Re: Tractor Supply has special warning against Horse Parasite Drug (being used for pandemic treatment)
- No difference in time to resolution of symptoms (median 10 days in IVM arm vs. 12 days in placebo arm; HR 1.07; 95% CI, 0.87–1.32; P = 0.53)
- Symptoms resolved in 82% of patients in IVM arm and 79% in placebo arm by Day 21.
- A 5-day course of IVM resulted in faster virologic clearance than placebo, but not a faster time to resolution of symptoms (fever, cough, and sore throat). Because time to virologic clearance is not a validated surrogate marker for clinical efficacy, the clinical efficacy of IVM is unknown.
- A 5-day course of IVM in hospitalized patients with severe COVID-19 did not result in clinical improvement at the end of treatment, and no reduction in mortality was observed.
- Faster improvement of oxygenation and more pronounced reduction in inflammatory markers were observed in IVM arm.
- Use of IVM did not reduce risk of oxygen requirement, ICU admission, invasive mechanical ventilation, or death in hospitalized patients with severe COVID-19.
- IVM showed no effect on symptom resolution in patients with mild COVID-19.
- Compared to SOC, use of IVM did not lead to faster recovery from mild to moderate COVID-19.
- In this small study with a young population, the authors suggested that IVM plus DOX was superior to HCQ plus AZM despite no statistically significant difference in time from recovery to negative PCR result and symptom recovery between patients who received IVM plus DOX and those who received HCQ plus AZM.
- Concentration-dependent virologic response was seen when using a higher-than-usual dose of IVM (600 μg/kg vs. 200 or 400 μg/kg once daily), with minimal associated toxicities.
- Patients who received IVM showed no difference in viral clearance compared to those who received placebo.
- IVM may shorten the time to recovery for patients with mild or moderate disease, but the lack of control for competing mortality causes in the study limits the ability to interpret the results.
- Though the rate of negative RT-PCR results was numerically higher in the IVM arms than in the placebo arm on Day 5, the result was not statistically significant.
- In hospitalized patients with COVID-19 pneumonia who were not critically ill, neither IVM nor HCQ decreased the number of in-hospital days, rate of respiratory deterioration, or mortality.
- IVM appeared to improve laboratory outcomes and some clinical outcomes (shorter duration of hypoxemia and hospitalization) and lowered mortality.
- IVM use was associated with lower mortality than usual care.
- Compared to SOC, IVM alone was associated with increased risk of death and/or ICU admission. Using IVM in combination with AZM was not associated with effects on mortality, ICU transfer, or oxygen prescription compared to SOC.
- Compared to SOC, IVM use was associated with faster rates of viral clearance and better clinical outcomes, including shorter hospital stay and lower mortality.
These discrepancies were similar to those that would later be raised for the Lancet paper—specifically, there appeared to be more cases in the Surgisphere dataset than official records captured, suspiciously high numbers of hospitalizations on continents where electronic medical records are rarely used, and surprisingly large effect sizes given what was known of the drugs in question.
Meanwhile, Patricia García, a Solidarity Trial investigator and the former health minister of Peru—one of the countries in which the ivermectin preprint has been widely cited in recommendations for COVID-19 treatment—expressed anger that Surgisphere had been able to damage public trust in scientists at a time when scientific expertise is needed most.
Two Huge Covid-19 Studies Are Retracted After Scientists Sound Alarms
The reports, published in two leading journals, were retracted after authors could not verify an enormous database of medical records.
President Martín Vizcarra announced the country had acquired 500,000 doses of ivermectin for distribution.
Ultimately the Peruvian government issued a warning against using the veterinary formula, but Chaccour said it is now encouraging hospitals and pharmacies to formulate their own ivermectin, a process that is normally highly regulated.
Rajter published the results of an analysis of his patients’ charts, which found a 10% reduction in mortality rate among severely ill COVID-19 patients who had been given ivermectin.NEW YORK, NEW YORK: —JANUARY 14, 2021: One week after Dr. Paul Marik and Dr. Pierre Kory—founding members of the Front Line Covid-19 Critical Care Alliance (FLCCC)— along with Dr. Andrew Hill, researcher and consultant to the World Health Organization (WHO), presented their data before the NIH Treatment Guidelines Panel, the NIH has upgraded their recommendation on ivermectin, making it an option for use in COVID-19.
This new designation upgraded the status of ivermectin from “against” to “neither for nor against”, which is the same recommendation given to monoclonal antibodies and convalescent plasma, both widely used across the nation.
During his testimony, Kory referred to a paper he authored -- Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 -- that was published in the May edition of the American Journal of Therapeutics.
The paper was also included in the Frontiers of Pharmacology journal in January but was then removed in March. Dr. Frederick Fenter, chief executive editor of the journal, said the paper was removed due to "strong, unsupported claims based on studies with insufficient statistical significance, and at times, without the use of control groups." Fender also said the authors promoted their own specific ivermectin-based treatment, which goes against editorial policies.
https://asiatimes.com/2021/07/
parasitic-politics-plague- ivermectin-use-in-indonesia/ A study listed in Kory's paper involved giving ivermectin to 234 uninfected health care workers in Argentina and found those who received the drug were far less likely to be diagnosed with COVID. For mildly ill patients, an Iraq study saw a quicker recovery time.
There are also studies that show otherwise. A clinical trial of 476 patients found ivermectin didn't improve the recovery time in patients who had COVID-19. A review of 10 random clinical trials, with more than 1,000 participants, also didn't find improvements with ivermectin. One Egyptian study claimed to show positive results, but it's since been redacted over ethical concerns.
A medical student in London, Jack Lawrence, was among the first to identify serious concerns about the paper, leading to the retraction. He first became aware of the Elgazzar preprint when it was assigned to him by one of his lecturers for an assignment that formed part of his master’s degree. He found the introduction section of the paper appeared to have been almost entirely plagiarised.
It appeared that the authors had run entire paragraphs from press releases and websites about ivermectin and Covid-19 through a thesaurus to change key words. “Humorously, this led to them changing ‘severe acute respiratory syndrome’ to ‘extreme intense respiratory syndrome’ on one occasion,” Lawrence said.
European Union members Greece, Bulgaria, Slovakia and the Czech Republic, have now brought Ivermectin into their Covid-19 management strategies
But as with Monash, numerous clinical trials have been encouraging. The American Journal of Therapeutics reported in late June that the drug significantly reduced mortality, compared with no Ivermectin, based on a meta-analysis of 15 trials conducted among 2,500 recipients.
The researchers say “low-certainty evidence” revealed that taken as a prophylactic, Ivermectin actually lowered infections by an average of 86%.
“Using Ivermectin early in the clinical course may reduce numbers progressing to severe disease,” it said. “The apparent safety and low cost suggest that Ivermectin is likely to have a significant impact on the SARS-Cov-2 pandemic globally.”
More than 30 countries, includi
In summary, there is no strong evidence here – but is it valid to line up a lot of weak evidence and claim that it adds up
to strong evidence?
In quantitative sciences, that can only make sense if you know what the error bars are and most of the studies cited by
Kory et al. are too weak even to know what the error bars are and even when the error is quantifiable, the studies measure
different outcomes or compare different cases and controls. If you do have studies that are reasonably constructed with
sources of bias eliminated or clearly quantified, you still have the issue of publication bias, particularly problematic
with small studies. Publication bias is also more likely a factor in observational studies [64] – and they rely almost
entirely on those.
Meta-analysis is best done using methods that preclude bias at all levels – in the studies included, inclusion of the
studies and analysis of the studies. Kory et al. do not use a systematic approach to include or exclude studies and the
South African NELMC reports illustrate how different the evidence looks if a systematic approach is in fact used.
To describe ivermectin as a “miracle drug” is a cruel hoax. While it is possible that a good study will show some effect,
the case Kory et al. make is flimsy and it is unethical to raise hopes without solid evidence.
More than a century of refinement of drug discovery protocols, research ethics and statistical tools tell us that the
approach of Kory et al. is more likely to produce a misleading outcome than a valid result. The fact that we are in the
midst of a dangerous epidemic that has cost many lives and caused serious economic disruption is no reason to abandon
best practice and to undermine public confidence in drug safety and efficacy certification – particularly as vaccines are
the target of a long-running and effective disinformation propaganda campaign.https://www.sciencedirect.com/
science/article/pii/ S2052297521000883 Ivermectin: a multifaceted drug of Nobel prize-honored distinction with indicated efficacy against a new global scourge, COVID-19
David E.ScheimPhD2Under a Creative Commons licenseopen accessAbstract
In 2015, the Nobel Committee for Physiology or Medicine, in its only award for treatments of infectious diseases since six decades prior, honored the discovery of ivermectin (IVM), a multifaceted drug deployed against some of the world’s most devastating tropical diseases. Since March 2020, when IVM was first used against a new global scourge, COVID-19, more than 20 randomized clinical trials (RCTs) have tracked such inpatient and outpatient treatments. Six of seven meta-analyses of IVM treatment RCTs reporting in 2021 found notable reductions in COVID-19 fatalities, with a mean 31% relative risk of mortality vs. controls. The RCT using the highest IVM dose achieved a 92% reduction in mortality vs. controls (400 total subjects, p<0.001). During mass IVM treatments in Peru, excess deaths fell by a mean of 74% over 30 days in its ten states with the most extensive treatments. Reductions in deaths correlated with extent of IVM distributions in all 25 states with p<0.002. Sharp reductions in morbidity using IVM were also observed in two animal models, of SARS-CoV-2 and a related betacoronavirus. The indicated biological mechanism of IVM, competitive binding with SARS-CoV-2 spike protein, is likely non-epitope specific, possibly yielding full efficacy against emerging viral mutant strains.
analysis here of the Meta-Studies
For example, they estimate a mean reduction in time to viral clearance
of 3 days (95%CI 1-5), a reduction in time to clinical recovery of 1.5 days (95%CI 0.4-2.8), a reduction
in duration of hospitalization of 4.3 days (95%CI 0.0-8.6) and 56% reduced risk of mortality (95%CIonly nine of the 24 studies (n=785) were rated as
having a low-risk of bias and fewer than half of studies (10) were placebo-controlled. Moreover, only
eight studies have been peer reviewed, with another 11 publicly available through pre-print or
clinical trial registry result reporting, and four unpublished at the time of this writing. Many were
also not pre-registered on clinical trial repositories. Perhaps the most glaring feature of these studies
is the heterogeneity between many aspects of the studies themselves, including ivermectin dose
(0.1 mg/kg – 24mg fixed dose) and duration (single dose through 1 week), stage of disease for
enrolled participants (mild to severe), use of combination therapies in the intervention arm (multiple
evaluated combinations of doxycycline with ivermectin) and a remarkably varied set of comparator
arms, ranging from placebo alone to use of favipiravir, hydroxychloroquine and/or azithromycin.Counterbalancing these arguments are the general lack of
biologic plausibility and coherence for the use of ivermectin in the treatment of a viral infection.
Since it does not appear to be active in standard doses as a direct-acting anti-viral, we are forced to
speculate about anti-inflammatory or indirect antiviral effects. Perhaps most puzzling is the degree
and extent of benefit identified – across disease stages, dosing regimens, and viral and clinical
outcomes – which strains belief, particularly for a disease that has been characterized by narrow
therapeutic windows for most other interventions.As of this writing, there at least five large, placebo-controlled clinical trials on the use of ivermectin
for COVID-19 underway that should be powered to allay residual concerns about the available data.
Until those data are released, ivermectin might be best considered as an extremely promising
therapy, but one not quite ready for public use.
a study claiming to have found beneficial effects in patients was withdrawn following allegations of data manipulation.
For example, nearly a third of the studies evaluated ivermectin alongside other treatments that varied between different groups of patients, making it difficult to extract the effect of ivermectin, specifically, from the data. Several studies classified people as COVID-19 patients without testing to make sure they had the disease with a PCR or antigen test.
The study, led by researchers in Egypt, claimed to have found a dramatic effect of ivermectin treatment on COVID-19 outcomes. However, researchers identified multiple inconsistencies in the data, The Guardian reported in July, particularly regarding the numbers of patients and their dates of hospital admission.
One patient was even reported to have left the hospital on the “non-existent date of 31/06/2020,” Jack Lawrence, a medical student in London who identified problems in the paper, tells The Guardian. epidemiologist and blogger Gideon Meyerowitz-Katz documented multiple inconsistencies—including numbers of patients that don’t add up and implausible effect sizes—on Twitter. “As far as interventional observational trials go, this is probably the worst one I’ve ever seen,” he writes.
The molecular structure of ivermectin is rather complex and made of a set of macrocyclic lactone isomers. It binds to glutamate-gated chloride channels and increases the permeability of chloride ions [30]. Ion channels are attractive antiviral targets for two reasons. First, viruses can also have ion channels, active in viral assembly, morphogenesis, and viral release (e.g., E-protein in SARS-CoV [31]). Additionally, the inhibition of host (human) ion channels can be detrimental to viral replication, hepatitis C virus (HCV) in particular [32]. Ivermectin itself was shown to be able to inhibit the replication of SARS-CoV-2 in vitro [33]. All this indicates that ivermectin, as a modulator of chloride channel permeability, is a potential anti-viral drug. It is, therefore, currently the subject of clinical trials as a potential COVID-19 treatment [34].Ginger binds to ACE-2 - a more direct pathway.The analysis (Figure 2) reveals that all three compounds (ivermectin, glycine, and AM-3607 (7c6)) bind to kinetically active and residues adjoining them [43], some of which are highly hydrophobic, with ivermectin binding almost exclusively hydrophobic residues. This means that this drug seeks similar sites on the surface of the COVID-19 proteins.. Our results indicate that small, drug-like compounds preferentially bind to kinetically active and adjoining residues, and thus seek stable residues characterized by fast normal modes with small amplitude fluctuations [43]. Some of the drugs we analyzed preferentially seek active patches that are hydrophobic (chloroquine, ivermectin), while others prefer hydrophilic surfaces (remdesivir, sofosbuvir, eflornithine). We can postulate that in a water environment, drugs that bind to hydrophilic patches will be more stable, as their removal will lead to the reduction in structural entropy, but a full account of this proposition will require calculations of binding free energy differences using, for instance, still numerically expensive molecular dynamics simulations [73,74,75,76]. We can also propose that the drugs/small molecules that bind to deep pockets will be more stable, and thus more effective. Our algorithm accurately recognizes such pockets as binding spots for drugs (Figure 1a, Figure 3, and Figure 10), and small peptides (see, in particular, Figure 6a in [43]).
hmm.Let's see what the follow up citations state.THE THERAPEUTIC POTENTIAL OF IVERMECTIN FOR COVID-19: A SYSTEMATIC REVIEW OF MECHANISMS AND EVIDENCE
They say it looks effective.
Too bad people don't know about Ginger!
A medical student in London, Jack Lawrence, was among the first to identify serious concerns about the paper, leading to the retraction. He first became aware of the Elgazzar preprint when it was assigned to him by one of his lecturers for an assignment that formed part of his master’s degree. He found the introduction section of the paper appeared to have been almost entirely plagiarised.
It appeared that the authors had run entire paragraphs from press releases and websites about ivermectin and Covid-19 through a thesaurus to change key words. “Humorously, this led to them changing ‘severe acute respiratory syndrome’ to ‘extreme intense respiratory syndrome’ on one occasion,” Lawrence said.
“The authors claimed they conducted the study between the 8th of June and 20th of September 2020, however most of the patients who died were admitted into hospital and died before the 8th of June according to the raw data. The data was also terribly formatted, and includes one patient who left hospital on the non-existent date of 31/06/2020.”
“The main error is that at least 79 of the patient records are obvious clones of other records,” Brown told the Guardian.
Meyerowitz-Katz told the Guardian that “this is one of the biggest ivermectin studies out there”, and it appeared to him the data was “just totally faked”.
This was concerning because two meta-analyses of ivermectin for treating Covid-19 had included the Elgazzar study in the results. A meta-analysis is a statistical analysis that combines the results of multiple scientific studies to determine what the overall scientific literature has found about a treatment or intervention.
“Because the Elgazzar study is so large, and so massively positive – showing a 90% reduction in mortality – it hugely skews the evidence in favour of ivermectin,” Meyerowitz-Katz said.
“Thousands of highly educated scientists, doctors, pharmacists, and at least four major medicines regulators missed a fraud so apparent that it might as well have come with a flashing neon sign. That this all happened amid an ongoing global health crisis of epic proportions is all the more terrifying.”
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