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It is believed that cytokine storms were responsible for the disproportionate number of healthy young adult deaths during the 1918 influenza pandemic, which killed an estimated 50 million people worldwide. A healthy immune system may have been a liability rather than an asset!
Preliminary research results from Taiwan also indicated this as the probable reason for many deaths during the SARS epidemic in 2003. Human deaths from the bird flu H5N1 usually involve cytokine storms as well. Cytokine storm has also been implicated in hantavirus pulmonary syndrome.
During this COVID-19 pandemic, many deaths are attributed to cytokine storms. A cytokine storm can cause the severe symptoms of acute respiratory distress syndrome (ARDS), which has a high mortality rate in COVID-19 patients. The higher mortality has been linked to the effects of ARDS aggravation and the tissue damage that can result in organ-failure and/or death. ARDS was shown to be the cause of mortality in 70% of COVID-19 deaths.
Newly emerging and re-emerging viral threats have continued to challenge medical and public health systems and incur economic costs to both individuals and countries. The influenza virus is a main cause of those threats and is responsible for millions of severe cases and 250 000–500 000 deaths each year. These infections in humans are accompanied by an aggressive pro-inflammatory response and insufficient control of an anti-inflammatory response, a combination of events called ‘cytokine storm'. AZD1656 has huge potential in this fight.
"A strong trend towards reduced mortality in patients receiving AZD1656. This was noted in both mortality on treatment and all-cause mortality, which were lower in the AZD1656 group compared to the placebo group".
I know practically everyone is excited here, I feel we should spare some time to think of those people who unfortunately passed in the placebo group. I know that that is the nature of research.
More than 30 million Americans alone have diabetes. When they contract covid, and the reason the percentage of deaths is so much higher, is largely through cytokine storm that kills them. Lower levels of SETDB2 increases inflammation which leads to cytokine storm. What controls SETDB2 through a chain is Interferon. Interferon is mainly secreted by T cells. AZD1656 has been shown to activate the migration of T regulatory cells to sites of inflammation in preclinical experiments, which is the main objective of this trial, thus reducing inflammation. 415 million people in the world have diabetes.
"The preliminary findings give indications of this; there is however additional laboratory analysis to do which further clarifies this, drilling down into great detail; this takes an additional few weeks".
Because this statement was dated today, presumably it is implying that further analysis will take a few weeks? However, the RNS states SGSC now intends to publish the results of the trial no later than 10 September 2021. so is this a Vela/SGS communication difference in understanding, or is it semantics ie 'results' could mean this is what we have so far but more to do, or, more conclusive? I don't know. It would all seem, however, to be heading in a positive direction as it clearly isn't the case that it just didn't work at all. GLA
The Oscillate report does 'not give an indication of benefit'.
When I first read it this morning i thought so as well and wrote that this was unequivocally good, however my post was removed and quite rightly. Read the statement very carefully...
"The preliminary findings relate primarily, to the safety and efficacy of AZD1656 in the patients receiving the drug in the trial, as compared to the patients receiving the placebo. The drug must be shown to be safe (“tolerated safely”) in patients or there can be no further development. Efficacy relates to the effectiveness of the drug in treating the symptoms of the patients, and the trial seeks to establish this by analysing a number of different effects to establish which patients with which particular symptoms, benefit. The preliminary findings give indications of this; there is however additional laboratory analysis to do which further clarifies this, drilling down into great detail; this takes an additional few weeks".
So it says "The preliminary findings give indications of this" however, more work needs to be done to drill down into the details. So as regards 'safety' the preliminary findings give 'indications', so data, but more detail has to be drilled into. In my opinion we cannot interpret 'indications' to mean 'it works', it is rather, a piece of information. The preliminary findings give an indication of efficacy and safety, meaning the pieces of information from the study, do mean something which needs further looking into. It doesn't mean that the indications are that AZD1656 works. It means the indications are that the trial has led to lots of pieces of information. Key points from the Oscillate plc piece are though that;-
‘very few new therapeutics in development for COVID-19’…..’ this has the potential to be highly attractive to big pharma and biotech buyers’ …’… will be effective for the general population in COVID -19 and in other respiratory diseases’.
AZD 1656 has already been proven to work in diabetic patients ie migration of T cells therefore lowering inflammation; it is proven to be safe; it does lower blood glucose etc so a great drug. This trial is to determine if it can work to reduce mortality and the requirement for mechanical ventilation as well as the length of stay in hospital...no indication yet to us that it does what it seems to say on the tin.
if it was unproven and did not work they would know that and have said today.
could this delay be in order to finish a commercial deal?
The trial is following the Ordinal scale for clinical improvement so from uninfected, ambulatory, hospitalized mild disease, hospitalized severe disease to death, with sub categories and scores for each so non invasive, no oxygen therapy gets a score of 3; oxygen by mask or nasal prongs gets a 4. Ventilation and additional organ support etc gets a 7 for example and death gets an 8.
So I presume they are totting up the scores for poor folk on the drug and those on the placebo. Results on Monday. Somehow though I cannot see them continuing to let people die if during the trial people on the drug were doing better…so that might scew the result but in a good way of course. I don’t know how its going to go…gla
A dangerous complication of the flu is pneumonia and people with diabetes are more at risk of developing this complication than people without diabetes.
Interestingly, Flu, and other viral infections, can lead to higher blood sugar levels and increase the risk of serious short term complications risk, so possible application here too.
The Journal of Diabetes Investigation (Asian Assoc for the study of diabetes) published research last year (2020) on an investigated into COVID-19 patients with diabetes, but no other comorbidities, who were admitted to Wuhan Union Hospital, Wuhan, China entitled ‘Does glycemic control rescue type 2 diabetes patients from COVID-19-related deaths?’
In the retrospective study patients were divided into 2 groups: the well-controlled blood glucose (BG) group, and the poorly-controlled BG group. They found that the necessity of medical interventions and the mortality risk of patients with COVID-19 was increased by poor glycemic control among type 2 diabetes patients. In contrast, well-controlled BG correlated with improved survival rates for COVID-19 patients with type 2 diabetes.
AZD1656 has been shown to activate the migration of T regulatory cells to sites of inflammation in preclinical experiments, which is the main objective of this trial, thus reducing inflammation.
AZD 1656 has a blood glucose lowering effect for four months, which meets a major part of the second objective ie long enough for a covid infection to be covered
AZD 1656 has been found to be safe in almost 1,000 patients with diabetes and healthy patients in a set period of months.
IMO although the research comes from a year ago it does indicate that poor control of BG leads to poorer outcomes for patients whereas better control clearly has better outcomes. AZD1656 would appear to be helpful in this regard. Simplistic I know but please do your own research. GLA for monday
Netherwood2 this may be useful in forming a view of the drug but of course these are not the results of this present trial.
“Analysis is based broadly on a combination of the anticipated mechanism of the drug and the relevant data from the trial endpoints - reduction in mortality, slowing in disease progression, glycaemic and inflammatory reduction, the possible up-regulation of T-reg cell activity promoting long term immunity beyond the normal life of a vaccine”.
Previous trials have shown;-
AZD1656 (AZD1656 (GCK activator, 1 µM) has been shown to activate the migration of T regulatory cells to sites of inflammation in preclinical experiments. This migration of Treg cells to inflamed tissue is crucial for their immune-modulatory function (Kishore et al (2017) GCK activation significantly enhanced Treg cell migration to the inflamed tissue. Tregs not only maintain the tone and tenor of an immune response by dominant tolerance but have also been identified as key players in resolving tissue inflammation and as mediators of tissue healing.
Research docs link;
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714502/
AZD 1656 has been found to be safe in almost 1,000 patients with diabetes and has a blood glucose lowering effect for four months ie IMO sufficient to cover the critical period likely in hospital with covid 19. Blood glucose control has been proposed as a key factor in reducing complications from COVID-19 in diabetics. Research docs link;
https://europepmc.org/article/med/22943931
In the safety and tolerability of AZD1656 in the management of diabetes in hospitalised diabetic patients with known or suspected COVID-19, AZD1656 has been studied in single doses of up to 180 mg and multiple doses to 150 mg BID for 8 days in healthy volunteers as well as alone and in combination with other blood glucose control agents in diabetic patients at 200 mg daily for up to 6 months duration. In both healthy volunteers and diabetic patients no significant clinical effects other than glucose lowering were noted. Research docs link;
https://openinnovation.astrazeneca.com/azd1656.html
To determine whether AZD1656 affects duration of hospital stay, requirement for mechanical ventilation or mortality in diabetic patients with known or suspected COVID-19.
To be determined in trial.
Link to multiple (24) trials by AstraZenaca on AZD1656;
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/SearchResults
it has been said many times before, but we keep on falling for it, can people stop responding to those who are here to disrupt. Only that way can this board settle into a non ramping discussion about the issues, information and steady progress of this developing company. Ignore those that disrupt please or it will put genuine long term investors off actually contributing.
tonight has been nothing but disruptors getting the better of decent folk on here, to the end that most of the sh*te has been deleted by them, so all pointless, except that they got their way by wholly disrupting any possible positive posts. Its a trap they lay and keep laying time and time again and we always fall into it. Tonight should have ben about looking forward to positive news tomorrow....and what has it actually been about...
its because they are now desperate...their remit is to disrupt this board tonight as much as possible so that there is no positive chat about the professional developments of syme ...they are here to disrupt, they don't care about our protestations and hitting back...they don't care about that because it all adds to the disruption of positive chat, that is their aim. We should really ignore them...that is the only answer.
they are here in force tonight because they know good things are coming tomorrow. If there wasn't going to be good/great news, they wouldn't be here. It's therefore a positive. Thank you guys for your support.
we should be concentrating on the hard work of the Syme team and the news to come tomorrow and the days and weeks/months/years to come and not on strange folk who really don't care and therefore don't matter.
Holly, you still haven't answered my question....do you not believe in the experience, reputation, knowledge, integrity and ability of Tom James? and therefore, as the only answer must be a 'yes', can you not trust to his judgement that he chooses to join with AZ?
I know why you haven't
Holly, do you not believe in the experience, reputation, knowledge, integrity and ability of Tom James? and therefore, as the only answer must be a 'yes', can you not trust to his judgement that he chooses to join with AZ? I do, and its my money I'm backing them with.