Category: Medicine

On fentanyl, from the comments

I always find it helpful to recall that the US was the not the first country to be hit by fentanyl. Estonia, for instance, had a massive wave of fentanyl deaths that started before the US, without all the US prescription opioid consumption, and peaked sooner. Currently, their opioid supply has moved beyond fentanyl to derivatives that are even less safe.

It seems to me that the problem was not overprescription per se. Rather, as in Estonia, there seems to be spiral where opioids are seen as acceptable drugs of abuse (entering into the space of marijuana, alcohol, tobacco, and ecstasy), illicit suppliers elect to increase the addictiveness and potency of their drugs, and we end up with much more deadly drugs.

The biggest problem US docs created was removing the social stigma against opioid use and abuse. We created a perception that being addicted to opioids was no big deal, mostly safe, and something that people could do without losing all their social standing.

Does decriminalization work? Nowhere near as well as cultural barriers. Portugal, for instance, has safe injection and all the rest, yet it is experiencing a new wave of heroin use as old addicts return to heroin thanks a weakened economy. And lest we forget the difference in price for legitimate opioids and heroin/fentanyl is not all that high. Legitimate heroin supplies are going to cost at least as much as black market opioids so I suspect we will still have a lot of users who end up on fentanyl derivatives (for which there are no safe prescribing guidelines, nor even data for simple things like LD-50).

As with most major problems, the cause and solution are likely to be social. Historically, these sorts of epidemics die down as people die and the younger users decide to not try the things that killed all their older peers. Quite possibly all our “harm reduction” strategies and treatments will delay this process and leave more people dead; a first pass analysis of mass naloxone treatment suggested that it was associated with difference in difference increase in the opioid death rate due to increased use.

Unfortunately, I see no way out of the current situation that does not risk leaving many, possibly more than current rates, people dying.

That is from a commentator named Sure.

Eliminate Journal Formatting on First Submission!

Many years ago I was incredulous when my wife told me she had to format a paper to meet a journal’s guidelines before it was accepted! Who could favor such a dumb policy? In economics, the rule is you make your paper look good but you don’t have to fulfill all the journal’s guidelines until after the paper is accepted.

In The high resource impact of reformatting requirements for scientific papers Jian et al. calculate the cost of reformatting–it’s $1.1 billion dollars annually! True, the authors simply surveyed 203 authors for the time it took to reformat and then multiplied that by an hourly wage and then multiplied that by all article submissions so, at best, this is a back of the envelope calculation. What is beyond doubt, however, is that reformatting typically takes several tedious hours for a high-wage professional.

Our data show that nearly 91% of authors spend greater than four hours and 65% spend over eight hours on reformatting adjustments before publication…Among the time-consuming processes involved are adjusting manuscript structure (e.g. altering abstract formats), changing figure formats, and complying with word counts that vary significantly depending on the journal. Beyond revising the manuscript itself, authors often have to adjust to specific journal and publisher online requirements (such as re-inputting data for all authors’ email, office addresses, and disclosures). Most authors reported spending “a great deal” of time on this reformatting task. Reformatting for these types of requirements reportedly caused three month or more delay in the publication of nearly one fifth of articles and one to three month delays for over a third of articles.

And for what? Most papers will be rejected so the reformatting serves no purpose.

What frustrates me about this inanity is that, as far as I can tell, almost no one benefits! We simple seem stuck in an inefficient equilibrium. What hope is there to deregulate zoning or pass a carbon tax–where benefits exceed costs but you can understand why the process is difficult because some people gain from the inefficiency–when we can’t even fix wasteful journal formatting policy? Can Elsevier or other publishing heavyweight not unilaterally move us to the Pareto frontier! Pick up those $1.1 billion bills! Come on humanity, just do it!

Addendum: Economics is good on the reformatting score but n.b. “A prior survey-based research study on biomedical journal publications times noted a median time of first submission to acceptance of five months but this seemingly included all delays in the publication process (including review time and changes to improving scientific content).” Five months would be unheard of speed in economics where you are lucky if you get referee comments in five months!

Air Pollution Reduces IQ, a Lot

The number and quality of studies showing that air pollution has very substantial effects on health continues to increase. Patrick Collison reviews some of the most recent studies on air pollution and cognition. I’m going to post the whole thing so everything that follows is Patrick’s.

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Air pollution is a very big deal. Its adverse effects on numerous health outcomes and general mortality are widely documented. However, our understanding of its cognitive costs is more recent and those costs are almost certainly still significantly under-emphasized. For example, cognitive effects are not mentioned in most EPA materials.

World Bank data indicate that 3.7 billion people, about half the world’s population, are exposed to more than 50 µg/m³ of PM2.5 on an annual basis, 5x the unit of measure for most of the findings below.

  • Substantial declines in short-term cognitive performance after short-term exposure to moderate (median 27.0 µg/m³) PM2.5 pollution: “The results from the MMSE test showed a statistically robust decline in cognitive function after exposure to both the candle burning and outdoor commuting compared to ambient indoor conditions. The similarity in the results between the two experiments suggests that PM exposure is the cause of the short-term cognitive decline observed in both.” […] “The mean average [test scores] for pre and post exposure to the candle burning were 48 ± 16 and 40 ± 17, respectively.” – Shehab & Pope 2019.
  • Chess players make more mistakes on polluted days: “We find that an increase of 10 µg/m³ raises the probability of making an error by 1.5 percentage points, and increases the magnitude of the errors by 9.4%. The impact of pollution is exacerbated by time pressure. When players approach the time control of games, an increase of 10 µg/m³, corresponding to about one standard deviation, increases the probability of making a meaningful error by 3.2 percentage points, and errors being 17.3% larger.” – Künn et al 2019.
  • A 3.26x (albeit with very wide CI) increase in Alzheimer’s incidence for each 10 µg/m³ increase in long-term PM2.5 exposure? “Short- and long-term PM2.5 exposure was associated with increased risks of stroke (short-term odds ratio 1.01 [per µg/m³ increase in PM2.5 concentrations], 95% CI 1.01-1.02; long-term 1.14, 95% CI 1.08-1.21) and mortality (short-term 1.02, 95% CI 1.01-1.04; long-term 1.15, 95% CI 1.07-1.24) of stroke. Long-term PM2.5 exposure was associated with increased risks of dementia (1.16, 95% CI 1.07-1.26), Alzheimer’s disease (3.26, 95% 0.84-12.74), ASD (1.68, 95% CI 1.20-2.34), and Parkinson’s disease (1.34, 95% CI 1.04-1.73).” – Fu et al 2019. Similar effects are seen in Bishop et al 2018: “We find that a 1 µg/m³ increase in decadal PM2.5 increases the probability of a dementia diagnosis by 1.68 percentage points.”
  • A study of 20,000 elderly women concluded that “the effect of a 10 µg/m³ increment in long-term [PM2.5 and PM10] exposure is cognitively equivalent to aging by approximately 2 years”. – Weuve et al 2013.
  • “Utilizing variations in transitory and cumulative air pollution exposures for the same individuals over time in China, we provide evidence that polluted air may impede cognitive ability as people become older, especially for less educated men. Cutting annual mean concentration of particulate matter smaller than 10 µm (PM10) in China to the Environmental Protection Agency’s standard (50 µg/m³) would move people from the median to the 63rd percentile (verbal test scores) and the 58th percentile (math test scores), respectively.” – Zhang et al 2018.
  • “Exposure to CO2 and VOCs at levels found in conventional office buildings was associated with lower cognitive scores than those associated with levels of these compounds found in a Green building.” – Allen et al 2016. The effect seems to kick in at around 1,000 ppm of CO2.

Alex again. Here’s one more. Heissel et al. (2019):

“We compare within-student achievement for students transitioning between schools near highways, where one school has had greater levels of pollution because it is downwind of a highway. Students who move from an elementary/middle school that feeds into a “downwind” middle/high school in the same zip code experience decreases in test scores, more behavioral incidents, and more absences, relative to when they transition to an upwind school”

Relatively poor countries with extensive air pollution–such as India–are not simply choosing to trade higher GDP for worse health; air pollution is so bad that countries with even moderate air pollution are getting lower GDP and worse heath.

Addendum: Patrick has added a few more.

Opioid deaths are not mainly about prescription opioids

A recent study of opioid-related deaths in Massachusetts underlines this crucial point, finding that prescription analgesics were detected without heroin or fentanyl in less than 17 percent of the cases. Furthermore, decedents had prescriptions for the opioids that showed up in toxicology tests just 1.3 percent of the time.

Alexander Walley, an associate professor of medicine at Boston University, and five other researchers looked at nearly 3,000 opioid-related deaths with complete toxicology reports from 2013 through 2015. “In Massachusetts, prescribed opioids do not appear to be the major proximal cause of opioid-related overdose deaths,” Walley et al. write in the journal Public Health Reports. “Prescription opioids were detected in postmortem toxicology reports of fewer than half of the decedents; when opioids were prescribed at the time of death, they were commonly not detected in postmortem toxicology reports….The major proximal contributors to opioid-related overdose deaths in Massachusetts during the study period were illicitly made fentanyl and heroin.”

The study confirms that the link between opioid prescriptions and opioid-related deaths is far less straightforward than it is usually portrayed. “Commonly the medication that people are prescribed is not the one that’s present when they die,” Walley told Pain News Network. “And vice versa: The people who died with a prescription opioid like oxycodone in their toxicology screen often don’t have a prescription for it.”

That is by Jacob Sullum at Reason, via Arnold Kling.

Mortality sentences to ponder paging Ross Douthat too

This paper uses complete death certificate data from the Mortality Multiple Cause Files with American Community Survey data to examine age-specific mortality rates for married and non-married people from 2007 to 2017. The overall rise in White mortality is limited almost exclusively to those who are not married, for men and women…

That is from Philip N. Cohen, via Arnold Kling.

USA fact of the day

More than a third of Ph.D. students have sought help for anxiety or depression caused by Ph.D. study, according to results of a global survey of 6,300 students from Nature.

Thirty-six percent is a very large share, considering that many students who suffer don’t reach out for help. Still, the figure parallels those found by other studies on the topic. A 2018 study of mostly Ph.D. students, for instance, found that 39 percent of respondents scored in the moderate-to-severe depression range. That’s compared to 6 percent of the general population measured with the same scale.

And this:

Twenty-one percent of respondents said they’d been bullied in their programs. Of those, 48 percent said their supervisor was the perpetrator.

Here is the full story from Colleen Flaherty at Inside Higher Ed.

Model this dopamine fast

“We’re addicted to dopamine,” said James Sinka, who of the three fellows is the most exuberant about their new practice. “And because we’re getting so much of it all the time, we end up just wanting more and more, so activities that used to be pleasurable now aren’t. Frequent stimulation of dopamine gets the brain’s baseline higher.”

There is a growing dopamine-avoidance community in town and the concept has quickly captivated the media.

Dr. Cameron Sepah is a start-up investor, professor at UCSF Medical School and dopamine faster. He uses the fasting as a technique in clinical practice with his clients, especially, he said, tech workers and venture capitalists.

The name — dopamine fasting — is a bit of a misnomer. It’s more of a stimulation fast. But the name works well enough, Dr. Sepah said.

The purpose is so that subsequent pleasures are all the more potent and meaningful.

“Any kind of fasting exists on a spectrum,” Mr. Sinka said as he slowly moved through sun salutations, careful not to get his heart racing too much, already worried he was talking too much that morning.

Here is more from Nellie Bowles at the NYT.

Can we spend another $52 trillion without raising middle class taxes?

The question seems like a joke, right?  Yet because so much of our elite media class wants Elizabeth Warren to win, they are contorting themselves into every possible direction to make this one sound coherent.  It is not a question of whether total nominal expenditures on health care go up or down, but rather of thinking through incidence and opportunity cost and where the real burdens of the plan will fall.  Those are the core themes of my Bloomberg column, here is one excerpt:

Another part of the plan is to pay lower prices — 70% lower — for branded prescription drugs. That is supposed to save about $1.7 trillion, but again focus on which opportunities are lost. Lower drug prices will mean fewer new drugs are developed. There is good evidence that pharmaceuticals are among the most cost-effective ways of saving human lives, so the resulting higher mortality and illness might be especially severe.

And the close:

Warren’s proposals, when all is said and done, are best viewed not as a way of paying for her program but as a series of admissions about just how expensive it would be. Whether or not you call those taxes, they are very real burdens — and many of them will end up falling on the middle class.

By the way, here is a good NYT summary of Warren’s financing plan.  Here is a good Maxim Jacobs tweet:

It’s really hard to pick out which part of her plan is most insane?: – Lowering brand drug pricing by 70%? – CMS paying specialists less money – Taxing unrealized capital gains – Claim hiring more IRS agents will raise $2.3 trillion – “Not one penny in middle-class tax increases”

Here is more from Peter Suderman.

The Global Kidney Exchange Programme

In my WSJ review of Al Roth’s excellent book Who Gets What—and Why I wrote about Roth’s proposal to extend the idea of kidney swaps globally:

It’s often the case that a living donor is willing to give a kidney to a loved one, but the loved one can’t accept it because of immunity mismatch. But if a pair of such mismatched donors could be found (call them A and A´ and B and B´), then perhaps a match could be found by a crisscross pairing: Donor A could give to recipient B´ and donor B could give to recipient A´, thus solving the mismatch problem and saving lives.

…Today such multi-way exchanges are becoming common….Mr. Roth, however, wants to go further….why not open U.S. transplants to the world? Imagine that A and A´ are Nigerian while B and B´ are American. Nigeria has virtually no transplant surgery or dialysis available, so in Nigeria patient A’ will die for certain. But if we offered a free transplant to him, and received a kidney for an American patient in return, two lives would be saved.

The plan sounds noble but expensive. Yet remember, Mr. Roth says, “removing an American patient from dialysis saves Medicare a quarter of a million dollars. That’s more than enough to finance two kidney transplants.” So offering a free transplant to the Nigerian patient can save money and lives.

It’s hard to think of a better example of gains from trade (or a better PR coup for the U.S. on the world stage).

Recently, Rees et al., (including Roth) announced the first such global kidney exchange:

We report the 1‐year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor’s kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow‐up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable.

Naturally, some people aren’t happy because of “ethical” objections. Minerva, Savulescu and Peter Singer write in defense of the program:

Lurking behind all the arguments against the GKE is the assumption that people who are poor are incapable of autonomous choices. So, if they appear to choose to act in ways that benefit not only themselves, but people in HICs, they must have been coerced, exploited, or commodified.

…Poverty does not necessarily make a person unable to choose to donate a kidney to a loved one, nor does it make someone incapable of weighing the pros and cons of an option like that offered by the GKE. Poverty does narrow down the options available to people, and often forces them to settle for an option that is not as good as a wealthy person would choose. That, however, is irrelevant to the ethics of the GKE if that programme provides a better option to patients in LMICs who need a kidney than any other option currently available to them.

…It would be tragic if such misguided objections were to prevent the GKE from realising its potential to reduce suffering and save the lives of rich and poor patients alike.

Hat tip: Frank McCormick.

The Prescription Escalator

Ask anyone and they will tell you that their prescription costs are rising. But generic drug prices are falling (also here) and generics are 80-90 percent of all prescriptions. Moreover, although branded drugs are expensive total out-of-pocket costs for the population as a whole are flat or even decreasing as Michael Mandel points out:

[A] May 2019 research report from the Agency for Healthcare Research and Quality reported that average out-of-pocket spending for prescribed medications, among persons who obtained at least one prescribed medication, declined from $327 in 2009 to $238 by 2016, a decrease of 27 percent. Data from the Bureau of Labor Statistics Consumer Expenditure Survey shows that average household spending on prescription drugs fell by 11% between 2013 and 2018.

Moreover, OECD data shows that average out- of-pocket spending on prescribed medicines in the United States ($143 per capita in 2017) is actually lower than countries such as Canada ($144), Korea ($156), Norway ($178), and Switzerland ($215).

So are people simply mistaken about what they are experiencing? Not quite. Mandel uses the metaphor of the prescription escalator to explain the apparent paradox:

It turns out that an escalator is the appropriate model for prescription drug costs for individuals. As people get older, they unwillingly ride the prescription escalator, with their average spending on prescription drugs rising by about 5-6% per year. This figure assumes no change in the underlying price of drugs. Rather, people fill more prescriptions as they age.

In other words, every individual experiences an increase in prescription costs as they age even though for the population as a whole prescription prices are flat or falling–a form of Simpson’s paradox. The driver of higher costs is usage not price. People aged 65-74 have on average 25 (!) prescriptions to fill, more than two and half times as many as people aged 25-34 (about 9 per year).

Understanding the prescription escalator is important because regulating drug prices–aside from being a bad idea–won’t solve the perceived problem.

…even if drug reform efforts were successful and there were no more increases in drug costs, every individual would still face a 5.6% increase each year in drug spending as they got older. That would total 30% after five years, and 70% after ten years, across the board.These are enormous increases.

Indeed, the prescription escalator is a sign of success. If drugs weren’t successful we wouldn’t buy more of them when we were older and sicker and costs wouldn’t rise.

Opioids and labor market participation

The onset of the opioid crisis coincided with the beginning of nearly 15 years of declining labor force participation in the US. Furthermore, the areas most affected by the crisis have generally experienced the worst deteriorations in labor market conditions. Despite these time series and cross-sectional correlations, there is little agreement on the causal effect of opioids on labor market outcomes. I provide new evidence on this question by leveraging a natural experiment which sharply decreased the supply of hydrocodone, one of the most commonly prescribed opioids in the US. I identify the causal impact of this decrease by exploiting pre-existing variation in the extent to which different types of opioids were prescribed across geographies to compare areas more and less exposed to the treatment over time. I find that areas with larger reductions in opioid prescribing experienced relative improvements in employment-to-population ratios, driven primarily by an increase in labor force participation. The regression estimates indicate that a 10 percent decrease in hydrocodone prescriptions increased the employment-to-population ratio by about 0.7 percent. These findings suggest that policies which reduce opioid misuse may also have positive spillovers on the labor market.

That is from a job market paper by David Beheshti at the University of Texas at Austin.

The Causal Effect of Cannabis on Cognition

Does smoking lots of pot make you dumb or do dumb people smoke lots of pot? Mostly, the latter. Ross et al. (2019) write:

Although many researchers have concluded that cannabis causes impairment in cognition, there are alternative explanations. First, poor cognitive functioning is a risk factor for substance use. Specifically, EF measured in childhood predicts later substance use and substance use disorders (SUDs; Ridenour et al., 2009). Thus, studies need to control for prior cognitive functioning (Meier et al., 2012). Second, poor cognitive functioning and cannabis use may also be related, not because one causes the other, but because they share common risk factors, like lower SES (Rogeberg, 2013). Lynskey and Hall (2000) proposed that early use is likely to occur in a social context characterized by affiliations with substance using peers, poor school attendance, and precocious adoption of adult roles including dropping out of school; such an effect on educational participation may also influence later cognitive functioning.

Indeed–twin studies which control for genetics and family environment–do not find that cannabis reduces cognition:

Lyons et al. (2004) examined MZ twins discordant for use 20 years after regular use, and found a significant difference between twins on only one of 50+ measures of cognition. Second, Jackson et al. (2014) found no evidence for a dose-dependent relationship or significant differences in cognition among MZ twins discordant for cannabis use. Similarly, Meier et al. (2017) found no evidence for differences in cognition among a combined sample of MZ and DZ twins discordant for cannabis dependence or use frequency. Thus, quasi-experimental, co-twin control designs have yielded little evidence that cannabis causes poorer cognition.

Ross et al. run a similar study but testing also for executive function skills–the ability to plan, focus, control impulses and so forth which are skills related to IQ but distinct–and they conclude:

Families with greater cannabis use showed poorer general cognitive ability. Yet within families, twins with higher use rarely had lower cognitive scores. Overall, there was little evidence for causal effect of cannabis on cognition.

Hat tip: The excellent Kevin Lewis.

 

Economists and non-economists on elasticity

From a recent paper by Joanna Venator and Jason Fletcher:

In this paper, we estimate the impacts of abortion clinic closures on access to clinics in terms of distance and congestion, abortion rates, and birth rates. Legislation regulating abortion providers enacted in Wisconsin in 2011-2013 ultimately led to the closure of two of five abortion clinics in Wisconsin, increasing the average distance to the nearest clinic to 55 miles and distance to some counties to over 100 miles. We use a difference-in-differences design to estimate the effect of change in distance to the nearest clinic on birth and abortion rates, using within-county variation across time in distance to identify the effect. We find that a hundred-mile increase in distance to the nearest clinic is associated with 25 percent fewer abortions and 4 percent more births. We see no significant effect of increased congestion at remaining clinics on abortion rates. We find significant racial disparities in who is most affected by abortion clinic closures, with increases in distance increasing birth rates significantly more for Black, Asian, and Hispanic women. Our results suggest that even small numbers of clinic closures can result in significant restrictions to abortion access of similar magnitude to those seen in Texas when a greater number of clinics closed their doors.

There are (at least) two possible responses to such results, and that is without even getting into one’s underlying view of the ethics of abortion.  One is to say that a great deprivation has occurred because many fewer women end up having abortions.  Another response is to infer that the marginal value of the abortions could not have been so high to begin with, if the number drops off so readily.

The same issue comes up with Obamacare.  If the price of health insurance goes up, quite a large number of people decide to go without coverage.  Is the size of that number a measure of the human tragedy resulting from the price increase?  Or is it a measure of how little those people actually value health insurance?  Or somehow both?

I have yet to meet a person who can think through these issues rationally and absorb what is interesting and valid in each of those two perspectives.

Release Bad News on a Friday

Politicians have long known to release bad news on a Friday and it appears that pharmaceutical firms may do likewise.

Safety alerts are announcements made by health regulators warning patients and doctors about new drug-related side effects. However, not all safety alerts are equally effective. We provide evidence that the day of the week on which the safety alerts are announced explains differences in safety alert impact. Specifically, we show that safety alerts announced on Fridays are less broadly diffused: they are shared 34% less on social media, mentioned in 23% to 66% fewer news articles, and are 12% to 51% less likely to receive any news coverage at all. As a consequence of this, we propose Friday alerts are less effective in reducing drug-related side effects. We find that moving a Friday alert to any other weekday would reduce all drug-related side effects by 9% to 12%, serious drug-related complications by 6% to 15%, and drug-related deaths by 22% to 36%. This problem is particularly important because Friday was the most frequent weekday for safety alert announcements from 1999 to 2016. We show that this greater prevalence of Friday alerts might not be random: firms that lobbied the U.S. Food and Drug Administration in the past are 49% to 56% more likely to have safety alerts announced on Fridays.

From The Friday Effect in Management Science by Diestre, Barber and Santalo.

Hat tip: Kevin Lewis.

The impact of the Affordable Care Act

The Impact of the Affordable Care Act: Evidence from California’s Hospital Sector
(with Mark Duggan and Atul Gupta) R&R, AEJ: Economic Policy

The Affordable Care Act (ACA) authorized the largest expansion of public health insurance in the U.S. since the mid-1960s. We exploit ACA-induced changes in the discontinuity in coverage at age 65 using a regression discontinuity based design to examine effects of the expansion on health insurance coverage, hospital use, and patient health. We then link these changes to effects on hospital finances. We show that a substantial share of the federally-funded Medicaid expansion substituted for existing locally-funded safety net programs. Despite this offset, the expansion produced a substantial increase in hospital revenue and profitability, with larger gains for government hospitals. On the benefits side, we do not detect significant improvements in patient health, although the expansion led to substantially greater hospital and emergency room use, and a reallocation of care from public to private and better-quality hospitals.

That is the job market paper by Emilie Jackson of Stanford.