The Long Read: The secret payments that made sure opioids kept flowing

Why didn’t PBMs do more to stop the flow of opioids? Because, it turns out, they were paid by drug makers to make sure patients got as many painkillers as possible.

For years, the benefit managers, or P.B.M.s, took payments from opioid manufacturers, including Purdue Pharma, in return for not restricting the flow of pills. As tens of thousands of Americans overdosed and died from prescription painkillers, the middlemen collected billions of dollars in payments.

I could paste quote after quote, but it’s worth reading the whole story — the New York Times investigation that uncovered how PBMs conspired with drug companies to remove roadblocks to opioid prescriptions. The two groups raced to the ethical bottom of the barrel: Pharma companies threatened to reduce rebates to PBMs, and PBMs threatened to restrict prescriptions.

Because the P.B.M.s often shared a portion of the rebates with the insurers and employers that hired them, these clients had a financial incentive not to impose restrictions. Purdue and the P.B.M.s sometimes reminded clients of this when they considered limiting access.

Now do we worry?

The CDC has reported the first severe case of H5N1 bird flu in a human — a hospitalized Louisiana patient who had contact with backyard, not commercial, poultry.

This is the 61st human case reported in the US, although there are probably a lot more going unreported. Our friends up north have already seen at least one severe case — a teenager who was hospitalized^* in critical condition in British Columbia last month. (The Canadian government refuses to comment on his or her condition.)

Feline danger: A new study says “that domestic cats could potentially prompt a public health crisis” because they can interact with both livestock and humans, and act as a “bridge” for the virus to become more transmissible to us.

^* Technically hospitalised

New Veosah warning

The FDA has given Veozah (fezolinetant) — the drug used to treat hot flashes from menopause — a new boxed warning because of the risk of serious liver injury.

We made this update after reviewing a postmarketing report of a patient with elevated liver blood test values and signs and symptoms of liver injury after taking the medicine for about 40 days.

The agency also recommends increasing the frequency of liver blood testing, especially for the two months after a patient starts using it.

Driving away Alzheimer’s?

Taxi and ambulance drivers seem to have lower rates of Alzheimer’s, although it’s unclear why this might be the case. Researchers from Mass General Brigham looked at the death certificates of about 9 million people whose occupation was listed, and they found that while overall Alzheimer’s was the cause of death for about 3.9% of people, only 1.03% of taxi drivers and 0.74% of ambulance drivers died from it — the lowest rates among any profession.

If you saw that two types of high-stress drivers had lower rates of Alzheimer’s death, you would raise an eyebrow, too. But why is this the case? The thought is that it has to do with the use of the hippocampus for spatial reasoning, but the authors are clear, “We view these findings not as conclusive, but as hypothesis-generating.”

Draw your own conclusions.

A little late….

The discredited study that claimed hydroxychloroquine could help treat Covid-19 has (finally) been withdrawn by the author and retracted by the journal that published it … but not before a lot of damage was done.

The French Society of Pharmacology and Therapeutics said the paper constituted a clear example of scientific misconduct, which was marked by manipulation and bias to “falsely present” the drug as effective against COVID-19. […]

“The promotion of the results led to the abusive prescription of hydroxychloroquine to millions of patients, leading to unwarranted risks to millions of people and potentially thousands of avoidable deaths.”

What’s with all the food recalls?

You might have noticed that there seem to have been a lot of food-borne disease outbreaks and recalls. In fact, “Food and cosmetic recalls […] nearly doubled from 2012 to 2024.”

What’s going on? It’s most likely a combination of factors, including people eating more processed foods, “increased globalization of food production,” and even some missed inspections.

Within US states, there are about 3,000 different jurisdictions for food safety […] “And not everyone’s on the same page.”

Perhaps taking science too far

Experts publishing in the British Medical Journal warn that princesses depicted in Disney movies (and remakes and remakes and remakes) are facing a slew of health risks.

As a scullery maid, Snow White, for example, finds “opportunities for social interaction are extremely limited,” increasing her risk of “cardiovascular disease, depression, anxiety, and all cause mortality.” Ditto for Jasmine: “[W]hile the Genie might sing ‘you ain’t never had a friend like me,’ the truth is that Jasmine has no friends at all.”

Rapunzel’s uncut hair probably means permanent damage to her follicles, while Belle — well, “Close contact with the Beast exposes Belle to many potentially life threatening infectious diseases, such as brucellosis or rabies.”

And Pocahontas? Ouch:

Her cliff dive has an impressive falling time of nine seconds. Based on the falling time, we estimated the height of the cliff through simulations using coupled differential equations for height and velocity with quadratic drag. Assuming average female anthropomorphic measurements […] and standard environmental constants (drag coefficient of 1.0, gravitational acceleration of 9.81 m/s², and air density of 1.2 kg/m³), the cliff height was estimated at 252 m. Studies on slamming dynamics of diving suggest that hand first dives from heights above merely 12 m could already be critical for clavicular compressions.

Don’t forget Kringle

He isn’t owned by Disney (yet), but Santa is facing his own health issues, as the director of Lancaster University’s Clinical Anatomy Learning Centre points out. Sure, all that body fat is good insulation, but a diet high in milk and cookies “increases the risk of developing obesity and chronic conditions such as heart disease, stroke, type 2 diabetes, osteoarthritis, and colorectal cancer.”

And, he point out, “Santa’s flushed complexion is often viewed as an indication of his cheery nature — but red cheeks can also be a symptom of rosacea, a chronic skin condition.”

Acetaminophen danger

We all know that too much acetaminophen can lead to liver issues, but at lower, less-frequent doses it’s great stuff. Well, that might not be true for people over 65.

A new British study found that “repeated doses of paracetamol in people aged 65 and over can lead to an increased risk of peptic ulcers, heart failure, hypertension, and chronic kidney disease.”

Caveat: Although it compared 180,000 acetaminophen ‘users’ with 400,000 ‘non-users,’ it was only based on prescription information — it didn’t take into account over-the-counter tylen— er, paracetamol use. So while there appears to be a connection, you know the drill: More research is needed.

A better SSRI target?

Instead of systemic SSRIs like we’re using today, what if the drugs were targeted at the gut? After all, “90% of our bodies’ serotonin is in the gut,” according to a cell biologist at NYU Grossman School of Medicine, and the vagus nerve connects it to the brain.

That’s why she co-led a study to see what would happen if they increased the serotonin in mice’s guts, rather than their brains. They genetically engineered some mice to have more serotonin signaling there (“which mimicked an SSRI delivered selectively to the gut”), and, lo and behold, those mice were less anxious and depressed than their littermates.

“[T]o see enhanced serotonin signaling in the gut epithelium produce such robust antidepressant and anxiety-relieving effects without noticeable side effects was surprising even to us.”

Even better: A guts-only delivery system would be good for pregnant women. Some studies have shown that taking ‘systemic’ SSRIs during pregnancy can affect the child in ways you don’t want to. So next up: Finding a way to target SSRI delivery.

Drug politics

CVS anti-trust questions

Republicans in the US House of Representatives are looking into whether CVS Caremark threatened independent pharmacies if those pharmacies participated in pharmacy hubs not controlled by CVS. That would be violating anti-trust law, and laws are occasionally enforced against pharma companies.

Georgia considers requiring coverage of alternative pain meds

A bipartisan group of Georgia state house members — a committee looking at ways to deal with the opioid crisis — “is considering introducing legislation next year forcing insurance companies to cover the cost of alternatives to opioid pain medications.” I.e., they would have to “cover nonopioid pain management options the same way they do for opioids.”

Unjustified price hikes (now there’s a shock)

I guess it’s Econ 101: When drugs show more benefits, pharma companies raise the price because more people will be taking them.

But sometimes, just sometimes, it seems pharma raises the price of drugs even when there’s no evidence of additional benefits. That’s according to the Institute for Clinical and Economic Review.

When it comes to the 10 drugs whose price increases contributed most to a rise in U.S. medical spending in 2023 — half of those price hikes “were not supported by clinical evidence and drove costs higher by $815 million.” (And yes, those price hikes were way above the rate of inflation.)

Johnson & Johnson’s cancer drug Darzalex was on the list of price increases not backed by clinical evidence for the second time this year. A 7.6% rise in the treatment’s list price added about $190 million to U.S. spending, according to the report.

Perspective: If Ford raised the price of its F-150 truck — the most popular vehicle in the world — by 7.6% a year from its introduction in 1975, it would cost more than $145,000 today.

^* The base model sold for $4,002, or $23,233 in 2024 dollars

A different kind of antiviral

Today’s antivirals are great, for sure, but like antibiotics they’re likely to become less effective over time. A way to prevent that (or at least delay it) is by creating an entirely new class of antivirals. That’s what researchers at Rockefeller University say they’ve done.

They’ve developed an antiviral — well, a proof-of concept of one — that they say represents “a wholly new way to treat SARS-CoV-2 infections.” It might also tackle other viruses including Ebola, dengue, and poxes.

In short, rather than disrupting a virus’s proteases as antivirals like Paxlovid do, this new type of drug targets methyltransferase.

“Even in isolation, a virus would have trouble escaping this compound. But as a combined therapy along with a protease inhibitor — escape would be almost impossible.”

It has the added benefit of only affecting the virus particles, not human methyltransferases, meaning side effects should be minimal. Next up: Testing it on other viruses and even some fungal infections. And they’re looking for a drug-industry partner to turn it into a human therapy.

Another drug microbot

The latest folks to develop a microscopic drug-delivery robot are at Caltech. Medical engineers there created the usual: microrobots that can withstand the brutal inside of the body long enough to deliver their drug cargo to the target. In this case, they used a “printable” hardening hydrogel that includes magnetic nanoparticles allowing the microbot spheres to be steered to wherever in the body they’re needed^*.

They’ve tested their bots on mice (successfully), but it’ll be a while before they can do a human study.

^* That could be Star Trek technobabble. All they need to do is invert the tachyon field and reroute the beam through the main deflector.

More people can get pneumonia shot

A reminder that the latest CDC recommendation for the pneumococcal conjugate vaccine is that people 50 and older should get it. (It had been 65 and older, but that changed this October.) Considering that pneumonia killed 40,000 Americans in 2022 alone, getting the vaccine seems like a no-brainer.

When anti-vax goes to a whole new level

Apparently Robert F. Kennedy Jr.’s lawyer — who is helping review candidates for HHS positions — is so off the deep end of the bell curve when it comes to vaccines, he actually petitioned the FDA to revoke its approval of the polio vaccine. In fact, his law firm specializes in trying to prevent vaccines from being required … or even available.

It’s not known whether he receives funding from iron-lung manufacturers.

Ah, the good old days.

Nicotine reduction moves closer

It’s been on the radar since 2018, and now the FDA might finally, really and for true officially limit the amount of nicotine allowed in tobacco products. The agency submitted a proposed rule to that effect to the Office of Management and Budget, which will pull out its abacus to determine how much of an impact it might have on the budget.

When you consider how much harm smoking does — and thus how much taxpayers pay to treat people — it could be a whopping big savings.

Short takes

Respiratory update

Flu activity is still low across the country, but it’s rising a bit. Covid levels are “moderate” and also starting to rise in some parts of the country (not Georgia, though). RSV activity continues to rise.

Not a good sign

So far this year, only 2 kids in the US have died of the flu. Last flu season the total number was 205, setting a new record — and that’s not counting the 521 kids who died from complications related to the flu. And last year saw the lowest flu vaccination rate among kids in more than a decade. Probably a coincidence.

That said, this year even fewer kids have gotten the flu vaccine than last year — only 37% compared to 43% at this time in 2023.

Skin in the (vax) game

The human body naturally produces antibodies against Staphylococcus epidermidis, a harmless bacteria that lives on our skin. Stanford Med researchers found that mice, which don’t have S. epidermidis, will not only generate the same immune response if you just dab the bacteria on their fur, that response is long-lasting.

In other words, you can vaccine mice against S. epidermidis with just a skin rub.

So the Stanfordians tried something (and this is a very broad-brush description): They genetically engineered S. epidermidis to contain the tetanus toxin. Then they swabbed it on the mice. And those mice “developed extremely high levels of antibodies targeting tetanus toxin.”

Then they tried it with diphtheria. Same result. Then they tried lower and lower amounts of the tetanus toxin. Same result.

So yeah, they’ve created a topical vaccine delivery system … for mice.

“We know it works in mice,” [said the lead researcher]. “Next, we need to show it works in monkeys. That’s what we’re going to do.” If things go well, he expects to see this vaccination approach enter clinical trials within two or three years.

HIV PrEP breakthrough

Current HIV PrEP antiretrovirals (e.g., Truvada) are taken orally, and they have to be taken daily … and consistently. But an alternative — a twice-yearly shot of Gilead’s lenacapavir — appears to be 96% effective at preventing HIV, according to the company’s phase 3 study conducted by Emory University and Atlanta’s Grady Health System.

99% of the participants in the lenacapavir group did not acquire an HIV infection. During the trial, only two participants in the lenacapavir group, comprised of 2,179 people, acquired HIV. This compares to nine new HIV infections in the Truvada group, which had 1,086 people.

In fact, lenacapavir is showing itself to be so effective against HIV that it was named Science magazine’s Breakthrough of the Year.

The Long Read: Country road edition

West Virginia started covering GLP-1 agonists for its state employees, figuring it would save on medical costs in the long run. Then a couple of years later, it changed its governmental mind, leaving thousands of employees in the lurch … and gaining back weight. Read about the fallout from “West Virginia’s Weight-Loss Experiment.”

Bill would prevent PBMs from owning pharmacies

ICYMI: A bipartisan bill was introduced in Congress that would prohibit health insurers or PBMs from also owning pharmacies. For example, CVS Health would have three years to divest itself of CVS Pharmacy, while PBMs like Express Scripts would need to divest their mail-order pharmacies.

If passed, the legislation would be the most far-reaching intervention yet into the operations of pharmacy-benefit managers, known as PBMs, and their parent companies, cutting off a major source of revenue for the companies and frustration for patients.

The chances of the bill passing in this Congress are just about zero, but look for it to appear again early next year.

Amusing note: You can tell how the Wall Street Journal headline writer feels — apparently it’s a congressional “plot” to force these breakups.

Walgreens enters the endgame

Walgreens is looking to sell itself to a private equity firm next year, which likely spells the beginning of the end for the pharmacy retail giant.

Private equity firms typically take a company, run it into the ground with cost-cutting, employee-burning-out, and quality-reduction measures until employees and customers give up. Then the company goes into bankruptcy and whatever remains of the carcass is sold off.

Anyone remember Toys ‘R’ Us? The Limited? Friendly’s? Red Lobster?

This is still just a possibility, though — “looking to sell itself” isn’t the same as “signing a contract.”

Short takes

It’s malaria

The Mysterious Respiratory Virus that’s killed more than 30 people in the “Democratic” Republic of the Congo contains the malaria virus. The question remains, though: Is it just malaria, or is something mixed in with it?

The latest GLP-1 trick

A study out of Harvard Med found that GLP-1 drugs reduce the risk of venous thromboembolism — i.e., serious blood clots. Here’s the twist: It works regardless of the patients’ weight, and even before patients start losing weight. So, “It may be beyond just weight loss that there is an impact.”

Coffee … with salt

A new study once again shows the benefits of coffee. This one claims that …

[M]oderate coffee consumption (three cups per day) not only contributes to a longer life but also enhances the quality of those additional years by reducing the risk of major age-related diseases and maintaining better overall health.

Wow! And that’s just three cups, which is about 1 ½ typical mugs!

Oh, wait. The study was funded by … coffee companies (via their “Institute for Scientific Information on Coffee”).

Here at Buzz we’re optimistic about the benefits of coffee, but we don’t trust any organization that tries to obscure its bias, so here’s your grain of salt:

SCOTUS upholds 340B

The Supreme Court said it wouldn’t hear a lawsuit from drug makers (via their trade association, PhRMA) challenging a provision in Arkansas’s 340B program. The Arkansas law required pharma companies to give “discounts on drugs dispensed by third-party pharmacies that contract with hospitals and clinics serving low-income populations.” (That emphasis is critical.)

Refresher:

• The federal 340B discount program requires drug makers to discount drugs sold to hospitals that serve low-income people.
• HHS said in 2010 that those hospitals could use either in-house or contract pharmacies and still get the discounts.
• Pharma companies didn’t like this one bit, claiming that there wasn’t enough transparency with contract pharmacies. (Yes, that’s hypocrisy right there.) They started restricting sales to those pharmacies.
• Some states, like Arkansas, passed laws saying that drug makers had to give those discounts to contract pharmacies.
• Cue the PhRMA lawsuit.

Now that the Arkansas law has effectively been upheld, the matter is settled: Drug makers must give discounts on medications used by low-income patients at hospitals or clinics, regardless of the dispensing pharmacy.

Until they find a workaround, of course.

A hint of a colon cancer vaccine

Of all the strains of E. coli that might live in your gut, two of them have an interesting adaptation: They produce colibactin, a carcinogen.

Researchers at the Wellcome Sanger Institute were curious about this, especially in light of rising rates of colorectal cancer. So they looked to see who was more likely to have these particular strains in their guts. What d’ya know — they’re more prevalent in Western countries with high (well, higher) rates of colorectal cancer.

This means that if there really is a fairly direct connection between that bacteria and colorectal cancer, it might be possible to develop a vaccine — or simply some probiotics — to reduce or eliminate those strains.

B vitamins and Parkinson’s

It’s a GPhA Buzz axiom that just about every medical condition seems to involve either gut bacteria or inflammation.

Take Parkinson’s. Japanese researchers found an interesting correlation: People with the disease had lower levels of gut bacteria that synthesize vitamins B₂ (riboflavin) and B₇ (biotin). Lacking those vitamins, they found, weakened the intestinal barrier — meaning more toxins could enter the bloodstream and cause Parkinson’s inflammation.

We’d like to say there was a huge breakthrough — that B-vitamin supplements reduced Parkinson’s symptoms. Unfortunately they haven’t gotten that far … yet. They agree, however, that “Supplementation therapy targeting riboflavin and biotin holds promise as a potential therapeutic avenue for alleviating [Parkinson’s disease] symptoms and slowing disease progression.” (And they think their findings might provide more clues to Parkinson’s progression.)

Speaking of Parkinson’s…

There are treatments for the physical effects of Parkinson’s disease, but not for the cognitive decline. That might change, thanks to a protein called PNA5.

According to University of Arizona researchers, it seems to reduce the particular kind of inflammation associated with Parkinson’s; it “dials back the microglia’s overly active immune response and brings it closer to a normal state.”

It’s still in the early stages of testing, but signs, they say, are hopeful.

Short takes

HPV vax is working. A new study out of the Medical University of South Carolina found that, from 2013 to 2021, cervical cancer among American women under 25 declined by 62%, “a finding largely attributed to the wide availability of HPV vaccination for this age cohort.”

The more you know. Did you know that alcohol is a serious risk factor for cancer? If not, you’re in the majority, according to a survey from the University of Pennsylvania. “Six in 10 surveyed were unaware that regular alcohol use increases odds for developing cancer.” (Worse, 20% of people thought alcohol could lower your risk.)

Prostate cancer ‘flip’

One of the ways to fight prostate cancer is to block a particular molecular signalling pathway that seems to help tumor growth. That pathway is started by a protein called glycoprotein 130 (GP130), and it eventually activates a molecule called STAT3 — and STAT3 is critical to tumor growth.

So if you stop GP130, that cuts back on STAT3 and slows the tumor’s growth … right? That was the assumption, until Swedish researchers questioned it. What if STAT3 didn’t do what we thought?

And that’s exactly what they found to be the case. When they deliberately activated that GP130 pathway (in mice), it increased STAT3 levels as expected. But then the twist: “They could then see that the result was that the growth of the tumour was clearly slowed down in the mice due to the activation of STAT3” (emphasis ours).

Then they looked at human tissue samples and found the same thing: “those high levels of GP130 positively correlated with better survival.”

What’s next? That old mantra: More research is needed. In this case, it’s to confirm the results and see if this opens a new, ‘opposite’ way to treat prostate cancer.

Resistance gets worse

According to the WHO, antimicrobial resistance (AMR) is getting so bad that in the next 25 years it could lead to more deaths worldwide than cancer does. One solution might be better vaccinations to reduce the use of antibiotics.

As one virologist put it:

“When vaccines prevent illness, they reduce the need for unnecessary antibiotic use. In the past, antibiotics were frequently prescribed for respiratory infections — typically caused by viruses — leading to misuse and heightened resistance. By preventing viral infections through vaccines, we reduce inappropriate antibiotic prescriptions and, subsequently, AMR.”

Non-pharma cool medical story of the week

The old way of monitoring brainwaves: a whole lot of wires attached to a complicated, finicky head covering, with EEG sensors glued to the patient’s head:

The new way: temporary tattoo sensors printed on the scalp — they can even work through hair. “[O]nce dried, it works as a thin-film sensor, picking up brain activity through the scalp.”

Even better, the tattoos last longer than the traditional sensors, which dry out and lose connectivity after a few hours.

And you thought it was those butter cookies

Those shifty Danes have a lot of eggs in the Novo Nordisk basket. Macroeconomics blogger Joseph Politano explains how “Weight Loss Drugs Continue to Power Denmark’s Economy”. The boom “has been so strong that it has almost singlehandedly made Denmark one of the fastest-growing economies in the European Union.”

Better dieting through chemistry

People may want to believe otherwise because it just feels more … natural? But one doctor looked at the studies and delivers the verdict, “No, Diet and Exercise Are Not Better Than Drugs for Obesity”.

The only reason that the world isn’t comfortable with the eminently provable truth that diet and exercise are inferior to obesity medications for weight management is weight bias. The message is that people simply aren’t trying hard enough.

Kill the pain, leave the treatment

Opioids are often part of cancer treatment to help patients deal with pain. But they can also interfere with the immune system — something you don’t want when you’re giving immunotherapy.

(Science: “[M]orphine binds to an opioid receptor called OPRM1 on CD8 T cells, suppressing their activity and canceling out the invigorating effects of anti-PD1 therapy.”)

Good news out of the University of Pittsburgh, where researchers found a potential work-around. They found that peripherally restricted OPRM1 antagonists (PAMORAs) — methylnaltrexone is one — “blocked opioid-induced immunosuppression and improved response rates to immune checkpoint inhibitor therapy.”

Big ol’ caveat: This was only in mouse models, and specifically head and neck cancers, but it certainly feels like a breakthrough.

ICYMI

Vicious crime, vicious reaction

The healthcare industry may be expressing sympathy for the murder of UnitedHealthcare CEO Brian Thompson, but patients? Not so much. One social post that got the most traction read, “When you shoot one man in the street it’s murder. When you kill thousands of people in hospitals by taking away their ability to get treatment you’re an entrepreneur.”

Side note: UnitedHealthcare denies more claims than any other health insurer — we’re talking a third of them. And the company has been facing protests, lawsuits, and even a Senate investigation for its practices.

Side side note: The vitriol on Twitter/X got so bad that the company — which allows Nazi sympathizers, Russian trolls, conspiracy theorists, and hate speech without blinking an eye — took some of them down.

Should we worry yet?

At least 79 people in the “Democratic” Republic of Congo have died — and almost 400 sickened — from “a mystery flu-like disease” that health authorities there are still trying to identify. They know it’s respiratory and likely airborne, but that’s about it.

Of course, how important can a mysterious flu-like disease be when it’s in a country on the other side of the world?

Embrace the dark side

Yet another study — this one using health data from about 192,000 people over 30 years — has shown that eating dark chocolate, but not milk chocolate, can reduce your risk of type 2 diabetes.

[T]he researchers found that people who ate at least five ounces of dark chocolate per week — equivalent to five servings — had a 21 percent lower risk of developing Type 2 diabetes compared with people who rarely or never ate dark chocolate.

Moving ahead, falling behind

The US already has one of the lowest life expectancies among developed nations. It’s getting better, but a new report finds that it’s slowing compared to the rest of the world. That means we’ll drop even further in the rankings by 2050 thanks to “drug use disorders^*, high body mass index, high blood sugar, and high blood pressure” combined with our well-below-average healthcare access.

Despite the progress the U.S. has made over the last three decades, the country is forecasted to rank progressively lower than other nations globally in the average number of years a person can expect to live in good health. Known as healthy life expectancy or health-adjusted life expectancy (HALE), its global ranking is forecasted to drop from 80th in 2022 to 108th by 2050.

^* “That’s the highest drug use–related mortality rate in the world and more than twice as high as the second-highest country, which is Canada.”

Nine months of flu protection

Don’t want to get a flu shot, ladies? There could be an alternative: Get pregnant. Canadian researchers found that “pregnancy may trigger a natural immunity to boost protection against severe flu infection.

How’s that work? Apparently — at least in mice — pregnancy produces “a powerful molecule^* that boosts the body’s antiviral defenses, especially in the nose and upper airways,” thus preventing the virus from getting to the lungs.

^* Interleukin-17+ γδ+ T cells, since you asked 

Reps to DOJ: Investigate PBMs

A bipartisan group of federal legislators, including Georgia’s Buddy Carter, is asking the Department of Justice to investigate PBMs for their role in the opioid epidemic.

The letter was sparked by an investigative report by Barron’s, “Confidential Files Detail PBMs’ Backroom Negotiations—and Their Role in the Opioid Crisis.” It suggested that “the three largest PBMs colluded and conspired to steer patients towards Oxycontin in exchange for $400 million” in rebates.

Wrote Barron’s:

In total, OxyContin prescriptions sent $85 million to Express Scripts, $146 million to Optum Rx, and $173 million to CVS Caremark, according to one year of sales data between 2016 and 2017. One set of contracts between Purdue and CVS Caremark indicates that rebates increased if health plans covered higher amounts of OxyContin.

The legislators not only want the DOJ to investigate the PBMs, they are also taking aim at the vertical consolidation of the industry, as single companies own insurers, PBMs, and pharmacies, driving up costs and limiting options for patients.

Disappearing pharmacies

In just one decade — from 2010 to 2020 — a whopping 29% of pharmacies in the US closed. That includes both independent pharmacies and chains, and it affected Black and Latino neighborhoods the most.

Why? Low reimbursement rates from Medicare and Medicaid could be one reason, as could indy pharmacies being cut out of PBM networks. And of course there are the chains closing their less profitable locations.

Twist: From 2010 to 2017 the number of pharmacies actually increased, but eventually the rate of closings blew past the rate of new storefronts opening.

Elsewhere: Across the Pond

Tattoo you

If you were thinking of moving to Wales either because you hate vowels or because you want to be able to give tattoos to your patients, we’ve got some bad news. Not about the vowels (they still don’t use them there) — rather, a new Welsh law prohibits pharmacists and pharmacy techs from giving tattoos without a license.

Since 2017, they’d been allowed to provide “tattooing, body piercing, electrolysis, and acupuncture” without a license, but a new law strips that exemption.

At least someone’s preparing

Seeing the writing on the wall, the UK Health Security Agency is buying more than 5 million doses of human H5N1 flu vaccine “to boost the country’s resilience in the event of a possible H5 influenza pandemic.”

Answering the important medical questions

“3 reasons why kids stick Lego up their nose[s]”

Quick reminder

Medicare open enrollment ends this coming Saturday, December 7.

Hormone therapy risks: Not so simple

A lot of older women take various kinds of hormone therapy, especially post-menopause. Lurking in the background, though, is a fear of cardiovascular disease — that’s thanks to a 1990s study that found a risk. It focused on a single kind of hormone treatment, though, so Swedish researchers wanted to see if it still applied to today’s varied therapies.

They looked at seven different hormone treatments, and what they found was nuance. I.e., “Different menopausal hormone treatments pose different risks.”

For example, the synthetic hormone tibolone^* […] was linked to an increased risk of both heart attack and stroke, but not to an increased risk of blood clots.

Combined preparations containing both oestrogen and progesterone instead increase the risk of blood clots, including deep vein thrombosis.

They also found that patches were less risky than other delivery methods, so their next task is to break down the effects by age, medication, and delivery method to uncover that nuance.

^* Not available in the US.

Short takes

Could lung cancer be detected with a nasal swab?

A startup called OncoSwab thinks so, based on the fact that “Tumors shed compounds that can be picked up in screening tests,” and lung cancer obviously affects the airways. Thus the OncoSwab test, which is still in the early stages of development, looks for lung cancer biomarkers that make their way to the nasal passages.

Timing your Covid shot

The best time for a Covid booster, found Yale researchers, depends on geographic location and whether you’ve had a breakthrough infection. “[O]ptimal booster dates precede peak Covid-19 transmission by about 2.7 months,” so in the Northern Hemisphere that means “Administering boosters in September or October can provide up to three to four times more protection against infection compared to booster shots given later in the year.” (But, if you get a breakthrough infection in the fall, it’s best to wait several months for a booster.)

The next long Covid suspect

Health researcher have barely agreed on what long Covid is, and they’re still trying to figure out what causes it. The latest suspect comes from Australia, where immunologists at the Burnet Institute think there’s a “compelling case” that long Covid is actually caused by the virus lingering in the body.

They reached this conclusion after looking at details from several studies on the condition, such as more than one that …

… detected replicating viral RNA and proteins in blood fluid of patients years after their initial infection, a sign that the virus is likely replicating for long periods in some hidden reservoirs in the body, perhaps including blood cells.

In fact, evidence of viral activity seemed to be common in these studies. (The GI tract is “of considerable interest.”) And while they can’t say so conclusively, “we and other scientists argue the cumulative evidence is now sufficiently compelling to galvanise action.”

Pot for thought: kids, psychosis, and cannabis

Earlier this year there was a study that found that kids who used cannabis were a lot more likely to develop psychotic disorders — 11 times more likely, in fact.

Well then.

But now the twist: A new study that looked at 4 years of data on almost 12,000 kids aged 9–10 found that those psychosis-spectrum symptoms tended to appear before they started using cannabis. And “symptoms typically did not increase after initiation.”

In other words, the arrow of causation seems to point to psychosis leading to cannabis use, rather than the other way around.

The Long(ish) Read: Drug-war casualties

The drug crisis has been around for decades, to the point that there are survivors who are now in their 70s. The Wall Street Journal looks at one of them.

When drugs beat surgery

When a kid gets appendicitis, surgery is the obvious solution; appendectomies are a dime a dozen. (Well, not here. In the US, while being incredibly common, they’re “one of the costliest surgical procedures performed during hospital stays.”)

They’re so expensive that surgeons, led by a team at Nationwide Children’s Hospital, looked into whether IV antibiotics are a way for parents to save money on their kids’ care.

And yep, publishing in the Journal of the American College of Surgeons (!), they concluded that it’s more cost effective to use drugs than to use surgery.

“This cost analysis demonstrates that nonoperative management for pediatric uncomplicated acute appendicitis is the most cost-effective management strategy over one year, compared to upfront surgery.”

Side note: Appendectomies cost almost three times as much here as in the UK or Switzerland, so an overseas vacation could be a cost-saving option, too.

Pleasure-free opioids

The problem with opioids is that they have a way of combining pleasure and pain relief, and the result (as we know) is addiction.

What if you could keep opioids’ pain-killing effect, but block its pleasure effect? That’s exactly what a couple of researchers in New York say they’ve done by combining opioids with a drug called an MAGL inhibitor, “which increases the level of an endocannabinoid, known as 2-AG, in the brain.”

Conventional wisdom said that endocannabinoids would increase the opioids’ pleasurable effect, but that turns out not to be the case. Instead, the MAGL inhibitor blocks the release of dopamine, thus removing the pleasure (other than the pleasure of not being in pain).

So far it’s only been tested — successfully — in mice, but if it works in humans it “[has] the potential to meaningfully change pain medicine.”

A better asthma treatment

For a flare-up of asthma or COPD, five days of prednisolone is the standard treatment. But British researchers have found a better option: a single, higher dose injection of benralizumab.

Typically, low-dose benralizumab is used for longer-term treatment, but when given in a higher dose during an asthma or COPD flare-up, it worked better and longer at keeping symptoms at bay.

After 28 days, respiratory symptoms of coughing, wheezing, breathlessness, and sputum were found to be better in those on benralizumab, whether or not they were also on steroids. After 90 days, there were four times fewer people in the benralizumab group who failed treatment compared with those receiving steroids.

They also found that the benralizumab injection’s effect lasted longer, meaning fewer trips to the doctor or hospital. And, of course, it also avoids the side effects associated with steroids.

Bonus: Yes, they do call it a “game-changer.”

Why GLP-1s fail

As many as 20% of people taking GLP-1 agonists don’t respond (or don’t respond well) to the drugs, but the drug makers claimed the number was only 10–15%. What happened?

Sure, the companies exaggerated the effect — they did the same when it came to hyping the amount of weight that’s typically lost. But that’s only part of the issue. A British physiologist explains all the other factors that didn’t appear in the clinical trials, from genetics to simple lack of formal support.

When your only tool is insulin, every problem is a carbohydrate

Automatic insulin delivery systems might have a problem. As British researchers found, there’s a lot more affecting blood glucose levels than just carbohydrates, but insulin delivery systems only have one tool: insulin. If something else is affecting glucose levels — e.g., hormones, exercise, stress — patients will still get a dose of insulin, even when there are no excess carbs to respond to.

The problem is that, while we might have a general idea of these other factors, we don’t have specific information about their effects.

For factors beyond carbohydrates to become more systematically included in clinical practice, scientists need to find a way to measure and quantify their impact and utilise this information in insulin-dosing.

In the meantime, clinicians are left with a single blunt instrument until more research can be done.

ICYMI

The Biden administration is proposing that Medicare and Medicaid cover GLP-1 agonists to help reduce obesity and all the issues that come with it. Although Medicare is prohibited from covering weight-loss drugs (to avoid cosmetic use), CMS’s angle is that the drugs are treatments for obesity.

This sets up a cage match between incoming HHS secretary-nominee Kennedy (anti GLP-1s) and incoming CMS administrator Oz (pro GLP-1s).

Saving you a click

“Need to sleep? Study pinpoints optimal melatonin dosage and timing”

4 mg of melatonin three hours before bedtime maximized the sleep-inducing effects of the hormone.

Bird flu follow-up

Canadian officials have given up trying to figure out where a British Columbian teen contracted bird flu: “an exhaustive investigation of the people and domestic animals the unnamed teen had contact with shed no light on how the teen became infected.”

The kid has improved from critical to serious condition, but still requires a ventilator. He or she is showing signs of recovery, though.

Weird science

Did you have to let it linger? (Press 1 for yes)

Concerned about “excessive flatulence,” the Australian national science agency is asking residents to sign up for the continent-wide “Chart your Fart” campaign. Participants download an app and record their gas-passing ‘events,’ with the option to rate them for (seriously) stench, loudness, duration, linger, and detectability.

The Chart Your Fart app is designed to better understand the flatulence patterns and concerns of Australians as part of our public-led research in the area of health and wellbeing.

Every one of you will look at your hands

Women whose ring finger is significantly longer than their pointer might be more likely to have alcohol-dependence issues. Yep, that’s what a new British study found.

There’s actually a logic behind it. The hypothesis is that a longer ring finger indicates more testosterone exposure before birth, and men tend to have more alcohol issues than women.

In fact, the same lead researcher — who really has a thing for finger length — previously found associations between finger-length ratio and Covid outcomes and oxygen consumption.

RIP, John Tinniswood

At 112 — born August 26, 1912 — the British man was the world’s oldest living man. He died this past Monday.