Category: Medicine

What has been driving America’s opioid problem?

Matt Yglesias had an excellent (gated) Substack on this question lately, now Jeremy Greenwood, Nezih Guner and Karen A. Kopecky have a new and quite valuable paper.  I found this to be the most interesting segment:

Through the eyes of the model, there were two key forces.  The first force is the decline in prices for bot prescription and black market opioids.  This had a big effect.  The second force is the increase in the dosages per prescription meted out by doctors.  This also had a significant impact.  The fact that doctors kept pain sufferers on prescription opioids for a longer period of time had little effect.  Last, an analysis is conducted on medical interventions that reduce either the probability of becoming addicted or the odds of an addict dying from an overdose.  Reducing the odds of addiction can result in even more deaths due to the rise in users.

The opioid problem is a very difficult one to solve!  I should stress that the paper has other results of interest.

Metaculus should restart its Lab Leak prediction aggregator

Here is the site.  The forecast never went above twenty percent, and then fell consistently, with the aggregator being discontinued in May and resolved as ambiguous.  I think the chance is below fifty percent, but still I would like to see this reopened, as the question does not seem to be going away.  Metaculus, how about it?

The Covid pandemic, circa February 2022

It is widely believed that speaking helps to spread Covid, including in public places.  Yet if you try to book a ticket on the Acela (a term also used sarcastically to describe a particular brand of Eastern elites), you can get tickets only in the Quiet Car.  The rest of the train is already sold out, because people prefer to be able to talk.

You may not think that is how things should be, but that is how they are.  And no, the Acela does not run from Alabama to West Virginia.

Covid markets in everything, foreign intelligence edition

A government-approved Covid testing firm is being investigated by the UK’s data privacy watchdog after it emerged that it plans to sell customers’ DNA to third parties.

Cignpost Diagnostics, which trades as ExpressTest and offers £35 tests for holidaymakers, said it holds the right to analyse samples from seals to “learn more about human health” – and sell information on to third parties.

Individuals are required to give informed consent for their sensitive medical data to be used – but customers’ consent for their DNA to be sold now as buried in Cignpost’s online documents.

When buying tests, customers were asked to tick a box agreeing to a 4,876 privacy policy which links to a separate document outlining the research programme, The Sunday Times reported…

Cignpost was founded last year and is believed to have sold as many as three million tests. It supplies pre-departure and arrival tests for travellers, with walk-in centres at sites including Gatwick and Heathrow.

Here is the full story, via Michael J.

An underdiscussed biomedical problem?

Including for longevity research, and perhaps most of all for longevity devices:

Neural implants—devices that interact with the human nervous system, either on its periphery or in the brain—are part of a rapidly growing category of medicine that’s sometimes called electroceuticals. Some technologies are well established, like deep-brain stimulators that reduce tremors in people with Parkinson’s disease. But recent advances in neuroscience and digital technology have sparked a gold rush in brain tech, with the outsized investments epitomized by Elon Musk’s buzzy brain-implant company, Neuralink. Some companies talk of reversing depression, treating Alzheimer’s disease, restoring mobility, or even dangle the promise of superhuman cognition.

Not all these companies will succeed, and Los Angeles–based Second Sight provides a cautionary tale for bold entrepreneurs interested in brain tech. What happens when cutting-edge implants fail, or simply fade away like yesterday’s flip phones and Betamax? Even worse, what if the companies behind them go bust?

Here is the full story, via Anecdotal.  Was Colonel Steve Austin built out of parts from start-ups?  How many of those companies still would be around?

Fractional Dosing Trials

My paper Testing fractional doses of COVID-19 Vaccines, co-authored with Kremer et al., has now been published at PNAS. I covered the paper in A Half Dose of Moderna is More Effective than A Full Dose of Astra Zeneca and other posts so I won’t belabor the basic ideas. One new point is that thanks to the indefatigable Michael Kremer and the brilliant Witold Wiecek, clinical trials on fractional dosing on a large scale have begun in Nigeria. Here are a few key points:

WHO SAGE Outreach: The authors have met and presented their work to the World Health Organization (WHO) Strategic Advisory Group of Experts on Immunization (SAGE), with follow-up meetings to present evidence coming from new studies.

DIL Workshop and Updates: In the fall of 2021, the Development Innovation Lab (DIL) at UChicago, led by Professor Kremer, hosted a workshop on fractional dosing, collecting updates from clinical researchers from multiple countries conducting fractional dosing trials for COVID-19 vaccines. The workshop also covered issues relating to trial design and included participants from Belgium, Brazil, Ghana, the Netherlands, Nigeria, Thailand, South Africa, UK and the US. 

CEPI Outreach: Professor Kremer has also presented this research to The Coalition for Epidemic Preparedness Innovations (CEPI), which is now pursuing a platform trial of fractional dosing.

Country Trials – Nigeria: With the support of DIL and the research team and generous support and advice from WAM Foundation, the charitable arm of Weiss Asset Management and Open Philanthropy, a trial is being conducted in Nigeria by the Nigerian Institute of Medical Research, National Institute of Pharmaceutical Research and Development, National Agency for Food and Drug Administration and Control, and the National Primary Health Care Development Agency, in coordination with the Federal Ministry of Health.

A comprehensive list of all the trials on fractional dosing conducted to date is at the link. Fractional dosing may come too late for COVID-19 vaccines but perhaps next time a shortage of a vaccine looms we will be more quick to consider policies to stretch supplies.

TheZvi on Long Covid

Here is a long and characteristically thoughtful post, from his Substack.  Here is the opening part of his summary (no double indentation):

“My core model of Long Covid after writing this post:

  1. Long Covid is real, but less common than many worry it is.
  2. Reports of Long Covid are often people who have symptoms, then blame them on Long Covid whether or not they even had Covid. The exception is loss of taste and smell.
  3. Long Covid severity and risk is proportional to Covid severity and risk.
  4. If you didn’t notice you had Covid, you’re at very very low risk for developing Long Covid.
  5. Vaccination is thus highly but incompletely protective against Long Covid.
  6. Children are thus at minimal risk.
  7. Omicron is thus less likely to cause serious Long Covid than Delta.”

Recommended.  Whether or not you agree with every point, I would say that Zvi has enough context to effectively reason across multiple domains — you can’t say the same for everyone!

The emergency is over. It’s time to pivot to preparedness

Jonathan Rauch has an excellent column in Persuasion, The emergency is over. It’s time to pivot to preparedness. One bit from yours truly:

A useful suggestion comes from Alex Tabarrok, an economist at George Mason University who has been saying smart things about the pandemic since it began. “When vaccines were coming, it made a lot of sense to put off a lot of other good things in life—to do what economists call intertemporal substitution,” he said in a recent interview. “Once vaccines are available and widespread, you can’t intertemporally substitute anymore because there’s no more cavalry coming. This is it. Before vaccines, costly actions can delay your getting COVID until after you’re vaccinated, which is highly valuable. But the corollary is that once you move to the permanent scenario and are vaccinated, costly actions that mostly delay when you get COVID have much less value.”

…That being the case, Tabarrok proposes a rule of thumb: “Whatever we do, we should be thinking about, ‘Do we make this permanent or not?’” If measures are not candidates for permanence, “We might as well stop them now or soon.”

Read the whole thing.

The Great Wall

APNews: For the thousands of athletes, journalists and others descending on Beijing for the Winter Olympics, China’s strict pandemic measures are creating a surreal and at times anxious experience.

China is isolating everyone coming from abroad from any contact with the general public for the duration of the Games, which open next week. That means being taken from the Beijing airport in special vehicles to a hotel surrounded by temporary barricades that keep participants in and the public out.

“I know the only experience of Beijing I’m going to experience is the Beijing I will see out of my bus window and my hotel window,” said Associated Press photo editor Yirmiyan Arthur, who arrived this week. “I’m not really going to experience China, I’m just going to experience the Olympics within the bubble.”

At the same time China has yet to approve the Pfizer-BioNTech vaccine despite having a Chinese firm, Shanghai Fosun Pharmaceutical, distributing it in Hong Kong, Macau and Taiwan. Sad.

How many lives were lost because of the vaccines holdup?

…economist Garett Jones recently opined that Trump’s scuttled hopes to release a COVID-19 vaccine a few weeks earlier “likely would have saved at least 100,000 American lives.”

…Pfizer did not reveal its trial’s favorable results until November 9—six days after the election. The company had originally planned to consider submitting an EUA request to the FDA with just 32 data points; instead it gathered 94, and it waited another 11 days to accrue the requested safety data, plus even more data showing how well the vaccine worked, before making its filing.

…If a compassionate use program for COVID-19 vaccines had gone forward, doctors would have been able to prescribe them to nursing-home residents, even as the vaccine makers completed their clinical trials with integrity and gathered all the safety data requested under the “EUA Plus” requirements.

According to Marks, Birx asked Anthony Fauci and FDA Commissioner Stephen Hahn to encourage Pfizer and Moderna to apply for that program…

The actual timing of the COVID-19 vaccines’ release resulted from a complicated mix of bureaucratic caution, political calculations, and the choices made by vaccine manufacturers. While the benefits of the vaccines have become very clear since then, the precise human cost of that short delay remains a mystery.

Here is the full Brendan Borrell piece in The Atlantic, excellent throughout.  And don’t forget Brendan’s new and exciting book The First Shots: The Epic Rivalries and Heroic Science Behind the Race to the Coronavirus Vaccine.

Via Rich Dewey.

Raise your hand if you think this is a good idea

…if the Food and Drug Administration decides to update Covid-19 vaccines to take better aim at Omicron or other variants, it is unlikely to go it alone.

Instead, a senior FDA official told STAT, the agency expects to take part in an internationally coordinated program aimed at deciding if, when, and how to update Covid-19 vaccines. The approach would ensure decisions are not left solely to individual vaccine manufacturers.

“We can’t have our manufacturers going willy-nilly [saying], ‘Oh well, the EMA decided they wanted this composition, but FDA wanted that composition,’” the official said, referring to the European Medicines Agency. “So we are very much of the mind that we would like to be part of a more global process in helping to come to what vaccine composition there should be now.”

Designed for flexbility and speedy response?  I guess we’ll see.  Here is the full StatNews article.  And obviously, the entire public health community is up in arms about this…

Model this and who are the real liberals anyway?

– Fifty-nine percent (59%) of Democratic voters would favor a government policy requiring that citizens remain confined to their homes at all times, except for emergencies, if they refuse to get a COVID-19 vaccine. Such a proposal is opposed by 61% of all likely voters, including 79% of Republicans and 71% of unaffiliated voters.

– Nearly half (48%) of Democratic voters think federal and state governments should be able to fine or imprison individuals who publicly question the efficacy of the existing COVID-19 vaccines on social media, television, radio, or in online or digital publications. Only 27% of all voters – including just 14% of Republicans and 18% of unaffiliated voters – favor criminal punishment of vaccine critics.

– Forty-five percent (45%) of Democrats would favor governments requiring citizens to temporarily live in designated facilities or locations if they refuse to get a COVID-19 vaccine. Such a policy would be opposed by a strong majority (71%) of all voters, with 78% of Republicans and 64% of unaffiliated voters saying they would Strongly Oppose putting the unvaccinated in “designated facilities.”

That is from a Rasmussen poll.  You might consider Rasmussen a right-leaning institution, but these kinds of results should not be possible even in somewhat slanted polls (methodology here).  Furthermore, this poll came out January 13, and it hasn’t exactly received a ton of attention from mainstream media, can you model that too?  Wouldn’t it be awful even if this poll were off by 2x?

One lesson is that it is not always good for your party if it is on the winning side of the culture wars.

Where are the Variant Specific Boosters?

I wasn’t shocked at the failures of the CDC and the FDA. I am shocked that our government still can’t get its act together in the third year of the pandemic. Consider how lucky, yes lucky, we have been. Here’s Eric Topol:

…the original vaccines were targeted to the Wuhan ancestral strain’s spike protein from 2019. The spike protein, no less the rest of the original SARS-CoV-2 structure, is almost unrecognizable now in the form of the Omicron strain (see antigenic drift from prior post). While there’s naturally been much focus on the extraordinary number of mutations in the receptor binding domain and the rest of the spike protein, over 50 mutations are spread out throughout Omicron, making the prior major variants of concern (Alpha, Beta, Gamma, Delta) lightweights with respect to changes in structure that are not just linear or uni-dimensional. Each mutation can interact with others (epistasis); any mutation or combination of mutations has the potential to change the 3D structure of the virus. In this sense, Omicron is an overwhelming reboot of the ancestral strain.

Omicron is very different from the Wuhan ancestral strain and it’s only a matter of luck that the vaccines continue to work and that Omicron is likely less severe than Delta. Don’t tell me that viruses evolve to be less severe over time–that isn’t correct in theory or practice. The most one might say is that a very deadly virus may be difficult to transmit but that only closes off a small part of the evolutionary design-space. There is plenty of room for transmission and lethality to both increase. So the vaccines continue to work well. We got lucky. But for how long will our luck last? Do we really have to wait for a more transmissible, more deadly, more vaccine escaping variant before we act?

Where are the variant-specific boosters? The FDA has said they would approve them quickly, without new efficacy trials so I don’t think the problem is primarily regulatory. Why not catch-up to the virus and maybe even get a jump ahead with pan-coronavirus vaccines?

More generally, in our February 2021 paper in Science my co-authors and I argued that we were still leaving trillion dollar bills on the sidewalk by not investing in more vaccine capacity. I am sorry to say that we were right. Why the failure to invest more broadly?

Mostly I blame American lethargy. After 9/11 the country was angry and united and we had troops in Afghanistan within a matter of weeks and we had taken over the country in a matter of months. For better or worse, we acted quickly and with resolve. Yet, when the virus was killing at 9/11 levels every day the public never reached the same level of anger or resolve. Even now Congress has spent trillions on unemployment insurance, business protection, money for schools and stimulus but has not passed the American Pandemic Preparedness Plan, a pretty decent, mostly science-based investment plan.

80,000 hours ranks research and investment against Global Catastrophic Biologic Risk (GCBR) as among the most pressing and yet tractable problems to work on and yet they estimate that quality-adjusted only about a billion dollars is being spent on these risks. Moreover, COVID doesn’t even count as a GCBR, i.e. 80000 hours at least recognizes that things could be much worse.

I understand that future people don’t vote but even so I expected a little bit more foresight.

How to elect Republicans

In New York, racial minorities are automatically eligible for scarce COVID-19 therapeutics, regardless of age or underlying conditions. In Utah, “Latinx ethnicity” counts for more points than “congestive heart failure” in a patient’s “COVID-19 risk score”—the state’s framework for allocating monoclonal antibodies. And in Minnesota, health officials have devised their own “ethical framework” that prioritizes black 18-year-olds over white 64-year-olds—even though the latter are at much higher risk of severe disease.

These schemes have sparked widespread condemnation of the state governments implementing them. But the idea to use race to determine drug eligibility wasn’t hatched in local health departments; it came directly from the federal Food and Drug Administration.

Here is the full story, I am very willing to issue a correction if it turns out anything posted from this is wrong.