Category: Medicine

Who is protected against Omicron?

The vaccine made by Sinovac Biotech Ltd., one of the most widely used in the world, doesn’t provide sufficient antibodies in two doses to neutralize the omicron variant and boosters will likely be needed to improve protection, initial lab findings showed.

While the first two studies to be released on the Chinese shot and omicron diverged on how much the vaccine’s immune response is degraded, they both indicated the standard two-dose course would not be enough, raising uncertainty over a shot relied on by millions of people in China and the developing world to protect against Covid-19.

Among a group of 25 people vaccinated with two Coronavac doses, none showed sufficient antibodies in their blood serum to neutralize the omicron variant, said a statement from a team of researchers at the University of Hong Kong released late Tuesday night.

Here is more from Bloomberg.

Will China ever get Pfizer?

As Covid-19 started spreading in Wuhan early last year, Chinese billionaire Guo Guangchang’s drugmaker appeared to have scored a big win: A partnership with Germany’s BioNTech SE, which went on to produce with Pfizer Inc. one of the world’s most successful vaccines against the coronavirus.

Yet almost a year later, the shot is yet to be approved in mainland China, and in recent weeks Beijing has thrown its heft behind a homegrown mRNA vaccine, allowing China’s Walvax Biotechnology Co. to test its own experimental shot as a booster. The developments are raising new questions about whether the U.S.-German vaccine, licensed for the potentially lucrative Greater China region by Guo’s Shanghai Fosun Pharmaceutical Group Co., will ever be used on the mainland, where President Xi Jinping’s administration has backed a nationalist agenda on all fronts, including in the fight against the virus.

Here is more from Bloomberg.  And will China ever get Omicron?  Yes.  Pfizer, maybe not.

Omicron in China

China’s efforts to keep the new coronavirus strain out of its borders have failed, with the country reporting its first case of the Omicron variant in the coastal city of Tianjin on Monday (Dec. 13).

The timing and location of the new case are not ideal for China’s leadership. Tianjin is right next door to Beijing, which is due to hold the Winter Olympics in a matter of weeks.

The news coincides with an expanding cluster of cases of the Delta variant in another coastal province, Zhejiang. The outbreak has seen at least a dozen publicly traded companies immediately suspend production in the province, according to a Guardian report.

Here is the full story.  Casualties issues aside (which remain unclear), this development may also be of considerable import to the political economy of China, a country that has promised near-zero Covid to its citizens, and derived legitimacy from its degree of success so far.  Yet China has low levels of natural immunity, and the effectiveness of its vaccine investments to date remains uncertain against Omicron, or for that matter against Delta.  And here is The Zvi’s update on Omicron more generally.

Those new vaccine service sector jobs MIE

A man in New Zealand who reportedly received up to 10 Covid vaccines in a day on behalf of others is under investigation by the country’s Ministry of Health, Newsweek reported.

Reports indicate that the unnamed man was paid by multiple individuals to pretend to be them while obtaining a vaccine, in an effort to avoid vaccination requirements.

Here is the full story, via Air Genius Gary Leff.  Not long ago I was wondering how many vaccines you could take in a day and still survive…this is data!

A cautionary note on Omicron

From my email from Ratufa:

I wanted to point out an issue with some of the metrics that are being used to assess the severity of Omicron.

The growth rate of an outbreak impacts the observed ratios of outcomes. Early in an outbreak those ratios will be biased towards lesser severity for faster spreading strains because more severe outcomes take longer to develop.

For example, it takes on average two days to be admitted to an ICU after hospital admission. The SA Omicron outbreak looks to have a growth rate of .21/day and the original Delta outbreak one of .1/day.  Based on that we would expect the proportion of ICU admissions to hospital admissions to be ~20% lower [1-e^(-2*.11)] than Delta early in the pandemic. And incidental admissions have the potential to confound that number even more.

The impact on hospitalizations and deaths is more dramatic. Positive tests tend to lead hospitalizations by about 5 days and deaths by 2 to 3 weeks. So we would expect the ratio of hospitalizations to positive tests to be ~40% lower and deaths/positive tests to be ~80% lower than in the delta outbreak holding severity constant. Though both those estimates are quite sensitive to the lag and estimate of r.

The growth effect probably doesn’t explain the majority of the difference in outcomes that have been observed. But it is potentially material. And makes me more skeptical of claims of lesser severity I’ve seen so far.

Psychedelics alter metaphysical beliefs

Can the use of psychedelic drugs induce lasting changes in metaphysical beliefs? While it is popularly believed that they can, this question has never been formally tested. Here we exploited a large sample derived from prospective online surveying to determine whether and how beliefs concerning the nature of reality, consciousness, and free-will, change after psychedelic use. Results revealed significant shifts away from ‘physicalist’ or ‘materialist’ views, and towards panpsychism and fatalism, post use. With the exception of fatalism, these changes endured for at least 6 months, and were positively correlated with the extent of past psychedelic-use and improved mental-health outcomes. Path modelling suggested that the belief-shifts were moderated by impressionability at baseline and mediated by perceived emotional synchrony with others during the psychedelic experience. The observed belief-shifts post-psychedelic-use were consolidated by data from an independent controlled clinical trial. Together, these findings imply that psychedelic-use may causally influence metaphysical beliefs—shifting them away from ‘hard materialism’. We discuss whether these apparent effects are contextually independent.

Here is the full piece, by Christopher Timmermann, et.al., via Anecdotal.

“What is wrong with physicians?” (from the comments)

My top candidates:

1. Loss of locus of control. People go into medicine to save lives. They believe that they will use their demonstrated intelligence and skills to make a difference. Unfortunately, modern medicine is ever more about turning physicians into box checkers. CPT codes, checklists, facility mandates, perpetual boards … a physician quickly loses control of their working day unless they are weird freaks who do extensively more work to retain control. And beyond that the average physician becomes enculturated to this much earlier. Which medical school you get into is largely a function of where you grew up, went to undergrad, and exactly how well you did on a test that everyone aces with a side of barely legal implicit racial quotas. Your residency is determined by where you went to medical school, where you went to medical school, where/what the top candidates want, and how well you did on a test that everyone aces with a side of barely legal implicit racial quotas. You spend a decade where your locus of control in life is minimal. Then you hit the real world and rather than being set free, you get hit by unending paperwork and yet a thousandth petty demand on your time. If you do research it is not uncommon to spend multiplicatively more time on compliance paperwork. If you head out to make money, you will find that your charge capture is more relevant than the quality of care you provide by an order of magnitude. All of this is a textbook case of loss of locus of control that we know is highly correlated with drug use and depression.

2. There is a wild disconnect between “being a physician” as understood by the public and what you actually live. The public thinks this is still the 1980s when you could pay for medical school working a summer job, residency was three years, and salaries were higher in real terms than they are today. Instead, physicians spend much closer to fifteen years going through training as the needed resume padding has grown at every step along the way. This means that they live longer at resident salaries which are close to US median, but typically are located in high population areas with expensive housing costs. And being a resident physician is not cheap. You have high commuting costs because the regs allow your boss to work you 24 out of 28 days. You can, and will, have weeks with over 100 hours of actual patient care. And again, remember that something like half of residencies are in violation of these rules. And all of this is while nursing a second mortage in undischargable medical school debt. Everyone will think you are rich and that you take fine vacations to Europe and the you will drive a flashy care. And maybe you will, but it will not be until after you are 40 and often 45 that the full physician lifestyle of the movies really comes into play.

3. And then we have the stakes. At every step in a physicians formative adult years you face massive ultra-high stakes events that we know are bad for mental health. College admissions (where you will hit a ceiling for medical schools if you get in too low), MCAT and medical school admissions (which will drastically lower your access to certain specialties if you end up having to go DO), Step and the Match (where you will spend five figures to beg for interviews, the folks on the other side will be unable to differentiate you from the thousands of other applicants, and when you get the interview the only thing of meaning that will come forth is if they like you and if you grew up nearby). Then you have boards and your first job. All of these are massively high stakes and they all require performing quite well relative to your peers. This sort of setup is known in experimental animals and people to lead to depression, anxiety disorders, and drug use.

3. Then we have the punctuated nature of the physician’s life. Going back to medical school, you routinely have long weeks with minimal time to enjoy because studying is rampant. Your entire career can theoretically hang on if you memorized which ultra-rare cancer is caused by which mutation in which gene – even if you want to be a psychiatrist. When you have time “off” this may be the only time you get and there is a very strong tendency toward binges and bacchanals. This will continue to residency where you might have one free weekend in a month (the others being taken up with working and studying), which again lends itself toward binging. And it may continue from there with horrid call schedules and long weeks punctuated by long vacations.

4. The stakes never get lower. You go through with your career riding on high stakes tests and your studying time never being accounted for in your official duties. Boards are now never ending and you face ever more theoretically threatening liability for your decisions.

5. And then there is the obvious stuff. Day in, day out you meet people at their worst. And all your coworkers are doing the same. People cry, threaten, swear, and otherwise abuse you. And nobody wants to get mad at somebody who was just paralyzed from the waist down. Likewise, you can only become so inured to death and dying, we are a social species with extremely large portions of our brains dedicated to feeling empathy for others, physicians see the 5% of humanity who is most obviously suffering as their modal patient.

6. Lastly, whatever you think about physician renumeration, it becomes painfully evident that the golden days were decades ago and there is a small army looking for ways to reduce your renumeration. It will fall disproportionately on you even when the major growth in medical expenses has been nursing, administration, and other warm bodies. Whatever you got paid for a highly taxing job last year, there will be a thousand signs that people think you should do it again for less. People who believe wholeheartedly in the stickiness of wages for reasons of morale and who hold that pay cuts are sufficiently difficult that we need to order international finance around inflation and obviating the need for explicit wage reductions will turn around and concoct wild schemes that explicitly reduce your income in real and nominal terms and question your character should your professional organization (to which you don’t belong) object. All, of course, while the administrators who are generally incompetent at understanding medical practice rake in an ever larger share of the money.

Some of this is US specific, but we have set up medicine to be highly backloaded with its rewards for physicians. We have risen the profession to a vocation and made it a truly arduous task to get through. And at every step along the way physicians have not had access to healthy coping mechanisms and repeated psychic injuries of the sort known to cause or exacerbate these conditions. Major life protective events (e.g. marriage, children, home ownership) are routinely delayed and disrupted by the demands of the training. Why again are we surprised that physicians come out bruised, batter, and willing to take the short term fix for some relief?

That is all from Sure.

One scenario for Omicron

That is the theme of my latest Bloomberg column, here is one excerpt:

How will institutions react to a proliferation of cases?

Imagine that a significant percentage of students in a school test positive, but no one is seriously ill. Will that school feel compelled to shut down and move to remote learning?

One possibility is that administrators will realize that virtually everyone is going to catch omicron anyway, articulate that reality to their constituencies, and plough ahead with face-to-face instruction. An alternate scenario is that the mere mention of Covid will prove so scary that closure will be inevitable. After all, how much will be known a month or two from now about the prospects of getting Long Covid from omicron? I am expecting a lot of school closures.

Another habit that will be hard to break is tracking the severity of the virus by counting cases. Until now, cases have been pretty good predictors of subsequent hospitalizations and then deaths. If cases become more detached from bad outcomes, will institutions and authorities be able to respond rapidly to that new reality? By the time they adjust, if they do, omicron might have come and gone.

To those who are inclined to worry, it will be scary how quickly omicron cases accumulate. It might feel as if the apocalypse has arrived, even if a lot of that short-term case activity is simply an acceleration of illness rather than an increase in the year’s total. (How scared would we get if most of the year’s murders happened in the first six or eight weeks of the year?) In any case, hospitals will have to be ready. But it is likely that a lot of health-care professionals might test positive early next year as well.

There is much more at the link.

Model this what is wrong with physicians?

Compared to differences among their male patient counterparts, female patients randomly assigned a female doctor rather than a male doctor are 5.0% more likely to be evaluated as disabled and receive 8.5% more subsequent cash benefits on average. There is no analogous gender-match effect for male patients.

And is it the male or female physicians who are at fault here?  Or is this diagnostic differential somehow optimal?

Here is the full NBER paper by Marika Cabral and Marcus Dillender.

What is wrong with physicians?

There is evidence that physicians disproportionately suffer from substance use disorder and mental health problems. It is not clear, however, whether these phenomena are causal. We use data on Dutch medical school applicants to examine the effects of becoming a physician on prescription drug use and the receipt of treatment from a mental health facility. Leveraging variation from lottery outcomes that determine admission into medical schools, we find that becoming a physician increases the use of antidepressants, opioids, anxiolytics, and sedatives, especially for female physicians. Among female applicants towards the bottom of the GPA distribution, becoming a physician increases the likelihood of receiving treatment from a mental health facility.

That is from a new NBER working paper by D. Mark Anderson, Ron Diris, Raymond Montizaan, and Daniel I. Rees.  Is it personality type?  Or the ease of opportunity?  The stress of the job?  Or something else?

Claims about placebos

…the placebo effect in the United States has actually become quite a lot stronger over time, meaning that drugs that once would have been approved may not be now – because their performance relative to that of placebo is less convincing. This study makes the point clearly – by 2013, drugs produced 8.9% more pain relief than placebos, compared to 27.3% in 1996. In the charts above, it can be seen that the effect of placebo drugs has increased a lot, whereas the effectiveness of pain relief drugs has barely changed, meaning that the treatment advantage (the effectiveness of active drugs as opposed to placebos) has fallen dramatically. Weirdly, it seems like this is only happening in the United States, whereas other countries haven’t seen particularly large increases in the effect size of placebos.

That is from the Substack of Sam.  Hail Bruno M.!

Jason Abaluck writes me about masks and the Bangladesh RCT study

This is all him, no double indent though:

“As a regular reader of your blog and one of the PIs of the Bangladesh Mask RCT (now in press at Science), I was surprised to see your claim that, “With more data transparency, it does not seem to be holding up very well”:

  1. The article you linked claims, in agreement with our study, that our intervention led to a roughly 10% reduction in symptomatic seropositivity (going from 12% to 41% of the population masked). Taking this estimate at face value, going from no one masked to everyone masked would imply a considerably larger effect. Additionally:
    1. We see a similar – but more precisely estimated – proportionate reduction in Covid symptoms [95% CI: 7-17%] (pre-registered), corresponding to ~1,500 individuals with Covid symptoms prevented
    2. We see larger proportionate drops in symptomatic seropositivity and Covid in villages where mask-use increased by more (not pre-registered), with the effect size roughly matching our main result

The naïve linear IV estimate would be a 33% reduction in Covid from universal masking. People underwhelmed by the absolute number of cases prevented need to ask, what did you expect if masks are as effective as the observational literature suggests? I see our results as on the low end of these estimates, and this is precisely what we powered the study to detect.

  1. Let’s distinguish between:
    1. The absolute reduction in raw consenting symptomatic seropositives (20 cases prevented)
    2. The absolute reduction in the proportion of consenting symptomatic seropositives (0.08 percentage points, or 105 cases prevented)
    3. The relative reduction in the proportion of consenting symptomatic seropositives (9.5% in cases)

Ben Recht advocates analyzing a) – the difference in means not controlling for population. This is not the specification we pre-registered, as it will have less power due to random fluctuations in population (and indeed, the difference in raw symptomatic seropositives overlooks the fact that the treatment population was larger – there are more people possibly ill!). Fixating on this specification in lieu of our pre-registered one (for which we powered the study) is reverse p-hacking.

RE: b) vs. c), we find a result of almost identical significance in a linear model, suggesting the same proportionate reduction if we divide the coefficient by the base rate. We believe the relative reduction in c) is more externally valid, as it is difficult to write down a structural pandemic model where masks lead to an absolute reduction in Covid regardless of the base rate (and the absolute number in b) is a function of the consent rate in our study).

  1. It is certainly true that survey response bias is a potential concern. We have repeatedly acknowledged this shortcoming of any real-world RCT evaluating masks (that respondents cannot be blinded). The direction of the bias is unclear — individuals might be more attuned to symptoms in the treatment group. We conduct many robustness checks in the paper. We have now obtained funding to replicate the entire study and collect blood spots from symptomatic and non-symptomatic individuals to partially mitigate this bias (we will still need to check for balance in blood consent rates with respect to observables, as we do in the current study).
  1. We do not say that surgical masks work better than cloth masks. What we say is that the evidence in favor of surgical masks is more robust. We find an effect on symptomatic seropositivity regardless of whether we drop or impute missing values for non-consenters, while the effect of cloth masks on symptomatic seropositivity depends on how we do this imputation. We find robust effects on symptoms for both types of masks.

I agree with you that our study identifies only the medium-term impact of our intervention, and there are critically important policy questions about the long-term equilibrium impact of masking, as well as how the costs and benefits scale for people of different ages and vaccination statuses.”

An update on the mask debate

I am long since tired of this debate, and I see that a lot of people are not joining it in the best of faith.  I can pass along a few updates, namely this study, with some critical commentary attached.  And here is more on the Bangladeshi mask RCT.  With more data transparency, it does not seem to be holding up very well.

That said, I am not sure that either calculation really matters.  Any good assessment of mask efficacy has to be radically intertemporal in nature, and I mean for the entirety of the pandemic.  “Not getting infected” now may well raise your chance of getting infected later on, and that spans for longer than any feasibly designed RCT.  And have you heard about the new “Nu” variant?  It may turn out not to matter, but it does remind us that the pandemic is not over yet.

As a simple first approximation, think of the real value of masks as “a) how many infections are delayed for how long, plus improvements in treatment in the meantime, plus b) how many infections are avoided altogether.”  Even a well-designed RCT is going to focus on a version of b), but only for a limited period of time.  The extant studies don’t at all consider “plus improvements in treatment in the meantime,” or when some of those protected by masks for say a year or two might nonetheless later catch Covid later yet.  So those RCTs, no matter what their results, are grabbing only one leg of the elephant.

To make matters more complicated yet, a “very small” efficacy for masks might (yes, might) translate into a much larger final effect, due to effective R (sometimes) being greater than 1.  So finding a very small effect for masks doesn’t mean masks are only slightly effective.  As the pandemic is ending, you might (again might) have had one less “pandemic cycle” than if you hadn’t tried masks at all.  You can think of masks as a kind of lottery ticket on “one big gain,” paying off only when the timing is such that the masks have helped you choke off another Covid wave.  Again, the RCT is not capable of estimating that probability or the magnitude of its effect.

Yet another part of my mental model of masks has evolved to be the following.  You have two sets of countries, countries that manage Covid well and countries that don’t, argue all you want who goes into which bin but that isn’t the point right now.

Now consider the countries that don’t manage Covid well.  They might wish to stretch out their epidemics over time, so that better treatments arrive, subject to economic constraints of course.  But the countries that manage Covid well probably want the poorly-managed countries to reach herd immunity sooner rather than later, if only to lower the ongoing risk of transmission from a poorly-managed country to a well-managed country.  And to lower the risk of those countries birthing new variants, just as southern Africa now seems to have birthed the Nu variant.

So we have two major points of view, represented by multiple countries, one wanting quicker resolution for the poorly managed countries but the other wanting slower resolution.  Does any study of masks take those variables into account?  No.  Nor is it easy to see how it could.

To be clear, I am not arguing masks don’t work, nor am I making any claims about how much masks may or may not protect you individually, or the people you interact with.  I am claiming that at the aggregate social level we are quite far from knowing how well masks work.

I say it is third doses we should be doubling down on, not masks.  To be clear, I am fine with wearing masks myself, I am used to it, and I dislike it but I don’t hate it.  On this issue, I am not one of those people translating his or her own snowflake-ism into some kind of biased policy view.

But the emerging science on third doses is much stronger, and most countries have been dropping the ball on that one.