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Everything posted by triplehorn
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Orange man say so yep. ultimately could end up being another chapter in the long history of broken clocks. In the meantime, only Trump could cause something with potential benefit in the proper context to devolve into mass chaos.
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Punjab directs all its frontline healthcare workers to take HCQ tablets the lede: "A MONTH after ICMR recommended use of hydroxychloroquine as prophylaxis (preventive treatment) for frontline healthcare workers and high risk population amid the COVID-19 outbreak, Punjab has directed all frontline healthcare workers across the state to take the recommended weekly dose of HCQ." "...the government is considering giving the medicine to other frontline workers as well, including police and government officials etc." ---> After a full month of doing this, they're not ditching the approach, they're expanding it. On the face of it, it suggests that not only are they not experiencing negative events, they're seeing some associated good. Also note their prophylactic regimen is once weekly dosing - the same regimen that has been dosed tens of millions of times for over half a century (established safety). On one hand, there is a need for RCT's, on the other hand we're in a war. A war where, if you wait and realize what's happening in real time, it's too late.
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Treatment Response to Hydroxychloroquine, Lopinavir–Ritonavir, and Antibiotics for Moderate COVID-19: A First Report on the Pharmacological Outcomes from South Korea (full text with charts and graphs visible clicking the 'preview .pdf' at the link) Methods: A retrospective cohort study of the 358 laboratory-confirmed SARS-CoV-2 – or COVID-19 - patients was conducted. Of these patients, 270 adult patients met inclusion criteria and were included in our analyses. The primary endpoints were time to viral clearance and clinical improvement. The mean duration to viral clearance and clinical improvements were displayed as bar-plots to visualize treatment responses. Conclusion: This first report on pharmacological management of COVID-19 from South Korea revealed that HQ with antibiotics was associated with better clinical outcomes in terms of viral clearance, hospital stay, and cough symptom resolution compared to Lop/R with antibiotics or conservative treatment. The effect of Lop/R with antibiotics was not superior to conservative management. The adjunct use of the antibiotics may provide additional benefit in COVID-19 management but warrants further evaluation. Important consideration is that "mild" and "moderate" cases were given the regimens, but again these are all people who were hospitalized. And hospitalization is an important indicator of duration of illness before treatment initiation. What happens when people get the treatments as soon as they test positive, as opposed to progressing to requiring hospitalization ? If viral loads and time to viral clearance are reduced with treatment, it suggests there's an opportunity to reduce probability of transmission within a population, particularly in asymptomatic people. But without adequate testing in place, none of this matters nearly as much.
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Extrapyramidal disease, peripheral motor neuropathy, hallucinations, mood changes, or suicidal behavior are definitely not to trifled with, absolutely. All of those are considered RARE side effects. It then follows, what is the approximate minimum number of doses needed for such a side effect to manifest? Toxic retinopathy in one study happened after 5 years of daily dosing in 7.5% of subjects. In another study, those at risk for hemolytic anemia from G6PD deficiency never had a hemolytic crisis during 700 months of combined subjects observation. The Covid protocols getting used variably around the globe last about 5 days, not daily dosing for 5 years or more. Show me where anyone had those kinds of rare effects happen within 5 days of dosing (could be, I haven't found any yet). From what I can tell, the acute effects of concern are the cardiac ones. Arrhythmia can result from a "threshold" electrophysiologic event and cause rapid onset dangerous effects. Because we're hearing about swollen arterial linings and coagulation events related to Covid, it makes sense to consider a cutoff in medical presentation where you just don't give HCQ due to the elevated risks that disease progression represents.
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here's your daily dose of HCQ news: CNN: Yet another study shows hydroxychloroquine doesn't work against Covid-19 ^^^ it's a study based on late administration of HCQ ---> 1438 ppl who had it long enough and had it advance enough to require hospitalization. Meanwhile, this article today out France (may need your PC to translate): Effectiveness of the measures, a factual point of view? Significant regional differences.
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It's going to be the dumbest timeline ever if HCQ verifiably has benefits if applied early enough to covid and Trump can claim credit. But he should not be the one talking about it. He can't communicate anything with any depth of understanding or nuance. Not only does he risk prompting people to take ill advised and unsupervised risks, he also stands to poison the well where some good may yet to be found.
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Time for another ‘my dog is awesome’ thread
triplehorn replied to Patricio Swayze's topic in Daily Texan
Chipmunk patrol resumed on the pacific crest trail yesterday (gifford pinchot nat forest trail heads opened friday) Had to head in the direction of lower elevations due to persistent snow pack. fwiw, almost got stuck in a random snow covered section of a forest road with deep tire ruts 10 miles into the wilderness having seen no one heading in. Would have survived, but man that would have sucked. -
bored punks
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Just need to demonstrate a sustained inversion of the slope of the growth curve for daily new cases. Maybe ? NIH is now asking better questions. With the start of its just announced study that includes mild (early-ish?) cases, the picture might shift. It's obvious that communication is lacking around important considerations including differences in timing of use and in risk alone or use in combination with other meds. And that the incidence of adverse effects like G6PD associated hemolytic anemia and toxic retinopathy really only become measurable once people have been on HCQ for thousands of doses spanning years, not over 5 days for covid. Check out this WaPo article today: Drug promoted by Trump as coronavirus ‘game changer’ increasingly linked to deaths the takeaway: “The question has been answered that if you have the infection and it’s significant enough to be in the hospital, the drug doesn’t seem to do anything for you,” The article fails to make any distinction between early treatment vs initiation once requiring hospitalization, the latter of which is what US studies to date have involved. The article also fails to make the distinction that combining AZ with HCQ appears to increase cardiovascular risk over HCQ alone, and HCQ given early may do just as well (if not better and more safely) as combining with zithro. And finally, no mention whatsoever of the potential critical role of co-administering HCQ with 100-150mg/d Zinc for ~5 days for clinical benefit. Dr. David Ho, who spearheaded successful treatments for HIV, explained "you have to hit the virus early and hard" - before it takes hold. Even the soon to be launched NIH study may not start subjects on HCQ until they've been positive or symptomatic for 7 days or more, mild or not, when it very well could be that starting within 72 hours makes all the difference. To date, I think we've been digging in the wrong place.
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Yeah, if people aren't going to wear a mask in public, the least they could do is shut the fuck up around others. Like don't talk, at all.
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Unless the volume of testing had an abrupt lurch upward in the last 3 days, I wouldn't expect 2 of the last 3 days to spike upward, but in this case there appears to be a reason for it. It so happens that two weeks ago almost to the day Abbott signaled the start of initial steps at re-opening. The time to double TX from 10k to 20k was 12 days. 20k to 40k was about 20 days. Re-opening started at about 30k known cases. With a reference number of about 47k known today, continued doubling even every 3 weeks will necessitate re-imposition of shut down measures to avoid crashing the health care system.
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If that's the case, the response will be one to behold after infections spike with that 2 week delay. Abbott announced Phase 1 re-opening beginning May1st. Now look 2 weeks later - May 13th and 15th had 1,636 and 2,012 new cases, the first days of over 1500 new cases ever for TX, with the 3rd highest day being back on May 1st at 1,438. Given that the prevalence of the virus increased by over 50% in TX compared to two weeks ago (16k new on top of 29k then), if it reverts back to exponential growth now or soon, the numbers could get jaw dropping pretty damn fast. Opinions and behavior for those resistant to accepting what is needed will be painfully tested.
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He is talking about a silver bullet, after all. 100% kill rate is what it is. You can be skeptical. You are not misreading him. Monoclonal antibodies make it to lung epithelium where they could have both preventative and treatment functions, and they can go pretty much everywhere in the body where Covid can go, with limits on crossing the blood brain barrier (Covid is thought to also have direct effects on the brain).
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Yep. Factors that support your timeline: blunt measures absolutely work. They are known and well defined, readily employable, and there are multiple other nations we can point to who have already successfully inverted their national curves using multimodal approaches. Factors that work against your timeline: we can't point to another country's success where the pandemic got as out of hand as it has in the US. Until we get a true national Zeitgeist with appropriate coordinated messaging and responses, it's going to be rough. For now, it's still two steps forward, one step backward. Personally I think things will look a lot better in the US by this fall, even late summer by way of continued improvement in public acceptance of and voluntary adherence to blunt force measures combined with ongoing improvements in medical management and mitigation of illness severity. The US operates differently than other nations which cuts both ways, but the tools are available. The thing to always keep in mind is the epidemiological math in play - relatively quick and small changes in bending the curve have very dramatic effects on absolute numbers visible within 2 weeks of changes being made (works both ways). The heavy lifting for ongoing success remains psychological.
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Suggesting vaccines are rendered unnecessary wasn't my takeaway from what the CEO said: “The problem with that is not every patient will respond to a vaccine. Some will have 10% efficacy, some will have 20% efficacy, some will have 90% efficacy. But until you’ve gone into large trials and assessed everyone, you won’t know the full extent a vaccine works. An antibody gives instantaneous protection against the virus.” The observation made above probably contributes in part to why it can take up to 10 years to develop effective vaccines. Vaccines depend on a human response that can be quite variable across populations. Vaccines still have advantages, but development time to safe and effective implementation isn't one. Monoclonal antibodies are simply a direct hit on virus particles. It appears this mAB, STI-1499, has both active treatment (akin to convalescent plasma infusion) and preventative capacities.
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Keep an eye on these folks using therapeutic monoclonal antibodies spearheaded by a San Diego based group doing initial work in conjunction with UTMB and Mount Sinai: Sorrento IDs Antibody Against COVID-19 That Appears 100% Effective
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"They Came 'From Russia, With Love' " have some spontaneous combustion
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That's great for where you are. Deschutes and Crook Counties are the only two that meet criteria in the state for Phase 1 opening. Still, it's good to see a county with a populace the size of Bend is ready to advance with a plan. OR's larger cities will be able to coordinate to boost emerging elements of success and to ID and address failures.
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Re: "The more safe people are convinced it is, the higher the potential risk for therapeutic misadventures." Our situation is the complete reverse - HCQ became a political football and scaremongering was stickum. It's showing up that QT prolongation grabs attention when azithromycin is added, but not so much with HCQ monotherapy. So consider eliminating azithromycin. From what I'm seeing, AZ isn't mentioned so much when used in pre-symptomatic or early mild cases, more so HCQ w/wo Zinc. Potential scaremongering also relates to other documented adverse events associated with HCQ like hemolytic anemia in G6PD deficiency folks, and the onset of toxic retinopathy. Regarding incidence of retinopathy: So after 1,825 doses of HCQ, 7.5/100 will get retinopathy, 20/100 after 7,300 doses. Realize the early/mild Covid HCQ protocols generally call for dosing over 5 days. Regarding HCQ associated hemolytic anemia in those with G6PD deficiency: So after about 21,000 total doses of HCQ in vulnerable G6PD deficient people, no adverse hemolytic events assoc with HCQ were observed. They don't even recommended monitoring G6PD levels while receiving HCQ. Again, realize the Covid HCQ protocols call for exposure to 5 days of dosing by comparison. I understand what you were saying about caution in applying safety standards to medications not tested with Covid given its multi-system involvement. But appreciate the difference in the scale of duration of exposure here. 5 days of dosing, not daily for multiple years. Also, we'd be hearing alarms going off and HCQ would be getting jettisoned if these adverse events were happening from 5 day trials with any level of concern in any number of countries employing it. Instead, more nations are incorporating it into national pandemic crisis protocols.
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thanks, not interested. lol. I agree there should be an HCQ only treatment group. My main interest lies in answering questions about early HCQ reducing severity and duration of illness (and total infectivity). A reduction in incidence of virus transmission to others is harder to measure directly but could be inferred from any shortening of severity and duration of illness with HCQ. I would also make the primary endpoint assess a reduction in need for higher level of care (hospitalization) as opposed to mortality. With the key being early intervention, you could measure both, but conceivably early HCQ might significantly reduce the number cases requiring hospitalization without changing final mortality outcomes across groups. Reducing severity/duration of illness, and infectivity, while reducing the need for hospitalizations, obviously would directly serve the interests of individuals, those of an overburdened health care system, and potentially allow greater confidence in opening back up. Reducing and preventing infections is what saves us in many ways even if the CFR is unchanged. Use in this manner is consistent with other vital measures we're using related to distancing, masks, hygiene, good ventilation etc.
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I can't satisfy your standard. That's not stopping the consensus medical decision making for incorporation of HCQ into national pandemic crisis response in a lot of countries faring better than us. The absence of a peer reviewed journal publication does not suggest to me they are operating on a coin toss. hey ho. and enrolling mild cases important for the long term. but for now, we've bungled way into being earth's self-appointed national control group.
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Countries I'm aware of that are doing better than us, and are employing/employed early treatment with HCQ/CQ (and notably not AZ), are South Korea, Iceland, Malaysia, Costa Rica, UAE, Bahrain, and Italy. Add Saudi and Qatar as well. And as far as I can tell, the CFR for the Gulf nations employing early/proph HCQ is way below world average:
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I'm just looking at what the national consensus is for multiple countries that happen to be kicking our butts in managing the pandemic. Ditch the AZ if that makes anyone feel better.
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I could be wrong, but I think what happened in one study was that more patients died who had received HCQ/AZ than who had not received it. That does not mean that HCQ/AZ contributed directly to them dying. I am not aware of any study showing that HCQ/AZ becomes less safe as a result of active Covid infection. That's an important distinction.
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I don't think it will turn on a dime. Take the safety example you reference. HCQ was approved for use in the US in 1955, has been dosed tens of millions of times, and has a well established and accepted track record for safety. Despite this, there was a lot of scaremongering that happened starting in March. I'm aware of one open study for HCQ prophylaxis that had willing subjects dry up right as a lot of political distortion and misinformation got fanned. The damage in safety perception will be hard overcome despite it being safe for over half a century of use in the US. I think it's unfortunate, putting it mildly. HCQ use has been associated with decreased adverse cardiovascular and thrombotic events in RA/SLE patients, and has not been associated with negative cardiac events despite some QT prolongation in patients with active covid infection. Safety of HCQ is one example. It's the lack of a coherent national approach, lack of truthfulness and transparency from the top, and manipulation of decision making driven by political calculus that will continue to subvert public trust and effective deployment of a national approach regardless of what the science says.
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