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It is Clear that Hydroxychloroquine and Chloroquine are Currently Used to Treat Covid 19 in the USA

Patient privacy prevents precise calculation of the fraction of Covid 19 patients in the USA being treated with Hydroxychloroquine or Chloroquine. However, Hospitals are purchasing hugely increased amounts

Christopher Rowland reports.

Data gathered in the first 17 days of March by Premier Inc., a large group purchasing organization for 4,000 U.S. hospitals, showed a 300 percent week-over-week increase in orders of chloroquine and a 70 percent week-over-week boost in orders of hydroxychloroquine.

I think that, because of the association with Trump, this is presented as a bad thing. Certainly there is a problem of short supplies. Hydroxychloroquine is used to treat Lupus Erythematosus and Rhumatoid Arthritis and those people have trouble making sure they get their medicine, because of the sudden new demand.

The article begins with the odd reference to the FDA as if the FDA regulated off label prescription of drugs. The only legal effect of an FDA finding that the drugs work when treating Covid 19 is that manufacturers would then be allowed to claim this in advertisements. This is extremely irrelevant. The drugs are off patent and produced by many firms — there are no huge profit margins there. Also the free publicity dwarfs any possible ad campaign. The FDA has no relevant authority here.

It seems that there is an idea among many people that doctors shouldn’t do anything unless it is proven to work in a clinical trial. I recall (but can’t find) and article in which Dr Arnold Relman (editor of the New England Journal of Medicine and pretty much head of the medical establishment) denounced this. Waiting for clinical trials is a decision. It is a decision which has caused deaths. There is no option to stop the clock while the trial progresses. Patients who could benefit from or be harmed by novel treatments exist.

The idea that the practice of medicine should be vaguely like the approval of pharmaceuticals is definitely new. I am 100% sure that the main driver is fear of malpractice suits. It is very necessary to have an official published standard of care — following this standard is the only protection against malpractice suits when outcomes are bad &, you know, we all end up dead in the end.

But doctors must practice also when there is no standard (that is no committee of respected doctors is willing to take the moral not legal responsibility of drafting one). Obviously there is no standard of care for Covid 19. Also obviously many doctors are sensible enough to look at the balance of evidence in the absense of proof and make decisions which they believe are best for the patient in the absence of certain knowledge and knowing that they might regret the decision with the benefit of hindsight.

I don’t understand why official talk about medical care is so different from the current actual practice. I think it is partly about practical action vs scientific research. In scientific research it is perfectly fine to have open questions. If there is a patient on the edge of death, it is necessary to decide now.

But I am more confident than I was that small c conservatism is not killing as many people in the USA as it might.

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Hydroxychloroquine, Anthony Fauci and Kevin Drum

This is a comment on “Is Anthony Fauci Really Our Truthteller-in-Chief?” by Kevin Drum. I will briefly summarize. Drum quotes from the latest press conference

“Is there any evidence to suggest that, as with malaria, it might be used as a prophylaxis against COVID-19?

DR. FAUCI: No. The answer is no.”

Later after Trump says hydroxychloroquine is the cure for Covid 19 Fauci changed his line to

Q I would like Dr. Fauci, if you don’t mind, to follow up on what the President is saying. Should Americans have hope in this drug right now? . . .

DR. FAUCI: No, there really isn’t that much of a difference in many respects with what we’re saying. The President feels optimistic about something — his feeling about it. What I’m saying is that it might — it might be effective. I’m not saying that it isn’t. It might be effective. But as a scientist, as we’re getting it out there, we need to do it in a way as — while we are making it available for people who might want the hope that it might work, you’re also collecting data that will ultimately show that it is truly effective and safe under the conditions of COVID-19. So there really isn’t difference. It’s just a question of how one feels about it.

Drum thinks more highly of Fauci’s first answer than of his second answer. He guesses

“It’s obvious what he really thinks, after all: hydroxychloroquine is nonsense, period. ”

The problem is that Fauci’s first answer was simply incorrect, wrong, a false assertion on a matter of fact. I am sure he was not lying, but there absolutely 100% no doubt about it and no grounds for debate, there is “evidence to suggest that, as with malaria, it might be used as a prophylaxis against COVID-19?@

I link to the top general science journal

Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro,” Jia Liu, Ruiyuan Cao, Mingyue Xu, Xi Wang, Huanyu Zhang, Hengrui Hu, Yufeng Li, Zhihong Hu, Wu Zhong & Manli Wang, Cell Discovery, 18 March 2020

That is not proof that it is effective in vivo. However, given the fact that side effects, interactions etc are very well understood, I think there is no excuse for not prescribing it absent the well known counter indications.

Asserting that it is clear that Fauci thinks Hydroxychloroquine for Covid 19 is nonsense, and that he should say so Drum and others risk convincing people not to use it and risk causing deaths.

Why do people assume that they understand the evidence ? I do because I have noted the pattern that when I disagree with doctors about patient care, they end up saying what I originally said (I promise you I am not the only person who perceives this pattern).

The rule that Trump is always wrong is as near to perfect as any rule of inference can be, but it is always best to double check. Say by googling [hydroxychloroquine inhibits Coronavirus ].

Also read angrybearblog

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What do we want ? Hydroxychloroquine (update without Azithromycin) and Remdesivir. When do we want it ? Now

I will never forgive Donald Trump for saying something exceedingly controversial with which I agree. I hate to say this but I agree with Trump and disagree with Fauci on hydroxychloroquine and Remdesivir.

Update: But don’t mix the Hydroxychloroquine with Azithromycin
“Azithromycin: (Major) Avoid coadministration of hydroxychloroquine and azithromycin.”

Thanks Ted Lieu

I will discuss hydroxychloroquine here because there is no legal issue. It can be prescribed for Covid 19 under current law and regulation. As noted here, the FDA has no say in the matter — they regulate food, drugs, and advertising and do not regulate the practice of medicine.

Consider the different treatment of Remdesivir, Hydoxychloroquine, and sever control measures. Because it is not proven that hydroxychloroqine works, it is considered a Trump average level outrage to say it should be tried. The side effects have been known for decades (and are acceptable given the circumstances). It inhibits SARS Cov2 replication in vitro https://www.nature.com/articles/s41421-020-0156-0 . There is anecdotal evidence that it has saved lives.

This does not amount to proof. Therefore, it is argued (by many people I respect) that it is irresponsible to type the following: all Covid 19 patients should be given hydroxychloroqine now. There is no morally acceptable alternative to doing this now. Now.

In contrast, there is extremely limited evidence on extreme control measures. There is no control group. The sample size is maybe one or two. And yet, it is perfectly responsible to advocate extreme control measures. Indeed it is perfectly responsible to impose them by decree (I am in Rome and have been ordered by prime minister Conte not to leave this apartment without a good reason).

Note the contrast here
The NYTimes.com presents a model graphically on page 1. It shows estiamtes. It is, in fact, theory, forecast not fact. The effectiveness of “severe control measures” is assumed. The data on which the estimate is based isn’t presented (on page 1)

Consider this published the same day (no longer on page 1)

“Trump’s Embrace of Unproven Drugs to Treat Coronavirus Defies Science”

Notice there is no headline about how Cuomo’s, Newsome’s and Conte’s embrace of unproven public health measures defies science (and I absolutely don’t assert that — I think they are making reasonable policy choices given necessarily incomplete knowledge)

It is absolutely clear that there is no general rule for acting without proof or solid knowledge. Sometimes, the rule is to not do something new until there is proof that it works. Usually, the rule is entirely different.

I do not think that anyone can justify the current dichotomy. I don’t think anyone tries. It is just assumed that the FDA rules are laws of nature and must be accepted.

I am trying to understand why this is. There are many possible good explanations which I will try to consider over after the jump

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Bailouts

Given the Coronavirus crisis, there will be bailouts. Should there be bailouts ? If so how should firms be bailed out ?

I think it is useful to look at the last round of bailouts from 2008-9 for lessons learned. First with the benefit of hindsight, does it seem that bailing out firms was a mistake ? On the one hand one can argue that it was necessary to prevent the Great Depression. It is hard to discuss whether it was worth the cost, because there was no cost. Instead, the US Federal Goverment obtained the highest profits recorded in human history by accident when focused on saving the financial system (and GM and Chrystler).

The many brilliant economists who argued that we should stick to laissez faire and that, in particular, socialism for bankers and ruthless capitalism for everyone else is no good, have not examined the outcomes. I think this is because the evidence is overwhelmingly damaging to their case.

OK so let’s bail out again. Looking back, can we decide on a better way to do it ? It is challenging. Preventing the second great depression while making hundreds of billions in profits is a good year’s work by any standard.

If things worked out rather well (and the bailouts did even if aggregate demand management was distorted by austerians) what can we learn ?

It seems to me that we learn that Treasuries should bear risk. Bearing risk is highly rewarded in expected value. Bearing risk is highly rewarded on long term average. This is what matters to Treasuries who are concerned about long term debt sustainability. Bearing risk is very very highly rewarded during crises, when it is buying at fire sale prices.

In general the riskier the positions taken by the US Federal Government in 2008/9 the more it helped the private sector and the more it profited.

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Remdesivir II

This is, in fact, another post on Coronavirus, but it will take me a while to get to the point. To put the conclusion here, I think that it is important to get the FDA out of the way (by executive order if necessary).

The Food and Drug Act, as currently interpreted, requires the assumption that people should (generally) not be treated with pharmaceuticals which haven’t been proven to be safe and effective. The rule is first do no harm, second do no harm. This only makes sense if results with current standard of care are acceptable. In this case, they aren’t. I think there should be mass production and use of Remdesivir starting on the 5th of March, based on one case where it seems to have cured a patient overnight.

To be honest, I think it should have been approved based on evidence that it is safe (from failed efforts to treat Ebola) and evidence that it inhibits the RNA dependent RNA polymerase of the MERS Coronavirus

Obviously one case is not proof. Still more obviously a pre-clinical study of a related organism isn’t strong evidence about the novel coronavirus.

So ?

It isn’t as if the current approach is working so well, that we should stick with it until there is proof that a new approach works better.

I think the trace of information is enough that, given almost no knowledge and a very diffuse posterior, one can conclude that the expected welfare of a patient treated with Remdesivir is higher than of one not treated with Remdesivir.

At this point, the standard ethical rule that decisions should be made in the patients’ intererests would mandate use of Remdesivir
(I personally do not accept that rule)

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Coronavirus Treatment Case Report

“First Case of 2019 Novel Coronavirus in the United States” Holshue et al 2020

I quote

Treatment with intravenous remdesivir (a novel nucleotide analogue prodrug in development10,11) was initiated on the evening of day 7, and no adverse events were observed in association with the infusion. Vancomycin was discontinued on the evening of day 7, and cefepime was discontinued on the following day, after serial negative procalcitonin levels and negative nasal PCR testing for methicillin-resistant Staphylococcus aureus.

On hospital day 8 (illness day 12), the patient’s clinical condition improved. Supplemental oxygen was discontinued, and his oxygen saturation values improved to 94 to 96% while he was breathing ambient air. The previous bilateral lower-lobe rales were no longer present. His appetite improved, and he was asymptomatic aside from intermittent dry cough and rhinorrhea. As of January 30, 2020, the patient remains hospitalized. He is afebrile, and all symptoms have resolved with the exception of his cough, which is decreasing in severity.

This suggests that Remdesivir is an effective treatment for Covid 19. I told you so. A guess in Angry Bear March 2 2020 a Case in the New England Journal of Medicine March 5 2020.

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Walter Bagehot Explains to the Fed What They Should Have Done on Thursday

The day before yesterday, the Fed made a somewhat unusual announcement of $500,000,000,000 of REPO offers a day for three days in a row. The idea was to let banks unload risky assets before they panicked nipping a financial crisis in the bud.

This move was controversial. Unfortunately many critics act as if the Fed was giving away $ 1,500,000,000,000 rather than buying assets with it. I hazard a guess that the Fed will profit from the operation (their efforts to save the financial system in 2009 generated the largest profits recorded in human history as an unintended side effect). However, it is also clear that the transaction amounts to a subsidy to banks. The Fed will pay a higher price than would have cleared the market. $ 1.5 Trillion will do that. Back in 2009 the Fed bought mortgage backed securities at the market rate when they were the only buyer in the market. This means that the open market operation was a massive subsidy (which also generated record profits).

The fact that the Fed pays much more than the market would without their intervention is pleasant for banks. Driving up the price of risky assets is part of the point of the operation. However it is also very irritating.

Fortunately someone figured out what they should have done. Walter Bagehot explained it clearly in 1873. The idea is that the central bank should lend freely accepting as collateral assets which would be accepted by private agents in normal times but not during the crisis. But Bagehot did not advise lending at the rate which prevailed before the crisis. Rather the maxim is lend freely at a penalty rate

 

First. That these loans should only be made at a very high rate of interest. This will operate as a heavy fine on unreasonable timidity, and will prevent the greatest number of applications by persons who did not require it. The rate should be raised early in the panic, so that the fine may be paid early; that no one may borrow out of idle precaution without paying well for it; that the Banking reserve may be protected as far as possible.

 

Another way of putting it is that the Fed should buy risky assets at a price markedly lower than the pre.crisis price and contract to sell them back to banks at normal prices after the crisis is expected to be over. This is the REPO is the same as a collateralized loan irritating finance terminology issue (also there is no O in repurchase so why the hell is it called a REPO).

Another way of putting it is that we don’t want solvent firms to go bankrupt and be liquidated. In plain English this means if one can save a firm with a loan, then one should. The idea is that the firm should still exist when the crisis is over. In other words, the shares of the firm will still have positive value and won’t be worthless pieces of paper.

Bagehot’s point is that we also want that positive value to be low. Firms (which must be depositary institutions according to the Federal Reserve Act) should still exist even if they have to borrow from the lender of last resort. But to make sure it is the lender of very last resort, they shouldn’t be worth much.

Any value of a firm which needed the lender of last resort is basically a gift to owners who messed up and a moral hazard.

To combine this with the need for equity capital, it is possible to TARP, that is make the penalty rate loan junior to other debt as preferred shares not bonds.

Another point is that sometimes obtaining annual profits of only $97,700,000,000 is not satisfactory performance.

The main point is that if the Fed can make $97,700,000,000 while also granting a massive subsidy, then the previous arrangement was not efficient. The problem is that entities with deep but not infinitely deep pockets can’t always bear risk. The solution is for the government to be the residual claimant. That’s called socialism and the market says it works.

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Life in Rome

I am in a city with a curfew (enforced ?) where only pharmacies, supermarkets and those stores where someone from China sells all sorts of household stuff are open. Rome hasn’t reached the dread levels of Wuhan and Milan, but the Italian government is trying to get ahead of the curve.

It is strange and alarming that there is little traffic (it is also impressive that Romans don’t obey the traffic code even when there is little traffic). People are really trying to stay home all the time (I was semi home bound before it was cool).

I have learned about the activities which people consider absolutely necessary. A large fraction of people walking around are walking dogs. Many people are wearing masks (absolutely sold out everywhere) and gloves. I discover there are some things I have to touch. These include an ATM (alarmingly often) and cash.

One striking thing is that people wait outside of the supermarkets and pharmacies. This is a rule that does not have to be enforced — people are scared. Good thing it’s not cold in Rome during March (or February or actually ever at all in the globally warmed year of our lord 2019/2020). This makes me notice the high rates of infection in Iceland and Norway. I guess up there (where I have been in July with a rain coat) the choice is risk of Covid 19 or of frostbite.

The extreme measures (not just ordered but orders which are actually obeyed, by Romans) are impressive because as of the day before yesterday there were only 200 cases in Lazio (region which includes Rome). The fact that one of the cases was governor Zingaretti (also head of the Italian Democratic Party) might have made a difference.

The news spreads even faster than the virus. Down here the health care system is under strain but not overwhelmed (yet) but people read about (and see on TV) reports on how in Lombardy Triage has reaquired it’s original meaning. During World War I, It was red = critical, yellow = serious monitor but not critical, black = doomed. In normal times black now means deceased.

In Lois Armstrong Airport New Orleans during Katrina there were living people with black tags (for will not survive a flight and so will die here). I was appalled. Now in parts of Northern Italy there aren’t enough respirators for patients who would die without one. This is part of why the Italian case fatality rate is high. It is also important that Italians have had low fertility for decades and are old on average.

I guess I haven’t written anything that people don’t know already. I will update when the wave of contagion overwhelms us. I fear that I will be giving readers a hint of future action in their home town.

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Novel Coronavirus and Better Unsafe than Sorry

It is possible that a known pharmaceutical called remdesivir inhibits the reproduction of the Covid-19 coronavirus. It inhibits (some) RNA dependendent RNA Polymerases — the type of enzyme the virus uses to replicated its genome and express its genes. It is known that it is a potent inhibitor of the RNA dependendent RNA Polymerases used by the MERS coronavirus

update: here is a good site for Covid-19 data.

So what will be done with remdesivir ? What should be done ? Is what will be done anything like what should be done ?

I think I can guess what will be done. Different groups will work on different projects. Some labs will attempt to produce and purify the Covid-19 RNA dependent RNA polymerase to check if remdesivir inhibits it too. The patent holder, Giliad Science will start a two Phase III trials of remdesivir. Results will be reported and then the FDA will decide whether to approve it for use.

This is good as far as it goes, but I don’t think it goes close to far enough.

I think that aside from the trials, Remdesivir should be given to patients and contacts of patients. It is known to be safe (from the trial which shows that it doesn’t cure Ebola). Also a whole lot of it should be produced starting a month ago.

The first proposal implies changing the law — making an exception to the Food and Drug Act. It also requires some organization without shareholders to bear the liability for side effects (The bill should make the US Federal Government liable). It goes completely against the standard logic that it is against patients’ interests to treat them with unproven drugs. There are two reasons to abandon that logic. First it is unconvincing in general. Second the risk of reacting too slowly to a budding pandemic is huge.

The mass production of Remdesivir is a simpler decision. The risk is a high chance of wasting tens or hundreds of millions of dollars. The risk of business as usual is a small chance of tens of millions of deaths, because drug shortages prevent effective control of the epidemic.

The logic of regulation and policy is first do no harm and better safe than sorry. Safety is not currently possible. A small c conservative approach is also small c crazy.

update:

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The Economic Anxiety Hypothesis has Become Absurd(er)

I am old enough to remember when many very serious people ascribed the rise of Donald Trump to economic anxiety. The hypthesis never fit the facts (his supporters had higher incomes on average than Clinton’s) but it has become absurd. The level of self reported economic anxiety is extraordinarily low

Gallup reports “Record High optimism about Personal Finances in U.S.” with 74% predicting they will be better off next year.

Yet now the Democratic party has an insurgent candidate candidate in the lead. I hasten to stress that I am not saying Sanders supporters have much in common with Trump supporters (young vs old, strong hispanic support vs they hate Trump etc etc etc). But both appeal to anger and advocate a radical break with business as usual. Both reject party establishments. Also Warren if a little bit less so.

Trump’s 2016 angry supporters still support him *and* they are still angry. He remains unpopular in spite of an economy performing very well (and perceived to be performing very well).

Whatever is going on in 2020, it sure isn’t economic anxiety.

Yet there is clearly anger and desire for radical change.

I don’t pretend to understand it, but I think it probably has a lot to do with relative economic performance and increased inequality. I can’t understand why the reaction of so many Americans to this would be to hate immigrants and vote for Trump, but, then I don’t watch Fox News.

One other thing which it isn’t is rejection of the guy who came before Trump. Obama has a Real Clear Politics average favorable rating of 59% and unfavorable of 36.1 % vastly vastly better than any currently active politician. (Sanders is doing relatively very well at net -2.7 compared to Obama’s + 22.9) He is not rejected. He is not considered a failure. Yet only a small majority is interested in any sort of going back to the way things were.

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