Category: Medicine

Why should they call us “professors”?

I’ve long wondered about this, and explore that question in my latest Bloomberg column.  I’ve discouraged this for a long time:

…I have insisted that my graduate students call me “Tyler.” My goal has been to encourage them to think of themselves as peer researchers who might someday prove me wrong, rather than viewing me as an authority figure who is handing down truth.

And:

Some of the strongest norms are around the title “Doctor.” Just about everyone calls their physician “Doctor,” though the esteemed profession of lawyer does not receive similar treatment. As a Ph.D.-toting academic, I’ve even had people say to me — correctly — “You’re not a real doctor.”

I fear that by ceding this unique authority status to doctors we are making it easier for them to oversell us medical care, a major problem in the U.S. If your doctor suggests that you need a procedure done, it can be hard to say no, especially if you have been deferring to that person for years through the use of an honorific title. On the upside, perhaps all that deference has encouraged many people to get their vaccinations.

There are some arguments for titles:

Sometimes a title can be used to suggest a subordinate position, such as the use of Nurse. It can be an honorific, but it also places the person below the Doctor. The advantage, however, is one of greater anonymity and remove. A woman in particular might prefer “Nurse Washington” over the use of her real full name, given the potential risk of harassment.

Title issues and gender issues intersect in tricky ways. A title such as doctor or professor can give a woman newfound respect, but perhaps the practice hurts respect for women as a whole, since they are titled at lower rates than men.

What I expect we will see is that “established” women and minorities will insist on title usage all the more, to command respect, and under the guise of societal feminization we will evolve a new set of non-egalitarian hierarchies, presented and marketed to us under egalitarian pretenses.  On related ideas, see my earlier post on the first date book walk out meme.

Biden, COVID and Mental Health in America

Using US Census Household Pulse Survey data for the period April 2020 to June 2021 we track the evolution of the mental health of nearly 2.3 million Americans during the COVID pandemic. We find anxiety, depression and worry peaked in November 2020, coinciding with the Presidential election. The taking of prescription drugs for mental health conditions peaked two weeks later in December 2020. Mental health improved subsequently such that by April 2021 it was better than it had been a year previously. The probability of having been diagnosed with COVID did not rise significantly in the first half of 2021 but COVID infection rates were higher among the young than the old. COVID diagnoses were significantly lower in States that had voted for Biden in the Presidential Election. The probability of vaccination rose with age, was considerably higher in Biden states, and rose precipitously over the period among the young and old. Anxiety was higher among people in Biden states, whether they had been diagnosed or not, and whether they were vaccinated or not. The association between anxiety and depression and having had COVID was not significant in Biden or Trump states but being vaccinated was associated with lower anxiety and depression, with the effect being larger in Biden states. Whilst being in paid work was associated with lower anxiety, worry and depression and was associated with higher vaccination rates, it also increased the probability of having had COVID.

That is a new NBER working paper from the highly regarded David G. Blanchflower and Alex Bryson.  Model that!

Second Doses Are Better at 8 Weeks or Longer

In Britain people are now being warned *not* to get their second dose at 3 or 4 weeks because this offers less protection than waiting 8 weeks or longer.

Warnings over the lack of long-term protection offered by jab intervals shorter than eight weeks come as scores of under 40s continue to receive second doses early at walk-in clinics, contrary to Government guidance.

…“There is very good immunological and vaccine effectiveness evidence that the longer you leave that second dose the better for Pfizer and eight weeks seems to be a reasonable compromise.”

Professor Harnden emphasised that “you’re definitely less protected against asymptomatic disease if you have a shorter dose interval”.

I’m so old I can remember when first doses first wasn’t “following the science.”

Covid protection in Oaxaca

On the flight from Houston to Oaxaca, not everyone took off their masks to eat and drink, as they would on most internal U.S. flights, even if only for “faux mask removal-motivated drinking” [FMRMD].

You have to fill out some forms, through an app, on your smart phone in advance.  When you arrive they ask: “Did you fill out the forms?”  Say yes if you did.

They let you in, no test required, no other questions asked.  They do check your baggage tag against the bag you take away.

Nearly everyone in central Oaxaca city wears a mask all the time in public, including outside.  It is like San Francisco at its mask-wearing peak.

They spray the sides of the parks with something that smells like hand sanitizer.

If you wish to enter a store, you have to accept some hand sanitizer.  This is perhaps an efficient tax on browsing.  Toward the end of the day, however, they dispense with the tax.

Some establishments spray your clothes when you enter, maybe it is water?  Some spray you front and back.  Staff compliance does not seem to be grudging, rather the “Mexican petty bureaucracy” seems to be mobilized and out in force and with real enthusiasm.

There is a place along the local highway where they stop all cars, and have everyone get out to accept a dose of hand sanitizer.

I wonder how the equilibrium operates.  Of all the above measures, perhaps only the masks stand a chance of helping?  Does the rest of the security theater make it easier for them to largely stay open?

Here is some NYT coverage of U.S. tourists in Mexico.

Supported decision-making vs. guardianship

In the last decade, and especially after the 2013 Virginia court case of Ross and Ross v. Hatch, there has been a dramatic increase in knowledge, use, and legal recognition of supported decision-making (SDM) in the United States. SDM is a methodology in which people work with trusted friends, family members, and professionals who help them understand their situations and choices so they may make their own decisions and direct their lives. After the Hatch case, in which a young woman with Down syndrome defeated a petition for permanent guardianship by demonstrating that she uses SDM, this methodology has increasingly been considered and used as an alternative to guardianship to enable people to retain their legal rights and make life choices to the maximum extent possible. This article reviews the guardianship laws of the 50 U.S. states and the District of Columbia. Using criteria we developed, in light of the findings and values expressed in Hatch, we assessed the extent to which those laws recognize or encourage the use of SDM as an alternative to guardianship and as a means to enhance self-determination for people in guardianship. We then offer recommendations for future SDM research, policy, education, and advocacy efforts.

That is from a recent paper by Jonathan Martinis, et.al., via the excellent Kevin Lewis.  Guardianship is not the only alternative to “chaos,” now is the time to be truly Woke.

John Aubrey’s account of his own life

In part:

Born at Easton Piers, march twelfth, 1621, about sun-rising: very weak and like to die, and therefore christened that morning before prayer.  I think I have heard my mother say I had an ague [fever] shortly after I was born.

1629: about three or four years old, I had a grievous ague.  I can remember it.  I got not health till eleven, or twelve: but had sickness of vomiting for thirteen hours every fortnight for…years…This sickness nipped by strength in the bud.

1633: eight years old, I had an issue (natural) in the coronal suture of my head, which continued running till twenty-one.

1634: October: I had a violent fever that was like to have carried me off. ‘Twas the most dangerous sickness that ever I had.

About 1639 (or 1640) I had the measles, but that was nothing: I was hardly sick.

1639: Monday after Easter week my uncle’s nag ran away with me, and gave a very dangerous fall.

1643: April and May, the small-pox at Oxford; and shortly after, left that ingenious place; and for three years led a sad life in the country…

1646: April — admitted of the Middle Temple.  But my father’s sickness, and business, never permitted me to make any settlement to my study…

1655 (I think) June fourteenth, I had a fall at Epsom, and broke one of my ribs and was afraid it might cause an apostumation [abscess]…

1656: December: Veneris morbus [venereal disease]

1657: November, twenty-second, obiit domina [died Lady] Katherine Ryves, with whom I was to marry; to my great loss

Nor were those the end of his troubles…

That is all from John Aubrey’s Brief Lives, the autobiographical section, an excellent book more generally.  Progress Studies!

Towards a COVAX Exchange

Israel had vaccine that was about to expire before it could be administered. South Korea needed vaccine immediately to stop a surge. They arranged a deal.

South Korea said it will receive 700,000 doses of Pfizer-BioNTech’s coronavirus vaccine from Israel on loan this week, in an attempt to speed up immunisation following a surge in infections around the capital Seoul.

…Under the vaccine swap arrangement announced by both governments on Tuesday, South Korea will give Israel back the same number of shots, already on order from Pfizer, in September and October.
South Korea has quickly distributed the COVID-19 vaccines it has, but has struggled to obtain enough doses in a timely manner as global supplies are tight, particularly in Asia.

“This is a win-win deal,”  [Israeli Prime Minister Naftali Bennett] said in an earlier statement.

One of the weaknesses of the COVAX facility for distributing vaccines is that distribution is primarily based on population with all countries guaranteed that “no country will receive enough doses to vaccinate more than 20% of its population until all countries in the financing group have been offered this amount.” That’s equitable, but it has dynamic challenges: different countries may have different needs and capabilities at different points in time. A country may be given vaccines, for example, when it may not yet be ready to administer them — and that can potentially lead to waste. The Israel-South Korea deal, for example, only narrowly averted 700,000 Pfizer doses from being tossed.  Countries may also have different preferences for vaccines, as different vaccines may fit better with their healthcare systems. A fixed distribution schedule doesn’t adapt to the unique circumstances of time and place, as Hayek might have said.

It’s not surprising that COVAX chose a fixed distribution rule as many people wouldn’t trust a centralized authority to decide who gets what vaccines when. But what about guaranteeing each country a right to vaccine but allowing them to trade? Trade wouldn’t be vaccines for dollars which could introduce ethical and agency issues but vaccine at time 1 for vaccine at time 2 as in the Israel-South Korea exchange or across other factors such as vaccine type. My colleagues on the Kremer team, most notably Eric Budish, Scott Duke Kominers and Canice Prendergast, have been helping think through the design of just such a system. Prendergast designed the now-famous distribution system for Feeding America, Budish helped to design Wharton’s Course Match system and Kominers has worked on mechanisms for allocating convalescent plasma, vaccines and many other goods.

A suitably designed exchange can increase efficiency while maintaining equity. The Israel-South Korea deal reminds us that this is a priority. Greater efficiency in this context means fewer vaccine doses wasted, and more lives saved.

Alternative Dosing

Close-up medical syringe with a vaccine.

Alternative dosing is finally getting some attention. This story in Nature recounts some of the recent arguments and evidence:

Two jabs that each contained only one-quarter of the standard dose of the Moderna COVID vaccine gave rise to long-lasting protective antibodies and virus-fighting T cells, according to tests in nearly three dozen people1. The results hint at the possibility of administering fractional doses to stretch limited vaccine supplies and accelerate the global immunization effort.

Since 2016, such a dose-reduction strategy has successfully vaccinated millions of people in Africa and South America against yellow fever2. But no similar approach has been tried in response to COVID-19, despite vaccine shortages in much of the global south.

“There’s a huge status quo bias, and it’s killing people,” says Alex Tabarrok, an economist at George Mason University in Fairfax, Virginia. “Had we done this starting in January, we could have vaccinated tens, perhaps hundreds, of millions more people.”

…Sarah Cobey, an infectious-disease researcher at the University of Chicago in Illinois and a co-author of a 5 July Nature Medicine commentary supporting dose ‘fractionation’, disagrees about the need for time-consuming data collection.

“We shouldn’t wait that long,” she says. “People are dying, and we have historical precedent for making very well-reasoned guesses that we think are going to save lives.”

…According to a modelling study published by Tabarrok and other economists, such an approach would reduce infections and COVID-linked deaths more than current policies.

Addendum: The reason for doing the modeling study is precisely to take into account variants like Delta. Our modeling suggests that even with efficacy significantly lower than that suggested by Figure 1 in our paper, alternative doses of more effective vaccines would still provide significant reductions in mortality, even when new variants dominate. The benefits derive from vaccinating more quickly.

Tabarrok on RADVAC, the DIY Vaccine

The RadVac vaccine, as you may recall, is the open-source, do-it-yourself vaccine. Here’s Technology Review from one year ago (July of 2020):

Preston Estep was alone in a borrowed laboratory, somewhere in Boston. No big company, no board meetings, no billion-dollar payout from Operation Warp Speed, the US government’s covid-19 vaccine funding program. No animal data. No ethics approval.

What he did have: ingredients for a vaccine. And one willing volunteer.

Estep swirled together the mixture and spritzed it up his nose.

…Estep and at least 20 other researchers, technologists, or science enthusiasts, many connected to Harvard University and MIT, have volunteered as lab rats for a do-it-yourself inoculation against the coronavirus. They say it’s their only chance to become immune without waiting a year or more for a vaccine to be formally approved.

Among those who’ve taken the DIY vaccine is George Church, the celebrity geneticist at Harvard University, who took two doses a week apart earlier this month. The doses were dropped in his mailbox, and he mixed the ingredients himself.

Church say…he believes the vaccine designed by Estep, his former graduate student at Harvard and one of his protégés, is extremely safe. “I think we are at much bigger risk from covid considering how many ways you can get it, and how highly variable the consequences are,” he says.

I’m a big fan of the RadVac vaccine and was recently asked to give a talk about the vaccine and the pluses and minuses of the open source approach. In my talk I cover patents, when it was rational to take an unapproved vaccine, the FDA, paternal medicine versus the Consumer Reports model and more. I’m especially pleased with this talk.

Addendum: Great set of posts from johnswentworth from LessWrong on making the vaccine and then testing it.

Book Review: Andy Slavitt’s Preventable

Like Michael Lewis’s The Premonition which I reviewed earlier, Andy Slavitt’s Preventable is a story of heroes, only all the heroes are named Andy Slavitt. It begins, as all such stories do, with an urgent call from the White House…the President needs you now! When not reminding us (e.g. xv, 14, 105, 112, 133, 242, 249) of how he did “nearly the impossible” and saved Obamacare he tells us how grateful other people were for his wise counsel, e.g. “Jared Kushner’s name again flashed on my phone. I picked up, and he was polite and appreciative of my past help.” (p.113), “John Doer was right to challenge me to make my concerns known publicly. Hundreds of thousands of people were following my tweets…” (p. 55)

Slavitt deserves praise for his work during the pandemic so I shouldn’t be so churlish but Preventable is shallow and politicized and it rubbed me the wrong way. Instead of an “inside account” we get little more than a day-by-day account familiar to anyone who lived through the last year and half. Slavitt rarely departs from the standard narrative.

Trump, of course, comes in for plenty of criticism for his mishandling of the crisis. Perhaps the most telling episode was when an infected Trump demanded a publicity jaunt in a hermetically sealed car with Secret Service personnel. Trump didn’t care enough to protect those who protected him. No surprise he didn’t protect us.

The standard narrative, however, leads Slavitt to make blanket assertions—the kind that everyone of a certain type knows to be true–but in fact are false. He writes, for example:

In comparison to most of these other countries, the American public was impatient, untrusting, and unaccustomed to sacrificing individual rights for the public good. (p. 65)

Data from the Oxford Coronavirus Government Response Tracker (OxCGRT) show that the US “sacrifice” as measured by the stringency of the COVID policy response–school closures; workplace closures; restrictions on public gatherings; restrictions on internal movements; mask requirements; testing requirements and so forth–was well within the European and Canadian average.

The pandemic and the lockdowns split Americans from their friends and families. Birthdays, anniversaries, even funerals were relegated to Zoom. Jobs and businesses were lost in the millions. Children couldn’t see their friends or even play in the park. Churches and bars were shuttered. Music was silenced. Americans sacrificed plenty.

Some of Slavitt’s assertions are absurd.

The U.S. response to the pandemic differed from the response in other parts of the world largely in the degree to which the government was reluctant to interfere with our system of laissez-faire capitalism…

Laissez-faire capitalism??! Political hyperbole paired with lazy writing. It would be laughable except for the fact that such hyperbole biases our thinking. If you read Slavitt uncritically you’d assume–as Slavitt does–that when the pandemic hit, US workers were cast aside to fend for themselves. In fact, the US fiscal response to the pandemic was among the largest and most generous in the world. An unemployed minimum wage worker in the United States, for example, was paid a much larger share of their income during the pandemic than a similar worker in Canada, France, or Germany (and no, that wasn’t because the US replacement rate was low to begin with.)

This is not to deny that low-wage workers bore a larger brunt of the pandemic than high-wage workers, many of whom could work from home. Slavitt implies, however, that this was a “room-service pandemic” in which the high-wage workers demanded a reopening of the economy at the expense of low-wage workers. As far as the data indicate, however, the big divisions of opinion were political and tribal not by income per se. The Washington Post, for example, concluded:

There was no significant difference in the percentage of people who said social distancing measures were worth the cost between those who’d seen no economic impact and those who said the impacts were a major problem for their households. Both groups broadly support the measures.

Perhaps because Slavitt believes his own hyperbole about a laissez-faire economy he can’t quite bring himself to say that Operation Warp Speed, a big government program of early investment to accelerate vaccines, was a tremendous success. Instead he winds up complaining that “even with $1 billion worth of funding for research and development, Moderna ended up selling its vaccine at about twice the cost of an influenza vaccine.” (p. 190). Can you believe it? A life-saving, economy-boosting, pandemic ending, incredibly-cheap vaccine, cost twice as much as the flu vaccine! The horror.

Slavitt’s narrative lines up “scientific experts” against “deniers, fauxers, and herders” with the scientific experts united on the pro-lockdown side. Let’s consider. In Europe one country above all others followed the Slavitt ideal of an expert-led pandemic response. A country where the public health authority was free from interference from politicians. A country where the public had tremendous trust in the state. A country where the public were committed to collective solidarity and the public welfare. That country, of course, was Sweden. Yet in Sweden the highly regarded Public Health Agency, led by state epidemiologist Anders Tegnell, an expert in infectious diseases who had directed Sweden’s response to the swine flu epidemic, opposed lockdowns, travel restrictions, and the general use of masks.

Moreover, the Public Health Agency of Sweden and Tegnell weren’t a bizarre anomaly, anti-lockdown was probably the dominant expert position prior to COVID. In a 2006 review of pandemic policy, for example, four highly-regarded experts argued:

It is difficult to identify circumstances in the past half-century when large-scale quarantine has been effectively used in the control of any disease. The negative consequences of large-scale quarantine are so extreme (forced confinement of sick people with the well; complete restriction of movement of large populations; difficulty in getting critical supplies, medicines, and food to people inside the quarantine zone) that this mitigation measure should be eliminated from serious consideration.

Travel restrictions, such as closing airports and screening travelers at borders, have historically been ineffective.

….a policy calling for communitywide cancellation of public events seems inadvisable.

The authors included Thomas V. Inglesby, the Director of the Johns Hopkins Center for Health Security, one of the most highly respected centers for infectious diseases in the world, and D.A. Henderson, the legendary epidemiologist widely credited with eliminating smallpox from the planet.

Tegnell argued that “if other countries were led by experts rather than politicians, more nations would have policies like Sweden’s” and he may have been right. In the United States, for example, the Great Barrington declaration, which argued for a Swedish style approach and which Slavitt denounces in lurid and slanderous terms, was written by three highly-qualified, expert epidemiologists; Martin Kulldorff from Harvard, Sunetra Gupta from Oxford and Jay Bhattacharya from Stanford. One would be hard-pressed to find a more expert group.

The point is not that we should have followed the Great Barrington experts (for what it is worth, I opposed the Great Barrington declaration). Ecclesiastes tells us:

… that the race is not to the swift, nor the battle to the strong, neither yet bread to the wise, nor yet riches to men of understanding, nor yet favor to men of skill; but time and chance happeneth to them all.

In other words, the experts can be wrong. Indeed, the experts are often divided, so many of them must be wrong. The experts also often base their policy recommendations on factors beyond their expertise, including educational, class, and ideological biases, so the experts are to be trusted more on factual questions than on ethical answers. Nevertheless, the experts are more likely to be right than the non-experts. So how should one navigate these nuances in a democratic society? Slavitt doesn’t say.

Slavitt’s simple narrative–Trump bad, Biden good, Follow the Science, Be Kind–can’t help us as we try to improve future policy. Slavitt ignores most of the big questions. Why did the CDC fail in its primary mission? Indeed, why did the CDC often slow our response? Why did the NIH not quickly fund COVID research giving us better insight on the virus and its spread? Why were the states so moribund and listless? Why did the United States fail to adopt first doses first, even though that policy successfully saved lives by speeding up vaccinations in Great Britain and Canada?

To the extent that Slavitt does offer policy recommendations they aren’t about reforming the CDC, FDA or NIH. Instead he offers us a tired laundry list; a living wage, affordable housing, voting reform, lobbying reform, national broadband, and reduction of income inequality. Surprise! The pandemic justified everything you believed all along! But many countries with these reforms performed poorly during the pandemic and many without, such as authoritarian China, performed relatively well. All good things do not correlate.

Trump’s mishandling of the pandemic make it easy to blame him and call it a day. But the rot is deep. If we do not get to the core of our problems we will not be ready for the next emergency. If we are lucky, we might face the next emergency with better leadership but a great country does not rely on luck.

Use Fractional Dosing to Speed Vaccination and Save Lives

I’ve been shouting about fractional dosing since January, most recently with my post A Half Dose of Moderna is More Effective Than a Full Dose of AstraZeneca and the associated paper with Michael Kremer and co-authors. Yesterday we saw some big movement. Writing in Nature Medicine, WHO epidemiologists Benjamin Cowling and Wey Wen Lim and evolutionary biologist Sarah Cobey title a correspondence:

Fractionation of COVID-19 vaccine doses could extend limited supplies and reduce mortality.

Exactly so. They write:

Dose-finding studies indicate that fractional doses of mRNA vaccines could still elicit a robust immune response to COVID-192,3. In a non-randomized open-label phase 1/2 trial of the BNT162b2 vaccine, doses as low as one third (10 μg) of the full dose produced antibody and cellular immune responses comparable to those achieved with the full dose of 30 μg (ref. 4). Specifically, the geometric mean titer of neutralizing antibodies 21 days after the second vaccine dose was 166 for the group that received 10 μg, almost the same as the geometric mean titer of 161 for the group that received 30 μg, and 63 days after the second dose, these titers were 181 and 133, respectively4. For the mRNA-1273 vaccine, a dose of 25 μg conferred geometric mean PRNT80 titers (the inverse of the concentration of serum needed to reduce the number of plaques by 80% in a plaque reduction neutralization test) of 340 at 14 days after the second dose, compared with a value of 654 for the group that received the standard dose of 100 μg (ref. 5). According to the model proposed by Khoury et al.6, if vaccine efficacy at the full dose is 95%, a reduction in dose that led to as much as a halving in the post-vaccination geometric mean titer could still be in the range of 85–90%. Although other components of the immune response may also contribute to efficacy, these dose-finding data are at least indicative of the potential for further exploration of fractionation as a dose-sparing strategy. Durability of responses after fractional doses should also be explored.

…Concerns about the evolution of vaccine resistance have been posited as a potential drawback of dose-sparing strategies. However, vaccines that provide protection against clinical disease seem to also reduce transmission, which indicates that expanding partial vaccination coverage could reduce the incidence of infection. As described in a recent paper, lower prevalence should slow, not accelerate, the emergence and spread of new SARS-CoV-2 variants8.

…In conclusion, fractionated doses could provide a feasible solution that extends limited supplies of vaccines against COVID-19, which is a major challenge for low- and middle-income countries.

Also a new paper in preprint just showed that 1/4 doses of Moderna create a substantial and lasting immune response on par with that from natural infection.

Here we examined vaccine-specific CD4+ T cell, CD8+ T cell, binding antibody, and neutralizing antibody responses to the 25 ug Moderna mRNA-1273 vaccine over 7 months post-immunization, including multiple age groups, with a particular interest in assessing whether pre-existing crossreactive T cell memory impacts vaccine-generated immunity. Low dose (25 ug) mRNA-1273 elicited durable Spike binding antibodies comparable to that of convalescent COVID-19 cases. Vaccine-generated Spike memory CD4+ T cells 6 months post-boost were comparable in quantity and quality to COVID-19 cases, including the presence of TFH cells and IFNg-expressing cells.

Finally, an article in Reuters notes that Moderna are preparing to launch a 50 ug dose regimen as a booster and for children. Thus, contrary to some critics of our paper, the technology is ready.

Frankly, governments are way behind on this–they should have been pushing the vaccine manufacturers and funding trials on alternative dosing since at least January. Indeed, imagine how many lives we might have saved had we listened to Operation Warp Speed advisor Moncef Slaoui who advocated for half doses in January. On a world scale, we could have vaccinated tens even hundreds of millions more people by now had we ramped up fractional dosing.

At this point, it’s my view that there is enough knowledge to justify rolling out alternative dosing in any hot spot or in any country worried about outbreaks. Roll it out in a randomized fashion (as Kominers and I discussed in the context of the US vaccination rollout) to study it in real time but start the roll out now. Lives can be saved if we speed up vaccination, especially of the best vaccines we have, the mRNAs. Moderna and Pfizer have together pledged to deliver (mostly Pfizer and mostly through the US) some 250m vaccine doses to COVAX in 2021 for delivery to less developed countries. If we go to half-doses that becomes 500m doses–a life saver. And recall these points made earlier:

Judging by neutralizing antibodies, a 50 ug dose of, for example, Moderna looks to be more effective than standard dosing of many other vaccines including AZ and J&J and much better than others such as Sinovac. Thus alternative dosing is a way to *increase* the quality of vaccine for many people.

A 50 ug dose vaccine available today is much higher quality than a 100 ug dose vaccine available one year from now.

If we have the will, we can increase vaccine supply very rapidly.

Facts and uncertainties about ear wax

Our attitude to ear wax is in some ways surprising. A review of impacted ear wax estimates that 2.3 million people a year in the United Kingdom suffer problems with wax needing treatment, with some 4 million ears being syringed annually.2 This makes it possibly the the most common therapeutic procedure carried out on any part of the body. Symptoms of excessive wax or impaction, especially in the elderly, include not only hearing loss but tinnitus, dizziness, infections, social withdrawal, poor work function and mild paranoia. Other problems include general disorientation and loss of an aural sense of direction. With unilateral wax, sounds can appear to be coming from the wrong side, leading to accidents as a driver or especially as a pedestrian. Inappropriate self-treatment (or even treatment by health professionals) can cause perforated eardrums and in very rare cases cochlear damage, leading to nystagmus and sensorineural deafness. In spite of this catalogue of harms, the clinical profile and management of excessive wax are poorly understood. The evidence base is poor and inconsistent, leading to few strong recommendations, even relating to the most commonly used treatments.

Low esteem for ear wax is surprising in other ways too. As a substance, it is unique in the human and mammalian body. This is due to its position in our sole anatomical cul-de-sac. Everywhere else on our body surface, dead and redundant skin cells fall off or are scrubbed away when we wash. In the ear canal – which points forwards and downwards and might otherwise turn into a dermatological garbage dump – ear wax binds these together, along with other assorted detritus that may have entered from the world outside. It is then moved up to the exit by jaw movements and as a result of the skin of the canal slowly moving outwards like an escalator. Wax also prevents multiplication of micro-organisms and infection. It is as essential as sweat and tears, although perhaps not quite as vital as blood. Wax is also fascinating in its own right.

Imagine an ear wax post that is not solely about Q-tips! (Have you ever wondered why they have to be so dangerous?  Can’t you just put them in a little way?  Or is there some indivisibility here?  I have never understood the anguished warnings here.  If you are not using Q-tips at all, you only have to put them in a little way to pull out a lot of earwax, right?  Solve for the equilibrium!)

Here is more by John Launer, about ear wax throughout, via Michelle Dawson.

The Premonition

In The Premonition Michael Lewis brings his cast of heroes together like the assembling of the Avengers. In the role of Captain America is Charity Dean, the CA public health officer who is always under-estimated because she is slight and attractive, until she cracks open the ribcage of a cadaver that the men are afraid to touch. Then there is Carter Mecher, the redneck epidemiologist who has a gift for assembling numbers into coherent patterns. And Richard Hatchett the southern poet who finds himself at the head of The Coalition for Epidemic Preparedness (CEPI), the world’s most important organization during the pandemic; and Joe DiRisi the brilliant, mad scientist picked by the Chan Zuckerberg Initiative as the person most likely to cure disease…all of them. As you might expect from Michael Lewis, it’s all terribly well done, albeit formulaic and  sometimes over-the-top, e.g.

Charity’s purpose was clear….she was put on earth to fight battles, and wars, against disease. To save lives and perhaps even an entire country. p. 200-201

But Lewis has a bigger problem than over-the-top writing.

The heroes were defeated. Lewis likes to tell stories of brilliant mavericks like Billy Beane and Michael Burry who go against the grain but eventually, against all odds, emerge victorious. But six hundred thousand people are dead in the United States and whatever victory we have won was ugly and slow. Indeed, Lewis assembles his mighty team but then The Premonition trails off as the team is defeated by bureaucracy, indecision, complacency and malaise before they even have a chance to enter the real battle against the virus. It’s telling that none of Lewis’s heroes are even mentioned in Andy Slavitt’s Preventable (about which I will say more in a future post).

To be fair, Lewis’s heroes are fascinating, brilliant people who did some good. As part of the Kremer team I interacted a bit with Richard Hatchett and CEPI. Hatchett headed CEPI and understood the danger of SARS-COV-II before anyone else and with Bill Gates’s support started funding vaccine production and shoring up supply lines before anyone else was off the starting line. CEPI was magnificent and their story has yet to be told in full measure. Had Lewis’s heroes been in charge I have no doubt that many lives could have been saved but, for the most part, the heroes were sidelined. Why and how that happened is the real question but Lewis’s story-telling skills aren’t the right skills to answer that question.

If there is one central villain in The Premonition, it’s the CDC. Lewis acknowledges that his perspective has changed. In The Fifth Risk, the system (the “deep state” used non-pejoratively if you will) is full of wisdom and power but it’s under threat from Trump. In The Premonition, Trump is an after-thought, at best a trigger or aggravating factor. Long before Trump or the pandemic:

Charity had washed her hands of the CDC. “I banned their officers from my investigations,” she said. The CDC did many things. It published learned papers on health crisis, after the fact. It managed, very carefully, public perception of itself. But when the shooting started, it leapt into the nearest hole, while others took fire. “In the end I was like ‘Fuck you’, said Charity. “I was mad they were such pansies. I was mad that the man behind the curtain ended up being so disappointing.” p. 42

As the pandemic starts the CDC fails repeatedly. At the beginning of the pandemic on January 29 the government had started to repatriate Americans from Wuhan bringing some of them to a National Guard base just outside of Omaha. But shockingly the CDC doesn’t test them for the virus.

Never mind that every single one of the fifty-seven Americans in quarantine wanted to be tested: the CDC forbade it. And [James] Lawler [US Naval Commander and national security coordinator on pandemic response] never understood the real reason for the CDC’s objections…Whatever the reasons, fifty-seven Americans spent fourteen days quarantined in Omaha, then left without having any idea of whether they’d been infected, or might still infect others. “There is no way that fifty-seven people from Wuhan were not shedding virus,” said Lawler. p. 176

Many of the people brought home from China are not even quarantined just told to self-quarantine:

…When local health officers…set out to find these possibly infected Americans, and make sure that they were following orders to quarantine, they discovered that the CDC officials who had met them upon arrival had not bothered to take down their home addresses.

…[Charity] posed a rude question to the senior CDC official moved on the call: How can you keep saying that Americans are at low risk from the virus if you aren’t even testing for the virus. She’d been answered with silence, and then the official move on to the next topic. [p.206-207, italics in original]

And all of this is before we get to the CDC’s famously botched test an error which was amplified by the FDA’s forbidding private labs and state governments to develop their own tests. Charity Dean wanted California to ignore the CDC and FDA and, “blow open testing and allow every microbiology lab to develop its own test.” But Dean is ignored and so by as late as February 19, “Zimbabwe could test but California could not because of the CDC. Zimbabwe!” p. 223. The failure of testing in the early weeks was the original sin of the crisis, the key failure that took a containment strategy ala South Korea and Taiwan off the table.

Lewis’s most sustained analysis comes in a few pages near the end of The Premonition where he argues that the CDC became politicized after it lost credibility due to the 1976 Swine Flu episode. In 1976 a novel influenza strain looked like it might be a repeat of 1918. Encouraged by CDC head David Sencer, President Ford launched a mass vaccination campaign that vaccinated 45 million people. The swine flu, however, petered out and the campaign was widely considered a “debacle” and a “fiasco” that illustrated the danger of ceding control to unelected experts instead of the democratic process. The CDC lost authority and under Reagan the director became a political appointee rather than a career civil servant. Thus, rather than being unprecedented, Trump’s politicization of the CDC had deep roots.

Today the 1976 vaccination campaign looks like a competent response to a real risk that failed to materialize, rather than a failure. So what lessons should we take from this? Lewis doesn’t say but my colleague Garett Jones argues for more independent agencies in his excellent book 10% Less Democracy. The problem with the CDC was that after 1976 it was too responsive to political pressures, i.e. too democratic. What are the alternatives?

The Federal Reserve is governed by a seven-member board each of whom is appointed to a single 14- year term, making it rare for a President to be able to appoint a majority of the board. Moreover, since members cannot be reappointed there is less incentive to curry political favor. The Chairperson is appointed by the President to a four-year term and must also be approved by the Senate. These checks and balances make the Federal Reserve a relatively independent agency with the power to reject democratic pressures for inflationary stimulus. Although independent central banks can be a thorn in the side of politicians who want their aid in juicing the economy as elections approach, the evidence is that independent central banks reduce inflation without reducing economic growth. A multi-member governing board with long and overlapping appointments could also make the CDC more independent from democratic politics which is what you want when a once in 100 year pandemic hits and the organization needs to make unpopular decisions before most people see the danger.

Lewis hasn’t lost his ability to write exhilarating prose about heroic oddballs. Page by page, The Premonition is a good read but the heroes in Lewis’s story were overshadowed by politics, bureaucracy and complacency–systems that Lewis’s doesn’t analyze or perhaps quite understand–and as a result, his hero-centric story ends up unsatisfying as story and unedifying as analysis.

Long COVID in a prospective cohort of home-isolated patients

Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients—247 home-isolated and 65 hospitalized—comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16–30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.

That is from a new Nature paper by Bjørn Blomberg, et.al. Via SK.  On vaccinating the young, here are further relevant observations from Francois Balloux.