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Viewing 15 posts - 46 through 60 (of 1,968 total)
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  • in reply to: Dr James with COVID-19 research. #30012
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    The data about Indometacin comes from several sources.

    It was first observed to work for SARS in Italy and that’s described here: https://fixrx.com/coronavirus-indomethacin-to-the-rescue/

    The Chinese repeated that study in SARS-CoV-2 https://www.biorxiv.org/content/10.1101/2020.04.01.017624v1

    In NYC Dr Jonathan Leibowitz tried it out on patients:

    Indomethacin in Covid-19

    And reported on it in the medical literature here:

    https://www.bmj.com/content/368/bmj.m1185/rr-3


    YMMV

    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Hello joy2world,

    Please don’t worry. If you were going to relapse you would have by now.

    I would be confident that a PCR at 24 weeks will come back negative.

    The tests have got a lot more sensitive over the years and detect down to very tiny residual traces.


    YMMV

    in reply to: Hazel Heal at it again #30007
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Hi Coral,

    Yes, there is no doubt Hazel is a force to be reckoned with!


    YMMV

    in reply to: Broken interface ? or is my cat on the Ipad again #29980
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Hi Jimmy,

    Yes, it’s weird! The website depends on its CSS and if you don’t get that file you get what you got.

    The problem then is that most browsers don’t really refresh properly!


    YMMV

    in reply to: Dr James with COVID-19 research. #29979
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Hey Jimmy42,

    Long time big fella! How is life treating you?

    There should be a bit of interesting news vis a vis HCV medication vs COVID-19 in the near future.


    YMMV

    in reply to: Dr James with COVID-19 research. #29975
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Thanks for posting it Hazel


    YMMV

    in reply to: Results of end of treatment #29865
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Congratulations! It must be time to roll out the happy dance…

    #dance


    YMMV

    in reply to: 12 week after treatment test results #29864
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Yes, you are cured.

    The antibody test >11 just says you have antibodies because you were once infected. That will fall slowly over time.

    The PCR test of < 15 done May 12, 2020 proves the infection is gone. #magic


    YMMV

    in reply to: Pre-Treatment VL and Bloodwork #29843
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Hello joy2world,

    While it’s possible your viral load will rise (a relapse) it’s far more likely you will still go on to SVR12.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834854/

    For that reason it is not appropriate to retreat yet. A simple repeat PCR at weeks 4, 8, 12 post treatment will tell us what is happening. If it goes undetected and stays there you are cured. If it rebounds you’re not.

    It would be premature to jump back on treatment until we confirm a relapse with a high viral load.

    Your watch, wait and see idea is spot on.

    Although your doctor is a bit over-enthusiastic on the retreatment front I’d look at it like this:

    1) You will probably SVR (so don’t worry too much)
    2) If you don’t your doctor looks like they can access retreatment (so don’t worry too much)

    So it’s most likely you’ll be fine with nothing more than a couple of blood tests to do. If not, you’ll get retreated and cured second time around. Either way you’re cured.


    YMMV

    in reply to: Chlorcyclizine as possible antiviral for Covid 19 #29842
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Hi fitz,

    I had the exact same response, although mine was more like “WTAF, if this is good I’d hate to think what bad looks like”


    YMMV

    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Hi Gordon,

    Thanks for your kind words. The timing is good. Currently, I’m dealing with a patient complaint where the complaint is basically that the patient did not like me telling them there was nothing wrong (despite the fact history has proven that to be the case) and that their self-diagnosis from Google was incorrect. It’s weird – on the one side we have life and death disease where help is appreciated. On the other we have hypochondriacs wasting their time by writing, and far more of my time by having to answer baseless complaints.

    Failing the only government-funded treatment first time around must have been shattering. It’s been a honour to be in a position to help you get the job done second time around.

    Please enjoy this video:

    https://www.youtube.com/watch?time_continue=2&v=yRf6wAR-eEY&feature=emb_logo


    YMMV

    in reply to: Chlorcyclizine as possible antiviral for Covid 19 #29826
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Not that that’s a bad thing at all if it works.

    Sadly it does not.

    https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext

    Interpretation
    In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits.

    Worse, the NIH did an emergency review and emergency press release because they knew this study was coming out.

    Ignoring the Anthony Fauci backed, non-peer reviewed, non-published, interim analysis from NIH from 2 days ago https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19 or not ignoring that and noting that report states:

    Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group (p=0.059) is far more accurately worded:

    Results FAILED TO DEMONSTRATE ANY STATISTICALLY SIGNIFICANT survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group (p=0.059)
    (despite being n=>1000…;)

    IF remdesivir delivers any benefit whatsoever it is, at best, in the ballpark of the benefit of ribavirin which, when added to Sofosbuvir and an NS5A is ~ 1% extra SVR12 ie so small you can barely measure it.

    In short, remdesivir

    • is not a potent NUC,
    • it is not even close to a potent NUC and
    • even at n > 1000 it has failed to demonstrate any significant benefit.

    Compared to a real NUC like sofosbuvir it is complete and utter rubbish, leaving aside the issues that it is IV only and exists only at experimental scale.

    Here is a reasonably thorough analysis of the remdesivir trials (credit Dr Andrew Hill)

    There are 5 main randomised trials of remdesvir. We need all the results from these 5 clinical trials to be combined. Then we could interpret the overall outcomes in a meaningful way.

    When the World Health Organisation review a drug, they always run a systematic review and meta-analysis of all available data.

    A: Chinese trial of remdesivir versus placebo showed no benefits (Lancet publication), n=237

    1. There is no effect of remdesivir on coronavirus viral load levels – they are the same as the control arm. With 237 patients, this trial show easily have enough statistical power to detect an effect on viral load.

    2. Remdesivir was stopped early for adverse events in 12% of patients, versus four (5%) who stopped placebo early.

    3. Mortality was 14% for remdesivir versus 13% for placebo.

    https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext

    B: Gilead’s trial in severe infection seem to suggest that 5 days of treatment is better than 10 days. What does this tell us about how well the drug works? Why should less treatment show trends for better outcomes?

    1. Clinical recovery: 65% for 5 days, 54% for 10 days of treatment

    2. Mortality: 8% for 5 days, 11% for 10 days

    3. Adverse events leading to discontinuation: 5% for 5 days, 10% for 10 days

    https://www.gilead.com/news-and-press/press-room/press-releases/2020/4/gilead-announces-results-from-phase-3-trial-of-investigational-antiviral-remdesivir-in-patients-with-severe-covid-19

    C: NIH trial. Why was the clinical endpoint and sample size changed in the middle of the trial? n=1063, unpublished interim analysis.

    This study, announced by Anthony Fauci, shows a slightly lower mortality for remdesivir (8.0%) versus placebo (11.6%), but this is not statistically significant. Remember that in the comparison of 5 versus 10 days of remdesivir, we also had 8% mortality for 5 days of remdesivir, versus 11% for 10 days of treatment. How do we interpret these two non-significant trends in the two trials?

    Combined with the Chinese survival data, any difference in survival between remdesivir and placebo will be small and not statistically significant.

    https://www.nih.gov/news-events/news-releases/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19

    D: Missing data from the second Chinese trial.

    This study of 308 patients was suspended for poor recruitment, but no results are available for the people who were actually recruited before April 15th. The website mentions 308 patients. What results are available? When will they be published?

    https://clinicaltrials.gov/ct2/show/NCT04252664?cond=remdesivir&draw=2&rank=4

    E: Main Gilead trial of remdesivir for people with moderate coronavirus infection (n=1600).

    This trial is still ongoing, with results not yet available. We should see these results by the end of May.

    https://clinicaltrials.gov/ct2/show/NCT04292730?cond=remdesivir&draw=2&rank=7

    Even if remdesivir does show overall efficacy, there is the question of drug supplies. Will there be enough drug to treat everyone in need? Also the daily IV infusions of remdesivir will be a large burden on healthcare services.


    YMMV

    in reply to: Chlorcyclizine as possible antiviral for Covid 19 #29808
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    I have some sitting on my desk for use in case of emergency too!


    YMMV

    in reply to: Chlorcyclizine as possible antiviral for Covid 19 #29783
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Hi fitz,

    Long time. The only things that look good are hydroxychloroquine and Indometacin.

    Main Point: A colleague just shared a Chinese pre-print that suggests Indometacin may be useful in COVID-19 with a good log kill and blood levels 10x IC50 at standard oral doses. The animals dosed with it recovered faster than the controls and this recovery rate was similar to that of other test animals given convalescent serum. 3/8 control dogs died, 1/9 convalescent serum dogs died, and all the dogs dosed with Indometacin survived.

    It may have got lost in the noise but there was an Italian observation about Indometacin working on SARS from back in 2006. I tried to get a high containment lab anywhere to check it without any success.

    Anyway, the Chinese have gone 1 step further than in vitro cell culture and found exactly the same as the Italians – Indomethiin appears effective in vivo in dogs against SARS-CoV-2

    Yes, not human trials but certainly encouraging with the usual pathway is cell culture, mice, rats, small vertebrates, large vertebrates ( dogs and pigs), primates, humans.

    Standard oral doses exceed 10x IC50 as opposed to Hydroxychloroquine where you’re looking at only 2x over IC50.

    The Chinese don’t state a log kill but do say it hit zero @ 48 hours.

    The Italians suggested a log kill of 3 (this is Daclatasvir/Ledipasvir strength). For comparison, Sofosbuvir has log kill of 4.5, Ribavirin is 0.5 and Interferon about 1-2 (initially) on HCV.

    Both the Italian (2006) and Chinese papers are attached. The Chinese paper is a pre-print but the technical detail looks solid. There is a US co-author FWIW.

    Given the runs of various things at our pharmacies, it might be worth getting Indometecin constrained like HCQ as I’d be tipping the mainstream media pick this up soon after it starts to bubble on social media.


    YMMV

    in reply to: Messaging members… #29779
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    Hi Sven,

    Hmm, there was the public chat that we turned off due to all the spruikers harassing patients kind of ruining it. I had not noticed the private messaging had gone.

    I’ve switched it back on.

    Best

    James


    YMMV

Viewing 15 posts - 46 through 60 (of 1,968 total)