an autodidact meets a dilettante…

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covid19: sensible testing, mostly

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Canto: So we’re looking at medcram coronavirus update 98 now, and it’s a fascinating one entitled ‘Rapid COVID 19 Antigen Testing at Home – A Possible Breakthrough’, though it comes with the clear proviso – this would require co-ordinated political action, and that won’t happen in the USA, not just under Trump, but at any time.

Jacinta: Well, but especially under Trump. But the issue is one of trying to get much more testing done, with far less emphasis on the sensitivity of the test, because rapid-fire, fast turnaround testing is far more useful than expensive, hard-to-evaluate slow-turnaround testing, which puts a premium on sensitivity. But before we get to all that, Dr Seheult looks at a paper on viral loads vis-à-vis covid19 patients. They looked at nasal and throat swabs, and then checked the Ct values over time. 

Canto: The Ct values are a measure of viral load and it works inversely – a 3.32 reduction in Ct value means a ten-fold-increase in viral load. 

Jacinta: Yes, so a low Ct value means a high viral load, and of course viral replication works exponentially, at least during the early infection period, so your viral load can be massively different from one day to the next – think about that for testing, and delayed results. 

Canto: A Ct value of 40 is close to undetectable, depending of course on the sensitivity of the test. And the value can go down as low as 5, all approximately of course. The course of the virus is generally, exponential growth, then a tapering off of the growth rate, reaching a peak, then a descent to finally a remnant population of largely disabled viral scraps, with of course mortality intervening along the way in the worst cases. 

Jacinta: Far from the majority of cases, thankfully. So the ‘gold standard’ test is the reverse transcriptase polymerase chain reaction (rt-PCR) test – also called real-time PCR, I’ve just found out. It’s relatively expensive at around $US100, with turnaround times – and this might depend on demand and other factors – of between 3 and 9 days. There aren’t enough of these tests to go round, but they are very sensitive, detecting the virus reliably from a Ct value of about 35, or maybe even 40 (for argument’s sake, Seheult says). But there are other, cheaper, less sensitive tests, called paper tests, that can be rolled out more easily to the general public. The paper is coated with monoclonal antibodies that can detect antigens – substances that evoke an immune response. These paper tests cost at most a couple of dollars each, and would be sensitive to a viral load measured at a Ct value of around 32. These figures aren’t exact but this would make the test around 50-55% sensitive. 

Canto: But there’s this issue called the ‘threshold of transmissibility’, which is important in all this, and a virologist, Dr Michael Mina, shown speaking on this update, explains:

So people who are transmitting probably have Ct values that are below 30 and the vast majority probably have them below 25 or so.

As Seheult explains, people may be testing positive at that range above 30 (i.e. low viral load) but not transmitting the virus. This is especially so if they’re on the downward trajectory, as described above, and what the rt-PCR test (or assay) is detecting are those remaining viral fragments. And as Dr Mina points out, it’s the downward trajectory that’s being picked up for the most part, because the initial upward trajectory is exponential. Here’s what he says:

A lot of people are saying, ‘we need the really sensitive tests to be able to detect people early on in their infection’, but almost all the time that people spend with this virus near the limit of detection of PCR is on the tail end of their infection. This is a virus that, once it hits PCR positivity levels, it’s growing well in its exponential phase and it’s probably a matter of hours, not days, before it passes the threshold to be detected on some of these slightly lower sensitivity assays. And then it may persist for weeks or possibly months even in some cases at very low RNA levels. So it’s after people are well beyond their transmissible period that we’re actually seeing the loss in sensitivity of these assays. It’s very rare that you actually detect somebody with a Ct value 0f 39 in that window on their way up, because they’re only sitting there for a few hours before they get down to a 33, so if you’re missing Ct values of 39… it’s really not that important..

Jacinta: Not that important, but the point Dr Mina is making is really important – if the threshold of transmissibility is at 33 or below vis-à-vis Ct values, then a high-sensitivity test may even be a barrier to focussing on getting at the most transmissible subjects. 

Canto: Yes, especially when you have an alternative test that can be applied much more regularly with a quick turnaround – results on these paper tests take ten minutes! And being cheap, you can test as often as you feel you need to. If you’re positive, you quarantine yourself for a while, keep testing, find yourself negative, wait for a few more days, considering the low sensitivity of the test, keep testing in case there’s a recurrence, and when it’s still ok after a few days you can resume your life, go back to work or school, whatever, being pretty sure you’re past the infectious phase. 

Jacinta: Yes, as Dr Mina says, 9 out of 10 people go undiagnosed with the virus in the USA, according to the CDC – indicating the inadequacy of testing. And he goes on to say, of the other one out of ten, those that are caught, are mostly post-infectious, at the ‘tail end’. The point is that, because of the woeful lack of testing and the long turnarounds, they’re catching far fewer of the transmissible cases, the ones they want and need to catch, than the pitiful few that they actually find testing positive. 

Canto: The bottom line being that if they tested with a far less sensitive, but cheap and readily available quick-result assay, they would capture far more of the transmissible cases, and save lives. 

Jacinta: Dr Mina and many colleagues have written a paper on this, entitled ‘test sensitivity is secondary to frequency and turnaround time for covid19 surveillance’, and he points out that with this approach they would drive down the ‘r effective’ – the reproduction number – which is the number of people who can be infected by a carrier at any specific time – to well below 1. So if you were to give a significantly high proportion of people in in the worst affected areas these types of tests, you could bring the numbers down very rapidly, and this would eliminate the need for contact tracing. It would have an effect on schools, workplaces and so forth – because if you’re given one of these long-turnaround tests and your results eight days later turn out negative, that may be because you had just contracted the virus when the test was taken, but it didn’t show on the test – so you go back to school and infect people. With regular testing this problem would be eliminated. Hate to belabour the point, but – people are dying. 

Canto: It seems the CDC put a high priority on sensitivity, and so rejected these cheap paper tests, neglecting the obvious problem of turnaround more or less completely. The low sensitivity tests usually miss the subjects that are beyond infectivity. If they were on the upward trajectory they would likely be caught by the next test. It’s this upward trajectory that is the infective period. You would think regulatory organisations like the FDA or the CDC would twig to this, but not so much in the Trump era, when non-scientists are put in charge. Yet another failing of the individualist, anti-collaborative, egotistical destruction of all government agencies…

Jacinta: Or just the unwieldiness, the lack of finesse, of lumbering bureaucracies. Or a mix of both. 

Canto: Anyway, as things deepen and darken in the USA, we might have to skip a number of updates to keep up with the chaos, the failures, the resistance and everything else. It isn’t a great time to be living in the USA, but as outsiders we’re kind of ghoulishly fascinated by the mess they’re making of this pandemic, and much else besides.

Jacinta: But also genuinely sympathetic to those who are trying to make thing work in the teeth of all the craziness. 

Canto: Today, September 16, marks the day that 200,000+ deaths from covid19 have been recorded next to the name of the USA, according to Worldometer’s stats. Taiwan, a country that is separated from the so-called ‘China virus’ only by the narrow Formosa strait, has suffered only seven deaths in the nine months that this virus has raged. It has a population of about 24 million, slightly less than that of Australia, into which we find ourselves thrown. Australia has had 824 deaths thus far, and we’re regarded as something of a model!

Jacinta: Yes, several cheers for Tsai Ing-wen and for female leadership, sans egotism. And a special thanks to Audrey Tang, Taiwan’s digital minister – but she’s actually real, and a life-saver. We need more of her. 

Audrey Tang

Written by stewart henderson

September 17, 2020 at 12:03 am

Posted in covid19, Taiwan, USA

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covid19: corticosteroids, male susceptibility, evaluating health, remdesivir, coagulation factors

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from The Lancet, ‘the four horsemen of a viral apocalpse’

 

Canto: So short-course use of some steroids was being advocated in the medcram update 88, though without thorough RCT evidence. 

Jacinta: Well, data was presented from the Oxford RCT on those on oxygen or on ventilators showing a statistically significant reduction of mortality from short-course (up to 10 days) low dosage of dexamethasone, a freely-available steroid medication. The study involved some 2000 patients, but only those severely afflicted were helped by the medication. 

Canto: An interesting aside to the data is that in the study males outnumbered females by almost 2 to 1, and that accords with the overall ratio of male to female covid19 patients Dr Seheult is finding, which rather shocked me. Why would more males be coming down with the disease? Presumably that’s not the infection rate, but the rate at which they need to be hospitalised. 

Jacinta: Yes, you’re right, according to this Australian site (unfortunately undated):

Reports continue to emerge that men are significantly more vulnerable to COVID-19 than women. The commonly held perception that more men smoke and this makes them more susceptible along with other lifestyle factors does not tell the whole picture. White House COVID-19 Task Force director Dr Deborah Birx highlighted a “concerning trend” that men in all age brackets were becoming seriously ill from the virus at a higher rate than women, including younger males.

They’re suggesting more research needs to be done on this gender difference, for health issues in general. Some are claiming that estrogen makes a difference. In any case I think cardiovascular problems are more common in males – but maybe not so much in younger males. 

Canto: So update 89 is fairly short, and deals with US data about cases and deaths, most of it out of date now, and more on corticosteroids and the dangers of unsupervised use. Update 90 introduces us to a tool I’ve never heard of called ‘Discern’. Very useful for we autodidacts in helping us, for example, to enlighten our doctors as to our condition. Discern is a tool for evaluating internet health info, such as medcram’s updates on youtube, or anything else on youtube. The instrument asks you to evaluate the material according to 16 different criteria. Interestingly, this tool has been tested on covid19 material by a study out of Poland done in March. The results weren’t so good, especially for news channels. 

Jacinta: Yes, physicians’ information did best – but of course we don’t go to news channels for health information, and we’d advise against anyone else doing so. The study evaluated the Discern tool itself and found it excellent, then used the tool to evaluate health information, specifically on youtube. Of course know that there’s ‘viral misinformation’ from various news outlets that gets posted on youtube. And good to see that the medcram updates were some of the most highly rated using the Discern tool. 

Canto: So we’re now into reporting from early July with update 91. It starts by looking at a ‘covid risk calculator’ in which you can type in your age, gender, BMI, underlying conditions, waist circumference, and other data which you might need a full medical checkup to find out about (and that’s overdue for me), including, for example, %FMD, a measure I’ve never heard of, but which has to do with endothelial function. 

Jacinta: FMD stands for fibromuscular dysplasia. The Johns Hopkins medicine site describes it as a rare blood vessel disease in which the cells of some arteries become more stiff and fibrous and less flexible. This leads to weakness and damage. Not sure how it relates to covid19 but surely any pre-existing blood vessel damage is a danger for those contracting the virus. 

Canto: Right, so it’s unlikely anyone will know offhand their percentage of FMD. I don’t even know my HDL and LDL levels, never mind my HbA1c or lipids. I’d love to be able to take measures of all these myself, without visiting a doctor.

Jacinta: Typical male control freak. So all of this is to measure your risk of covid19 hospitalisation, ICU admission or mortality. Fun times. So next the update looks at Gilead, the makers of the antiviral remdesivir, who donated all their supplies of the drug to the USA in early May. But of course they kept manufacturing the drug and have to recoup the money they spent researching, developing and trialling it etc. The Wall Street Journal reports that a typical course of the drug will cost over $3000 per patient. Interestingly the Trump administration is wanting the drug to stay in the USA as much as possible, rather than be available overseas, and is spending money to that effect. 

Canto: Hmm. Is that protectionism? 

Jacinta: Yes I suppose. It’s not surprising that a country wants to look after its own first, especially via a product produced within its own borders. But I suspect this government would’t be interested in helping any other country – unless there was a quid pro quo. And there’s another antiviral, favipiravir, currently being trialled in Japan and the USA (I mean as of early July), and a vaccine, developed in China, is being used on the Chinese military in what seems a rather rushed and somewhat secretive fashion – we don’t know if they got the soldiers’ permission on this seemingly untried vaccine. At least at the phase 3 level.

Canto: Very CCP. 

Jacinta: So onto update 92, and we revisit the electron transport chain, with four successive electron transfers converting molecular oxygen into water. Problems within this chain can produce reactive oxygen species (ROS) such as superoxide, hydrogen peroxide and hydroxy radicals, which are destructive in excess. We also look, yet again, at covid19’s impact on angiotensin and particularly the production of superoxide, which in turn causes endothelial dysfunction, increased von Willebrand factor activity, which leads to thrombosis. People were presenting as ‘happy hypoxics’, looking and feeling fine but with very low oxygen levels, and autopsies revealed ‘microthrombi in the interalveolar septa’ of victims’ lungs. All this leading to a paper published in The Lancet which looked at factors in this process of coagulation and thrombosis:

We assessed markers of endothelial cell and platelet activation, including VWF antigen, soluble thrombomodulin [a marker of endothelial cell activation], soluble P-selectin [a marker of endothelial cell and platelet activation], and soluble CD40 ligand [a marker of platelet and T-cell activation], as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes.

So this was about getting to the bottom of the increased clotting. And the results were hardly surprising, but the final discussion section is worth quoting at length, as it seems to capture much that we know about covid19’s effects (at least short-term effects) at the moment: 

We therefore propose that COVID-19-associated coagulopathy is an endotheliopathy that results in augmented VWF release, platelet activation, and hypercoagulability, leading to the clinical prothrombotic manifestations of COVID-19-associated coagulopathy, which can include venous, arterial, and microvascular thrombosis. The factors responsible for this endotheliopathy and platelet activation are uncertain but could include direct viral infection of endothelial cells, collateral damage to the tissue as a result of immune infiltration and activation, complement activation, or any number of inflammatory cytokines believed to play a role in COVID-19 disease.

They suggest anti-platelet therapy and endothelial cell modification treatments as well as anticoagulation treatments, and they suggest some agents ‘which might have therapeutic potential’.

Canto: Potential? You’d think they’d be onto all this by now. 

Jacinta: Well there’s also potential for untried medications – at least untried in this context – to go terribly wrong. And it’s also likely that some hospitals are already onto using the safer forms of treatment. Dr Seheult speaks of the antioxidant N-acetylcysteine (NAC) in this context, as it has been shown to be a thrombolytic when used intravenously. There are studies pending on the effects of NAC in treating covid19 patients. 

Canto: Now, I’ve just been watching something on monoclonal antibodies as perhaps the most promising treatment yet, short of a vaccine. Can you explain….

Jacinta: Yes I’ll try, maybe next time.

References

Coronavirus Pandemic Update 88: Dexamethasone History & Mortality Benefit Data Released From UK

Coronavirus Pandemic Update 89: COVID 19 Infections Rising in Many States; Dexamethasone Cautions

Coronavirus Pandemic Update 90: Assess The Quality of COVID-19 Info With A Validated Research Tool

Coronavirus Pandemic Update 91: Remdesivir Pricing & Disparities in Drug Availability

Coronavirus Pandemic Update 92: Blood Clots & COVID-19 – New Research & Potential Role of NAC

amhf.org.au/covid_19

http://www.discern.org.uk

https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(20)30216-7/fulltext

 

Covid 19: hopes, failures, solutions

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under pressure

Covid-19 continues to be devastating, especially in the USA, where there are vastly more cases than anywhere else, and vastly more deaths, though the picture there is complex. The hardest-hit region, the New York area, is seeing devastation in poorer districts such as Queens, where the Elmhurst public hospital is inundated with uninsured, critically ill patients. New York has suffered almost half of US deaths. Some other states and regions, especially physical outliers such as Alaska, Hawaii and the Virgin Islands, have very low numbers, and it would be hard to explain why the spread of cases across the mainland has been so uneven. Of course it’s obvious that there has been no federal leadership on the pandemic.

Here in Australia, where the numbers seem to be improving (we’re 33rd on the list of total cases, down from 18th when I first started paying attention to the list about three weeks ago, and 52nd on the list of total deaths), our conservative federal government is keen to open up the country again, and has released modelling to the effect that the virus will be eliminated from the mainland if we maintain current physical distancing measures, though it’s likely to take weeks rather than months:

The model suggests that every 10 people infected currently spread the virus to five more people, on average. At that level, the virus would eventually be unable to circulate and would die out within Australia.

Sydney Morning Herald, ‘Australia in course to eliminate Covid-19, modelling shows’

Australia’s current reproduction number (R0) is just a little over .5. A maintained R0 of 1 or less will eventually eliminate the virus. Of course, there will be fluctuations in that number, so it will be difficult to project a time when things are ‘all clear’. Another difficulty with modelling is that the number of infected but asymptomatic people is unknown and difficult to estimate. For example, recent Covid-19 testing of the entire crew of the aircraft carrier Theodore Roosevelt found that a substantial majority of those who tested positive were asymptomatic, casting doubt on previous estimates (already worrying for transmission) of one in four cases being asymptomatic.

The asymptomatic/presymptomatic transmission issue was addressed by Bill Gates in this article back in February. It’s what makes SARS-CoV-2 a much more serious threat than the previous SARS and MERS viruses. Gates, in this very important article, also provides an outline of what needs to be done globally to fight this pandemic and to prepare for inevitable future ones. If only…

It’s worth comparing Gates’ call for national and global co-ordination, and more expenditure, in the fields of epidemiology and disease prevention, with another more recent article, also published in the New England Journal of Medicine, which tells a tale of Britain and its NHS, gutted by years, in fact decades of ‘reforms’ and budget cuts:

Thanks to government “reforms” of the NHS, it has become highly decentralized, with over 200 commissioning groups in England that can make independent decisions about staffing and procurement of equipment — far from the monolithic “socialist” health care system it is often assumed to be. The devolved governments in Wales, Scotland, and Northern Ireland have substantial health system autonomy. At a time when central management of staff and resources might be most helpful, the decentralized decision-making structure leads to competition for resources and inconsistent policies.

One can hope that the travesty of this virus, especially in places like the US and the UK, will lead to a rethinking of the importance of a well-funded, centralised, co-ordinating and interventionist government in modern states, with particular emphasis on the healthcare system. But I suspect that, in the USA at least, things will go the other way, and the government-hating and government-blaming will only intensify. I’d love to leave this topic and look at solutions – that’s to say I’d love to focus more on the science, but I’m barely equipped to do so. Still, I like to have a go. A very technical and comprehensive review review of pharmacological treatments has been posted recently on the JAMA website, which includes an account of how SARS-CoV-2 enters host cells and utilises those cells for reproduction.

The review claims that currently the most promising therapy is the antiviral drug remdesivir. So what is it and how does it work? I’ll try to answer that question next time.

References

https://www.news.com.au/world/coronavirus/global/epicentre-of-the-epicentre-this-queens-ny-hospital-is-coronavirus-ground-zero/news-story/6d0213ab9d5dd82fa12339f551be99ce

https://www.theguardian.com/world/ng-interactive/2020/apr/16/coronavirus-map-of-the-us-latest-cases-state-by-state

https://www.smh.com.au/national/australia-on-course-to-eliminate-covid-19-modelling-shows-20200416-p54kjh.html

https://www.nejm.org/doi/full/10.1056/NEJMp2005755?query=recirc_artType_railA_article

https://www.nejm.org/doi/full/10.1056/NEJMp2003762

https://jamanetwork.com/journals/jama/fullarticle/2764727

Written by stewart henderson

April 18, 2020 at 1:18 pm

the science of Covid-19: possible treatments, herd immunity

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Australia is now 22nd in the list of total COVID-19 cases and dropping down. There are still of course new cases every day, but far fewer than many countries below us on the list. Experts are now talking about a flattening curve, but they also warn that the virus is ‘here to stay’. Here in South Australia, there were no fatalities when I last posted, but there have been three in the last couple of days. There are a large number of cases recently linked to our Barossa wine-growing region, a popular tourist destination.


So let me take a closer look at the SARS-CoV-2 virus. It’s a positive-sense single-stranded RNA virus. RNA is generally single-stranded in nature, though apparently can be double-stranded on occasion. The positive-sense term refers to the polarity, or sense, of the RNA. It’s also called ‘positive-strand’, facing 5’ to 3’, which means it acts as mRNA and can be translated into viral proteins in the host cell.

These types of virus are very common. They include common cold rhinoviruses as well as the SARS and MERS coronoviruses. SARS-CoV-2 is genetically similar to bat coronaviruses, causing virologists to believe that it was transmitted from bats to humans through an intermediate species such as a pangolin. The reproduction number of the virus (R0) is currently ranged from 1.4 to 3.9, in a scenario of no immunity and no preventive measures taken.

It has often been repeated that a vaccine will take 12-18 months, if not longer, to be safe, ready and effective. Science communicators such as the ABC’s Dr Norman Swann are telling us that stay-at-home orders may need to stay in place until that time, which is surely alarming economists and the business community. So, unsurprisingly, people are looking to short-cuts and desperate remedies. Perhaps the most publicised of these is the anti-malarial drug hydroxychloroquine, aggressively promoted by the US President. It turns out, also not surprisingly, that he has some financial interest in the French company that has branded the drug, according to the New York Times. There doesn’t appear to be any clear evidence on the benefits of the drug. Best reports speak of ‘mixed results’.

There are reports also of the benefits of blood plasma from people who have recovered from Covid-19. A small Chinese study involved 10 severely affected patients being given a few hundred millilitres of ‘convalescent plasma’ containing viral antibodies, and results were described as promising. The approach is being tried in the US, with the Red Cross and the American Association of Blood Banks seeking to recruit suitable ‘fully recovered’ donors.

As people continue to be alarmed and frustrated at the massive disruption to their working and social lives caused by Covid-19, some world leaders (e.g Boris Johnson and his chief science adviser Patrick Vallance, and Netherlands PM Mark Rutte) have come up with not-so-encouraging solutions, such as allowing the virus to run its course so that the population can build up herd immunity. This would actually be a disastrous policy in the case of a virus with a high (but not precisely known) fatality rate, involving millions of severe cases requiring intensive care treatment at any one time.

Herd immunity occurs when enough people have antibodies to the virus that it has nowhere to go. This can occur through the work of our immune systems or through antibodies created by effective vaccination. The former obviously comes at a much greater cost in terms of lives lost, in the case of a highly infectious (the R0 is now estimated – the data changes as I write – at between 2.0 and 2.5), high-fatality virus. Also, because Covid-19 is new, we don’t have sufficient data as yet about the degree of immunity it confers upon recovered patients, or whether it is able to mutate to any degree. Experts are generally counting on low or no mutation, but none of them see relying on herd immunity to be a humane solution to the problem. Suppression is the name of the game at the moment (even though it will reduce herd immunity). That’s to say, the R0 mentioned above (which might be higher) is the figure without the application of physical distancing or other containment measures. The R0 number, if it can be ascertained, gives an indication of the percentage of immunity required to ‘protect the herd’. An R0 number of 2 will require about 50% immunity. If the R0 number is 3, some 66% immunity will be required. Measles has a very high R0 of 12, requiring 90% immunity, which explains why anti-vaccination movements can imperil whole communities.

So it’s a trade-off. Physical distancing measures will reduce the possibility of herd immunity – the production of antibodies. Going back to business as usual will increase infection rates – ok for those who recover, not so much for those who don’t. The cost of the second option, most will agree, is just too great.

References

https://www.technologyreview.com/2020/04/08/998700/blood-plasma-taken-from-covid-19-survivors-might-help-patients-fight-it-off/

https://www.technologyreview.com/2020/03/17/905244/what-is-herd-immunity-and-can-it-stop-the-coronavirus/?itm_source=parsely-api

https://www.worldometers.info/coronavirus/

Bloomberg news interview: Dr Josh Sharfstein (video)

Written by stewart henderson

April 9, 2020 at 9:14 pm

My current health condition 3: nerves

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I’ve been to see a physiotherapist/sports medicine specialist, on the advice of a couple of people, and I’m happy with the result. It won’t mean an immediate cure, but the session has provided me with hope and a pathway to recovery.

Today and yesterday, the pain has been fairly minimal, after an excess of pain the day before. It seems to be about managing the medication.
So, to the physio. I described my situation in minute detail, describing as best I could the type of pain I felt, its sudden onset, how it responds to head movements and so forth. He very quickly conjectured that it was a nerve problem, which in fact had been my first intuition before I began researching the problem. He described the ‘queerness’ of nerve injury, or nerve impingement as it’s often termed – how damage in one place can be felt in another seemingly unrelated region. Interestingly, it was my description of how, since this condition has struck me, I’ve had difficulty moving my head back (this causing my shoulder pain to increase), and so not being able to gargle with mouthwash – which I do because of my bronchiectasis – it was this description which made him feel more certain that it was a nerve problem. He could be wrong but I think he’s right.

He did a lot of physical manipulation of the shoulder region and gave me advice. Keep up the medication, maintain activity of the shoulder and arm regions – not too much but not too little – and keep the area warm. He gave me some shoulder exercises to do, and assured me things would come good in time. I’ll revisit him next week.
Now, on this concept of impingement. It’s a term that comes up in the literature, and it was used by the physiotherapist today, so I asked him about it. He obliged by giving an explanation that was complex and difficult to follow, much like the material I’ve been reading online about the subject. So I’ll have a go at explaining it to myself.
Nerve impingement is one term among many (e.g pinched nerve, nerve compression, nerve entrapment), which indicates the trickiness of the condition and its description. In my case the suprascapular nerve is probably involved. As Wikipedia puts it ‘the nerve passes across the posterior triangle of the neck parallel to the inferior belly of the omohyoid muscle and deep to the trapezius muscle.’ I don’t know exactly what this means, but it seems to explain the pain at the back of my neck, left side, when I throw my head back.

The posterior triangle of the neck is a technical term with its own Wikipedia page. Here’s an image of it. As can be seen, it connects the omohyoid muscle and the massive trapezius which goes well down the back.
So nerve impingement/compression/entrapment is what it implies – something is impinging on the nerve, entrapping it, compressing it, pinching it. It could be bones, muscles, tendons, ligaments, cartilege, and that just about exhausts the possibilities. Carpal tunnel syndrome, for example, generally involves a pinched nerve in the wrist. The causes of course, are various. It could be a particular injury – but I can’t trace my own sudden onset to a particular injury (which doesn’t mean that no injury occurred) – or physical stress from repetitive work or sports activity, or some rheumatoid problem (which presumably would’ve shown up as some sign of inflammation, and I’ve never shown any signs of rheumatism) – or obesity.

The possibility that this was caused by lawn bowling remains real, if remote. Fascinatingly, when I told the physiotherapist that the only sports activity I’d taken up in recent times was lawn bowling, he asked me if I played at Walkerville – it turns out that he recognised me as he played in the competitions there too – out team had thrashed his only a few weeks ago! He agreed that bowling as a cause seemed unlikely – but being a bowler himself, he would say that, wouldn’t he?

But whatever the cause – and I won’t be bowling again for a while, if ever – the diagnosis and cure are the things, and it’s amazing what a seemingly effective diagnosis can do to calm the – nerves! I feel I can cope much better now, and I’ve had the humbling experience of knowing what severe pain is like. This is important as I’ve tended to be dismissive of the pain of others, with thoughts of ‘low pain threshold’ and ‘get over it’. So, it’s a lesson.

I’ll be returning to the physiotherapist next week, hopefully for the last time. His feeling was that just one more session would be enough, that if I simply followed the light exercise regime he suggested, things would come good. The pain has risen and fallen since then, but there’s been no relapse into anything agonising. I worked at Eynesbury yesterday, a relief day, but hopefully there won’t be any work for a while. In any case Covid-19 means we probably won’t be getting many, if any, students coming in from overseas over the next few months.

Of course, it’s not all back to normal, though I’ll try to get back to regular reading, writing and the like. Here’s a final quote from the Mayo Clinic on my situation:

If a nerve is pinched for only a short time, there’s usually no permanent damage. Once the pressure is relieved, nerve function returns to normal. However, if the pressure continues, chronic pain and permanent nerve damage can occur.

We’ll have to wait and see.

References

https://www.mayoclinic.org/diseases-conditions/pinched-nerve/symptoms-causes/syc-20354746

https://www.healthline.com/health/nerve-compression-syndrome

https://orthoinfo.aaos.org/en/diseases–conditions/cervical-radiculopathy-pinched-nerve/

https://en.wikipedia.org/wiki/Suprascapular_nerve

Written by stewart henderson

March 18, 2020 at 2:02 pm

My current health condition 1: it’s bizarre

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I can bear any pain as long as it has meaning

Haruki Murakami

stuff to learn about

I haven’t written for a while because I have a new health problem which flared up last Saturday, February 29, 2020. I had been feeling mild pain in my shoulder and I was lying on my bed reading when I tried to get up. Shooting pain from my shoulder down my left arm was so excruciating that I fell back on the bed and and lay down for a while before trying to get up again. Again I couldn’t get up because of the pain. I called for help but even with two of us it was difficult. I may have had a panic attack and exaggerated the pain of rising – I was gasping a lot. To cut a long story short Sarah called an ambulance (and the paramedic got me into a sitting position easily enough). I spent the next few hours in emergency at the Royal Adelaide Hospital.

Due to being given Panadol in the ambulance, and a long wait in reception while the painkiller took effect, by the time the friendly, efficient and strikingly beautiful (oh dear) young intern saw me, the pain, my only symptom, had much reduced. She found that, yes, I could move my arm above my shoulder, flex my elbow and my wrist, and no, I couldn’t precisely describe the nature or location of the pain. She checked my arm for swelling or redness (none), and asked about any recent history of injury to the region (none). I was beginning to feel like a fraud, a malingerer, a milquetoast.

So after some more prodding and questioning and advice from higher authorities, I was released with a report for my local doctor.

I’m very left-handed, so this left arm pain is quite a problem for me. I was due to work on the Monday and I needed some pain relief. It would have to be over the counter at first. The report’s only solid conclusion was ‘skeletal-muscular pain’. Since I needed to work on Monday and Tuesday I could only get to the GP on Wednesday. So on Sunday I started doing what research I could. I’ve never taken regular medication for anything, and I’ve never experienced regular pain like this. The only over-the-counter treatments for pain are ibuprofen and paracetamol as far as I know. Only ibuprofens is an anti-inflammatory. Paracetamol works on pain centres in the brain. Which one would work best? Was it all in my mind? But don’t we always feel pain via the brain? Isn’t that how the nervous system works?

I obtained both medicines. Over the next day or so I experimented with both, singly and in combination, and I got through Monday and Tuesday’s work. The pain never went completely away, though the teaching days, when I had to concentrate on and interact with my students and other teachers, helped to distract me from it, which gave me that guilty ‘it’s all in the mind’ feeling.

Even so, on Wednesday (March 4), the pain came roaring back. My subjective sense told me that the paracetamol was much more effective than the ibuprofen, another surprise. I visited my GP, who smiled at the hospital report, saying, ‘yes, they wanted you out of there as soon as possible – they’re there for acute, intensive care stuff, it’s understandable – a GP can refer you to a specialist, and we can go from there’. So he filled out a referral form for St Andrews Hospital, for an x-ray and an ultrascan. I rang them and organised an appointment, for Friday, March 6 at 11am.

I was still in pain, though. The OTC medication had reduced the pain to more bearable levels, but I still hadn’t worked out which worked best. Unlike me, Sarah was on many medications, for pain and other problems, including Prodeine (paracetamol plus codeine) and a set of tablets which combined paracetamol and caffeine. I was taking the tabs at the upper level of what was recommended, and beyond. I was trying to monitor the pain, what it felt like. It was always a low-level throbbing, which increased and became a shooting pain if I used the arm too much. It was a strange delayed pain – I would engage in a flurry of physical activity, such as preparing a quick meal, and then lie down, knowing that the pain would rise up as a result of the activity, then slowly subside. I had difficulty sleeping, and I dreaded dressing myself in the morning. Typing this is giving me an ache, and I’m experimenting with dictation – I find the Apple dictation system a pain (mentally speaking). I have to learn more about how to use it effectively.

Stupidly, I hadn’t asked my GP about stronger prescription medication. The day after the consult (Thursday, March 5) I had Sarah ring the surgery – I was experiencing bouts of serious pain, and was finding it hard to track what medication was working, or not. The doctor wrote a prescription, which Sarah collected and had made out at the pharmacy around the corner. It was for ibuprofen (200mg) and codeine phosphate hemihydrate (12.8mg). I was skeptical about the efficacy of ibuprofen, and I had been researching anti-inflammatories, and inflammation generally.

What, exactly, is inflammation? There are, supposedly, five signs of it, remembered under the acronym PRISH – pain, redness, immobility, swelling and heat. My only symptom was pain. There was certainly no redness or swelling. Immobility wasn’t a real problem either. I could move my arm above the shoulder, I could flex my elbow, etc, but some pain would come afterwards. Heat wasn’t something I could measure, but it didn’t seem an issue. Only pain. And I hadn’t pinpointed any cause of all this. I remembered what I’d said, quite often (or at least I thought I did – maybe I was mostly saying it to myself) to the intern at emergency: ‘It’s bizarre!’

Anyway, I’ll wind up this piece, and start on a new one, dealing with my time at St Andrews Hospital, the x-ray and the ultrasound.

Written by stewart henderson

March 8, 2020 at 12:43 pm

coronavirus – a journey begins

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this is an electron micrograph of 2019-nCoV – ref JOHN NICHOLLS, LEO POON AND MALIK PEIRIS/THE UNIVERSITY OF HONG KONG. The cell is infected with the virus (the little black dots), which migrates to the cell surface and is released

Lots of information and disinformation around the recent outbreak of coronavirus, and my own occasional workplace, a college that teaches academic English to overseas, predominantly Chinese students, is naturally affected by the precautionary procedures and the possibly OTT concern.

This is a new strain of coronavirus, first detected late in 2019. It hasn’t been given a specific name, as far as I’m aware (apart from 2019-nCoV,  which I doubt will catch on) so lay people tend to think this is the one and only coronavirus, since most have never heard the term before. These viruses are zoonotic, transmitted between animals, from bats to humans. My interest is most personal, because when I read that the signs are ‘respiratory symptoms, fever, cough, shortness of breath and breathing difficulties’, I recognise my life over the past several years. I wouldn’t go as far as to say I have a fever, but all the other signs are just features of my life I’ve become inured to over time. I’m reluctant to even talk to people lest my voice catch in my throat and I have to give myself up to hideous throat-clearing, which I do scores of times a day. I’m also afraid to get too close as I assume my breath smells like rotten meat. I should probably wear a face mask at all times (hard to get one for love or money at this point). My condition has been diagnosed as bronchiectasis, possibly contracted in childhood, but I’m fairly sure it was exacerbated by a very severe bout of gastro-enteritis in the late eighties, which left me bed-ridden for several days, too weak to even get to the toilet. When I eventually recovered enough to drag myself to the doctor, she arranged for me to go to the hospital next door for blood tests. It was unspoken but obvious to me she thought I might have AIDS, which I knew was impossible given my non-existent sex life and drug habits. It seems to me, but I might be wrong, that my life of coughing, sniffling and raucus throat-clearing took off from that time.

All this by way of explaining why these types of illness catch my attention. WHO advice is for people to, inter alia, wash hands regularly, cook meat and eggs thoroughly, and keep clear of coughy-wheezy-sneezy people like me. 

Coronaviruses are RNA viruses with a long genome, longer than any other RNA virus. According to Sciencealert they’re so called because of the crown-shaped set of sugar-proteins ‘that projects from the envelope surrounding the particle’. This one is causing perhaps a larger panic than is warranted, when you compare its fatalities (and the numbers should be treated with skepticism at this stage) with those associated with regular flu season. Of course, the difference is that this coronavirus is largely unknown, in comparison to seasonal flu, and fear and wariness of the unknown is something naturally ‘programmed’ into us by evolution.  

There’s an awful lot to be said about this topic, biochemically, so I’ll write a number of posts about it. It’s not only of great interest to me personally, but of course it fits with my recent writings on DNA and its relations, including RNA of course, and to a lesser extent epigenetics. I’m becoming increasingly fascinated by biochemistry so it should be an enjoyable, informative journey – for me at least.

References

Cases of the new coronavirus hint at the disease’s severity, symptoms and spread

Updated: Your most urgent questions about the new coronavirus

https://www.who.int/health-topics/coronavirus

Written by stewart henderson

February 8, 2020 at 10:57 am

Posted in coronavirus, health, RNA, viruses

Tagged with , , ,

some thoughts on regression to the mean and what causes what

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Regression effects are ubiquitous, and so are misguided causal stories to explain them. Daniel Kahneman

Canto: So here’s an interesting thought, which in some ways is linked to the placebo effect and our attributing recovery from an illness to something we ate, drank or did, rather than to the silent and diligent work of our immune system. You know about the regression to the mean concept?

Jacinta: Of course. It’s a statistical phenomenon that we tend not to account for, because we’re always looking for or imagining causal effects when they don’t exist.

Canto: Well, they do exist but we attribute the wrong causal effects – we don’t account for ‘bad luck’, for example, which of course is caused, usually by factors we can’t easily uncover, so for convenience we give it that name. For example, a golfer might be said to have had an unlucky day with the putter because we observe that she she went incredibly close to dropping a number of difficult long putts, but none of them went in, so she made five over par instead of even. Of course every one of those failed putts was caused – one because her aim wasn’t quite true, another due to a tuft of grass, another because of a last moment gust of wind and so on… 

Jacinta: And some of those causes might be deemed unlucky, because on a less windy day, or with a better maintained green, those putts might’ve gone in.

Canto: Okay okay, there is such a thing as luck. But luck, I mean real luck, like the effect of a sudden gust of wind that nobody could’ve factored in, tends to even itself out, which is part of regression to the mean. But let me get back to illness. Take an everyday illness, like a cold, a mouth ulcer (which I suffered from recently)…

Jacinta: Or a bout of food poisoning, which I suffered from recently…

Canto: Yes, something from which we tend to recover after a few days. So the pattern of the illness goes something like this – Day 1, we’re fine. Day 2, we feel a bit off-colour. Day 3 we definitely feel much worse. Day 4, much the same. Day 5, starting to feel better. Day 6, definitely a lot better. Day 7, we’re fine. So it follows a nice little bit of a sine wave – two peaks and a trough – as shown above. 

Jacinta: So you’re saying that getting back up to the peak again is regression to the mean?

Canto: Well, sort of, but you’re getting ahead of me. Maybe it isn’t precisely, because a mean is the midpoint in a fluctuation between two extremes. Sort of. Anyway, let me explain. When you’re ill, you can choose to ride it out, or you can go to a doctor, or take some sort of medication, or some concoction recommended by a friend, or a reflexologist, whatever. But here’s the thing. You’re not likely to go to the doctor/acupuncturist/magus on day 2, when you’re just starting to feel queasy, you’re much more likely to go when you’re at the bottom of the trough, and then you’ll attribute your recovery to whatever treatment you’ve received, when it’s really more about regression to the mean. Sort of.

Jacinta: Hmmm. I agree that we’re unlikely to rush to the doctor or even the medicine cabinet when we’re just feeling a bit queasy, but that’s probably because experience tells us we’ll feel better soon – that maybe we’re already at the bottom of a little trough. But when we start going into a deeper trough, naturally we start getting worried – maybe it’s pneumonia, or tuberculosis…

Canto: Or diphtheria, malaria, typhoid, cholera, bubonic plague, acute myeloid leukaemia….

Jacinta: Don’t mock, I’ve had all of those. But it’s interesting to think of illness and wellness in this wave form. I’m not sure if it works as regression to the mean. Because wellness is just, well, feeling well. Feeling ‘normal’ or okay. We don’t tend to feel super-well – do we?

Canto: You mean you don’t believe in biorhythms? So you think the line pattern would be like, a straight horizontal one with a few little and big troughs here and there, and then finally off the cliff and straight down to death?

Jacinta: Well, no, isn’t it a slow decline into second childhood and mere oblivion – sans teeth, sans eyes, sans taste, sans everything?

Canto: Haha well not so much with modern medicine – though my hearing’s starting to go. But one of them-there invisible implants should fix that, at a price. But you’re probably right – what we call wellness at sixty is a lot different from the wellness we felt at twenty, but we’re probably lucky we can’t feel our way back to that twenty-something feeling. But getting back to the case of the person who applies a treatment and then gets better, there are, I suppose, three scenarios. The treatment caused the improvement, the treatment had no effect (the person improved for other reasons – such as our super-amazing immune system), or the treatment actually had a detrimental effect, but the person got better anyway, probably due to our wondrous immune system.

Jacinta: So that’s where the placebo idea comes in. And our tendency to over-determine for causality. You mention something like a cold, which is generally a viral infection, and mostly rhinoviral. The symptoms, like a runny nose and a sore throat, are actually caused by a mixture of the virus itself and the immune system fighting it, but mostly the latter….

Canto: Yeah, is that about antigens, or antibodies, I always get confused…

Jacinta: Well, it’s very very complicated, with T cells, immunoglobulin and whatnot, but essentially antigens are the baddies which trigger an antibody response, so antibodies are the goodies. So, if someone has a cold then unless they know their immune system is compromised in some way, the best thing is to let their immune system do its job, which might cause a few days’ discomfort, like extra phlegm production as the system, the antibodies or whatever, attempts to expel the invaders.

Canto: Yes, but the immune system is invisible to us, and is vastly under-estimated by many people, who tend to like to see something, like a big bright red pill, or a reflexology foot massage, or a bunch of needles needling their chi energy points, or unblocking their chakras…

Jacinta: Can they see their chakras?

Canto: No, but the magus can, with his various chakra-probing methods, and aural and oratorical senses developed over a lifetime – that’s why he’s a magus, dummy.

Jacinta: Yeah, and I’m sure we can all feel when our chakras are unblocked. It’s sort of like body plumbing.

Canto: So, getting back to reality, there is definitely something like this regression to the mean, to our own individual ‘normal’, but maybe ever-declining physical and mental state, that our wonderful immune system helps us to maintain, a system we rely on more than we realise….

Jacinta: Yes, but you know, it’s good that we don’t realise it so much, because think of all the acupuncturists, Alexander technicians, anthroposophicalists, antipharmaceuticalists, aromatherapists, auriculotherapists and ayurvedicists whose jobs might be on the line – and that’s just the A’s! Then we have the baineotherapist, the bead therapists and the bowen therapists, not to mention the chakra scalpel weaponmasters… can you imagine all those folk not being able to make a living?

Canto: Okay, that’s enough. It truly is a sad thing to think upon, but never fear, your horror scenario will never eventuate, my faith in human nature tells me….

The statin controversy

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Never edit your own writing! Brian J Ford.

one thing thing you can be sure of – this claim (posted by a British chiropractor) is meaningless bullshit

I read Ben Goldacre’s quite demanding book Bad pharma some years ago, and that’s where I learned about statins, but I don’t recall much. I do recall that, not long after I read the book, I was at a skeptics meet-up when Dr Goldacre’s name came up. The man next to me started literally spitting chips at the mention – he was eating a massive bowl of chips and was grossly overweight (not that I’m assuming anything from this – just saying, haha). He roolly didn’t like Dr Goldacre. What went through my head was – some people may be really invested in having a magic pill that allows them to live forever and a day no matter what their diet or lifestyle.

I’ve just discovered that Goldacre has a new book out, entirely on this topic, which I intend to read, but my current decision to explore the issue is based on listening to Dr Maryanne Demasi’s talk, ‘statin wars – have we been misled by the evidence?’, available on YouTube. I very much recall the massive Catalyst controversy a few years ago, when a two-part special they did on statins led finally to the demise of the program. Without knowing any details, I thought this was a bit OTT, but when I heard Dr Norman Swann, a valued health professional and presenter of the ABC’s Health report, railing about the irresponsibility of the statin special, I frankly didn’t know what to think.

So statins are lipid-lowering medications that come in various flavours, including atorvastatin, fluvastatin, lovastatin and rosuvastatin. Lipitor, a brand name for atorvastatin manufactured by Pfizer, is the most profitable drug in the history of medicine. I’ve never taken statins myself, and I’m starting this piece as a more or less total beginner on the topic. I’ve read the Wikipedia entry on statins, which is quite comprehensive, with a very long reference list. Of course it’s not entirely comprehensible to a lay person, but that’s not a criticism – immunobiology and related research fields are complex. It’s also clearly pro-statin. It includes this interesting sentence:

 A systematic review co-authored by Ben Goldacre concluded that only a small fraction of side effects reported by people on statins are actually attributable to the statin.[63]

It’s interesting that Goldacre, and nobody else, is mentioned here as a co-author. It makes me wonder…

My only quibble, as a lay person, is that the positive effects of these statins, and their relatively few side-effects, seems almost too good to be true. I speak, admittedly, as a person who’s always been ultra-skeptical of ‘magic bullets’.

Which brings me to issues raised in Dr Demasi’s talk, and not addressed in the Wikipedia article. They include the idea, promoted by an ‘influential group’, that statin use should be prescribed for everyone over 50, regardless of cholesterol levels. Children with high cholesterol levels are being screened for statin use and Pfizer has apparently designed fruit-flavoured statis for use by children and adolescents. Others have suggested using statins as condiments in fast-food burgers, and even adding statins to the public water supply. It’s easy to see how such ‘innovations’ involve making scads of money, but this isn’t to deny that statins are effective in many if not most instances, and we should undoubtedly celebrate the work of the Japanese biochemist Akiro Endo, who pioneered the work on enzyme inhibitors that led to the discovery of mevastatin, produced by the fungus Penicillium citrinum.

But Demasi made some other interesting points, firstly about how drug companies like Pfizer might seek to maximise their profits. One obvious way is to widen the market – for example by lobbying for a lowering of the standard level of cholesterol in the blood considered dangerous. From the early 2000s in the US, ‘high cholesterol’ was officially shifted down from as high as 6.5 down to below 5, moving vast numbers of people onto having a ‘need’ for these cholesterol-lowering drugs. Demasi points out that this lowering wasn’t based on any new science, and that the body responsible for these decisions, the National Cholesterol Education Program (NCEP), was loaded with people with financial ties to the statin industry. To be fair, though, one might expect that doctors and specialists concerned with cholesterol to be invested, financially or otherwise, in ways of lowering it. They might also have felt, for purely scientific reasons, that the level of cholesterol considered dangerous was long overdue for adjustment.

Another change occurred in 2013 when two major heart health associations in the US decided to abandon a single number in terms of risk factors for heart disease/failure. Instead they looked at cholesterol, blood pressure, weight, diabetes and other factors to calculate ‘percentage risk’ of cardiovascular problems. They evaluated this risk so that if it was over 7.5% in the next 10 years, you should be prescribed a statin. A similar percentage risk system was used in the UK, but the statin prescription started at 20%. Why the huge discrepancy? Six months later, the Brits brought their threshold down to 10%. The US change brought almost 13 million people, mostly elderly, onto the radar for immediate statin prescription. The method of calculation in the US was independently analysed, and it was found that they over-estimated the risk, sometimes by over 100%. Erring on the side of caution? Or was there a lot of self-interest involved? It could fairly be a combination. The term for all this is ‘statinisation’, apparently. It’s attributed to John Ioannidis, a Stanford professor of medicine and a noted ‘scourge of sloppy science’. If you look up statinisation, you’ll find a storm of online articles of varying quality and temper on the issue – though most, I notice, are five years old or more. I’m not sure what that signifies, but I will say that, while we’ll always get the anti-science crowd baying against big pharma, vaccinations and GM poison, there’s a clear issue here about vested interests, and the need to, as Demasi says, ‘follow the money’.

This brings up the issue of how trials of these drugs are conducted, who pays for them, and who reviews them. According to Demasi, the vast majority of statin trials are funded by manufacturers. Clearly this is a vested interest, so trial results would need to be independently verified. But, again according to Demasi (and others such as Ioannidis and Peter Gotzsche, founder of the nordic Cochrane Collaboration) this is not happening, and ‘the raw data on statin side-effects has never been released to the public’ (Demasi, 2018). This data is held by the Cholesterol Treatment Triallists’ (CTT) collaboration, under the Clinical Trial Service Unit (CTSU) at Oxford Uni. According to Demasi, who takes a dim view of the CTT collaboration, they regularly release meta-analyses of data on statins which advocate for a widening of their use, and they’ve signed agreements with drug companies to prevent independent examination of research findings. All of this is described as egregious, which might seem fair enough, but Elizabeth Finkel, in a long-form article for Cosmos magazine in December 2014, takes a different view:

.. [the CTT] are a collaboration of academics and they do have access to the raw data. It is true that they do not share that data outside their collaboration and are criticised by other researchers who would like to be able to check their calculations. But the trialists fear mischief, especially from drug companies seeking to discredit the data of their rivals or from other people with vested interests. Explains [Professor Anthony] Keech, “the problem with ad hoc analyses are that they can use methods to produce a particular result. The most reliable analyses are the ones done using the methods we published in 1995. The rules were set out before we started.” And he points out these analyses are cross-checked by the academic collaborators: “Everything is replicated.”

As a regular reader of Cosmos I’m familiar with Finkel’s writings and find her eminently reliable, which of course leaves me more nonplussed than ever. I’m particularly disturbed that anyone would seriously claim that everyone over fifty (and will it be over forty in the future?) should be on these medications. I’m 63 and I take no medications at all, which I find a great relief, especially when I look at others my age who have mini-pharmacies in their homes. But then I’m one of those males who doesn’t visit doctors much and I have little idea about my cholesterol levels (well yes, they’ve been checked and doctors haven’t raised them to me as an issue). When you get examined, they usually find something wrong….

In her talk, Demasi made a comparison with the research on Tamiflu a few years ago, when Cochrane Collaboration researchers lobbied hard to be allowed to review trial data, and it was finally revealed, apparently, that it was certainly not as effective and side-effect free as its makers, Roche, claimed it to be. The jury is still out on Tamiflu, apparently. Whether it’s fair to compare the Tamiflu issue with the statin issue is a matter I can’t really adjudicate on, but if Finkel is to be believed, the CTT data is more solid.

There’s also an issue about more side effects being complained of by general users of statins – complaints made to their doctors – than side effects found in trials. This has already been referred to above, and is also described in Finkel’s article. Many of these complaints of side-effects haven’t been able to be sheeted home to statins, which suggests there’s possibly/probably a nocebo effect at play here. But Demasi suggests something more disturbing – that many subjects are eliminated from trials during a run-in period precisely because the drug disagrees with them, and so the trial proper begins only when many people suffering from side-effects are excluded. She also notes, I think effectively, that there is a lot of play with statistics in the advertising of statins (and other drugs of course) – for example a study which found that the risk of having a heart attack on statins was about 2% compared to 3% on placebos was being advertised as proving that your heart-attack risk on statins is reduced by a third. This appears to be dodgy – the absolute percentage difference is very small, and how is risk actually assessed? By the number of actual heart attacks over period x? I don’t know. And how many subjects were in the study? Were there other side-effects? But of course we shouldn’t judge the value of statins by advertising guff.

Another interesting attack on those expressing doubts about the mass prescription of statins has been to call them grossly irresponsible and even murderers. This seems strange to me. Of course doctors should be all about saving lives, but they should first of all be looking at prevention before cure as the best way of saving lives. Exercise (mental and physical) really is a great form of medicine, though of course not a cure-all, and diet comes second after exercise. Why the rush to medicalise? And none of the writers and clinicians supporting statins are willing to mention the financial bonanza accruing to their manufacturers and those who invest in them. Skepticism is the lifeblood of science, and the cheerleaders for statins should be willing to accept that.

Having said that, consider all the life-saving medications and procedures that have preceded statins, from antibiotics to vaccines to all the procedures that have made childbirth vastly safer for women – who cares now about the pharmaceutical and other companies and patentees who’ve made their fortunes from them? They’re surely more deserving of their wealth than the Donnie Trumps of the world.

So, that’s my initial foray into statins, and I’m sure the story has a way to go. In my next post I want to look at how statins work. I’ve read a couple of pieces on the subject, and they’ve made my head hurt, so in order to prevent Alzheimer’s I’m going to try an explanation in my own words – to teach myself. George Bernard Shaw wrote ‘those who can, do, those who can’t teach (it’s in Man and Superman). It’s one of those irritating memes, but I prefer the idea that people teach to learn, and learn to teach. That’s why I love teaching, and learning…

By the way, the quote at the top of this post seems irrelevant, but I keep meaning to begin my posts with quotes (it looks cool), so I’m starting now. To explain the quote – it was from a semi-rant by Ford in his introduction to the controversial dinosaur book Too big to walk (I’ve just started reading it), about writers not getting their work edited, peer reviewed and the like, and being proud or happy about this situation. This, he argues, helps account for all the rubbish on the net. It tickled me. I, of course, have no editor. It’s hard enough getting readers, let alone anyone willing to trawl through my dribblings for faults of fact or expression. Of course, I’m acutely aware of this, being at least as aware of my ignorance as Socrates, so I’ve tried to highlight my dilettantism and my indebtedness to others. I’m only here to learn. So Mr Ford, guilty as charged.

References

Dr Maryanne Demasi – Statin wars: Have we been misled by the evidence?

https://en.wikipedia.org/wiki/Statin

https://cosmosmagazine.com/society/will-statin-day-really-keep-doctor-away

https://en.wikipedia.org/wiki/John_Ioannidis

https://www.smithsonianmag.com/science-nature/what-is-the-nocebo-effect-5451823/

http://www.center4research.org/tamiflu-not-tamiflu/

Written by stewart henderson

September 9, 2019 at 9:44 pm

bronchiectasis once more – resistance, viruses, treatment

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Having fallen ill again, for the first time really in a few years, with debilitating dry coughing, breathing problems and fatigue, and having had no great relief from a first course of broad-spectrum antibiotics, I think it’s a good time to review the condition I suffer from – bronchiectasis.

I’ve tried to put it in the back of mind and have been mostly successful, except now and then to marvel that it hasn’t come roaring back for a year, then two years, then three years. Still, I’ve never quite gotten rid of a niggling cough, and every time I have a sneezing fit my mind turns, however briefly to what might finally await me…

Bronchiectasis literally means ‘widened or widening airways’. The airways leading to the lungs have become permanently distended and develop ‘cul de sacs’ in which bacteria gather as in a stagnant backwater. The increased bacterial load means that those with the condition are easier prey for bacterial and viral pathogens. The causes of this condition are various, including genetic conditions such as cystic fibrosis, or a general immunodeficiency. In my case it was most likely an early childhood infection, the cause in about a third of all adult cases. The sad thing is that with each new flare-up the damage to the airways is increased, the condition worsens, and there’s no cure, but it can be contained through specific exercises designed to clear the airways, postural drainage and other techniques. Above all (he adonishes himself) always get regular flu and pneumococcal jabs. I was diagnosed with this condition about four and a half years ago, but I think I’ve been suffering from it for much longer. Like many stupid men I’ve tended not to go to the doctor till I’m at death’s door. I’ve improved a little in that area in recent years, but not enough.

The recent flare-up has been traced to a relatively common virus, called respiratory syncytial virus (RSV). My doctor sent me for a virology swab after my second visit. On my first visit I presented with my severe cough, and I explained my bronchiectasis, which he knew something about as I’d had my records transferred to him from a previous establishment. Although I expressed concern about antibiotics, having experienced what I presumed to be resistance to erythromycin previously, I was prescribed a broad-spectrum antibiotic called roxithromycin GH. Desperately wanting to get rid of this debilitating and spirit-weakening cough, I got the set of ten tablets – a five-day dose – together with a repeat dosage. I’m currently two tablets away from finishing the repeat. It was also recommended that I get a bottle of Bisolvon®, which ‘thins, loosens, clears mucus from the chest’ and ‘helps clear stubborn chest congestion’.

This first consultation was on a Friday. I was contracted for a two-day work week at Eynesbury College starting the following Thursday, and I really wanted to be fit by then. However, by Monday-Tuesday I was worried. The antibiotics, I felt, had been initially successful but then my condition seemed to deteriorate. On Wednesday I had my second consultation. I explained my amateur theory that the antibiotics had an immediate impact, but then the resistant strain of the bacteria continued to multiply, took over the territory of the non-resistants, and the illness came sweeping back. Classic evolution, in a sense: from random variation the environment of my body selects the stronger, resistant strain. The doctor agreed, or said he did, but pointed out that the problem was that my infection was probably viral rather than bacterial. In my enthusiasm for my own cleverness I hadn’t thought of this. And this probably explained the ineffectiveness of the erithromycin in the past. Maybe I’m not resistant at all.

So I was sent to the nearest Clinical Labs testing centre for a swab. I was also advised to continue with the antibiotics. The swab is applied by means of a long needle-like instrument wrapped in something like cotton wool at one end. This material is soaked in a virus-detecting solution and inserted fairly deeply into the nasal cavity. I visited the testing centre more or less immediately after the consultation, and received word the next day that the results were out. On Friday, I think, I attended my third consultation and was given the read-out. Ten viruses tested for were presented, including influenza A and B, and types 1 to 4 paraainfluenza, all undetected. The other undetected viruses were adenovirus, rhinovirus and metapneumovirus. RSV, an RNA virus (as are most viruses), was the only one detected.

So, progress has been made, and I was prescribed one more medication, a Turbuhaler® called Symbicort®, often used for symptomatic treatment of asthma. Instructions are to inhale two doses a day of the oral powder, which consists of budesonide and eformoterol fumarate dihydrate. There are 120 doses in my inhaler.

Budesonide is a corticosteroid, commonly used in this inhaled form for long-term treatment or management of asthma and COPD. It’s been around for a while, having been patented in 1973, and in commercial use as an asthma medication since 1981. It’s also on the WHO list of essential medicines. According to Wikipedia, ‘common side effects with the inhaled form include respiratory infections, cough, and headaches’, and at the moment I have a headache, and have suffered from severe coughing fits.  I’m also producing quite a lot of mostly clear mucus, through the nose. I’ve attributed these symptoms to the virus, not the medication, but who knows?

Eformoterol is a more recent addition to the arsenal of anti-asthma type medications. This 1997 article in Australian Prescriber describes it as ‘a long-acting beta2 adrenoceptor agonist’ – a type of beta-blocker. Here’s some further interesting info from this site:

After inhalation of eformoterol powder, bronchodilatation begins within 3 minutes. This effect lasts for 12 hours with a peak effect within two hours of inhalation. These properties make eformoterol suitable for twice daily inhalation in patients who require regular, long-term treatment of reversible airways obstruction. It is not recommended for use in acute asthma. Patients should have a short-acting agonist, such as salbutamol, available to help deal with acute attacks.

Unfortunately my airways problems aren’t reversible, though particular obstructions and their causes may be treated effectively.

So what I have in my little Turbuhaler is a combo of a corticosteroid and a long-acting betaagonist (i.e. a bronchodilator). According to Wikipedia ‘combinations of inhaled steroids and long-acting bronchodilators are becoming more widespread’.

It doesn’t seem as if there’s much I can do but wait for my condition to slowly improve. It’s been nine days since my first consultation, and I’ll be revisiting my doctor in a day or two. Mucus still flows freely and the distinctive, whistling wheeze I developed about a week ago is still present (I’ve never experienced this before). Physical exertion quickly makes me exhausted, but I’m hoping I can soon be sufficiently recovered to consider specific exercises to improve my condition and support me against further setbacks. Don’t want to end up slowly drowning in my own phlegm.

Written by stewart henderson

July 30, 2018 at 3:13 pm