triplehorn

That Ho article is good, and accessible. He also offered a word of caution about rushing vaccines: "And, of course, people are working on vaccines. A lot of companies are working on vaccines and those vaccines are at various stages. A couple are within weeks of entering human testing and that's quite, quite remarkable. There is one thing about vaccines, though: Some of the experiments previously done on SARS suggested that when animals developed antibodies and then were given the virus, they had greater lung injury due to the presence of the antibodies. The scientific community would have to resolve that issue quickly and its resolution would either halt the current approaches or unleash them to move full speed ahead. [cont.]" ^^^ it's a contributing reason, but he lays out multiple variables that contribute an unlikely solution in the next several months. At home antibody tests could radically shift our understanding of the pandemic, where we stand as a population, and have that inform our path. We have to have that data asap. I'm still holding out hope with effective med cocktails, but increasingly think it will hinge on application happening as early in the infection as possible. Of course that depends on mass access to testing and rapid turnaround. Ho did have some positive observations about how fast mobilization is happening, but we're about to take some heavy near term lumps.

the fecal shed.

He's no Winston Churchill. Ignoring emergency production needs while withholding and personally auctioning off the National Strategic Reserve of ventilators could be a quite a haul. Am I doing this right ?

The bigger the hammer, the faster we move on.

Intersting. realize that Viagra etc. work by increasing nitric oxide production which results in vasodilation. Inhaling this keeps it pretty local. These bolded parts stand out: At first glance, one thing I'd want to understand better is if there's a point in clinical progression of illness where Nitric Oxide gas causing pulmonary vasodilation becomes counterproductive. From what I've read, it sounds like the advanced pneumonia phase causes "leaky" alveoli with a breakdown of the blood/air barrier in alveoli with resultant blood entering the lung airspace and pink frothy sputum or frank blood getting produced or spit up. In this case vasodilation might start to be counterproductive if you're opening the spigot into leaky lungs with vasodilation, which could actually worsen oxygen/blood exchange. Think of it like a decongestant - it causes vasoconstriction of blood vessels in the sinuses so there's less fluid pressure to transfer across membranes to form to mucus to clog your sinuses. So I'm guessing this procedure probably definitely would call for some clear clinical guidelines with some contraindications. Maybe these cases get inhaled NO while also hooked up to ECMO.

Between patients, the study incorporated patients and initiated treatment at different points in course of illness and with varying degrees complications. When you try to separate those subgroups out of an already small study, you lose statistical meaning. Doesn't mean you can't make observations when they hit you in the face and try things when time is not on your side (with appropriate patient consent and competent medical risk assessment). Intuitively, early intervention offers better outcomes. That's the case with so many conditions that involve a cascade of complications that quickly get beyond reach.

The med supply part should be getting relief as of last week. The lag right now is best recommendations for use. The French study showed that viral loads largely went undetectable in 6 days post med cocktail initiation. Covid patients who go unmedicated have shed virus for up to 20 days. Also, once the pneumonia sets in and you're on a vent, there's a scale of damage that's been done that is likely a lot less responsive to HCHQ/Azith. As the specter of rationing care looms, to the extent med supplies are inadequate (don't think that's the bottleneck), who gets the meds ? Steering supplies to uncomplicated cases likely helps improve total outcomes while also reducing spread. Ultimately, it may be that treating those with early testing/diagnosis will result in fewer hospitalizations/ICU beds/vents, so this needs to be urgently addressed. We're getting hit with the surge over the next 2-3 weeks and unfortunately there are too many complex factors with too little time to stop that today.

I agree with that. I suspect early detection and rapid med initiation (HCHQ/Azith) before complications arise will end up being very helpful (certainly hope so). The front line health care prophylaxis part is TBD, but I do not fault a single one for attempting it if constant exposure without adequate PPE is their reality.

Need to designate *plinkers* as essential workforce infrastructure. better than warring monkey hordes, I guess.

Keeping liquor stores open keeps a fair number of people out of the ERs due to acute withdrawal. It's a thing ERs do not need right now.

Right, hospitalization is a function of clinical condition that dictates the need for a higher level of care, irrespective of positive tests or diagnosis. Global numbers: 67 days from the first reported case to reach 100,000 cases 11 days for the second 100,000 cases, 4 days for the third 100,000 cases.

curves flattening the curve ---> vid inside

US two days ago was on a rate of deaths doubling every 3 days. It takes about 20 days for physical distancing measures to be reflected in an increased doubling time for deaths. So if 21 days equals 7 doubles, with he numbers below, the US will be at ~5,300 deaths per day beginning 18 days from 3/21 and ~11,000 deaths per day after 21 days. I do think those numbers will be less by 18-21 days because of the effects of physical distancing that started at the end of the first week of March in hot spots like Washington and other locales. But for the curve to really flatten, has to be national hammer drop. What percent of US population is adhering to strict social distancing today? Can't delay any longer anywhere. key graphic:

190 proof with intent dilute ? Anything less than 120 proof won't work.

TBD factors that could help a lot: 1) dial in med protocols to maximally reduce morbidity/mortality, need for hospitalization/length of stay. 2) get self administered IgG/IgM antibody tests available asap along with better understanding of immunity profiles to get 'safe' people back into daily routines to further national recovery. The immunity profile info should be aided by collaborating with China/SoKo who have had an important head start understanding their populations.

Look at this map so far today. It's like a nighttime satellite photo. And the entire E/SE part of the country ? That is ominous as hell.

lol. iswyd. Another general point of emphasis: in order to get statistically significant results with a relatively small 'n' number of subjects in the study, you have to have a pretty robust treatment effect. Contrast that with pharma where they take a med relegated to the dustbin and examine data from 10k subjects to find that the data shows statistical significance for the medication increasing total sleep time by 15 minutes! Then spend $300M marketing dustbin med as a new sleep med, because statistical significance detecting a very small useful treatment side effect by runing a huge amount of data.

fwiw, from the French hchq/azith study I think a case could be made for prophylactic use of the combo in critical human infrastructure, esp. healthcare. The study reports: "Mean hydroxychloroquine serum concentration was 0.46 µg/ml+0.2 (N=20)." That value is at least a starting reference point for therapeutic dosing. HCQ has a long half-life (malaria prophylaxis is once per week dosing). The question is what might be an effective dose interval for prophylaxis if less than daily for sustained prevention. Macrolide abx like Azithromycin have previously been considered for prophylactic use to prevent COPD exacerbation. Half-life of azithromycin is 68hrs which possibly makes it a candidate for less than daily dosing for covid prophylaxis. One bit I did see suggested that the anti-viral effects of Azithromycin possibly relate to stimulation of interferon production during an active immune response. So taking Azith without active infection may be less useful.

- From the French HCHQ/Azithromycin paper: "We enrolled 36 out of 42 patients meeting the inclusion criteria in this study that had at least six days of follow-up at the time of the present analysis." This suggests patients already had a positive PCR dx at least 6 days prior to inclusion in the study. It's important to consider that immediate treatment with detection could further improve outocmes. - Re potential drug interactions with negative effects on cardiac conduction: "Speculated potential risk of severe QT prolongation induced by the association of the two drugs has not been established yet but should be considered." so that's reassuring. Also regarding risk for HCHQ retinopathy, it's low: "The incidence of HCQ retinopathy is very low. In fact, HCQ is estimated at having a 0.5% incidence of retinal toxicity after 5 years of therapy." G6PD deficiency is probably the biggest risk factor which can result in hemolytic anemia crisis. - Re: "The cause of failure for hydroxychloroquine treatment should be investigated by testing the isolated SARS-CoV-2 strains of the non-respondents and analyzing their genome, and by analyzing the host factors that may be associated with the metabolism of hydroxychloroquine. The existence of hydroxychloroquine failure in two patients (mother and son) is more suggestive of the last mechanism of resistance." The above also makes me wonder how sensitive drug levels are to efficacy. Sometimes people are genetically predisposed "fast metabolizers" and can clear drugs a lot faster than average, hence potentially could be dosed at sub-therapeutic levels. Overall, the results are very encouraging, I think with a more than acceptable safety risk after consent using some basic screening questions including personal/family medical history, current medications taken, and allergies to meds, we should be going forward with this. The downside to inaction is a lot greater. So one path would be to aggressively ramp up testing of everyone in "hot spot" regions and rapid application of HCHQ/Azith with consent for positive tests whether you're symptomatic or not. That last point is supported by the observation in the French study that HCHQ/Azith patients go to undetectable viral levels in 6 days versus reports from China that untreated cases can shed for up tp 20 days. So even if you're asymptomatic or mild, taking the combo lowers risk of transmission, especially if you're a part of critical work infrastructure.

You probably have figured it out, but you've also got your own supplies to rig yourselves N95 masks: