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3 hours ago, iain said:

What do you make of the content of this review Peter. Lots to digest. Not least Horlick being in the pocket of manufacturers of D3 supplements. I  careless whether he discloses his interests, from personal experience attending medical seminars in the States, the dollar rules the pen!

https://www.cnbc.com/amp/2020/09/26/how-to-know-if-you-have-a-vitamin-d-deficiency.html

Iain

Hi Iain,

Hundreds of thousands of dollaers for his research is not impressive, I won ca 3 million for mine. But all the cash goes into  staffing and running a lab not into our own pockets (or in the USA system to pay the pricipal investigators salary for thr several months when the unversity salary is not paid)

The failure to measure 25(OH) routinely contributes enormously yo lack of data on D3 and health. Without it clinicians are bludering in the dark. The signs of very low D3 are in adutls osteomalacia, perhaps hair coming out in tufts, weak muscles, aches and pains. Nothing that cannot be confused with eg folate deficincy, lack of excercise, "getting old". So D3 deficiency is largely hidden.

A 25(OH)D test can be done through the post with a finger-prick blood sample costing £28, City Assays Birmingham are a PHLS lab, completely pukka. I use them. Nothing beats a measurement for peace of mind, for me and family.

My personal experience three months after starting to supplement with 2000IU was improved mood, quicker resolution of muscle aches after a day in the garage, swollen lymph nodes under jaw shrank, and two visits to dentist a year no longer needed. The lack of bleeding when brushing teeth is by far the most spectacular result !

Peter

 

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Hi Peter

It’s still industry money....

I find your total scepticism of NICE a totally  independent organisation, WHO, BillGates, big Pharma et al at complete odds with this report of financial benefit to a key proponent of the D3 story. 

As for the clinical benefits, no one is arguing that D3 has a significant role in our immune system , it's the significance of that role in Covid that’s for debate.

Iain

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Picked this up this morning off the net, dont know if its helpful or not.

Stuart.

 

 

Some people have sent me some questions, so I thought I’d offer some brief (ish) opinions in a post, rather than replying individually.

**Why aren’t doctors allowed to use Hydroxychloroquine (HCQ) for COVID-19**

The first thing is to clear up what we’re ‘allowed’ to do, and what we’re not. Drugs are licensed for specific indications – some drugs are only useful for one disease, others are useful for a wide range of diseases. Each drug is licensed for each indication based on the benefit/risk ratio. A drug generally has the same side effect profile regardless of indication, but the benefits are very different: it’s more likely a drug will be licensed if the benefits are very large, even if the side effect profile is significant; if the benefits are small, the drug is unlikely to be licensed, even if the side effect profile is small. The licensing agency asks area experts to review the evidence and decide if the drug is useful, safe, beneficial, and cost effective. I am occasionally asked to review drugs in this way, for areas of my expertise, such as it is. If a drug is licensed, we can use it for that indication, if it’s not we have to apply to a panel of our peers to use it ‘off-licence’ if we can argue for its use. I have done this, as most doctors in hospitals will have done in their careers.

HCQ has a licence for connective tissue disorders, and malaria infection, where the benefits have been shown in clinical trials to be significant, and repeatable. There are side effects, but the benefits outweigh the risks. The main side effect of quinine containing medicines is prolongation of the QT interval, which means it affects the conduction of the electricity in the heart, increasing the risk of arrhythmias. HCQ does not have a licence in COVID-19 because the current evidence base does not support its use. An initial observational trial was published in the Lancet in May – observational studies are basically the lowest level of evidence we look at, they’re not controlled in any way, there’s no randomisation to treatment, there’s no placebo, so they give us an idea of what’s going on. The study suggested a worse outcome for people treated with HCQ. It was subsequently retracted by the journal because the authors refused to divulge the raw data to allow an independent analysis. Rightly so.

https://www.thelancet.com/.../PIIS0140-6736(20.../fulltext

In June the Recovery trial chief investigators posted a statement about the HCQ arm of the study. By that point 110,000 patients had been recruited into this partially blinded randomised trial, the biggest of its kind in the UK. The MHRA (The licensing agency of the UK) asked the independent monitoring committee, set up to oversee the RECOVERY trial, to do an interim review of the data. That independent review lead to the unblinding of the trial data, and the announcement that “We have concluded that there is no beneficial effect of hydroxychloroquine in patients hospitalised with COVID-19. We have therefore decided to stop enrolling participants to the hydroxychloroquine arm of the RECOVERY Trial with immediate effect. We are now releasing the preliminary results as they have important implications for patient care and public health”. The mortality at 28 days was the same in each arm, around 25%. This was a big study, and a very big deal to break the randomisation. https://www.recoverytrial.net/.../statement-from-the...

Since then there have been more controlled studies on the use of HCQ. The COALITION trial in Brazil: randomised patients to normal care, normal care plus HCQ, and normal care plus HCQ plus azithromycin in a 1:1:1 ratio. There was no difference in 15 day mortality, or 15 day symptom scores in mild to moderate patients with COVID-19, but the incidence of side effects, including the prolonged QT interval mentioned above, were significantly higher in the groups containing HCQ. This was published in the New England Journal of Medicine: https://www.nejm.org/doi/10.1056/NEJMoa2019014

The same group tried again, because they thought the HCQ plus azithromycin arm might work, given the push from the US to use this combination (despite the fact that it’s well known that HCQ and azithromycin both prolong the QT interval independently). There was again no improvement with the addition of azithromycin to HCQ. https://www.thelancet.com/.../PIIS0140-6736(20.../fulltext

The US Food and Drug Administration (FDA – the US version of the MHRA) reported on June 15th that HCQ should not be used to treat COVID-19 due to lack of efficacy at clinically used doses, and reports of serious side effects. https://www.fda.gov/.../fda-cautions-against-use... summary of the findings of the sub-committee that reviewed the evidence is here: https://www.accessdata.fda.gov/.../OSE Review...

This has not stopped about 200 different research centres around the world starting their own research into HCQ in COVID-19. Those results are pending. If these data contradict the high quality research in this area already published, the guidelines will be revised to take that into account.

If any doctor in the UK doesn’t feel these data, and the opinions of the clinical area experts, are sufficient reason to avoid HCQ, they can apply to a panel of their peers to prescribe it ‘off-licence’. The hierarchy of evidence must, and will be adhered to: randomised controlled studies, in large numbers, will always take precedence over anecdotes from anyone who has ‘seen this drug work’.

**Is it true that masks contain all these bacteria after wearing it for 20 minutes, and it’s worse than not wearing a mask? – this is usually accompanied by a photo of a petri dish with a lot of bacterial colonies, and a quote that a nurse has posted this picture on their Instagram account**

While it is true that we inhale, and exhale about a million bacteria a day, these are not pathogenic, they don’t cause infection, or disease, and are not a risk to us. If you swab anything, you’ll grow something – anyone who has done a-level biology, or a biology degree will have plonked their hand on a petri dish, come back 3 days later to find that their hands were covered in coagulase negative staph, and probably the odd enterococcus (wash your hands after the loo, folks). We are using the masks to catch any hazardous bacteria and viruses that do come out of our mouths, that’s the point. So it would be very bizarre if there weren’t bacteria in there, and if you swab it, some will grow. I don’t think anyone has every denied this, it’s kind of the point of masks. The bit that people are missing is that the guidance is, and always has been, that once you’ve worn your mask for the session of time you’re wearing it, you should put it into a sealable bag, and wash it. On ward rounds we wear one mask for the session (the ward round) then we put it in an orange bin. I have a mask I wear to get to work, one for going to lunch, and one I wear to come back from work. I wash all three at night. I don’t use other types of face covering like a buff, or scarf, because of exactly this – they’re single use items, not reusable.

The photo that is sent to me and gets posted? It’s a hoax: https://www.truthorfiction.com/does-this-petri-dish-full.../

***Sweden***

Sweden took a different path, with far less restriction, and a more liberal attitude to the whole thing. I am no politician, and certainly no economist, but I found this article very useful: https://www.theguardian.com/.../welcome-to-libertarian... Sweden had fewer deaths than the UK, but then only the US has had more deaths than the UK, so that’s hardly surprising. It still had a lot of cases; their economy has been hit as hard as Denmark; and they are now looking at localised lockdowns to mitigate a potential wave 2. They took a different path, and it will be interesting to see how they manage with a second wave, and how much long-COVID they have, if their population exposure has been higher, which we presume it has been.

***Why is a vaccine so important?***

Ultimately we have two ways out of this: the virus disappears, presumably because everyone in the world isolates themselves from everyone else for 40 days (this is the etymology of the word quarantine, incidentally: quarantine, 40s days was the length of time visiting sailors to Italian ports had to wait out in the harbour before being allowed onto land, to ensure they did not carry the plaque, or the pox); or the population develops sufficient immunity that the virus exists in the wild, but infective pockets are small, and wiped out quickly because of the herd immunity. Clearly we can’t all quarantine for 40 days, so we have to build up the immunity of the community to a level where pockets of infection stop quickly. We can do that by exposing everyone to COVID (the chicken pox party approach) or we can vaccinate as many people as we can.

If, after COVID infection, everyone returned to normal, one could argue for letting people get it, get the immunity, and get on with it. But people don’t return to normal, and we don’t know how long they’ll take to get back to normal, if ever. Measles is a highly contagious disease that can be lethal, can lead to deafness, blindness, cognitive issues; but most people get a rash and a fever for a week. There’s a highly effective measles vaccine, which when taken by the majority of the population, all but wiped out measles. Once people stopped getting it, measles deaths and disability increase.

I’ve had COVID, so it’s very likely I have some antibodies, and it’s likely I have some immunity to re-infection. But once a vaccine is available, I will get it, because I want more immunity, to last longer, through more mechanisms, and to reduce the risk of passing it on to other people.

240 research centres are developing COVID vaccines worldwide. 40 are in clinical trial stages already. These vaccines are based on the principles of vaccination used in other widely accepted vaccines, be they: attenuated virus (flu, and many many others); protein (hepatitis, and others), conjugated and non-conjugated carbohydrate (pneumococcal vaccine, and others), or the new RNA vaccines, which have not yet been licensed, but show promise in a range of diseases. They are being fast tracked, this doesn’t mean they’re being rushed. They will have to be tested, they will have to be shown to be effective and safe, and they will have to be made and paid for. This will take time, but there are 2 vaccines already in the later stages of clinical trials in the UK. Vaccines save lives, they have not been shown to cause serious side effects, and any vaccine we get for this can’t come soon enough – the sooner herd immunity hits 80%, the sooner we’re through this, and it’s probably at about 10% at the moment.

***Can we treat COVID-19 now?***

We have 2 proven treatments. Dexamethasone (a steroid) reduces death by about one third in patients hospitalised with severe COVID. https://www.recoverytrial.net/.../low-cost-dexamethasone... This is a massive effect, but there remains 2/3 of patient in whom it doesn’t prevent death. Remdesevir was shown in an observational study to improve the outcome of 68% of patients https://www.nejm.org/doi/full/10.1056/NEJMoa2007016then a randomised double blind study showed a “non-statistically significant, numerical difference in time to improvement for patients who had symptoms for 10 days or less”; 12% of patients had to stop the treatment due to side effects. We’re better off than we were 6 months ago, but we still have limited options. Other things have either been shown to not work, or not shown to work. If there is a second wave, treatment will likely involve enrolment into a clinical trial.

Still very few admissions locally, so we’re doing something right in the region. Numbers of admissions certainly rising in other centres around the UK, so my thanks go out to colleagues in those areas who are working now in COVID units. I really hope that the mortality figures in this second wave are lower than they were in March and April, and I really hope that the number of mild and moderate cases is low, so as much of normal service can be provided over the more stressed winter months. I hope that anyone who has long-COVID symptoms continues to improve. I hope the wait for a vaccine is over quickly.

A friend said to me over the weekend that I should not confuse science with government policy. Thankfully I don’t make government policy, I just try to interpret the science to make clinical decisions, and give my opinion when asked, sometimes to Scottish Government, sometimes to Facebook!

I’ll leave you with this editorial from the BMJ today, in which executive editor Kamran Abbasi says “… it is too early to reach those conclusions on the basis of science, however intellectually seductive. The sensible alternative is caution, the precautionary principle. It is a message that chief scientists and medical advisers are now rightly delivering to politicians.” We will never know if we over-reacted, but we will learn quickly if we under-react. The science will drive the understanding, which will drive the policy.

https://www.bmj.com/content/370/bmj.m3714...

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Stuart,

Interesting, valuable and clearly by someone who knows of what they write.

May we know where you found it, please?    I'd like to share it, but as a reference, "TR Register" doesn't have the medical authority it should have!

John

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14 hours ago, iain said:

Hi Peter

It’s still industry money....

I find your total scepticism of NICE a totally  independent organisation, WHO, BillGates, big Pharma et al at complete odds with this report of financial benefit to a key proponent of the D3 story. 

As for the clinical benefits, no one is arguing that D3 has a significant role in our immune system , it's the significance of that role in Covid that’s for debate.

Iain

Iain,

I dont doubt NICE's independence, it's clearly independent of most D3 science.

The debate is in its closing stages. The importance of D3 in covid meets all of Sir Austin Bradford Hill's criteria for causal inference:

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

The BH approach led to smoking risks being established and the need to supplement with D3 in pregnancy. NICE do not use BH criteria, so to prove smoking is dnagerous they would need to enforce smoking, when science had already shown it was dangerous. That is unethical, as would denying D3 in pregnancy or in COVID.

NICE do not commission trials yet at present have the last word on D3. NICE is a block to progress. Gradually MPs are beginning to become aware, quesitons are being asked of DoHSC. 

I am confident the COVID pandemic will turn out to be the result of a global pandemic of D3 deficiency. But it looks like millions will die and countless millions survive with impaired health before that is obvious to all. Just as smoking is obviously dangerous.

Peter

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2 hours ago, john.r.davies said:

Stuart,

Interesting, valuable and clearly by someone who knows of what they write.

May we know where you found it, please?    I'd like to share it, but as a reference, "TR Register" doesn't have the medical authority it should have!

John

Strangely it was here https://www.facebook.com/tom.fardon.3

Stuart.

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"Sweden had fewer deaths than the UK, but then only the US has had more deaths than the UK, so that’s hardly surprising. "

This is often stated but is at best out of date. Looking at deaths per million of population (data from https://ncov2019.live/data) shows many South American countries, as well as Spain and Belgium, have higher rates than the UK.

The top 16 are shown in the attached file. Given the generally lower population density in Sweden compared to the UK, and the different protocols for stating the cause of death, I would not say that outcomes in Sweden have been much different from the UK.

Pete

 

Peru.odt

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Peru: Up in the mountains of Peru deaths are 10% of Lima's per head of population. Much more UVB up there, but the authors were unaware of its role in D3 production

https://medicalxpress.com/news/2020-06-experts-andean-virus-resistance-puzzle.html

Many Swedes run around naked in the summer sunshine and D3 from that source lasts twice as long (its buffered) so there's another angle, one that wont appear in simple 25(OH)D data sets.

Peter

 

 

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6 hours ago, ntc said:

As much as many have learned from Peter and others and I thank you, but the topic has now gone away from the title, would it not now be better to stick to the very important topic and post how it is affecting you and your area?

Stay Safe. 

Thanks Neil, excellent point. While the Vitamin D discussion continues to be very educational there is other stuff going on. Better than a vaccine is everyone wearing a face mask when outside the home and cant guarantee the required separation. How are people doing where you live with that ?. Where I live each state has different requirements but the stores all pretty much require it and I dont see anyone objecting or refusing to do what is needed. Infection and death rates had stayed pretty flat for a while but now that schools are starting up we are seeing things tick up again. Hand sanitizer and face masks all generally available. Chlorine wipes still hard to find.

Stan

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9 hours ago, foster461 said:

Thanks Neil, excellent point. While the Vitamin D discussion continues to be very educational there is other stuff going on. Better than a vaccine is everyone wearing a face mask when outside the home and cant guarantee the required separation. How are people doing where you live with that ?. Where I live each state has different requirements but the stores all pretty much require it and I dont see anyone objecting or refusing to do what is needed. Infection and death rates had stayed pretty flat for a while but now that schools are starting up we are seeing things tick up again. Hand sanitizer and face masks all generally available. Chlorine wipes still hard to find.

Stan

Hi Stan,

I think face masks are ingrained in the American (wild West) Psyche. 

In all the TV programmes I watched as a child they all had masks - The Cisco kid, Lone Ranger, Hopalong Cassidy etc  the baddies even more so.

 

Roger

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Surely in the early days the government repeatedly and forcefully said masks were rubbish and did no good and we all had to stay apart or die.

Suddenly with testing demand exceeding supply and a vaccine years away a magic device is needed to get everyone back to work, poof the face mask rides to the rescue just as in Rogers wild west.

Alan

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Not quite Alan - in the early days the government (actually PHE) advice was that masks do not offer any significant protection to the wearer. Further research showed that, while that is true, masks can reduce the rate of transmission between individuals.

Pete

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1 hour ago, stuart said:

Hi Stuart, NEJM is a serious journal so the information cna be trusted. However I do wonder if vaccines can keep up with mutations in the virus. A "planned 13 month follow up..." gives the virus loots of time to mutate. They were lucky the Houston mutant was still recognised by their vaccine, but we cannot assume all spike mutations will be susceptible. When a range of different vaccines agaisnt the spike ( and most are)  start to be  widely used the mutations will be driven faster by natural selection, and what looks usefull now could become rapidly redundant. Unlike flu where many of a population have antibodies and immune memory to many earlier mutations, SARS-Cov-2 has many more variations to try out in order to escape control.  My glass in half empty on vaccines.

Peter

 

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16 minutes ago, stillp said:

Not quite Alan - in the early days the government (actually PHE) advice was that masks do not offer any significant protection to the wearer. Further research showed that, while that is true, masks can reduce the rate of transmission between individuals.

Pete

+1 and perhaps whilst locked down, the need for the general public to use masks was low and created a convenient period of time in which "the powers that be" could scour the globe to find supplies for those that did need them. 

Iain

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1 hour ago, RogerH said:

There there Peter

 

Roger

Friday aft a couple of weeks ago the A5 through Llangollen was nose to tail with holiday traffic, far more than usual. Fortunately they dont linger here but Snowdonia  was heaving. First Minister wants a ban on travelling into Wales from England lock-down areas. Peter

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4 hours ago, stuart said:

Interesting, but a raised antibody response at two months does not mean a sustained one that will protect anyone for long, especially us aged, whose immune systems have begun to fail to respond.   That is why 'ordinary' flu jab were only available up to age 65 - they worked too poorly to be worthwhile if you are older.     This Gov, desperate for something, anything, that will make them appear effective, has authorised them for all ages above 50.   I've had mine, but my practice believed that it was worthwhile up to 85 anyway!

And, still not wishing any aspersion or slight, it's good to read of some aspect of Covid that isn't VitD.    So here's another!    Two tests for Covid that are quick, cheap and simple to do are now available, one from Abbott, one from SD BioSensor, a Korean company.     The Abbott test (BinaxNOW  https://www.fda.gov/media/141570/download) has received emergency approval from WHO and the Korean one is expected to be approved shortly.     They are done on nasal samples, detect viral antigen, take 15 mins to produce results, and may be done with minimal training, as they show a result as a line on a window, like a pregnancy test.

Both tests cost about $5 (£3.90), much less than the present Polymerase Chain Reaction (PCR) test, which requires a laboratory, people trained to use one and can take 24hors to show a reaction.    No doubt several other pharamceuticals companies have tests in the pipeline and will seek approval asap, I hope bringing prices down further.

This could make the difference, IF governments use them for Track & Trace.   That would need a reorganisation of those services, as people could be informed almost immediately of the result.     I wonder if the UK Government even knows about it?

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23 minutes ago, john.r.davies said:

Interesting, but a raised antibody response at two months does not mean a sustained one that will protect anyone for long, especially us aged, whose immune systems have begun to fail to respond.   That is why 'ordinary' flu jab were only available up to age 65 - they worked too poorly to be worthwhile if you are older.     This Gov, desperate for something, anything, that will make them appear effective, has authorised them for all ages above 50.   I've had mine, but my practice believed that it was worthwhile up to 85 anyway!

And, still not wishing any aspersion or slight, it's good to read of some aspect of Covid that isn't VitD.    So here's another!    Two tests for Covid that are quick, cheap and simple to do are now available, one from Abbott, one from SD BioSensor, a Korean company.     The Abbott test (BinaxNOW  https://www.fda.gov/media/141570/download) has received emergency approval from WHO and the Korean one is expected to be approved shortly.     They are done on nasal samples, detect viral antigen, take 15 mins to produce results, and may be done with minimal training, as they show a result as a line on a window, like a pregnancy test.

Both tests cost about $5 (£3.90), much less than the present Polymerase Chain Reaction (PCR) test, which requires a laboratory, people trained to use one and can take 24hors to show a reaction.    No doubt several other pharamceuticals companies have tests in the pipeline and will seek approval asap, I hope bringing prices down further.

This could make the difference, IF governments use them for Track & Trace.   That would need a reorganisation of those services, as people could be informed almost immediately of the result.     I wonder if the UK Government even knows about it?

That came via a Scottish friend of mine who is in the NHS

Stuart.

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No need to excuse it, Stuart!  It's interesting, but the study was really to justify (or not) Phase III trials of that candidate vaccine.     Very necessary and proper, but not 'the answer'.  Looks hopeful we shall see.     I might get to be with my grandkids again one day!

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