within a few months that the DC proposal for minimal dosing sent HIV viral in those unlucky enough to be randomised to that group. Yet the study was allowed to run four years, and only at the 5th meeting of the ‘safety’ board was the trial stopped and everyone treated with full ART. The study had been funded for six years to investigate cardiovascular outcomes, which didn’t eventuate, but the money kept coming.

The doctors then ran another similar proposal – deferred start of ART until CD4+ (T-helper cells are your immunity) counts drop below 350. Again apparent as a terrible idea within months. This time it was stopped after five years, as an unsafe practice. Another five thousand recruits were allocated 50/50 by the toss of a coin to an alternative that not only increased their risk of AIDS, but also that of spreading HIV.

I’ve written to Vice-Chancellors at Monash and UNSW, two of the participating institutions, complaining that the only Ethics Committee response had been: “Professor Emery is now at the University of Queensland. He is neither the lead or contact author for the relevant article...” finger-pointing by the Director of Research Ethics. No replies. Now consider the only, poor quality study of * Hyperbaric Oxygen (HBOT) for HIV by a nurse and clinic director. Six HIV+ patients, each having received 3-300 sessions of HBOT all dropped their HIV count to 5 or less virions per million cells – thus now considered HIV negative. Never cured, n.b. as with ART’s cocktail of ~3meds, it’s just life-preserving. Indeed CD4+ counts never recovered – once transcribed into your DNA, the virus has wrought permanent damage. But an interesting idea, worthy of further study… however such has never been undertaken in the subsequent two decades. Only two people globally have actually been cured of HIV, due to transplanting an immune system. ART remains vital.

[Victorian Health Minister] Ms Hennessy wants the ACCC to investigate claims made by Hypermed surrounding treatments for cancer, HIV and cerebral palsy. Leaving aside the actual claim being ‘adjunct therapy’ to chemo/radiotherapy (as is also delivered by Monash/Alfred hospital hyperbaric), along with the fact that the consumer watchdog ACCC has no jurisdiction on medical matters, it’d seem more appropriate to demand answers of those institutions refusing to conduct more rigorous investigations. Here’s my limited understanding of the justifications for doing such.

Oxidative Stress. Lipids are structural components of cell membranes. It’d been suggested that lipid peroxidation was analogous to ‘rusting’, that free radicals damaged cells, so antioxidants would help us live longer & look more beautiful etc. When oxygen is breathed in, eventually exiting in carbon dioxide, gaining electrons (thus causing oxidation) creates free radicals at each step. This is normal, and sometimes really slimming too. When glucose is depleted fatty lipids are burned instead, so best we ignore advertising’s simple assumption that free radicals are damaging. We run on them: superoxide (1 electron stolen) and hydrogen peroxide (2 e-).

An HBOT advocate discusses the concept of attacking viruses’ protective lipid envelope, suggesting potential against HIV, Epstein-Barr ie glandular fever (EBV), and Herpes Simplex (HSV). My interest is suddenly piqued, given the early trial successes of IMC-1 against fibromyalgia using a combo of HSV antiviral famciclovir and celecoxib (HSV replication is reliant on imflammatory COX, and the benefit of inhibitors has been known for 4 decades). Then link to HSV’s association with Alzheimer’s (AZH) and excitement mounts… oooh there’s a study of HBOT for AZH … ohhh sorry, it’s on mice. EBV is implicated in chronic fatigue syndrome so three of the greatest medical perplexes could well be treated, just with something in the air we breathe!

But nobody’s looked into it. Institutions don’t care for much but pharmacology, since research is costly. Their industry is profitable tho’.

Smashing together of data

A study has been run on HBOT for shingles (caused by varicella-zoster virus) by Peng et al, and it looked promising. I conducted a systematic review of the literature on other gold-standard Randomised Controlled Trials of HBOT for various other painful neuropathies believed by some to result from viruses. Monash’s chief biostatistician, Prof Forbes, questioned my ‘fudging data’ since it was rare for such consistent results especially across disparate conditions.

Note that the 5 studies came from China, Turkey & Israel. Pharma totally controls what investigations are allowed to happen in the West.

* What/why is Hyperbaric? Oxygen is a vasoconstrictor, so the body’s wonderful homeostasis balances richer oxygen intake with reduced vascular flow. But administering O2 under pressure cheats the system: it floods every tissue without regard for bloodflow.

 

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Bad Medicine (Pt4)

cont’d…

A few years back I was volunteer non-emergency driver for Red Cross ambulant patients going to clinical appointments. The car was fully booked, and the third for the backseat was my last pickup. They had an an older Left Ventricle Assist Device, with huge powerpack. “Would you all squeeze up on the backseat to make room for the artificial heart?”

Talking to the new client en route to the Alfred’s Heart Failure clinic, ‘Chris’ went to the same Uni as me. Did the same course! I tell my anecdote of mathematician Tom Peachey, how I’d been restoring an old BSA and was tardy in attendance at lectures by this angry little man. “You’ll fail and make nothing of your life, Kirwood“, but I shrugged – I was on my way to 98% … Chris agreed, Tom annoyed him too, “so I slept with his girlfriend“.

Karma. Tom may’ve been ultimately right about me, but Chris sure was heartless!

In the most privileged portion of my career, working at the HyperMed clinic with high level of autonomy in dealing with seriously ill patients, there was a fatality. The deceased, Craig, was stage9 MS, and there is no stage10 *. He’d been rushed to ICU repeatedly, including an airlift from the Latrobe Valley. At the committal for trial pathologist Dr Sarah Parsons claimed cause of death was “Too much oxygen“. The planet certainly would benefit if we evolved to breathe CO2 instead, and I hope her team at Monash are working on this. Sure O2 is a vasoconstrictor, which is why hyperbaric is under pressure of around 30ft underwater – every moist tissue then carries oxygen. And this isn’t quackery – Monash’s physicians at the Alfred hospital also have novel uses for hyperbaric eg adjunct therapy in cancer. Perhaps The Age journo misunderstood Sarah’s evidence (after all, she claimed I had ‘no medical background’ despite the court transcript showing I’ve two decades as a skifield paramedic and a postgrad Dip in Clinical Research)?

Craig also suffered epilepsy. Dr Parson seemingly hasn’t heard that Sudden Unexplained Death in EPilepsy (SUDEP) is actually a thing, despite Prof Chris Semsarian hailing from Sydney and his ‘Post-Mortem Review and Genetic Analysis of SUDEP Cases’ begins: “Sudden unexpected death in epilepsy (SUDEP) is the most frequent epilepsy-related cause of death and is characterized by an absence of any identifiable cause of death…” (Brain Pathology, 2010). And he goes on to point the finger at familial long QT syndrome genes.

QT-interval-long

The QT interval is the time for the heart’s ventricle to get the signal to pump, and then recharge. Long QT can cause otherwise healthy people to suddenly die, and is the #1 monitoring of concern in ‘first-in-humans’ drug trials. The anti-epileptic drug Lyrica/pregabalin is known to lengthen QT in rabbits, but there’s no data in humans. When Pfizer’s Phillip Berry was asked where’s this key safety info, the reply was Dunno. Yet he received Medicine Australia’s Code of Conduct Award in 2013! Pfizer’s chief pharmacist Manal Nessim also couldn’t help. Cardiologists notice this danger however: Pregbalin induced recurrent syncopal attacks with prolong QT interval – PubMed (nih.gov)

The US FDA’s approval letter of Lyrica for neuropathic pain section Safety Q19 “Has the applicant submitted adequate information to assess the arythmogenic potential of the product e.g., QT interval studies?” is answered NA. And Q25 “Have narrative summaries been submitted for all deaths and adverse dropouts?” is answered No (will request from sponsor).

Craig was on many drugs, including Lyrica. But the chiropractor killed him, right everyone?

* Stage classification is now obsolete.

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Are you a morning person?

Series 7 episode 1 of Michael Mosley’s BBC program ‘Trust Me, I’m a Doctor’ featured a study comparing gardening against yoga against mindful meditation in beating stress. The outcome was an objective measure – salivary cortisol, for which the latter activity outscored all others. 😮 Wow! But sadly, this trial hasn’t ever been written up for publication, and furthermore the premise of showing increased cortisol awakening response (CAR)  as indicative of de-stressing  is counter to the evidence. Trust me, I’m a skeptic.

Dr Mosley as coach for the Rat Race

From the beginning. Cortisol is a restorative hormone – the benefits of the synthetic corticoid, prednisolone, in suppressing auto-immune response are well understood. In evolutionary terms it’s a clever output from an activated fight/flight HPA axis, halting anti-inflammatory effects so as to concentrate energy and strength. Focus on survival, consequences be damned. It shows a strong peak half an hour into the morning, the CAR, as we prepare to take on the world. It’s so consistent, that it’s been analysed for decades. The CAR peak is flattened when in pain, or fatigued – that makes sense. “Think I’ll sit this battle out, Genghis  – tell the truth, I’m pretty knackered“. But there’s half a dozen studies showing that CAR is boosted in stressful circumstances, such as angrier teachers preparing for work or ‘Perceived work overload and chronic worrying predict weekend-weekday differences in the cortisol awakening response‘.

The Mosley program had results consistent with another, scientifically rigorous trial of yoga. The CAR peak indeed up-regulates after gentle ‘Yoga as Awareness’ classes, just as it does when making ready for battle. Though counter-intuitive, this is the lesson. Meditation isn’t just avoidance, a cozy retreating into a safe place. It’s a pep talk for the body, giving gratitude for past valour, ready for a call of “Once more unto the breech, good friends” (Henry V). A similar increase in morning cortisol resulted from an 8-week Mindfulness program delivered to military helicopter pilots – complementing and enhancing their readiness for a stressful workday.

Humans are not deterministic – the feedback mechanisms are a workaround to any change. To take a pill, or supplement, on the simplistic basis that it has a directly measurable effect shown in clinical studies overlooks the complexity of the body systems that maintain our balance (homeostasis). Mindful meditation and stress both alter CAR in identical ways, yet have opposite effects on your wellbeing. To navigate the contradictory claims there’s only one answer – treat mind&body holistically. Integrative Medicine practitioners are being supplanted by accredited wellness coaches, providing lifestyle counsel but without reliance on a script pad. America’s healthcare travails have fostered two dozen accredited university courses, and the same from private suppliers, for Health & Wellness Coaching. theMindfulGap.com.au is also servicing this need.

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There is a cult of ignorance in the United States, and there always has been. The strain of anti-intellectualism has been a constant thread winding its way through our political and cultural life, nurtured by the false notion that democracy means that “my ignorance is just as good as your knowledge.” Isaac Asimov, 1980

More scientist than sci-fi novelist, the Biochemistry Prof at Boston Med School was a keen observer of humanity. Pres-elect Trump is a man foretold by this futurist, emerging from an ideas vacumn borne out of presentation pizazz. In life’s great reality show, it’s hardly surprising that the winner of the popularity contest would be another actor rather than an intellectual. Nonsensical lies, regardless whether delivered with aplomb or hysteria, can be convincing – and internet memes circulate too fast for any factual repudiation, particularly if response is limited to 140 characters on social media.

Cardiologist and Dean of Harvard Med School from 1935-’49 Dr Burwell advised new students: “Half of what we are going to teach you is wrong, and half of it is right. Our problem is that we don’t know which half is which.” Facts must constantly be re-evaluated in light of new understanding, but that doesn’t happen. Just as the consumer swallows whatever their doctor says, the faculty implicitly trusts their academics. Their faith isn’t tested by apparent misconduct – because it’s not placed in the person, but rather in the institution of medicine. Which intersects with politics.

 

twitter.com/DanielAndrewsMP/status/751641006144036865

twitter.com/DanielAndrewsMP/status/751641006144036865

Glib words, easily misinterpreted. The Victorian Premier was commenting on a maverick colleague of Dankenstein, and not necessarily everyone who gains financial advantage from their chosen career in healthcare. But there’s underlying truth. Commercial influence on treatment decisions isn’t just a risk due to the ‘bad apples‘ experimenting recklessly. Universities contribute to global evidence bases regardless of their fictional truth’s lack of veracity. No better example is given than the UNSW’s sacking of whistleblower Dr Ying Morgan, and exoneration of Prof Levon Khachigian – despite inarguable guilt. Photoshop is a new inclusion to the researcher’s armamentarium, equally as valid as ‘Adjusted for’. Perhaps the governance applied to physicians in practice can correct for this corruption of the evidence base? The Medical Board’s public listings of judgements are over 12 months delayed after decision (and an indeterminate time after the complaint), and any miscreants are protected by anonymity. Sadly, no.

Number 1 in scrips written is Lipitor, for obvious reasons (nothing to do with actually working tho’ – improved life expectancy from statin usage in an ideal, ie recruited into the trial, population is just 4 days). Our number 1 expenditure on medications, running at $3bn p.a., are the Hep C drugs – priced exorbitantly because they work. This could be considered extortion, and sets dangerous precedents. The up and coming big tickets on the PBS are the BioDiseaseModifyingAntiRheumaticDrugs, the _mab immunosuppressants (Enbrel fails to follow the _mab suffix naming convention). The early phase (I & II) drug trial centre Nucleus Network at the Alfred Hospital is fast expanding, largely due to rapid developments of these expensive, specifically targeted bio-agents. By the time efficacy is proven in a phIII Clinical Trial, and it will be proven, the drugs budget will be under assault.

There’s inadequate reports from phIV comparisons of treatment options among the general community, although 10 registries across Europe and the US have been collecting _mab outcome data for half a dozen years. One recent example published is that an incremental increase of 4 Quality-Adjusted Life Years results in a net saving to the healthcare bill with adalimumab, hence it’s recommended for younger patients. Though slowly, the picture is becoming clearer.

If only the politicians refrained from unsupervised social media usage, and also didn’t mistakenly boast of initiatives to supply psychotropic drugs to kiddies thus: “Last month, I visited a secret facility. I can’t tell you where it is, but I can tell you what’s going on there. It’s where we’re growing Victoria’s first crop of medicinal cannabis – a crop that will improve the lives of hundreds upon hundreds of kids suffering from severe epilepsy.”

Premier Andrews confused cannabis with cannabidiol.

Premier Andrews confused cannabis with cannabidiol (source:FaceBook).

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Positivity – soon to be classified as an illness?

Radio presenter and psychiatrist Assoc Prof Steve Ellen has informed listeners that the American Pschological Association is considering inclusion of Excitable Optimism (EO) as a mental disorder. The Diagnostic & Statistical Manual (DSM) draft has been circulated, as was the case with DSM-5, and evaluation will include prevalence and burden assessments. Steve said “My wife finds my intolerable cheerfulness to be just that, but if the proposed change in DSM-6 goes ahead then it’ll validate my illness, and remove that stigma from other sufferers”. Steve’s upbeat persona might seem invaluable in his role as a director at Peter MacCallum Cancer Centre, but its intrusiveness into personal relationships led him to study the condition through Monash Alfred Pschiatry research centre.

Steve runs a selfie-help group

Steve runs a selfie-help group

A formal diagnosis of EO will require more than just positivity, the discriminant being a manic aspect of excitement on top of delusional belief in things getting better. EO is mooted to join ADHD in the standalone category formed in DSM-5, having both cognitive and behavioural domains (Coghill & Seth, 2011). The plan has already been bookmarked in the International Classification of Disease (ICD) update at ftp://ftp.cdc.gov/pub/Health_Statistics/NCHS/Publications/ICD10CM/2017/ where ADHD is renamed HyperKinetic Disease, and sits alongside HyperAffective Disorder (HAD) – an extended definition of the previous ICD coding for Death & Injury Resulting from Terrorism.

These examples are the first application of ideas about endogenous disease affecting others globally, although the association between EO and ADHD isn’t new, indeed being well documented. What isn’t known, but is being keenly investigated, is the contribution of nature or nurture in positivity. “Shared environmental influences on low extreme ADHD traits may reflect passive gene-environment correlation, which arises because parents provide environments as well as passing on genes”, said behavioural geneticist Dr Corina Greven from the Dept of Cognitive Neuroscience at Radboud University.

The proposal reflects growing divisions within Psychology due to the increased adoption of Eastern Buddhist traditions into therapy, most obviously arising from mindfulness in treating disorders. “Positive Psychology is plagued with problems of confusing directionality, and submerged in a lack of rigorous science.” writes psychologist Michael Booth from the Science-Based Medicine organisation. “Mindfulness introduces many things that cannot be refuted or invalidated, and can be used as an ad hominem against an individual. For example: you aren’t meditating correctly, which is why we did not obtain the promised result.”

Results are much clearer in clinical trials. Of the 16 persons reporting persistent high-intensity backpain in a two-year community study, negativity was strongly associated. Positivity affect from family and peers was also associated, but not significantly so. “This is a statistical limitation of the small numbers of participants, with a tripling of study size the p value of 0.08 would have decreased and achieved significance”, author Assoc Prof Anita Wluka advised. “Larger investigations are warranted, to show that pathological optimists are literally a pain in the backside”. The Monash team already has an application in for funding to trial amitriptyline in households with a chronic pain patient where an EO sufferer also resides. Medicating persons other than the patient is controversial, with few precedents being available. Director of NHMRC grants, Saraid Billliards declined to comment, due to the matter still being under review. Further details are available on the clinical trials registry under ref ACTRN12612000131853.

In the immediate term if you, or a person you know has been affected by HAD, the Australian Government has a support line: 1800 123 400

 

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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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Bad medicine (Part 1)

“People have died from the drugs I have prescribed…..We Doctors have a destructive therapeutic mind set and this is causing widespread and long term harm to society “. So begins a typically thought-provoking Bad Medicine view and a discussion excerpt in the British Medical Journal, in response to the report by a forensic toxicologist that 35% of heroin overdose victims had misused gabapentin or pregabalin (editorial 15 Aug 2013). How apt are the asps of the caduceus – adopted erroneously by the medical profession in the 19th century as a result of a mistake by the US Army Medical Corps? The Hippocratic Oath began with the words “I swear by Apollo the Physician and by Asclepius …… (whose staff in mythology had only the one snake!)…. I will neither give a deadly drug to anybody if asked for it, nor will I make a suggestion to this effect”. To err is truly human, and physicians are no more exempt from blunders. The two snakes of the medical caduceus actually belong to the staff of Hermes – God of commerce and thieves, and guide to the Underworld. Hellarious!cad

The fatalities’ poisoning was associated with abuse in order to enhance euphoric effects of opioids, and GPs have been alerted to avoid iatrogenic involvement (remember do no harm!). Information is readily accessible, however overly abundant. Distilled summaries are published by the Cochrane Collaboration. Investigating any benefits of the GABA-likes gabapentin or pregabalin would reveal systematic reviews of studies by Üçeyler, Sommer and Häuser et al finding that “The amount and quality of evidence were insufficient to draw definite conclusions on the efficacy and safety of gabapentin …………. The anticonvulsant, pregabalin, demonstrated a small benefit over placebo in reducing pain and sleep problems. Pregabalin use was shown not to substantially reduce fatigue compared with placebo. Study dropout rates due to adverse events were higher with pregabalin use compared with placebo.”  Häuser co-authored an 11-year study of fibromyalgia outcomes with Dr Fred Wolfe which reported in the European Journal of Pain Sept 2012 a conclusion that “Drug costs are substantially higher because of NCAD (pregabalin, duloxetine, milnacipran) use, but we found no evidence of clinical benefit for NCAD compared with prior therapy.”(tri-cyclic anti-depressants ie amitriptyline). Confirmed by Prof Beth Smith’s meta-analysis of 51 publications in 2011 concluding “Amitriptyline was similar to duloxetine, milnacipran, and pregabalin on outcomes of pain and fatigue“. Wolfe’s colleague Dr John Quintner wrote that “a minority of patients will report substantial benefit with Lyrica… Many will have no or trivial benefit, or will discontinue the drug because of adverse events“. Which somewhat contradicts the tick of approval given by the US FDA, and it gets no better. The April 2010 Journal of the American Medical Association article ‘Anticonvulsant Medications and the Risk of Suicide, Attempted Suicide, or Violent Death’ points to an increased risk with the taking of gabapentin. Which is where we started…. and whence we shall return

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