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).

Advertisements

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

 

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.

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