87 replies to this topic

[gamesguru]

Useful is an interesting word. I suppose methylmercury was useful as an anti-choke agent in gasoline, though unforeseen damages were rapidly and vicously inccurrd as a result.

It's not useful as a reactionary treatment and it's not safe as an ongoing prophylactic. Not to rain on anyone's parade but that's been my opinion from the start, as dictated by evidence not emotion

[Dorian Grey]

CDC isn't spooked about HCQ prophylaxis for malaria: 

 

https://www.cdc.gov/...vWCxZT5dcbB4MuM

 

Medicines for the Prevention of Malaria While Traveling Hydroxychloroquine (Plaquenil™)

 

Who can take hydroxychloroquine?  

 

Hydroxychloroquine can be prescribed to adults and children of all ages. It can also be safely taken by pregnant women and nursing mothers.

 

Who should not take hydroxychloroquine?

 

People with psoriasis should not take hydroxychloroquine.

 

--------------------

 

They do caution overdoses can be fatal though: "Overdose of antimalarial drugs, particularly hydroxychloroquine, can be fatal."

 

Recovery trial was dosing 12 tablets during the first 24 hours, Solidarity 10 (both in critically ill patients).  Guaranteed to sabotage the trial & generate headlines about how the trials had to be halted due to cardiac side effects and increased mortality.  This wouldn't have been so sinful if we had any other options for prophylaxis or outpatient treatment, yet here we sit, half a year into the plague with NOTHING but Tylenol until we turn blue and are hospitalized.   

[Dorian Grey]

Chris Martenson's latest update had some interesting info on zinc + ionophore, gleaned from a researcher (R Baric) doing gain of function research on coronavirus back in 2015.  The guy monekying around with the bugs noted:

 

"Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein".  

 

file:///home/chronos/u-3eb91ea958ff0d91e3487b82dff1ebd4db1641a7/MyFiles/Downloads/2015SARS.pdf

 

Oh well...  If monoclonal antibodies & vaccines aren't likely to be effective against these bugs, what else might work?

 

Here's the same researcher included in a paper on zinc + ionophore from 2010: 

 

Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture

 

https://www.ncbi.nlm...les/PMC2973827/

 

Ahh, so the bottom line, when it comes to SARS type coronavirus, good luck with your vaccines & monoclonal antibody therapies, but never forget zinc + ionophore (HCQ / Quercetin / Quinine) will inhibit coronavirus activity while you work on your magic bullet remedies.  I'm starting the video at 28:13 where it gets interesting.  

 

https://youtu.be/1plkwhi5KUE?t=1692

 

The first half of the video (Vindication! HCQ+ & Ivermectin Work!) is also good if you have time.  

Edited by Dorian Grey, 09 July 2020 - 04:44 AM.

[gamesguru]

Brazil uses HCQ as well, and represents a higher death toll.  To what extent do any of these nations actually use HCQ, and to what extent is its use responsible for their success?  One can only investigate, actually I lied, one can also jump to early conclusions as well.

 

Seems like HCQ could have its utility in opening up avenues to explore more effective derivatives and analogues (see 2nd study for analogue, and remainders for non-results).

 

Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates.

PMID: 32698191

Jul 23, 2020

 

COVID-19 has rapidly become a pandemic for which no antiviral drug or vaccine is yet available(2-4). Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals worldwide but definitive evidence for HCQ efficacy in treatment of COVID-19 is still missing(6,7,17,18). We evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (VeroE6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to placebo, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor HCQ+AZTH showed a significant effect on the viral load levels in any of the tested compartments. When the drug was used as a pre-exposure prophylaxis (PrEP), HCQ did not confer protection against acquisition of infection. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral treatment for COVID-19 in humans.

 

Antimalarial-agent artemisinin and derivatives portray more potent binding to Lys353 and Lys31-binding hotspots of SARS-CoV-2 spike protein than hydroxychloroquine: potential repurposing of artenimol for COVID-19.

PMID: 32696720

Jul 23, 2020

 

Medicinal herbs have proved along history to be a source of multiple cures. In this paper, we demonstrate how hydroxychloroquine can act as a good inhibitor of SARS-CoV-2 Spike protein receptor-binding-domain using molecular docking studies. We also unveil how hydroxychloroquine can interfere in the prevention of Lys353 in hACE2 from interacting with the corresponding binding hotspot present on the Spike protein. Further screening of artemisinin & derived compounds produced better Vina docking score than hydroxychloroquine (-7.1 kcal mol(-1) for artelinic acid vs. -5.5 kcal mol(-1) for hydroxychloroquine). Artesunate, artemisinin and artenimol, showed two mode of interactions with Lys353 and Lys31 binding hotspots of the Spike protein. Molecular dynamics analysis confirmed that the formed complexes are able to interact and remain stable in the active site of their respective targets. Given that these molecules are effective antivirals with excellent safety track records in humans against various ailment, we recommend their potential repurposing for the treatment of SARS-CoV-2 patients after successful clinical studies. In addition, an extraction protocol for artemisinin from Artemisia annua L. is proposed in order to cope with the potential urgent global demand. Communicated by Ramaswamy H. Sarma.

 

Antimalarial and cytotoxic drugs on COVID-19 and the cardiovascular burden: Literature review and lessons to be learned.

PMID: 32691699

Jul 22, 2020

 

BACKGROUND: The world is witnessing an unprecedented crisis with Coronavirus disease 2019 (COVID-19). It is important to accurately analyze the available evidence to provide correct clinical guidance for optimal patient care. We aim to discuss current clinical evidence regarding chloroquine, hydroxychloroquine, azithromycin, remdesivir, and the cardiovascular burden of COVID-19. METHODS: A literature review was performed using PubMed and Google Scholar. Additional clinical trials were identified through the "TrialsTracker" project. RESULTS: We found conflicting evidence of chloroquine, hydroxychloroquine plus azithromycin, and remdesivir in COVID-19 despite promising early reports of in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2. Some of the current studies have demonstrated adverse drug reactions to chloroquine and hydroxychloroquine + azithromycin. Widespread systemic inflammation and procoagulant/hypercoagulable state, including thrombotic microangiopathy, endothelial dysfunction, bleeding disorder, and thrombosis are increasingly being witnessed in COVID-19. Evidence of cardiac injury and stroke is mostly reported in hospitalized patients; however, large specialized studies that focus on cardiac or neuropathology are lacking. DISCUSSION: There is no convincing clinical evidence of chloroquine, hydroxychloroquine with or without azithromycin, and remdesivir use in COVID-19. As evidence of systemic inflammation is rapidly unfolding, there is a dire need to maximize our resources to find the best possible solutions to the current crisis while conclusive evidence from clinical trials emerges.

 

Hydroxychloroquine and Chloroquine in COVID-19: A Survey of Prescription Patterns Among Rheumatologists.

PMID: 32694358

Jul 23, 2020

 

Treatment

OBJECTIVE: With hydroxychloroquine (HCQ) and chloroquine (CQ) emerging as potential therapies for coronavirus disease 2019 (COVID-19), shortages have been reported. We aimed to understand how rheumatologists, one of the most common prescribers of HCQ/CQ, prescribed these medications to manage COVID-19 and to understand if their patients are affected by shortages. METHODS: Between April 8 and April 27, 2020, an online survey was distributed to a convenience sample of rheumatologists who practice medicine in a diverse range of settings globally, resulting in 506 responses. Adjusted Poisson regression models were calculated. RESULTS: Only 6% of respondents prescribed HCQ/CQ for COVID-19 prophylaxis, and only 12% for outpatient treatment of COVID-19. Compared to the United States, the likelihood of prescribing HCQ/CQ for prophylaxis was higher in India (adjusted risk ratio [aRR], 6.7; 95% confidence interval [CI], 2.7-16.8; p < 0.001). Further, compared to the United States and those with 1 to 5 years of experience, rheumatologists in Europe (aRR, 2.9; 95% CI, 1.6-5.3; p < 0.001) and those with 10+ years of experience (11-20 years: aRR, 2.5; 95% CI, 1.2-5.3; p = 0.015; 21+ years: aRR = 3.3; 95% CI, 1.4-7.4; p = 0.004) had a higher likelihood of prescribing HCQ/CQ for outpatient treatment. Of note, 71% of all rheumatologists reported that their patients were directly affected by HCQ/CQ shortages. CONCLUSION: The results suggest that only a small percentage of rheumatologists are prescribing HCQ/CQ for prophylaxis or outpatient treatment of COVID-19. Medication shortages experienced by large numbers of autoimmune disease patients are concerning and should play a role in decisions, especially given poor efficacy data for HCQ/CQ in COVID-19.

[Dorian Grey]

Saw the result of the Brazil "lower dose" HCQ study was declared a failure today over on yahoo news.  Noticed also it was done on "hospitalized patients".  The Tamiflu model came to mind again.  How well would Tamiflu work if trials were restricted to influenza patients who were sick enough to be hospitalized?  How well might HCQ work if it was given early/outpatient, like they do in Costa Rica (CFR less than 0.5%)

 

On page 1, I noted Brazil didn't start widespread outpatient use of HCQ until Mid May and their Case Fatality Rate, which had been consistently higher than the USA promptly dropped below that of the USA.  Found an interesting chart on another site rating Case Fatality Rate by country, by HCQ use.  Res ipsa loquitur!

 

 

Attached Files

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Edited by Dorian Grey, 25 July 2020 - 03:17 AM.

[Daniel Cooper]

Useful is an interesting word. I suppose methylmercury was useful as an anti-choke agent in gasoline, though unforeseen damages were rapidly and vicously inccurrd as a result.

It's not useful as a reactionary treatment and it's not safe as an ongoing prophylactic. Not to rain on anyone's parade but that's been my opinion from the start, as dictated by evidence not emotion

 

I have a strong suspicion that when you say "methylmercury" you actually mean "tetraethyllead" and that when you say "anti-choke agent" you actually mean "anti-knock agent". 

 

Other than that, you're spot on.

 

 

[gamesguru]

Other than that, you're spot on.

 

Exactly, so let us not split hairs and most important let's not eagerly promote HCQ

 

You'd eat a rotten snail if Mittledorf gave it a French name.

Edited by gamesguru, 25 July 2020 - 12:17 PM.

[Oakman]

"The study shows that chloroquine does not prevent SARS-CoV-2 entry into human lung cells and subsequent spread of the virus in these cells. “In this study, we show that the antiviral activity of chloroquine is cell type-specific and that chloroquine does not block the infection of lung cells. This means that in future tests of potential COVID-19 drugs, care should be taken that relevant cell lines are used for the investigations in order not to waste unnecessary time and resources in our search for effective COVID-19 therapeutics,” says Stefan Pöhlmann, head of the Infection Biology Unit at DPZ, adding: “COVID-19 is primarily caused by the infection of lung cells, for this reason these cells should be given priority in efficacy tests.”

 

https://scitechdaily...man-lung-cells/

[Dorian Grey]

Great find Oakman!  This explains how HCQ hasn't been the miracle cure indicated by the original cell culture research.  This said, although COVID is thought of primarily as a pulmonary infection, it has subsequently been found to wreak havoc throughout many other tissues, particularly the vascular endothelium.  Don't know if the benefits some have seen with HCQ may be due to limiting spread throughout other tissues or not.  It will be interesting to dig deeper into this.  

 

The original research indicated HCQ limits coronavirus 3 different ways.  By alkalizing sialic acid at the ACE2 receptor site, alkalizing the multiple organelles (endosome, endoplasmic reticulum, & golgi apparatus) all of which are utilized for viral replication, and acting as a zinc ionophore; which is also supposed to effect viral replication.  

 

https://www.scienced...924857920300881

 

New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?

 

From your link above: "First, after attaching to the cells, the virus can fuse directly with the plasma membrane and introduce its genetic material into the host cell. Second, it can enter the interior of the cells upon uptake via transport structures, called endosomes. In both cases, the attachment of the virus to the cells and subsequent entry is mediated by the viral spike protein."

 

How does the virus attach to the cells?  I was under the impression (from Dr Been) sialic acid at the ACE2 receptor was the mechanism used, & that this was one of the inhibitory effects created by HCQ.  Does the virus also not require an acidic environment in the organelles for efficient replication?  Might increased zinc in the cytoplasm not also have an effect?

 

 

Doctor Been goes into detail here (starting at 13:00) https://youtu.be/yjkPdwlhI8A?t=780

 

Don't know if the discovery of an alternate entry point in pulmonary cells means none of the other factors apply, but definitely something to sink our teeth into. 

 

Thanks for the valuable input!  

 

 

Edited by Dorian Grey, 25 July 2020 - 03:08 PM.

[Mind]

The AAPS is trying to get Hydroxychloroquine back in use in the U.S. https://aapsonline.o...-A9cirPIMBWAvcQ

 

Other countries use Hydroxychloroquine. They have found it provides some benefit. It has minimal side effects. It is not controversial. Only in the U.S. do we have to suffer....because.....I am unsure, but I agree with Mitteldorf that it is a scandal.

[Daniel Cooper]

The Key to Defeating COVID-19 Already Exists. We Need to Start Using It (Hydroxychloroquine)

Op Ed by Harvey A. Rish, MD, PHD , Professor OF Epidemiology, Yale School of Public Health

I am referring, of course, to the medication hydroxychloroquine. When this inexpensive oral medication is given very early in the course of illness, before the virus has had time to multiply beyond control, it has shown to be highly effective, especially when given in combination with the antibiotics azithromycin or doxycycline and the nutritional supplement zinc.

 

First, as all know, the medication has become highly politicized. For many, it is viewed as a marker of political identity, on both sides of the political spectrum. Nobody needs me to remind them that this is not how medicine should proceed. We must judge this medication strictly on the science. When doctors graduate from medical school, they formally promise to make the health and life of the patient their first consideration, without biases of race, religion, nationality, social standing—or political affiliation. Lives must come first.

In the future, I believe this misbegotten episode regarding hydroxychloroquine will be studied by sociologists of medicine as a classic example of how extra-scientific factors overrode clear-cut medical evidence. But for now, reality demands a clear, scientific eye on the evidence and where it points. For the sake of high-risk patients, for the sake of our parents and grandparents, for the sake of the unemployed, for our economy and for our polity, especially those disproportionally affected, we must start treating immediately.

Edited by Daniel Cooper, 28 July 2020 - 01:38 PM.

[Florin]

But that stuff has zero RCTs, AFAIK. The latest and greatest HCQ+Z RCT shows no benefit. But unfortunately, it doesn't provide any zinc dosage data. There's just too many buts. Big buts.
 
For early treatment of mild COVID-19, University of Minnesota trial shows hydroxychloroquine has no benefit over placebo
https://twin-cities....oroquine-has-no
 

The randomized placebo-controlled trial, which rapidly launched on March 22, tested if hydroxychloroquine could decrease severity of COVID-19 symptoms and prevent hospitalization. The trial enrolled 491 non-hospitalized adults from across 40 U.S. states and three Canadian provinces. Participants were enrolled in the first four days of symptoms with 56% enrolled within one day of symptom onset.

In addition, there was no benefit in faster resolution of symptom severity among those who also took zinc or vitamin C with either hydroxychloroquine or placebo.

Edited by Florin, 27 July 2020 - 10:39 PM.

[geo12the]

 

The Key to Defeating COVID-19 Already Exists. We Need to Start Using It (Hydroxychloroquine)

Op Ed by Harvey A. Rish, MD, PHD , Professor OF Epidemiology, Yale School of Public health

 

 

 

At the end of the day what matters is if it actually works. Not the silly tribal political wars. I haven't yer seen any real evidence that it helps very much. 

[Dorian Grey]

At the end of the day what matters is if it actually works. Not the silly tribal political wars. I haven't yer seen any real evidence that it helps very much. 

 

preliminary injunction sought to release hydroxychloroquine to the public

 

https://aapsonline.o...-to-the-public/

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Edited by Dorian Grey, 28 July 2020 - 06:35 AM.

[Dorian Grey]

What I find fascinating about the HCQ war is the fanaticism of the resistance to the simple time honored tradition of the doctor/patient relationship, and the historical acceptance of off-label prescribing of prescription meds.  

 

https://en.wikipedia...i/Off-label_use

 

"Up to one-fifth of all drugs are prescribed off-label and amongst psychiatric drugs, off-label use rises to 31%."

 

HCQ is a remarkably benign med when used correctly:  WHO monograph on the cardiotoxicity of antimalarials (2017): “Despite hundreds of millions of doses administered in the treatment of malaria, there have been no reports of sudden unexplained death associated with quinine, chloroquine or amodiaquine, although each drug causes QT/QTc interval prolongation.”

 

The USA procured 70 million doses of HCQ early on, so there's no possibility of shortage.  The Right to Try Act, or the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act, was signed into law May 30, 2018.  

 

Now here we are in the heat of a pandemic, and the only plausible outpatient therapeutic has effectively been BANNED.  Doctors are cautioned not to prescribe it, and even if a doctor and patient wish to try HCQ, pharmacists are instructed not to fill prescriptions.  It's puzzling.  

 

No one is trying to force HCQ on anyone, though I'm confident the experimental mRNA vaccine rushed through at Warp Speed will probably be mandatory for anyone who wants to leave their home.  This mandate would be much more difficult to ordain if we had an effective outpatient therapeutic, which fuels the flames of conspiracy.  Why exactly were the HCQ trials simultaneously sabotaged all around the world with overdoses, guaranteed to produce serious cardiac side effects in a 70 year old drug where this has never been seen before when used responsibly?  

[Hebbeh]

https://www.thedaily...roxychloroquine

[Mind]

 

But that stuff has zero RCTs, AFAIK. The latest and greatest HCQ+Z RCT shows no benefit. But unfortunately, it doesn't provide any zinc dosage data. There's just too many buts. Big buts.
 
For early treatment of mild COVID-19, University of Minnesota trial shows hydroxychloroquine has no benefit over placebo
https://twin-cities....oroquine-has-no
 

 

 

If you actually dig into the charts of this study, every single clinical outcome was improved with HCQ use, but did not rise to statistical significance. If you check out the other larger thread about COVID treatments, you will find a catalog of small studies for which the U.S. media says "HCQ is useless". However, if you actually look at the data, the vast majority of the small studies show benefits to HCQ use, but not reaching statistical significance.

 

All of the large observational studies show significant benefits. The two studies that were reported far and wide by the U.S. media showing that HCQ was not beneficial or was harmful, were junk and/or completely fake as has been detailed widely on the Internet (but not in most U.S. media outlets, in fact they allow their reporting of the completely faked Lancet study to remain on their websites without corrections)

 

In India HCQ is in widespread use (hundreds of thousands have taken it). They recently report significant benefits in using HCQ. It is not controversial. It has benefits. They use it. It is unfortunate that people in western Europe and the U.S. have to suffer and die needlessly, just because the president of the U.S. said HCQ could be a good treatment for COVID.

 

When you have many small studies showing small benefits (but not statistically significant) to using a therapeutic;

 

When you have literally thousands of doctors around the world using it safely and claiming the therapeutic provides significant benefits;

 

When you have large observational studies showing dramatic benefits from using the therapeutic;

 

When time is of the essence in preventing more death from a new(?) respiratory illness;

 

That usually means most people and health authorities would clamor for more studies and more usage, yet that is not what is happening.

 

It is a tragedy. It is a scandal.

Edited by Mind, 28 July 2020 - 06:07 PM.

[Florin]

If you actually dig into the charts of this study, every single clinical outcome was improved with HCQ use, but did not rise to statistical significance.

 

But if there's no statistical significance, there's no evidence of benefit by definition.
 

In India HCQ is in widespread use (hundreds of thousands have taken it). They recently report significant benefits in using HCQ. It is not controversial. It has benefits. They use it.

But it doesn't seem to be an RCT. Zinc dosage? Link to the actual paper?
 

That usually means most people and health authorities would clamor for more studies and more usage, yet that is not what is happening.
 
It is a tragedy. It is a scandal.

 

Yes, it is, and it's not at all surprising. As you know, there's an even bigger tragedy and scandal in the chronic, non-communicable disease areas of medicine. Poor performance seems to be built into the system. What to do about it remains unclear.

Edited by Florin, 28 July 2020 - 08:23 PM.

[Dorian Grey]

But if there's no statistical significance, there's no evidence of benefit by definition.
 

But it doesn't seem to be an RCT. Zinc dosage? Link to the actual paper?
 

 

Yes, it is, and it's not at all surprising. As you know, there's an even bigger tragedy and scandal in the chronic, non-communicable disease areas of medicine. Poor performance seems to be built into the system. What to do about it remains unclear.

 

Doctors who "study" HCQ rarely get their patients tested, enrolled & started on the med until they've been symptomatic for 4-7 days or more and prove they got bad results.  .  

 

Doctors who "treat" with HCQ often say they start their patients on the med before the test results even come back and claim to get good results.  

 

If you're familiar with Tamiflu, the timing is everything with antivirals.  If you can't get your patients on their med within 48 hours of symptom onset...  Don't bother!  

Edited by Dorian Grey, 28 July 2020 - 10:27 PM.

[Florin]

72% took HCQ within 48 hours of the onset of symptoms and the rest within 4 days.

 

But besides lack of dosage info, it wasn't mentioned which subgroups used zinc. If most of the zinc was used by the subgroups that took HCQ after 48 hours of the onset of symptoms, that could be a fatal Attack of the Buts.

 

https://www.acpjourn..._Supplement.pdf

[Hebbeh]

If HCQ only demonstrates positive results against covid when used as a prophylaxis (as with malaria) or when administered in the very early stages of symptoms (hours), the issue as I see it:

 

As a prophylaxis we never know when we might be exposed (the pandemic has been amongst us for more than 6 months now and many "experts" are predicting another year or more) and as such, how long does one continue with a long (almost never ending) course of HCQ?  Individuals that have used it as a temporary prophylaxis against malaria report it's not completely benign and does have an uncomfortable side effect profile at the least even in short duration dosing.  And the longer you take it, I'm betting side effects will build.  And when you quit, any protection will relatively quickly taper off.

 

And in regards to attempting to beat the onset of this virus, it seems that with many, the virus gets a firm foothold before obvious symptoms appear after which the disease progresses rapidly.  Often, with many, by the time they actually seek medical care and get to the emergency room, it has rapidly progressed beyond simple initial symptoms and some can go straight to a vent (or oxygen) within the first 12 hours after admittance.  Often, by the time you may actually get medical treatment, the critical initial window has long passed.  That is why most business now require employees to be temperature checked at the beginning of each day... because the infected are contagious before they even realize they are sick... until it's too late.  Even to get routine medical or dental care, now you must be screened first and if you are found with a temperature or fail the questionnaire, you are denied entry or treatment.  And if you think you may have covid (or the clinic thinks you may have covid), don't even think about going to a clinic or your PCP as they won't allow you in and will direct you to the emergency room

 

And apparently when administered after the critical initial window has passed and severe symptoms have manifested, HCQ can make the situation worse.  And this situation is where higher doses were probably used in useless desperation and the negative results became apparent (which is apparently the case in most situations).

 

This is the dilemma as I see it based on stories I've heard from both covid patients and their families, and medical providers.

[gamesguru]

Dr. Fauci says all the ‘valid’ scientific data shows hydroxychloroquine isn’t effective in treating coronavirus

So either:

A) HCQ doesn't work against Covid-19 as shown by 5 published RCTs and 2 unpublished RCTs.

or

B) HCQ is incredibly efficacious against Covid, a "cure" so to speak. The usage of HCQ is being suppressed by a vast international cabal consisting of thousands of scientists, doctors, government health agencies worldwide costing hundreds of thousands of lives solely to affect the outcome of the american election. These doctors worldwide despite their oaths to do no harm are intentionally killing people just to affect the US election. In fact if HCQ was widely used, the pandemic would end, costing this vast cabal their attempt at controlling the world.

I don't know both options seem pretty plausible. One option definitely doesn't seem as crazy as "Demon semen". I'll never understand the mind of conspiracy theorists, I can't ignore data and reality to follow some weird narrative that takes multiple preternatural leaps of faith to seem even remotely possible.

I tend not to see conspiracies in every outcome I dislike. I tend not to be inscrutably judgmental of every negative result that comes my way. When I saw the 3% fatality coming out of China, I wanted to doubt it, but I rarely found good enough reasons to. Why I saw HCQ having negative results and getting "suppress", I smelled a rat but I was more convinced of the veracity of the scientific data than I was of any global conspiracy that could be discreetly carried out

 

List of HCQ RCTs, he has cited or that we're aware of:

 

1. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19

https://www.nejm.org...6/NEJMoa2019014

Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin**, did not improve** clinical status at 15 days as compared with standard care.

 

2. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19

https://www.nejm.org...6/NEJMoa2016638

After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure.

 

3. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

https://www.bmj.com/...t/369/bmj.m1849

Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients.

 

4. A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease

https://www.medrxiv....7.20.20157651v1

There was no significant difference in the primary outcome of PCR-confirmed, symptomatic Covid-19 disease (6.2% usual care vs. 5.7% HCQ; risk ratio 0.89 [95% confidence interval 0.54-1.46]), nor evidence of beneficial effects on prevention of SARS-CoV-2 transmission (17.8% usual care vs. 18.7% HCQ).

 

5. Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial

https://academic.oup...89#.XxCYlMdGoJM

No significant differences were found in the mean reduction of viral load at day 3 (-1.41 vs. -1.41 Log10 copies/mL in the control and intervention arm, respectively; difference 0.01 [95% CI -0.28;0.29]) or at day 7 (-3.37 vs. -3.44; d –0.07 [-0.44;0.29]). This treatment regimen did not reduce risk of hospitalization (7.1%, control vs. 5.9%, intervention; RR 0.75 [0.32;1.77]) nor shortened the time to complete resolution of symptoms (12 days, control vs. 10 days, intervention; p = 0.38). No relevant treatment-related AEs were reported.

 

6. Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial

https://www.acpjourn...0.7326/M20-4207

Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, −0.27 points [95% CI, −0.61 to 0.07 points]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non–COVID-19–related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).

 

7. Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial.

https://www.medrxiv....7.15.20151852v1

In patients hospitalized with COVID-19, hydroxychloroquine was not associated with reductions in 28-day mortality but was associated with an increased length of hospital stay and increased risk of progressing to invasive mechanical ventilation or death.

A concluding reminder about scientific methods..
 

RCTs almost perfectly control for variation between the tested groups. The only difference between the 2 groups in a good RCT is the treatment. Unlike observational studies that have unmeasured/unobserved confounding factors between the groups. It's why RCTs are the gold standard in research.

[Dorian Grey]

Dr. Fauci says all the ‘valid’ scientific data shows hydroxychloroquine isn’t effective in treating coronavirus

So either:

A) HCQ doesn't work against Covid-19 as shown by 5 published RCTs and 2 unpublished RCTs.

or

B) HCQ is incredibly efficacious against Covid, a "cure" so to speak. The usage of HCQ is being suppressed by a vast international cabal consisting of thousands of scientists, doctors, government health agencies worldwide costing hundreds of thousands of lives solely to affect the outcome of the american election. These doctors worldwide despite their oaths to do no harm are intentionally killing people just to affect the US election. In fact if HCQ was widely used, the pandemic would end, costing this vast cabal their attempt at controlling the world.

I don't know both options seem pretty plausible. One option definitely doesn't seem as crazy as "Demon semen". I'll never understand the mind of conspiracy theorists, I can't ignore data and reality to follow some weird narrative that takes multiple preternatural leaps of faith to seem even remotely possible.

I tend not to see conspiracies in every outcome I dislike. I tend not to be inscrutably judgmental of every negative result that comes my way. When I saw the 3% fatality coming out of China, I wanted to doubt it, but I rarely found good enough reasons to. Why I saw HCQ having negative results and getting "suppress", I smelled a rat but I was more convinced of the veracity of the scientific data than I was of any global conspiracy that could be discreetly carried out

 

I try not to be too gullible when it comes to conspiracy theories, but the mismanagement of the HCQ issue is one for the books.  

 

HCQ, like Tamiflu works not by killing virus, but by inhibiting replication.  With this mode of action, initiation of therapy early in the disease process, before viral load has climbed to the sky (maximum 48 hours for Tamiflu) becomes imperative.  What did the FDA do?  They BANNED outpatient prescribing and limited HCQ trials solely to hospitalized patients in or near critical condition.  Even the "early stage" outpatient trials typically required a PCR lab confirmation, which takes 3-5 days.  Add another day or two to get enrolled and started on the med, & most patients were symptomatic for 5-7 days before getting their first dose of HCQ.  I'm not a doctor, but I'm not dim either.  It doesn't take a genius to see the problem.  

 

HCQ has been around for 70 years, and has a remarkable safety record.  Not a single sudden cardiac death attributed to HCQ when used according to medical advice in the entire history of the med.  It is known to prolong Q/T though, and there are strong cautions about exceeding standard / established dosages.  What did the WHO do?  They increased the dose for all of the major HCQ trials (Solidarity/Recovery) all around the globe to known near fatal levels in critically ill patients.  This all but guaranteed cardiac side effects would occur, which would likely end the trials prematurely, and they did.  Almost every major trial halted due to cardiac issues; this in a med that has never been known to cause serious cardiac issues.  

 

Call me crazy, but I simply can't believe the doc's involved couldn't possibly have noticed the fatal flaws in their protocols.  I worked in healthcare for 35 years, and there is a code of silence about questioning superiors.  You do as you're told, & collect your pay.  Blow a whistle and you can get yourself cancelled.  I never would have believed things could get this crazy until now, but the HCQ SNAFU was sheer madness.  

 

What motive could there possibly be for this kind of malpractice?  Well, there are billions of dollars going into vaccine research, & the two prime contenders in the USA are both mRNA format, never successfully done before.  It's going to be a tough sell getting universal compliance.  An effective outpatient therapeutic would greatly complicate the vaccine issue, as many would choose to treat rather than vaccinate with the experimental new jab.  Sabotage any and all outpatient therapeutics, & the sheep will line up on cue with little coercion for their vaccinations.  If this sounds like something from George Orwell's 1984, it's because it is!  

 

We live in interesting times!  

[gamesguru]

I try not to be too gullible when it comes to conspiracy theories, but the mismanagement of the HCQ issue is one for the books.  

 

HCQ, like Tamiflu works not by killing virus, but by inhibiting replication.  With this mode of action, initiation of therapy early in the disease process, before viral load has climbed to the sky (maximum 48 hours for Tamiflu) becomes imperative.  What did the FDA do?  They BANNED outpatient prescribing and limited HCQ trials solely to hospitalized patients in or near critical condition.  Even the "early stage" outpatient trials typically required a PCR lab confirmation, which takes 3-5 days.  Add another day or two to get enrolled and started on the med, & most patients were symptomatic for 5-7 days before getting their first dose of HCQ.  I'm not a doctor, but I'm not dim either.  It doesn't take a genius to see the problem. 

 

Well if that's the case, it just needs to be taken a lot longer than some of these studies used.  But that makes it less practical in patients already presenting to the ER with severe symptoms.

 

It's also important to remember Spain continued with HCQ treatment, they didn't ban any kind of prescribing afaik.

In-vitro data suggest that high concentrations and thus high doses [of HCQ] are needed for COVID-19 infections, but as yet there is no convincing evidence of clinical efficacy.

 

And we'll see that's exactly the riskiest way to use it.

HCQ has been around for 70 years, and has a remarkable safety record.  Not a single sudden cardiac death attributed to HCQ when used according to medical advice in the entire history of the med.  It is known to prolong Q/T though, and there are strong cautions about exceeding standard / established dosages.  What did the WHO do?  They increased the dose for all of the major HCQ trials (Solidarity/Recovery) all around the globe to known near fatal levels in critically ill patients.  This all but guaranteed cardiac side effects would occur, which would likely end the trials prematurely, and they did.  Almost every major trial halted due to cardiac issues; this in a med that has never been known to cause serious cardiac issues. 

 

Call me crazy, but I simply can't believe the doc's involved couldn't possibly have noticed the fatal flaws in their protocols.  I worked in healthcare for 35 years, and there is a code of silence about questioning superiors.  You do as you're told, & collect your pay.  Blow a whistle and you can get yourself cancelled.  I never would have believed things could get this crazy until now, but the HCQ SNAFU was sheer madness. 

What motive could there possibly be for this kind of malpractice?  Well, there are billions of dollars going into vaccine research, & the two prime contenders in the USA are both mRNA format, never successfully done before.  It's going to be a tough sell getting universal compliance.  An effective outpatient therapeutic would greatly complicate the vaccine issue, as many would choose to treat rather than vaccinate with the experimental new jab.  Sabotage any and all outpatient therapeutics, & the sheep will line up on cue with little coercion for their vaccinations.  If this sounds like something from George Orwell's 1984, it's because it is! 

We live in interesting times!

 

Vaccine adoption rates are likely to be as low as 30%[1], suppression of other therapeutics can't be sustained anyways, and this effort is unlikely to be staged across continents. More likely just genuinely benevolent doctors acting on what they sincerely believe, that HCQ is often as harmful as it is helpful, which it probably is.

 

While it's true HCQ hasn't had any reported deaths, most of its use occurs in 3rd world countries where the absence of an active drug safety surveillance system in limits reassurance of these findings.

 

HCQ can also cause non-lethal arrhythmia and eye damage if used too long.  This is known to countries plagued by malaria

[Dorian Grey]

Well if that's the case, it just needs to be taken a lot longer than some of these studies used.  But that makes it less practical in patients already presenting to the ER with severe symptoms.

 

It's also important to remember Spain continued with HCQ treatment, they didn't ban any kind of prescribing afaik.

 

And we'll see that's exactly the riskiest way to use it.

 

Vaccine adoption rates are likely to be as low as 30%[1], suppression of other therapeutics can't be sustained anyways, and this effort is unlikely to be staged across continents. More likely just genuinely benevolent doctors acting on what they sincerely believe, that HCQ is often as harmful as it is helpful, which it probably is.

 

While it's true HCQ hasn't had any reported deaths, most of its use occurs in 3rd world countries where the absence of an active drug safety surveillance system in limits reassurance of these findings.

 

HCQ can also cause non-lethal arrhythmia and eye damage if used too long.  This is known to countries plagued by malaria

 

Lupus & RA patients take fairly high dose HCQ for decades on end, & yes some of them do eventually develop arrhythmias & retinopathy.  The standard course for COVID is 5-10 days, so very unlikely to be a substantial issue.  

 

Taking it longer is likely not nearly so important as starting it earlier.  In Costa Rica, they hand you a card of HCQ when you go in for your test, and tell you to start on this right away (before test results even come back).  Their Case Fatality Rate?  0.4-0.6%.  Not too shabby if you ask me.  

 

COVID vaccine compliance will likely be the first world war of Big Pharma against the common man.  I have no idea what kind of arm twisting will happen, but I expect it will be as hot an issue as COVID itself has been this year.  The availability of a safe & effective outpatient therapeutic (or NOT!) will probably tip the scale.  

 

As to HCQ safety, the CDC says it best on their malaria / travel page: 

 

Medicines for the Prevention of Malaria While Traveling Hydroxychloroquine (Plaquenil™)

 

Who can take hydroxychloroquine?

 

Hydroxychloroquine can be prescribed to adults and children of all ages. It can also be safely taken by pregnant women and nursing mothers.

 

Who should not take hydroxychloroquine?

 

People with psoriasis should not take hydroxychloroquine.

Edited by Dorian Grey, 30 July 2020 - 03:40 AM.

[Dorian Grey]

June 2020: India expands use of controversial drug (HCQ) for coronavirus despite safety concerns

 

https://www.nature.c...586-020-01619-8

 

July 2020: India's COVID-19 case fatality rate is progressively falling and is currently at 2.49 per cent, which is one of the lowest in the world

 

https://economictime...ow/77049660.cms

 

Way to go guys!

Edited by Dorian Grey, 01 August 2020 - 06:28 AM.

[geo12the]

I don't like the political cheer-leading, either for or against a drug to work. At the end of the day the science will lead us to truth. With HCQ I hear many anecdotal reports from Docs " i gave it patients and they got better". BUT most people who get this do get better, so how can you be sure it was the HCQ? Maybe they got better on their own. That is why we must rely on studies where there is a placebo to compare. As opposed to anecdotal reports of Doctors who believe in aliens, reptilians, Demon seed etc. I have not seen a convincing study that shows there is a strong effect of HCQ. At best it may help if given at the right time. Why then are the befits being exaggerated to portray it as a "cure"? Politics

[Dorian Grey]

I don't like the political cheer-leading, either for or against a drug to work. At the end of the day the science will lead us to truth. With HCQ I hear many anecdotal reports from Docs " i gave it patients and they got better". BUT most people who get this do get better, so how can you be sure it was the HCQ? Maybe they got better on their own. That is why we must rely on studies where there is a placebo to compare. As opposed to anecdotal reports of Doctors who believe in aliens, reptilians, Demon seed etc. I have not seen a convincing study that shows there is a strong effect of HCQ. At best it may help if given at the right time. Why then are the befits being exaggerated to portray it as a "cure"? Politics

 

Nothing wrong with proper trials, provided they are done properly.  If you read through this thread you'll see the major multi-million dollar global trials (Solidarity and Recovery) sponsored by the Wellcome Trust and Bill & Melinda Gates Foundation took the dosing guidelines from the WHO and about doubled them; this with a med with a remarkable safety record UNLESS excessive doses are used. 

 

They also delayed initiation of therapy until patients were in critical condition at or near the point of ICU; this with a med with a mode of action similar to Tamiflu (inhibition of viral replication), where delayed initiation is known to result in a futile outcome.    

 

What was the result?  Cardiac side effects from overdosing critically ill patients, and little to no clinical benefit, as delayed initiation of treatment was known to be futile from the start.  These guys aren't dumb, & I find it difficult to believe both of these simple concepts went right over their heads.  These large expensive trials were designed to fail in two different ways and grab headlines, drowning out smaller retrospective trials, along with any public confidence our only outpatient therapeutic might help bridge the gap between pandemic & vaccine.  

 

Speaking of vaccines, there are tens of billions of dollars being poured into their development, and any outpatient therapeutic might jeopardize mandates all must get vaccinated if they wish to go to school, work, or travel.  You won't hear Dr Fauci recommend Vitamin-D be mailed to every household any time soon, and cold water will continue to be poured down on any glimmer of hope coming from doc's using HCQ or any other outpatient med.  

 

In the mean time, countries who aren't afraid of HCQ are seeing remarkably low Case Fatality Rates.  Something I'd like to have available for me if I want it.  

Attached Files

•  CFRbyHCQ.jpg   98.1KB   0 downloads

Edited by Dorian Grey, 01 August 2020 - 09:50 PM.

[geo12the]

This Week in Virology discussed hydroxychloroquine in last Thursday podacst. it's about 26 or 27 minutes in. 

 

https://podcasts.app...5FkCrkPQOIh_Mh4

[Dorian Grey]

Gave your podcast a listen Geo.  They kick off with yet another study on "hospitalized patients" that showed no benefit.  Important to note most patients who require hospitalization are a week or more into their symptomatic phase, and often have become quite ill (hypoxic with pulmonary blood clots & massive viral load), which is why they are hospitalized in the first place.  As I may have mentioned before, antivirals that work by inhibiting replication (like Tamiflu) typically require initiation of therapy quite early in the disease process, or the therapy will be futile.  

 

Oakman posted on the alternate TMPRSS2 infection pathway in pulmonary tissue above.  To be honest, I haven't dug into this properly, but I replied with the multiple stages of viral replication HCQ is thought to have an inhibitory effect on, which is discussed in detail in the youtube I posted near the top of the page.  The lipid penetrating HCQ alkalizes sialic acid at the cell membrane, alkalizes the endosome, lysosome, endoplasmic reticulum & golgi apparatus; all of which are utilized during different stages of viral replication, and all of which are supposed to work more efficiently in an acidic environment which is neutralized by HCQ.  

 

Don't really know if the TMPRSS2 infection pathway bypasses ALL of the stages of viral replication HCQ alkalization is supposed to effect, or renders the immunomodulatory effect of HCQ useless, but I'd be surprised if this was true.  My favorite observation is still, those doing HCQ trials can't seem to initiate treatment until patients get their 3-5 day PCR results back and have been symptomatic for a week or more.  Meanwhile, doctors treating patients early (often before test results even come back) are reporting good results in many countries all around the world.  If the FDA hadn't BANNED outpatient prescribing in the US, this wouldn't be a big deal, but why this historically safe & cheap generic suddenly became forbidden fruit is beyond me.  Patients in the heat of a pandemic should have the "right to try", & licensed doctors should have the right to prescribe as they see fit. The war on HCQ only arouses suspicion about what motives could possibly have been behind such a frantic effort to stifle the traditional doctor/patient relationship; not to mention whether or not those sponsoring the large, expensive Solidarity and Recovery trials (Gates/Wellcome) may have been biased.  

 

The mocking of professor Risch (MD/PhD)'s paper didn't help their cause.  His abstract is quite clear & concise: 

 

More than 1.6 million Americans have been infected with SARS-CoV-2 and >10 times that number carry antibodies to it. High-risk patients presenting with progressing symptomatic disease have only hospitalization treatment with its high mortality. An outpatient treatment that prevents hospitalization is desperately needed. Two candidate medications have been widely discussed: remdesivir, and hydroxychloroquine+azithromycin. Remdesivir has shown mild effectiveness in hospitalized inpatients, but no trials have been registered in outpatients. Hydroxychloroquine+azithromycin has been widely misrepresented in both clinical reports and public media, and outpatient trials results are not expected until September. Early outpatient illness is very different than later hospitalized florid disease and the treatments differ. Evidence about use of hydroxychloroquine alone, or of hydroxychloroquine+azithromycin in inpatients, is irrelevant concerning efficacy of the pair in early high-risk outpatient disease. Five studies, including two controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. Hydroxychloroquine+azithromycin has been used as standard-of-care in more than 300,000 older adults with multicomorbidities, with estimated proportion diagnosed with cardiac arrhythmias attributable to the medications 47/100,000 users, of which estimated mortality is <20%, 9/100,000 users, compared to the 10,000 Americans now dying each week. These medications need to be widely available and promoted immediately for physicians to prescribe.

Edited by Dorian Grey, 06 August 2020 - 02:12 AM.