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Yes to all of those. But why a slower decline in deaths than most other countries?
Highest daily deaths in all of Europe for the last 10 days or so.
There are several factors that suggest ongoing systemic deficencies, beyond the inadequate early response.
"Italy Finally Starts Mass Treatment with Hydroxychloroquine"
This article was some 6 weeks ago.
Doctors in Italy have finally began widely prescribing hydroxychloroquine in certain combinations in Rome and the wider region of Lazio with a population of around six million.
According to Corriere della Sera, a well known Italian daily newspaper, Dr. Pier Luigi Bartoletti, Deputy National Secretary of the Italian Federation of General Practitioners, explains that every single person with Covid-19 that has early signs, like a cough or a fever for example, is now being treated with the anti-malaria drug.
The drug “is already giving good results,” Bartoletti says while Malaysia reveals they have been using it since the very beginning. Bartoletti further adds that the drug:
“Must be used with all the necessary precautions, it must be evaluated patient by patient. It can have side effects. But those that take it are responding really well.
We have just understood that the virus has an evolution in two phases and that it is during the second phase, after a few days (about a week), that the situation can suddenly, in 24 or 48 hours, worsen and leads to respiratory failure requiring intensive care.
The results that we are starting to accumulate suggest that hydroxychloroquine administered early, gives the possibility of avoiding this evolution in a majority of patients and is also helping us to prevent hospitals from filling up.”
Incredible. What is more incredible are the statements of Professor Christian Perronne, Head of the Infectious Diseases Department at the Garches University Hospital, made in an interview with a French weekly magazine.
Referring to the European Discovery trial in which UK is taking part with only 800 patients, Perronne says:
“I refused to participate because this study provides for a group of severely ill patients who will only be treated symptomatically and will serve as control witnesses against four other groups who will receive antivirals. It is not ethically acceptable to me.
We could perfectly well, in the situation we are in, evaluate these treatments by applying a different protocol. In addition, the hydroxychloroquine group (which was added to this study at the last minute), should be replaced by a hydroxychloroquine group plus azithromycin, the current reference treatment according to the most recent data.
Finally, the protocol model chosen will not provide results for several weeks. Meanwhile, the epidemic is galloping. We are in a hurry, we are at war, we need quick assessments.”
America is to start yet another study which is to take one month even while one thousand people or more are dying worldwide today. In Italy however doctors are finally not waiting anymore with Perronne saying:
“Even though the overwhelming evidence from large randomized studies is still lacking, I am in favor of a broad prescription for the following reasons:
1. We have a large body of evidence showing that in vitro hydroxychloroquine blocks the virus. We also have several clinical results indicating that this product is beneficial if administered early and we have no mention that it harms or is dangerous in this infection (only one study, poorly detailed, Chinese, on 30 patients with control group, did not observe any benefits but also no harmful effects). What is the risk of administering chloroquine straight away: nothing!
2. This drug is very inexpensive 3. It is well tolerated in long-term treatment. Personally, I have successfully used it clinically in the chronic form of Lyme disease for 30 years at a dose of 200 mg or even 400 mg/day.
I and hundreds of other doctors are able to judge its excellent tolerance in humans. The main contraindications are severe retinal and unbalanced heart disease.
Cardiovascular events remain exceptional if care is taken: to proscribe self-medication – to check with the elderly taking a lot of drugs that there are no drug interactions (with long-term diuretics in particular) and that the rate of blood potassium is within the norm.
Apart from these precautions, the undesirable effects are minor. They are even more so as the treatment is short, which is the case against Covid-19.
It would therefore be wise to produce hydroxychloroquine in very large quantities without further delay, to make it easily accessible to infected people…
This 30% rise in two days appears qualitatively different to what we have seen many times before, when the price is briefly inflated due to a putative catalyst or no catalyst at all, only to go back to the starting point 36 or 48 hrs later.
In other words, a short term price manipulation, or just clever swing trading.
Yesterday's rise consolidated on Monday's gains.
Though even a 5m volume obviously doesn't amount to a lot of money.
I'm inclined to think that there may be an element of substance underlying this move, and I've speculated previously as to what that might be.
Time will tell.
Merck is developing a placebo for Covid which will cost $250,000.
Due to be fast tracked to approval next month.
Drowned in a sea of dilution predictions.
"Doctors Rate Hydroxychloroquine Most Effective Therapy for Coronavirus Infection"
https://www.precisionvaccinations.com/fda-issued-emergency-authorization-hydroxychloroquine-treatment-covid-19-patients-usa
Ososilver.
Yes, Captain, but we are not talking about a new unapproved untried drug with an unknown safety profile.
We are talking about about the possible re-purposing of a dirt cheap drug that has been around for 40yrs in approved use, and is a known entity from a safety point of view.
From the NCBI article:-
There are few drugs that can seriously lay claim to the title of ‘Wonder drug’, penicillin and aspirin being two that have perhaps had greatest beneficial impact on the health and wellbeing of Mankind. But ivermectin can also be considered alongside those worthy contenders, based on its versatility, safety and the beneficial impact that it has had, and continues to have, worldwide—especially on hundreds of millions of the world’s poorest people. Several extensive reports, including reviews authored by us, have been published detailing the events behind the discovery, development and commercialization of the avermectins and ivermectin (22,23-dihydroavermectin B), as well as the donation of ivermectin and its use in combating Onchocerciasis and lymphatic filariasis.1
I know very little about Ivermectin, other than it's an already approved anti-parisitic, used for scabies and rosacea, and head lice, and many third world parasitic diseases.
In vitro studies have shown it to be effective against Covid, but more human studies for Covid are ideally required.
There are probably many already approved drugs that can exert anti-viral effect on this virus.
At a quick glance, it appears to be getting similar derogatory reporting in the West to hydroxychloroquine.
This is an example:-
The current approach to finding a viable therapy for the SARS-CoV-2 is to repurpose existing drugs. All over the world, ivermectin came into widespread use of off-label in response to the news of the in vitro success against the virus.
At a dose of 150 µg/kg, observation of 52 patients on mechanical ventilation appeared to show clinical benefit with the drug in contrast to over 1,900 patients on conventional treatment. Though these results need to be analyzed to rule out confounding factors and biases, on the surface, they would seem to suggest that very low lung concentrations of ivermectin are able to inhibit the virus.
In other words, even when the ivermectin concentration is not anywhere near the IC50, it appears to have antiviral activity. This could suggest that the lung distribution or accumulation of this drug is far greater in humans than in cattle.
In contrast, the concentrations of ivermectin reported inhibiting the coronavirus in vitro were markedly higher than those achieved in human lung or plasma with the approved doses of ivermectin. As a result, say the researchers, “the likelihood of a successful clinical trial using the approved dose of ivermectin is low.”
This should be a warning to conduct in vitro studies of repurposed drugs at concentrations that are safe and tolerable in humans.
The wholesale cost in the developing world is about US$0.12 for a course of treatment as of 2014.[10] This is down from an initial cost of US$6 proposed by Merck in 1987.[60] The company however has donated 100s of millions of courses of treatments since 1988 in more than 30 countries.[60] Between 1995 and 2010 the program using donated ivermectin to prevent river blindness is estimated to have prevented 7 million years of disability well costing US$257 million.
Not sure what this is trying to say, but the point should be that we should all abide by the precautionary principle. Those of us on the NWBO message board, most of all, should recognize that only drugs that are safe and effective (for a given population) are the ones that should be endorsed or encouraged by those in positions of authority.
At least equal volume to this time yesterday.
Not silly money, imo...
Yes, I've been watching the Sermo surveys for some time.
I think I was first to refer to them.
You would hope that physicians around the world could report their experiences anonymously, without fear or favor.
But I wonder if that is truly the case. Perhaps less than it was a month ago.
And Italy and Spain only started widespread use of HC when their deathrate was out of control.
Its use coincides with the subsequent decline in mortality!
And the point about HC is that it is most effective for mild to moderate cases, where viral load is likely lower.
Once a patient gets to the ARD stage, HC won't help.
That's when you need to use Tocilizumab!
Which Sermo also report on, but its use gets virtually no mention in any media anywhere in the world. Why?
I have no doubt it is saving lives of critically ill patients, where it is in use.
The poorer, less developed parts of the world, or those outside the Western world are largely relying on HC, because they haven't got anything else.
It is in wide usage in India. But then you get crazy articles criticising India for using it, and at the same time criticising India for restricting its export.
UAE are importing it from India, I know that much.
And India are also using it as a preventative for health workers and other other hig risk groups.
Pakistan is using it, and has enough stock to be exporting to many other countries:-
the government had allowed export of one million tablets to Saudi Arabia, five million to the UK, one million to the US, half a million each to Turkey and Italy, 300,000 to Qatar, and 700,000 to Kazakhstan.
An anonymous Pediatrician on Sermo commented, “I took Chloroquine for a year in southeast Asia to prevent malaria. So did another 3,000,000+ soldiers. I suffered no ill effects and this letter is proof of no death. The dead do not have time for the FDA’s randomized clinical trials. Just ask them.”
Thanks.
Well, I wouldn't put it quite that way.
But looking at NY, if you compare infections and deaths in the Bronx with those in Manhattan, then yes, there is an obvious link with population density (and poverty) and high Covid rates.
https://www.nytimes.com/2020/05/18/nyregion/coronavirus-deaths-nyc.html
Similar picture elsewhere:-
Inside Sweden's immigrant communities, anecdotal evidence emerged early in the outbreak that suggested that some — particularly those from Somalia and Iraq — were hit harder than others. Last month, data from Sweden’s Public Health Agency confirmed that Somali Swedes made up almost 5 percent of the country's COVID-19 cases, yet represented less than 1 percent of its 10 million people.
Many in these communities are more likely to live in crowded, multigeneration households and are unable to work remotely.
An experimental coronavirus vaccine will go into production this summer at a “rapid deployment facility” before clinical trials have established whether the shots are safe and protect against the infection.
The business secretary, Alok Sharma, said the £38m centre would allow manufacture to begin “at scale” this summer in anticipation of the vaccine being shown to work by the end of the year.
The centre will churn out doses of vaccine before a larger facility, called the Vaccines Manufacturing and Innovation Centre (VMIC), opens next summer at the Harwell science and innovation campus in Oxford.
“The centre, which is already under construction, will have capacity to produce enough vaccine doses to serve the entire UK population in as little as six months,” Sharma announced at the No 10 daily press conference, where a technical glitch meant journalists’ questions were read out loud because they were unable to ask them in person via Zoom.
“But if, and it is a big if, a successful vaccine is available later this year, we will need to be in a position to manufacture that to scale and quickly,” he added. The rapid deployment facility would help ensure a vaccine is widely available for the UK public “as soon as possible”.
Yep, it's become a political football, and a source of mucho info and mucho more counterinfo.
But it's in use in most of the world, with a few countries being notable exceptions. Curiously enough, those few are the ones with highest deaths to cases...
And nobody is making any money from it.
I mean, what's the point of having a pandemic, if you can't monetize it?
Might as well not have had it in the first place.
HB.
Are we perhaps beginning to know why Advent want to employ dozens more staff right now, when UK Specials alone won't need that many..?
The Government is to invest £93 million to bring forward the opening of a new vaccine-manufacturing centre ready to begin production if a coronavirus vaccine is found.
The Department for Business, Energy and Industrial Strategy (Beis) said the Vaccines Manufacturing and Innovation Centre (VMIC) will now open in summer 2021 – 12 months earlier than planned.
The not-for-profit facility – located on the Harwell Science and Innovation Campus in Oxford – will have the capacity to produce enough doses for the entire UK population in as little as six months.
A further £38 million is being invested in a rapid deployment facility which will be able to begin manufacturing at scale from the summer of this year if a vaccine becomes available before the new centre is complete.
Serum envisages a price of 1,000 rupees per vaccine but governments would give it to people without charge, he said.
Ok. So why the price hike yesterday?
Is it just the usual manipulation of running it up one day, and running it back down the next?
Such as we saw right after the ASM.
It's proved me wrong, because I was convinced that this was nailed down to 0.17 for the time being.
But, I want to know why I was wrong.
This just doesn't have the feel of one of those overnight manipulations, though it might yet be one.
And the hike is just too big to be general market afterglow from a lessening of Covid rates and vaccine developments.
I'm reckoning a specific Covid-related business opportunity might have come their way.
MRNA's vaccine appears frontrunner in US, while University of Oxford's “ChAdOx1 nCoV-19” (with Cognate on board) appears frontrunner in UK and possibly wider.
Just when it's becoming clear that the virus is beginning to fizzle out naturally...
For instance, it's nothing wrong by Les saying the top 100 patients in the trial out of a total of 331 patients lived about 5 years. He was not talking about median OS, or HR or K-M curve about the trial and patients. He was talking to a general audience in a term most would understand better, and in a limited window of a few minute time.
He was talking to a general audience in a term most would understand better, and in a limited window of a few minute time.
Theoretically perhaps.
But in reality, I think it'll be 28.2 - 28.4%.
IMO, Top 100 median will reach and probably surpass 72 months.
So if I'm correct, that would be a minimum of 51 patients surviving for 6 yrs.
Actually, in investment terms, NWBO could be a hedge against global uncertainty and volatile markets.
Come what may, we will stick resolutely at 0.17 (at least until topline!).
Thanks.
I think we can safely say OS36 of 28.2% won't deviate downwards, and maybe it will go up a very tiny smidge.
Psst. Don't tell anybody, but stick any spare cash in a gold tracker. JMO!
CT. Look at the slide on Senti's post:-
'Last patient was enrolled in November 2015.'
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=155681462
We've long known that last recruitment (randomisation) wasn't until the November.
Should we expect a datalock announcement?
Hi Senti.
Yes, I'd never really clocked this slide before.
If the data collection was done back in Oct, then the slide is inaccurate, because the last patients were enrolled (randomised?) in Nov '15, so how could all patients have reached 36-month follow-up?
If 'all patients have reached 36 months follow up', means that all patients 3yr data are included in the 28.2% OS36, it means that figure is pretty well set in stone.
Not impossible, but I think most of us previously thought that there was some lag, and that the figures only went up to maybe some point in October, so might be subject to a bit of subsequent updating for the last few entrants.
If the 28.2% figure is a final one, then the meth / unmeth OS36 will also be final at 49.1% meth and 14.3% unmeth.
So won't get better (or worse).
Though Top 100 median would definitely continue to change (upwards, I suggest) as we moved on in time from the SNO readout.
That slide also represents the last public reference to PFS, I believe..
(Just sayin'..)
How could he have been clearly accurate in a way that the typical audience of this show could comprehend correctly?
(I do agree his language was sloppy at best, misleading at worst.)
The Top 100 is an awful metric in the first place, imo.
You should only be allowed to quote it, if you give the bottom 100 at the same time. And who is going to do that?
Does that show actually have any impact in terms of getting new investors on board? I doubt it.
It gives us something to debate about, I suppose.
Be interesting what he says if he goes back on the show after topline.
45.9 - 94.5 is the 95% confidence interval but does not mean what many think. Even if all the data exists there will still be a wide CI because it is a measure of what the underlying distribution being sampled is. It is not an indicator of the error estimate on K/M vs the trial full dateset median.
Even if all the data exists there will still be a wide CI because it is a measure of what the underlying distribution being sampled is.
What I mean is this. Say the trial comes in at 61 months. The K/M would converge on that as you get more data. And with all data it would be exact.
The tallest 1 million 18 year olds in China will be taller on average than the tallest 1 million in NYC.
Is that permitted in the Dept. of Motor Vehicles?
At least you spared us the pic.
The trouble is Sukus, getting my approval isn't worth a bean and won't move the dial at all, unless it's backwards!
If you were looking at OS60, you really have to to look at cross-trial comparisons, rather than with SOC.
And Stupp did 9.8% for his pivotal trial treatment arm (which is now SOC). Which was suspiciously good for the time.
And when, a few years later, that was the control arm in Optune EF-14, it only did 5%.
Somehow, the Optune treatment arm 'achieved' 13%.
You really can't compare our trial result with typical OS60 'in the real world', because in the real world, patients tend to be older and sicker. Weak immune systems, poor blood counts, older, comorbidities etc etc.
So you won't hear me talk about 400% improvements.
But notwithstanding the above, my calculated guess for L treatment OS60 of 20-21%, if born out, would be better than anything else previously, and I'd be amazed if any current trials like the Inovio one could match that. Not that we will find out, because they will end their trial long before they get that far.
Of course, if L treatment returns 20% or better for OS60 and it is accompanied by perfect safety and a decent maintenance of Q of L, then it should be approved, despite the actual trial design shortcomings.
That would be double the pivotal Stupp figure and 50% better than the Optune figure.
But should and will are not always the same thing.
Survival extension along with Q of L (living longer and / or better) are the only outcomes that matter to a patient.
And regulators should make decisions in accordance with that.
If there any fair and objective regulators out there, who actually believe in the importance of patient-centred, real world outcomes, then things would look good.
JMO.
If TLD is as good as we hope, I will give them my approval immediately.
No promise beyond that...
I thought Ed Sullivan died some time ago.
Is he still drawing a paycheck?
Well hopefully it will be fully ramped when it gets a licence, Tilt..
So, taken from diagnosis or surgery, 82 / 70 is just your guess, right, for DCVax trial (a double blind P3) whole population OS12?
Seeing as it's not a known figure.
And where do you place median Day 0 in the Inovio trial, in relation to diagnosis? It's probably between 4 and 8 weeks, imo.
As to maintenance TMZ in the Inovio trial, you're correct on unmeth not getting it.
But for meth; patients get it, if 'clinically indicated'. So that's probably most of them. Not that that necessarily offers an advantage over not getting it.
And though several of us have already scrutinised it, here is the link for the Inovio trial CT listing, to make it simple for others to look at it.
https://clinicaltrials.gov/ct2/show/NCT03491683?term=inovio&cond=glioblastoma&draw=2&rank=1
Yes indeed. You would have to look beyond the inclusion / exclusion criteria, and closely examine actual patient make-up, which we cannot do.
What is the mean age of these 52 patients?
How many had a total resection? (Only small amount of residual tumor allowed.)
What was the actual mean KPS?
Do they have a 50 / 50 gender split? Men do worse in GBM (and Covid-19!)
Do they have more than 5% with IDH mutation?
These are effectively hand-picked, good bet patients, receiving best attention.
Not blaming them. It's what everybody does.
The other thing worth noting is that they could have, but didn't, quote PFS12.
So you might have 85% alive at a year, but how many of those are progression-free?
We can see from their blurb that 25% of unmeth had already progressed by 6 months, though 84.4% were still alive at 12 months. My guess would be that anything between 40 and 70% of the unmeth patients had progressed by the 1yr mark.
If the PFS12 had remained impressive, they would have told us what that figure was, and they didn't!
They stated themselves that:-
Currently, the median overall survival with standard of care therapy, which includes radiation and chemotherapy (temozolomide: TMZ), is approximately 15 to 22 months.
Hey, what's this flirting with the 0.16's all about?
We need to get back to the 0.17's, which is what we're used to.
Just a line from the Novavax site:-
Maternal immunization allows for the mother’s immunity to certain diseases to be passed to her baby during pregnancy, which can protect the baby during the first few months of life, until the baby can be effectively vaccinated.