Microsoft Says Its AI Medical Tool is 4x Better Than Doctors at Diagnosing Patients

By Crystal Lindell

Microsoft is making some bold claims about the medical diagnosis tool it’s developing using artificial intelligence (AI). The company claims it is four times more accurate than a group of experienced physicians and can “solve medicine’s most complex diagnostic challenges.”.

Specifically, Microsoft’s AI Diagnostic Orchestrator – MAI-DxO for short — was able to correctly diagnose 85% of complex medical cases published in the New England Journal of Medicine (NEJM).

By comparison, when the company asked 21 practicing physicians from the US and UK to look at the same medical cases and provide a diagnosis, the human doctors were only accurate 20% of the time. 

In a demonstration video, Microsoft showed that MAI-DxO was able to order medical tests and provide the estimated financial costs for each test. It was then able to evaluate the test results and arrive at the correct diagnosis, even if the diagnosis was for an incredibly rare disease. 

“Our MAI-DxO orchestrator can handle some of the world’s toughest diagnoses with higher accuracy and lower costs. It puts us on the path to medical superintelligence - a big step towards better, more accessible care for all,” Microsoft said.

The company said it began testing its medical AI diagnosis systems with the United States Medical Licensing Examination, which is the same exam that physicians must pass to practice medicine in the United States. The test is a standardized assessment of clinical knowledge and decision making. 

But the fact that it was a standardized test made it too easy for AI. Microsoft said its orchestrator was able to get near-perfect scores within just three years. 

"These tests primarily rely on multiple-choice questions, which favor memorization over deep understanding," the company said. "By reducing medicine to one-shot answers on multiple-choice questions, such benchmarks overstate the apparent competence of AI systems and obscure their limitations."

To make its evaluations more challenging, Microsoft turned to having its AI evaluate the real-life cases published in the NEJM. 

MAI-DxO was configured to operate within different sets of cost constraints – just like in the real world when a patient’s care may be determined by what kind of health insurance they have, if any. That’s an important feature because without financial constraints, the orchestrator might default to ordering every possible test – regardless of cost, delays in care, or patient discomfort.

They also found that MAI-DxO delivered both higher diagnostic accuracy and lower overall costs than physicians or any other model they tested.   

"AI [could] reduce unnecessary healthcare costs,” the company said. "This kind of reasoning has the potential to reshape healthcare.”

Microsoft also touched on something that many patients with complex health challenges already know: the medical system is often overly reliant on siloed medical specialists. That’s another area where the company sees AI potentially improving patient care. 

With general practitioners treating a wide array of conditions and specialists focused on a single area of expertise, the hope is that AI would essentially be able to pull medical knowledge from both. 

While MAI-DxO seems to excel at tackling the most complex diagnostic challenges, Microsoft says further testing is needed to assess its performance on more common, everyday health conditions.

They also acknowledged that the clinicians in their study worked without access to colleagues, textbooks, or even AI – all tools that they may have in their day-to-day clinical practice. This was done to enable a fair comparison to raw human performance, but it also means that its unclear just how well AI actually competes against real-world physicians.

MAI-DxO is not available for commercial use yet. Microsoft said they need to do more testing to evaluate its reliability, safety, and efficacy. That could take about a decade. 

“It’s pretty clear that we are on a path to these systems getting almost error-free in the next 5-10 years. It will be a massive weight off the shoulders of all health systems around the world,” Mustafa Suleyman, chief executive of Microsoft AI, told The Guardian.

Descending Pain: A New Way to Control Severe Chronic Pain

By Dr. Forest Tennant and Ingrid Hollis

The control of severe chronic pain in medical practice today is almost exclusively based on “ascending” or “neuropathic” pain:

Ascending pain occurs when a pain signal is transmitted from the site of injury or disease up the spinal cord to the brain. Neuropathic pain is the pain that results when there is damage or dysfunction of nerve tissue in the brain, spinal cord or peripheral nerves. 

In recent years, researchers discovered that when chronic pain centralizes, it creates a third type of pain called “descending” pain. This is a critical issue for persons with adhesive arachnoiditis and other diseases that cause severe chronic pain, because descending pain requires different medications than those used for ascending and neuropathic pain.

A person with constant pain will produce excess bioelectricity (central sensitization or centralized pain) in the glial cell matrix of the brain. This bioelectricity “descends” or travels down the spinal cord and vagus nerve. It not only produces pain, but over-stimulates the cardiovascular system. 

Descending pain is controlled by the noradrenergic receptor.  The neurotransmitter to this receptor is called noradrenalin or norepinephrine. 

Symptoms of Descending Pain

Descending pain will be present in persons who have constant, unremitting pain. Here are the symptoms:

  • Pulse rate elevates

  • Periodic hot flashes

  • Cold hands/feet

  • Excess sweating

  • Allodynia (pain upon light touch) 

Over-Reliance on Opioids and Neuropathic Agents

The lack of awareness about descending pain is one reason why high doses of opioids and neuropathic agents (i.e., gabapentin, diazepam) may be over-prescribed. Physicians may simply raise the opioid or gabapentin dosage if they are not aware that the cause is descending pain.  What’s more, the increase in dosage may be ineffective or even harmful.

This also applies to opioids in implanted pumps.  Countless persons have been treated with an implanted device or “pain pump” with the erroneous belief that no medication, except intrathecal opioids, are needed.  Patients with these devices soon learn that their pain is poorly controlled by opioids alone. 

Opioids and neuropathic agents have little effect on descending pain.  It must be treated separately.

Pain treatment and relief are based on a medicinal that activates or stimulates a specific receptor (think “action point”) that is present in nerve cells in the brain, spinal cord or peripheral nervous system. Here is how the three types of pain and their receptors can be treated:

  1. Ascending pain needs to be treated with medications that activate the endorphin or opioid receptor. 

  2. Neuropathic pain control depends on activation of a receptor called gamma amino butyric acid (GABA). 

  3. Descending pain control must activate the norepinephrine (noradrenalin) receptor.

To achieve good control of severe, chronic or intractable pain, all three of these receptors must be simultaneously activated.  Severe chronic pain is commonly undertreated, because all three receptors are not simultaneously activated.

Medication Classes for Descending Pain

Three medication classes are used to treat descending pain.  Medical practitioners and patients have choices, and can experiment to help decide which medications and supplements bring the most comfort.

  1. Bioelectric Blockers: Tizanidine, propanolol, clonidine, tapentadol (Nucynta).

  2. Receptor Activators: Modafanil (Provigil), methylphenidate (Ritalin), dextroamphetamine, amphetamine salts (Adderall), phentermine, lisdexamfetamine (Vynanse). Non-prescription activators: lion’s mane, mushroom extract, St. John’s wort, rhodiola, mucuna, whole adrenal gland.

  3. Precursor (Amino Acids) of Noradrenaline: Phenylalanine at 1,000 to 2,000mg a day. Tyrosine at 1,000 to 2,000mg a day.

When not controlled, chronic pain, inflammation and autoimmunity will deplete a number of neurotransmitters and hormones.  When that happens, noradenaline (norepinephrine) will often be depleted. 

Supplements of either amino acids (phenylalanine or tyrosine) and daily protein intake may help reduce both background and flare pains. Phenylalanine and/or tyrosine need not be taken every day, but they are highly recommended at least two days a week. They can and should be taken with a bioelectric blocker or receptor activator.

Noradrenergic receptor activators do not raise pulse rate or blood pressure in a constant pain patient like they do in a normal person.  They may actually lower blood pressure and pulse rate.  That’s because chronic pain, inflammation and autoimmunity deplete noradrenalin.

One medication, tapentadol (Nucynta), is both an opioid and norandrenergic blocker. It is highly recommended.

Descending pain is a new discovery that must be recognized and controlled to achieve relief from severe chronic pain.  A sole reliance on opioid and neuropathic agents may often provide inadequate pain relief.

To learn more about descending, ascending and neuropathic pain, you can watch a recent episode of DocToks with Dr. Forest Tennant and Friends.

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. Readers interested in learning more about his research should visit the Tennant Foundation’s website, Arachnoiditis Hope. You can subscribe to its bulletins here.

Ingrid Hollis is a person in pain, patient advocate, and advisor to the Tennant Foundation.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.   

Why Ice Cream May Be Bad for Your Gut Health

By David Hilzenrath, KFF Health News

It’s a marvel of food technology: ice cream that resists melting. In a video explaining the science behind it, a seller of food chemicals shows scoops of ice cream holding their shape under hot lights. The super ingredient? Polysorbate 80.

Polysorbate 80 is an emulsifier, a chemical used to control the consistency of thousands of supermarket products. Other widely used emulsifiers or stabilizers include carboxymethyl cellulose, carrageenan, and maltodextrin.

Recently, such ingredients have been showing up in scientific studies for another reason: Researchers say they may cause a variety of health problems.

Studies have found that emulsifiers can alter the mix of bacteria in the gut, known as the microbiome or microbiota; damage the lining of the gastrointestinal tract; and trigger inflammation, potentially contributing to problems elsewhere in the body.

Emulsifiers and stabilizers are among the most common ingredients in ultra-processed foods, a prime target of the “Make America Healthy Again” campaign by Health and Human Services Secretary Robert F. Kennedy Jr.

They are on the department’s radar: Their potentially harmful effects were flagged in a document HHS recently produced to support Kennedy’s drive to eliminate petroleum-based food dyes. But they illustrate the complexity of the war on food additives.

They show how, when it comes to food science, regulators are chronically playing catch-up. In the meantime, for many ingredients, regulators and consumers alike are left in a gray zone between suspicion and proof of harm in humans.

Emulsifiers’ assault on the microbiome could help explain inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis, metabolic disorders, and even cancer, the studies suggest.

“There is a lot of data showing that those compounds are really detrimental for the microbiota and that we should stop using them,” said Benoit Chassaing, a research director at the French National Institute of Health and Medical Research and a co-author of several related studies.

Yet much larger and more ambitious clinical trials in humans are needed, Chassaing added.

For Lewis Rands, who has suffered from gastrointestinal illness, the research fits his own experience as a consumer. Changing his diet to avoid emulsifiers has made a shocking difference, easing symptoms that were debilitating, Rands said.

“Clinically, many patients have reported an improvement in symptoms with such changes,” said Ashwin Ananthakrishnan, a gastroenterologist and researcher at Massachusetts General Hospital.

The scientific findings come with caveats. For instance, much of the research has been done in mice, or by mimicking the human gut in a tube. There are many unknowns. Not all emulsifiers have bad effects, or the same effects, and some people are thought to be much more vulnerable than others.

Even some researchers who have co-authored papers say that the substances have not been proven harmful to humans and that it’s too soon to say regulators should ban them.

Still, the research poses a challenge for the FDA. When emulsifiers began spreading through the food supply, the agency wasn’t focusing on the gut microbiome, a relatively recent scientific frontier, researchers said.

Martin Makary, appointed by President Donald Trump to head the FDA, mentioned the microbiome at his Senate confirmation hearing in March. Though he didn’t cite emulsifiers specifically or identify chemicals by name, he said substances that affect the microbiome deserve the FDA’s attention.

“There’s a body of research now that suggests concern with some of these ingredients,” Makary said. “We have to look at those ingredients, and you have my commitment to do so if confirmed as FDA commissioner.

“These chemicals are creating an inflammatory response in the gastrointestinal tract, and with an altered microbiome lining that GI tract, kids feel sick.”

The FDA and the Department of Health and Human Services did not respond to questions about Makary’s testimony.

However, when journalist Emily Kopp asked HHS for the science behind its recent announcement that it is phasing out petroleum-based food dyes, the agency provided a compilation of information on potentially harmful compounds commonly found in ultraprocessed foods. The document, which appeared to be a draft, included a section on emulsifiers, such as xanthan gum and carrageenan. It noted that the section needed more work.

HHS subsequently provided the document to KFF Health News.

As far back as 2020, an international organization for the study of inflammatory bowel diseases advised that, for people with those conditions, it “may be prudent to limit intake” of maltodextrin, carrageenan, carboxymethyl cellulose, and polysorbate 80.

Emulsifiers are developed from a variety of sources, including plants and bacteria. Some ingredients that might affect the microbiome show up in foods because they were deemed “generally recognized as safe,” or GRAS.

“New information may at any time require reconsideration of the GRAS status of a food ingredient,” the Code of Federal Regulations says.

Ben & Jerry’s vs Häagen-Dazs

Rands, a genetic scientist, took matters into his own hands to battle severe inflammatory bowel disease. The illness caused bloating, stomach pain, cramps, frequent bowel movements, and bleeding, he said.

It left him in a constant state of anxiety and stress, he added, wondering where the nearest bathroom was and whether he’d reach it in time. Even taking a walk around the block with his wife and baby near their home in Australia was problematic.

Then, on the advice of a dietitian, Rands began avoiding foods with emulsifiers: chemicals such as carboxymethyl cellulose, carrageenan, guar gum, xanthan gum, and maltodextrin — plus other additives.

For instance, instead of eating Ben & Jerry’s ice cream, he switched to Häagen-Dazs ice cream that is free of the substances at issue. The relief was dramatic.

“It’s a huge difference,” Rands said. “To me, it’s made more of a difference than any drug.”

He has been able to scale back or stop taking several drugs, which is an added relief — not least because some can have harmful side effects, and, he said, one was taking its toll.

Rands said he used a scientific approach, isolating variables in his diet and logging the results. Avoiding artificial sweeteners helps, he said, but most of the benefit relates to avoiding the emulsifiers.

Ben & Jerry’s did not respond to a request for comment.

‘Science That Hasn’t Been Done Yet’

The Consumer Brands Association, which represents makers of processed foods, stands behind use of the chemicals.

“Food safety and protecting the integrity of the food supply is priority number one for the makers of America’s food and beverage products,” Sarah Gallo, the group’s senior vice president of product policy, said in a statement. “Emulsifiers and thickening agents play an important role in improving food texture and consistency, and have been studied by the FDA through a rigorous scientific and risk-based process.”

Asked for specifics on how the FDA had analyzed potential effects on the microbiome, the group did not respond.

Chassaing said the chemicals were “never considered for the potential effect on the microbiota.”

Robert Califf, who led the FDA under Presidents Barack Obama and Joe Biden, said in an interview that scientists are just beginning to understand the microbiome. He compared it to where the field of genomics was 20 years ago, only much more complicated — “multiplied by a thousand dimensions.”

He said the substances “fell within the standards” when they were greenlighted. “But hopefully most people agree that the standards need to be upgraded,” he added.

“This is different than traditional food safety thinking about, ‘Does it cause an immediate problem?’” Califf said. “We’re talking about long-term health outcomes here.”

And has the FDA evaluated those?

“How could it? There was no way to do it,” Califf said. The answers will vary depending on the emulsifier, and “proving whether it’s bad or good is going to require rigorous science that hasn’t been done yet.”

More recent scientific capabilities expand the possibilities, he said.

‘A Lot of Confusion in the Field’

For a consumer, trying to steer clear of emulsifiers can be difficult. Without realizing it, people can consume a variety of emulsifiers from a variety of foods — and the same chemicals from multiple sources.

Polysorbate 80 was listed as an ingredient on the labels of 2,311 products as of May 12, according to an online database posted by the Environmental Working Group using information from NielsenIQ. Carrageenan was listed on 8,100 product labels; maltodextrin, 12,769; and xanthan gum, 17,153.

Some emulsifiers have multiple names, making them harder to recognize. Some names can apply to more than one emulsifier. And some chemical names that appear on product labels don’t appear in the FDA’s “Substances Added to Food” inventory.

Carboxymethyl cellulose — not to be confused with methyl cellulose — is also known as carboxymethylcellulose  and cellulose gum. Maltodextrin can be derived from substances such as cornstarch, rice starch, and wheat starch — but the FDA doesn’t consider it synonymous with the term “modified food starch.”

The naming practices can frustrate efforts to track the chemicals in food, to measure how much of the stuff people are taking in, and even to figure out precisely which chemicals a scientific study evaluated, researchers said.

“There’s a lot of confusion in the field,” said Christine McDonald, a researcher at the Cleveland Clinic who has studied maltodextrin. She called for more consistent naming of additives in the United States.

The very term “emulsifier” is problematic. By strict definition, emulsifiers create an emulsion — a stable blend of liquids that would not otherwise mix, such as oil and water. However, the term is used broadly, encompassing chemicals such as maltodextrin that thicken, stabilize, or alter texture.

Gummed Up

Emulsifiers can be found in foods marketed as natural or healthy as well as ones that look artificial. Some products contain multiple emulsifiers.

Products sold at Whole Foods, for instance, list a variety of emulsifiers on their labels. 365 brand Organic Vegan Ranch Dressing & Dip contained organic tapioca maltodextrin and xanthan gum.

Pacific Seafood Starfish brand Cornmeal Crusted Fishsticks — marked as wild-caught and MSC-certified (sustainably sourced) — contain guar gum. Flour tortillas by 365 included monoglycerides of fatty acids and “stabilizer (guar gum, xanthan gum, carrageenan).”

At a Safeway supermarket, Healthy Choice Grilled Chicken Pesto With Vegetables listed modified potato starch, modified corn starch, carrageenan, xanthan gum, and guar gum.

The label on Newman’s Own Caesar salad dressing said the product contained no artificial preservatives or flavors, no colors from an artificial source, and was gluten-free. The ingredient label listed, “as a thickener,” xanthan gum.

In response to questions for this article, Whole Foods Market said it prohibits more than 300 ingredients commonly found in food.

“Our experts evaluate ingredients for acceptability in all food products we sell based on the best available scientific research,” the company said in a statement provided by spokesperson Rachel Malish.

Safeway’s parent company, Albertsons Companies, did not respond to inquiries. Nor did Pacific Seafood, Newman’s Own, or Conagra Brands, which makes Healthy Choice.

A Growing Body of Research

Research on emulsifiers has been building in recent years.

For example, a study published in January by the Journal of Crohn’s and Colitis concluded that a diet low in emulsifiers is an effective treatment for mild or moderate Crohn’s disease. The eight-week clinical trial, which tracked 154 patients in the United Kingdom, focused on carrageenan, carboxymethyl cellulose, and polysorbate 80.

A study published in February 2024 in the journal PLOS Medicine found that higher intakes of carrageenan and mono- and diglycerides of fatty acids were associated with higher risks of cancer. The study observed 92,000 French adults for an average of 6.7 years.

A study published in September 2023 in The BMJ, formerly known as the British Medical Journal, found that intake of several types of emulsifiers was associated with the risk of cardiovascular disease. The study observed more than 95,000 French adults for a median of 7.4 years.

A series of earlier studies found that emulsifiers “can promote chronic intestinal inflammation in mice”; that two in particular, carboxymethyl cellulose and polysorbate 80, “profoundly impact intestinal microbiota in a manner that promotes gut inflammation and associated disease states”; and that, based on a laboratory study of human samples, “numerous, but not all, commonly used emulsifiers can directly alter gut microbiota in a manner expected to promote intestinal inflammation,” as recounted in a 2021 paper in the journal Microbiome.

Other findings diverge. A study from Australia, published in February in Alimentary Pharmacology and Therapeutics, followed 24 Crohn’s patients over four weeks and concluded that, in the context of a healthy diet, the emulsifier content had “no influence over disease activity.”

The authors declared conflicts of interest, including payments from PepsiCo, drug companies, and Mindset Health Pty, which promotes hypnosis-based therapy. One of the authors, gastroenterology professor Peter Gibson of Monash University in Australia, said the conflicts of interest “have nothing whatsoever to do with the study.”

“It is important not to overinterpret results of studies,” he said, adding that his team’s report “does not mean that emulsifiers are good for you or that there are no health benefits in avoiding emulsifiers.”

Häagen-Dazs ‘Keeps It Real’

Häagen-Dazs touts the absence of such chemicals as a virtue. “Keeping it real, the way it should be,” it said in an online plug for its vanilla ice cream. “No emulsifiers. No stabilizers.”

However, at the company that makes Häagen-Dazs in the United States, Dreyer’s Grand Ice Cream, there are limits to that approach.

Under other brand names — such as Edy’s, Dreyer’s, and Drumstick — it markets products that contain emulsifiers or stabilizers. The company did not respond to questions. In addition, a spokesperson for Nestlé, which markets Drumstick and Häagen-Dazs brands internationally, did not respond.

Drumstick Vanilla Caramel Sundae Cones have no artificial flavors or colors, the package says — but they feature an array of other ingredients, including soy lecithin, guar gum, monogylcerides, and carob bean gum.

The cones, the company’s website says, offer “one incredibly creamy experience.”

But the creamy filling doesn’t melt. Instead, over 24 hours on a KFF Health News reporter’s kitchen counter, it bled a caramel-tinged fluid and shrank into a sticky white foam that could be cut with a knife.

KFF Health News is a national newsroom that produces in-depth journalism about health issues.

RFK Jr. Wants Everyone To Use Health Wearables. Should Patients Be Worried?

By Crystal Lindell

Call me a conspiracy theorist if you want, but I’m skeptical about a governmental push to get everyone to use health wearables. 

How much day-to-day or even minute-to-minute data do we really need about patients? And how much health data do we really want stored in the data cloud in the sky, for anyone to access? 

Health wearables is a broad category that typically includes everything from Apple Watches to blood glucose patches. And Robert F. Kennedy Jr., Secretary of Health and Human Services, has launched a new initiative to get everyone to use them. 

He spoke about it during a recent hearing of the House Subcommittee on Health, as reported by ABC News. 

"It's a way … people can take control over their own health," Kennedy said. “They can take responsibility. They can see, as you know, what food is doing to their glucose levels, their heart rates and a number of other metrics as they eat it, and they can begin to make good judgments about their diet, about their physical activity, about the way that they live their lives.

"We think that wearables are a key to the MAHA agenda -- Making America Healthy Again. My vision is that every American is wearing a wearable within four years."

It might sound good at first. After all, a continuous glucose patch is more convenient for a diabetic than having to constantly prick their finger for their glucose readings. 

But I think patients should remain skeptical of such a push for more health wearables – especially when it's coming from the government. 

First, I do think there’s such a thing as too much data. Most people don’t need to know exactly what their blood glucose level is at every moment of the day. I have relatives who’ve used glucose patches, and not only were the readings often inaccurate, but the very expensive patches were also hard to apply and fell off early.

In other words, having continuous data does not inherently make a health monitor better than alternatives. 

Also, having access to how many steps you’re taking daily or what your heart rate is during a workout can quickly turn into an obsession, trying to get arbitrary numbers to show up on your device. 

Can Tech Be Trusted?

Beyond that though, I do think people should be skeptical about multiple stakeholders having access to a bunch of our health data. 

Tech companies that create the devices can’t be trusted to use the data responsibly or to keep it private. They already routinely hand over cell phone data to law enforcement agencies

Recently a bankruptcy judge approved the sale of 23andMe's genetic data on 15 million people to a research institute. Many of those users are now scrambling to delete their data before the sale is completed. 

I’m also not convinced health care providers can be trusted with it either. I can imagine a world where doctors look at heart rate data from your Oura Ring and declare that it’s too steady, and thus you must not really have chronic pain. 

Patients will never win though, as I’m sure doctors will be just as likely to dismiss data that would show that your pain is legitimate as “some gimmicky” information from a tech company. 

And God forbid they create a mass-produced device that can measure something like opioid use through our sweat and then make pain patients wear it to show doctors if they’re using their medication exactly as prescribed.

That’s not so far-fetched. Years ago, a tech company developed an experimental wristband device that tracked skin temperature and movement, and tested it on ER patients given opioids for acute pain. The theory was that opioid users are more likely to fidget or show restless activity when they feel it’s time for another dose, so that would be an easy way to track their opioid use.  

More recently, another company has been developing a smartphone app that can evaluate your health and vital signs just by analyzing a selfie image taken by the camera on your phone.

But again, it’s the fact that this whole push for more wearables is coming from a government agency that should really alarm people.

If they gain access to it, they could use it to kick people off programs like Medicaid, increase insurance premiums, and potentially even arrest people. I especially worry that low-income patients could be coerced into using health wearables in order to continue to qualify for benefits and access to services. 

Remember the COVID vaccine conspiracy theory that the government was using the vaccines to inject small microchip trackers into everyone? It was obviously untrue, but now the government literally wants everyone to wear health trackers. That should alarm anyone who was ever concerned about governmental surveillance.

My advice to patients is to resist using too many health data trackers. Yes, they can be helpful in some cases. But there is a point where both the wearer and the monitors have too much access to data. 

At the end of the day, the real question is, who will be tracking the health trackers?

Poor Pain Treatment in ER Raises Risk of Opioid Misuse Later

By Pat Anson

Patients with acute pain who are dissatisfied with their pain treatment in emergency departments are more likely to misuse opioids three months later, according to a new study. The findings are particularly true for black patients, who are more likely to be unhappy with their treatment and to be sent home without an opioid prescription.

“While a great deal of studies on opioid misuse focus on overprescribing, this study flips the script by showing that under-prescribing—or more precisely, ignoring a patient’s pain treatment preferences—can also lead to harmful outcomes, especially when patients are dissatisfied with their care,” said Max Jordan Nguemeni Tiako, MD, an assistant professor at the David Geffen School of Medicine at UCLA and lead author of the study in the Journal of General Internal Medicine.

Previous studies have found disparities in pain treatment between white and black patients in emergency rooms, with white patients 26% more likely to get opioid medication. This new study has similar findings, but went a step further to see what the long-term consequences of poor treatment could be.

Nguemeni Tiako and his colleagues analyzed data for 735 ER patients treated for acute back or kidney stone pain, and surveyed them about their experiences 90 days later. The survey asked a series of questions about their medication use, appointment problems, emotional/psychiatric issues, and drug misuse --- and then assigned a current opioid misuse (COMM score) based on their answers.

Researchers found that black patients (21.8%) were more likely than white patients (15%) to have an “unmet opioid preference” when they were discharged from the ER. They were also more likely to be dissatisfied with their pain treatment overall.

Black patients with poor satisfaction and unmet opioid preferences had higher COMM scores compared to white patients. Both blacks and whites who were highly satisfied with their pain treatment had low risk of opioid misuse.

“The finding that unmet opioid preference had a unique effect on opioid misuse risk among Black participants is consistent with our prior analyses of this cohort, in which we found that receiving a prescription for opioids at discharge was associated with lower odds of reported non-prescribed opioid use,” researchers reported.

“Similarly novel to our study is the finding that satisfaction with pain treatment significantly mediates the impact of unmet preference on opioid misuse, especially among Black participants.”    

While an unmet preference for opioids may lead some patients to seek relief through nonprescribed opioids, researchers think other factors in the ER could mitigate such risks, such as more empathy by providers, more patient-centered communication, and patient education about effective therapies and opioid risks.

Brain Receptor May Hold Key to Treating Neuropathic Pain  

By Pooja Shree Chettiar and Siddhesh Sabnis  

Pain is easy to understand until it isn’t. A stubbed toe or sprained ankle hurts, but it makes sense because the cause is clear and the pain fades as you heal.

But what if the pain didn’t go away? What if even a breeze felt like fire, or your leg burned for no reason at all? When pain lingers without a clear cause, that’s neuropathic pain.

We are neuroscientists who study how pain circuits in the brain and spinal cord change over time. Our work focuses on the molecules that quietly reshape how pain is felt and remembered.

We didn’t fully grasp how different neuropathic pain was from injury-related pain until we began working in a lab studying it. Patients spoke of a phantom pain that haunted them daily – unseen, unexplained and life-altering.

These conversations shifted our focus from symptoms to mechanisms. What causes this ghost pain to persist, and how can we intervene at the molecular level to change it?

More Than Just Physical Pain

Neuropathic pain stems from damage to or dysfunction in the nervous system itself. The system that was meant to detect pain becomes the source of it, like a fire alarm going off without a fire. Even a soft touch or breeze can feel unbearable.

Neuropathic pain doesn’t just affect the body – it also alters the brain. Chronic pain of this nature often leads to depression, anxiety, social isolation and a deep sense of helplessness. It can make even the most routine tasks feel unbearable.

About 10% of the U.S. population – tens of millions of people – experience neuropathic pain, and cases are rising as the population ages. Complications from diabetes, cancer treatments or spinal cord injuries can lead to this condition. Despite its prevalence, doctors often overlook neuropathic pain because its underlying biology is poorly understood.

There’s also an economic cost to neuropathic pain. This condition contributes to billions of dollars in health care spending, missed workdays and lost productivity. In the search for relief, many turn to opioids, a path that, as seen from the opioid epidemic, can carry its own devastating consequences through addiction.

GluD1: A Quiet But Crucial Player

Finding treatments for neuropathic pain requires answering several questions. Why does the nervous system misfire in this way? What exactly causes it to rewire in ways that increase pain sensitivity or create phantom sensations? And most urgently: Is there a way to reset the system?

This is where our lab’s work and the story of a receptor called GluD1 comes in. Short for glutamate delta-1 receptor, this protein doesn’t usually make headlines. Scientists have long considered GluD1 a biochemical curiosity, part of the glutamate receptor family, but not known to function like its relatives that typically transmit electrical signals in the brain.

Instead, GluD1 plays a different role. It helps organize synapses, the junctions where neurons connect. Think of it as a construction foreman: It doesn’t send messages itself, but directs where connections form and how strong they become.

This organizing role is critical in shaping the way neural circuits develop and adapt, especially in regions involved in pain and emotion. Our lab’s research suggests that GluD1 acts as a molecular architect of pain circuits, particularly in conditions like neuropathic pain where those circuits misfire or rewire abnormally. In parts of the nervous system crucial for pain processing like the spinal cord and amygdala, GluD1 may shape how people experience pain physically and emotionally.

Fixing the Misfire

Across our work, we found that disruptions to GluD1 activity is linked to persistent pain. Restoring GluD1 activity can reduce pain. The question is, how exactly does GluD1 reshape the pain experience?

In our first study, we discovered that GluD1 doesn’t operate solo. It teams up with a protein called cerebellin-1 to form a structure that maintains constant communication between brain cells. This structure, called a trans-synaptic bridge, can be compared to a strong handshake between two neurons. It makes sure that pain signals are appropriately processed and filtered.

But in chronic pain, the bridge between these proteins becomes unstable and starts to fall apart. The result is chaotic. Like a group chat where everyone is talking at once and nobody can be heard clearly, neurons start to misfire and overreact. This synaptic noise turns up the brain’s pain sensitivity, both physically and emotionally. It suggests that GluD1 isn’t just managing pain signals, but also may be shaping how those signals feel.

What if we could restore that broken connection?

In our second study, we injected mice with cerebellin-1 and saw that it reactivated GluD1 activity, easing their chronic pain without producing any side effects. It helped the pain processing system work again without the sedative effects or disruptions to other nerve signals that are common with opioids. Rather than just numbing the body, reactivating GluD1 activity recalibrated how the brain processes pain.

Of course, this research is still in the early stages, far from clinical trials. But the implications are exciting: GluD1 may offer a way to repair the pain processing network itself, with fewer side effects and less risk of addiction than current treatments.

For millions living with chronic pain, this small, peculiar receptor may open the door to a new kind of relief: one that heals the system, not just masks its symptoms.

Pooja Shree Chettiar and Siddhesh Sabnis are neuroscience PhD candidates at Texas A&M University.

This article originally appeared in The Conversation and is republished with permission.

When Doctors Don’t Care: The High Cost of Untreated Pain

By Neen Monty

I just returned from seeing my GP.

I explained to her what happened while she was away — that the doctor who filled in for her refused to prescribe the full amount of my pain medication. As a result of being shortchanged, I went through four days of untreated, severe pain.

My GP said nothing.

I asked why the other GP said she couldn’t prescribe. My GP responded with, “I can’t comment on that.”

I was wondering who was lying to me, and assumed it wasn’t my GP. My GP believed my medications would be prescribed, in good faith.

They weren’t. The other GP lied to her.

And in doing so, she knowingly left someone with a painful, progressive, incurable disease to suffer in agony. Because she could. That’s not medicine. That’s abuse.

That GP should not be practicing.

The most fundamental job of a doctor is to relieve suffering. To relieve pain.

We are now in a world where doctors refuse to treat pain -- and most other doctors say nothing about it. There are no consequences for being derelict in their duty of care.

We’re in a world where people with long-term diseases and permanent disability are being left in agony, discarded by a medical system that sees us as burdens, not as patients. We are not being treated, we are being tortured.

Doctors who refuse to treat pain in people with serious, documented illness are not neutral. They are sadists. And they have no business practicing medicine.

I’m not talking about someone with a mild headache or a sore knee. I’m talking about severe, constant, intractable pain. Pain from MS, RA, Parkinson’s, adhesive arachnoiditis, spinal cord injuries, cancer, and many, many more horrible diseases. Diseases that destroy lives.

And yet, doctors are allowed to ignore us. Abandon us. Deem us unworthy of relief.

Like I was.

My own GP, who knows me and knows my history, did nothing. She simply "fixed" the problem by giving me the rest of my prescription: 90 tablets. Enough for 14 days.

But where was her anger? Her outrage? She promised I’d be looked after while she was away. I wasn’t.

She was betrayed by this other GP as much as I was. But she said nothing. She will accept that this other GP decided not to treat my pain and won’t mention it at all.

And next time my GP goes away? What then? I can’t see the other GP again.

Insult to injury is that I’ve now had to pay for three GP visits this month. That’s $180 I didn’t have.

I endured four days of relentless, unmanaged pain. Because one GP decided I don’t matter.

Because she looked at me and saw garbage. Not a person. Not worthy of her time. Her disgust and disdain towards me were open and palpable.

And no one held her accountable. No one will hold her accountable. She is a law unto herself.

If you ever wondered what it feels like to be dehumanized in real-time, to be made invisible because you're sick and in pain, to be deemed worthless, this is it.

I am very unwell. And I’m in a lot of pain. When pain goes untreated for many days in a row, it is not so easy to get it back under control again.

Treating pain patients like garbage has to stop!

Neen Monty is a writer and patient advocate in Australia who lives with rheumatoid arthritis and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), a progressive neurological disease that attacks the nerves.

Neen has created a website for Pain Patient Advocacy Australia to show that prescription opioids can be safe and effective, even when taken long term. You can subscribe to Neen’s free newsletter on Substack, “Arthritic Chick on Chronic Pain.”

Despite Controversies, Many Older People Have Faith in Vaccines

By Paula Span, KFF Health News

Kim Beckham, an insurance agent in Victoria, Texas, had seen friends suffer so badly from shingles that she wanted to receive the first approved shingles vaccine as soon as it became available, even if she had to pay for it out-of-pocket.

Her doctor and several pharmacies turned her down because she was below the recommended age at the time, which was 60. So, in 2016, she celebrated her 60th birthday at her local CVS.

“I was there when they opened,” Beckham recalled. After getting her Zostavax shot, she said, “I felt really relieved.” She has since received the newer, more effective shingles vaccine, as well as a pneumonia shot, an RSV vaccine to guard against respiratory syncytial virus, annual flu shots and all recommended covid-19 vaccinations.

Some older people are really eager to be vaccinated.

Robin Wolaner, 71, a retired publisher in Sausalito, California, has been known to badger friends who delay getting recommended shots, sending them relevant medical studies. “I’m sort of hectoring,” she acknowledged.

Deana Hendrickson, 66, who provides daily care for three young grandsons in Los Angeles, sought an additional MMR shot, though she was vaccinated against measles, mumps, and rubella as a child, in case her immunity to measles had waned.

For older adults who express more confidence in vaccine safety than younger groups, the past few months have brought welcome research. Studies have found important benefits from a newer vaccine and enhanced versions of older ones, and one vaccine may confer a major bonus that nobody foresaw.

The new studies are coming at a fraught political moment. The nation’s health secretary, Robert F. Kennedy Jr., has long disparaged certain vaccines, calling them unsafe and saying that the government officials who regulate them are compromised and corrupt.

On June 9, Kennedy fired a panel of scientific advisers to the Centers for Disease Control and Prevention, and later replaced them with some who have been skeptical of vaccines. But so far, Kennedy has not tried to curb access to the shots for older Americans.

The evidence that vaccines are beneficial remains overwhelming.

The phrase “Vaccines are not just for kids anymore” has become a favorite for William Schaffner, an infectious diseases specialist at Vanderbilt University Medical Center.

“The population over 65, which often suffers the worst impact of respiratory viruses and others, now has the benefit of vaccines that can prevent much of that serious illness,” he said.

Vaccines Reduce Hospitalizations

Take influenza, which annually sends from 140,000 to 710,000 people to hospitals, most of them seniors, and is fatal to 10% of hospitalized older adults. 

For about 15 years, the CDC has approved several enhanced flu vaccines for people 65 and older. More effective than the standard formulation, they either contain higher levels of the antigen that builds protection against the virus or incorporate an adjuvant that creates a stronger immune response. Or they’re recombinant vaccines, developed through a different method, with higher antigen levels.

In a meta-analysis in the Journal of the American Geriatrics Society, “all the enhanced vaccine products were superior to the standard dose for preventing hospitalizations,” said Rebecca Morgan, a health research methodologist at Case Western Reserve University and an author of the study.

Compared with the standard flu shot, the enhanced vaccines reduced the risk of hospitalization from the flu in older adults, by at least 11% and up to 18%. The CDC advises adults 65 and older to receive the enhanced vaccines, as many already do.

More good news: Vaccines to prevent respiratory syncytial virus in people 60 and older are performing admirably.

RSV is the most common cause of hospitalization for infants, and it also poses significant risks to older people. “Season in and season out,” Schaffner said, “it produces outbreaks of serious respiratory illness that rivals influenza.”

Because the FDA first approved an RSV vaccine in 2023, the 2023-24 season provided “the first opportunity to see it in a real-world context,” said Pauline Terebuh, an epidemiologist at Case Western Reserve School of Medicine and an author of a recent study in the journal JAMA Network Open.

In analyzing electronic health records for almost 800,000 patients, the researchers found the vaccines to be 75% effective against acute infection, meaning illness that was serious enough to send a patient to a health care provider.

The vaccines were 75% effective in preventing emergency room or urgent care visits, and 75% effective against hospitalization, both among those ages 60 to 74 and those older.

Immunocompromised patients, despite having a somewhat lower level of protection from the vaccine, will also benefit from it, Terebuh said. As for adverse effects, the study found a very low risk for Guillain-Barré syndrome, a rare condition that causes muscle weakness and that typically follows an infection, in about 11 cases per 1 million doses of vaccine. That, she said, “shouldn’t dissuade people.”

The CDC now recommends RSV vaccination for people 75 and older, and for those 60 to 74 if they’re at higher risk of severe illness (from, say, heart disease).

As data from the 2024-25 season becomes available, researchers hope to determine whether the vaccine will remain a one-and-done, or whether immunity will require repeated vaccination.

People 65 and up express the greatest confidence in vaccine safety of any adult group, a KFF survey found in April. More than 80% said they were “very “or “somewhat confident” about MMR, shingles, pneumonia, and flu shots.

Although the covid vaccine drew lower support among all adults, more than two-thirds of older adults expressed confidence in its safety.

Shingles Vaccine Reduces Dementia Risk

Even skeptics might become excited about one possible benefit of the shingles vaccine: This spring, Stanford researchers reported that over seven years, vaccination against shingles reduced the risk of dementia by 20%, a finding that made headlines.

Biases often undermine observational studies that compare vaccinated with unvaccinated groups. “People who are healthier and more health-motivated are the ones who get vaccinated,” said Pascal Geldsetzer, an epidemiologist at the Knight Initiative for Brain Resilience at Stanford and lead author of the study.

“It’s hard to know whether this is cause and effect,” he said, “or whether they’re less likely to develop dementia anyway.”

So the Stanford team took advantage of a “natural experiment” when the first shingles vaccine, Zostavax, was introduced in Wales. Health officials set a strict age cutoff: People who turned 80 on or before Sept. 1, 2013, weren’t eligible for vaccination, but those even slightly younger were eligible.

In the sample of nearly 300,000 adults whose birthdays fell close to either side of that date, almost half of the eligible group received the vaccine, but virtually nobody in the older group did.

“Just as in a randomized trial, these comparison groups should be similar in every way,” Geldsetzer explained. A substantial reduction in dementia diagnoses in the vaccine-eligible group, with a much stronger protective effect in women, therefore constitutes “more powerful and convincing evidence,” he said.

The team also found reduced rates of dementia after shingles vaccines were introduced in Australia and other countries. “We keep seeing this in one dataset after another,” Geldsetzer said.

In the United States, where a more potent vaccine, Shingrix, became available in 2017 and supplanted Zostavax, Oxford investigators found an even stronger effect.

By matching almost 104,000 older Americans who received a first dose of the new vaccine (full immunization requires two) with a group that had received the earlier formulation, they found delayed onset of dementia in the Shingrix group.

How a shingles vaccine might reduce dementia remains unexplained. Scientists have suggested that viruses themselves may contribute to dementia, so suppressing them could protect the brain. Perhaps the vaccine revs up the immune system in general or affects inflammation.

“I don’t think anybody knows,” said Paul Harrison, a psychiatrist at Oxford and a senior author of the study. But, he added, “I’m now convinced there’s something real here.”

Shingrix, now recommended for adults over 50, is 90% effective in preventing shingles and the lingering nerve pain that can result. In 2021, however, only 41% of adults 60 and older had received one dose of either shingles vaccine.

A connection to dementia will require further research, and Geldsetzer is trying to raise philanthropic funding for a clinical trial.

And “if you needed another reason to get this vaccine,” Schaffner said, “here it is.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues.

Scientific Review Dismantles Myths Behind ‘Opiophobia’

By Crystal Lindell

“There is little evidence that physicians and surgeons prescribing opioids for short-term pain relief leads to substantial levels of opioid use disorder (OUD), addiction, or death.”

That one sentence, found in a new scientific review, cuts straight to the heart of America’s irrational fear of opioids — also known as opiophobia.

Published in ACS Pharmacology & Translational Science and authored by John Bumpus, PhD, the paper looks at the irrational fear that prescribing opioids in any capacity is harmful – and how little evidence there is to back up such claims. 

Bumpus opens his report by saying that there is a false narrative that “even short-term (seven days or less) use of opioids under medical supervision to treat acute pain will often lead to opioid use disorder (OUD) and/or addiction.”

As a result of that narrative, many healthcare professionals and policy makers believe that the best way to address this problem is to “avoid using opioids altogether or to severely limit the use of prescription opioids, especially after surgery.” 

Bumpus says many providers also assume that limiting prescriptions will significantly reduce overdose deaths. Then he adds the line that cuts to the heart of opiophobia: 

“There is, however, substantial evidence that this is not the case.”

In that one sentence, Bumpus dismantles the main argument that’s often used to claim that opioid restrictions are necessary: the idea that such restrictions are “evidence-based.” 

His report lays out how opioid-related misconceptions have led to policy decisions that are not only unsupported by evidence — but are often harmful. Anyone who has had trouble accessing needed opioid medications over the last few years will find the article both cathartic and affirming.  

Bumpus, who’s a Professor of Chemistry and Biochemistry at the University of Northern Iowa, starts the paper by defining "'opiophobia'" based on the definition shared in a 2023 paper, “Opiophobia and the tragedy of needless pain

Opiophobia led many patients and providers to “fear, avoid or condemn the use of these compounds,” which Bumpus calls ‘the most effective family of analgesics known.”

While large chunks of the report focuses on surgical patients in post-operative pain, Bumpus says that many chronic pain patients use opioids “successfully and appropriately,” but have been “adversely affected by the catastrophization of issues and misinformation surrounding the use of opioids and the opiophobia it has generated."

Bumpus asserts that anti-opioid zealots have gone too far. 

“Although opioid-free protocols and policies may have their benefits and role, for some physicians, researchers, administrators, and politicians, the elimination of opioids appears to have become a goal in and of itself,” he warns. 

Bumpus says there's an underlying assumption "that physicians and surgeons are currently overprescribing opioids." He then adds, "Nationally, this does not appear to be the case."

While the number of opioid prescriptions decreased by about 50% from 2010 to 2022, Bumpus says deaths involving prescription opioids have remained constant. Meanwhile, fatal overdoses from illicit fentanyl and other synthetic opioids have skyrocketed.

“It does not appear that prescription opioids are the major problem here,” Bumpus concludes

He says those advocating for severe opioid limitation often ignore the adverse effects of alternatives like acetaminophen.

"For example, annually in the U.S., acetaminophen overdose is responsible for over 56,000 emergency department visits, 2600 hospitalizations and 500 deaths,” he writes. “Acetaminophen overdose is also the most common cause of acute liver failure and the most common reason for liver transplants in the U.S."

He says that "the narrative that the opioid crisis is caused by the prescribing habits of ethical, conscientious, and caring physicians is patently untrue."

Rather, what is true is that the “undertreatment of postoperative pain is a serious ongoing concern.”

Misleading Data Used to Justify Opioid Restrictions

While opioid-restricting polices may be well-intentioned, Bumpus says there is little evidence that physicians prescribing opioids for short-term pain leads to substantial levels of misuse.

For example, some of the claims used to justify opioid restrictions rely on a study that found 30% of Medicaid patients prescribed an opioid for the first time developed opioid dependency.

That is claim is misleading. The researcher was simply citing the fact that 30% of patients who filled a single opioid prescription needed a refill 3 to 9 months later. Getting a refill alone hardly meets the criteria for opioid dependency, much less addiction.

Bumpus says opioid restrictive policies have had the unintended effect of encouraging patients to store leftover opioids at home, which only makes them more likely to be misused by someone else. 

"Ironically, programs aimed at reducing access to opioids and their long-term storage may actually incentivize the hoarding of these medications," he says. 

People storing leftover opioids is understandable though, when patients fear their future pain will be untreated or they won’t be able to see a doctor.

"Long-term storage of opioid medications and self-medication may not be behaviors endorsed by the medical profession,” Bumpus says. “However, such behaviors are understandable human reactions, and they undoubtedly occur." 

Bumpus argues that while it’s illegal and medically unsupervised, using leftover prescription opioids is safer than turning to street drugs:

“These drugs serve as a relatively safe supply of opioids for people who use them,” he writes.

Ultimately, Bumpus says the public “should have access to information that accurately portrays the benefits as well as the risks associated with the medicinal use of opioids.” 

His paper is heavily researched and includes over 200 footnotes, including several PNN articles that debunk the narrative about opioid misuse being common. 

Bumpus says his paper is important for administrators, policymakers, and lawmakers to read, “so that mistakes of the past are not repeated, making sure that ill-conceived laws and policies are not put in place that do more harm than good.”

Bumpus is correct, of course, and his message is urgent. Now the medical community and policymakers just need to actually listen to him. 

Cactus-Like Plant Shows Promise as Treatment for Intractable Cancer Pain

By Pat Anson

Throughout history, humans have often turned to plants and herbs for pain relief. Poppy plants gave us opium, aspirin was derived from willow trees, and peppermint oil is used to relieve everything from migraines to joint pain. Turmeric, ginger, lavender, eucalyptus and capsaicin are staples in many topical analgesics.

Researchers at the National Institutes of Health (NIH) say a cactus-like shrub native to Morocco also shows promise as a treatment for severe cancer pain and other types of intractable pain.

In a small pilot study recently published in the journal NEJM Evidence, they reported that injections of resiniferatoxin (RTX), a molecule derived from resin spurge (Euphorbia resinifera), provided durable pain relief to patients with terminal end-stage cancer.

"The effects are immediate," lead author Andrew Mannes, MD, chief of the NIH Clinical Center Department of Perioperative Medicine, said in a press release. "This is a potential new therapy from a new family of drugs that gives people with severe cancer pain an opportunity to return some normality to their lives."

The study involved 19 patients with terminal end-stage cancer who did not get adequate pain relief from opioids and other pharmaceutical drugs. But after a single injection of RTX, their worst pain intensity fell by 38% and their use of opioids by 57%. Quality of life also improved, allowing the patients to reengage with family and friends in their final days.

NIH scientists believe RTX has the potential to treat other pain conditions, including other types of cancer pain, neuropathy, post-surgical pain, trigeminal neuralgia, and chronic nerve pain caused by chemotherapy.

"Targeting specific nerves brings many pain disorders into the range of RTX and allows physicians to tailor the treatment to the patient's pain problem. This interventional approach is a simple path to personalized pain medicine," said senior author Michael Iadarola, PhD, a research scientist in the NIH Clinical Center Department of Perioperative Medicine.

RTX acts similarly to capsaicin, the active molecule in chili pepper, by numbing nerve fibers in damaged tissue and blocking them from sending pain signals to the brain. RTX enters the TRPV1 ion channel in the peripheral nervous system, allowing an overload of calcium to flood into the nerve fiber. Patients are still able to feel mild sensations like touch, pressure and pin pricks, but more severe pain signals are blocked.

"Basically, RTX cuts the pain-specific wires connecting the body to the spinal cord, but leaves many other sensations intact," Iadarola said. "These TRPV1 neurons are really the most important population of neurons that you want to target for effective pain relief."

"What makes this unique from all the other things that are out there is that it is so highly selective," Mannes said. "The only thing it seems to take out is heat sensation and pain."

People in North Africa knew this thousands of years ago. The first written record of Euphorbia resinifera being used for pain control dates back to the time of the Roman Emperor Augustus, when dried latex from the plant was used as medicine.

The NIH is planning further studies of RTX in clinical trials.

OxyContin Fueled the Opioid Crisis, But Not How You Might Think

By Crystal Lindell

Attorneys General from 55 U.S. states and territories recently accepted a $7.4 billion settlement with Purdue Pharma and the Sackler family, potentially ending over a decade of legal wrangling over the company’s role in the opioid crisis.  

But much of the media coverage still doesn’t seem to grasp what Purdue Pharma actually did wrong with its marketing of OxyContin. Purdue Pharma’s original sin was not flooding the market with too many OxyContin pills – it was too few.

OxyContin’s share of the opioid market was never more than 4 percent. That small share, however, was magnified by higher dose pills, which made OxyContin more likely to be misused. 

The company drove misuse by claiming that OxyContin pills lasted for 12 hours. In reality, they only lasted 4-6 hours. I know, because I’ve been on them myself for chronic pain.

This is how the Los Angeles Times described Purdue’s marketing campaign in 2016: 

“Purdue tells doctors to prescribe stronger doses, not more frequent ones, when patients complain that OxyContin doesn’t last 12 hours. That approach creates risks of its own. Research shows that the more potent the dose of an opioid such as OxyContin, the greater the possibility of overdose and death."

So if a patient wasn’t getting steady relief from two 10mg OxyContin a day, the doctors would be encouraged to up it to two 20mg OxyContin pills a day. In reality, it would have been better to keep the dose at 10 mg and increase the frequency to four pills a day.

Purdue was well aware of the problem. They knew the pills did not last the full 12 hours. But it was OxyContin’s 12-hour dosing regimen that was its main selling point. It was supposed to set it apart from much cheaper opioid options like hydrocodone, morphine and oxycodone. 

Here’s what happened when doctors prescribed more OxyContin pills to give patients relief, according to the LA Times:

“When many doctors began prescribing OxyContin at shorter intervals in the late 1990s, Purdue executives mobilized hundreds of sales reps to ‘refocus’ physicians on 12-hour dosing. Anything shorter ‘needs to be nipped in the bud. NOW!!’ one manager wrote to her staff.”

Purdue then encouraged doctors to prescribe higher dose 80mg pills, because the higher the dose, the more Purdue made off the pills. While the company charged wholesalers about $97 for a bottle of 10mg pills, a bottle of the 80mg version went for $630. 

The company also based the commissions and performance evaluations for its sales team on the proportion of high-dose pills they sold. 

‘The Dose Makes the Poison’

Over 500 years ago, Swiss physician Paracelsus coined the phrase, “The dose makes the poison.” For Purdue Pharma, that was especially true. It was the high doses at long intervals that made OxyContin so dangerous.

Patients would go through cycles of withdrawal as their high doses wore off early, or they would just take a few extra pills each day. That meant they would run out of their prescription early, leaving them to go through days or even weeks of withdrawal. 

And make no mistake, even short intervals of withdrawal from 80mg OxyContin would make anyone feel like hell. God forbid you run out early and have to go through that. It’s the perfect recipe for driving patients to seek other sources of relief, whether that means buying pills from someone else or buying street opioids. 

Understanding that the root cause of OxyContin’s danger was not that doctors were prescribing too many pills, but prescribing too few of them challenges the popular narrative of how the opioid crisis started.  

The actual problem was not that doctors were treating pain with opioids. They were treating pain with opioids at the wrong intervals. 

Media coverage of Purdue still often frames OxyContin as the same as every other opioid though. But OxyContin isn’t fentanyl and it’s not hydrocodone, either.

Low and frequent doses of hydrocodone are relatively safe for the vast majority of patients. Which makes sense, since the reason OxyContin led some patients to misuse was because it was literally the opposite: High doses taken infrequently. 

That message seems to get lost in current opioid-phobia coverage. Just last week, the LA Times ran a column headlined, “Surgeons give patients too many opioids. A few simple steps could curb excess prescribing

The column is authored by Zachary Wagner, PhD, a health economist at USC, and Craig Fox, PhD, a psychology professor at UCLA who specializes in studying behavioral risk. Neither of them are medical doctors.

In their op/ed, Wagner and Fox spread the misinformation that it’s leftover post-op pills that are driving opioid deaths. They think surgeons should be encouraged to prescribe fewer opioids. 

“If we could get surgeons to prescribe only the number of pills patients need for their own use, this could greatly reduce the number of excess pills available for diversion and misuse,” they wrote. 

This is dangerous and misleading. Opioids are so difficult to get today that pain patients are far more likely to hoard their “excess pills” than to sell or divert them. Opioid diversion rates are quite low, according to the DEA, which estimates less than half of one percent of oxycodone (0.493%) and hydrocodone (0.379%) are used by someone they are not intended for. 

Do surgeons really need lectures from economists and psychology professors about what they should prescribe?

I have seen first-hand how many surgeons already give post-op patients a regimen of only ibuprofen or acetaminophen due to opioid-phobia laws and regulations. Providing adequate post-op pain relief isn’t just the ethical thing to do, it’s also important for the healing process and to prevent acute pain from becoming chronic.. 

The bottom line is that pain refuses to be ignored. People will find ways to treat it, regardless of whether or not their doctor helps them. Simply refusing to give people opioids won’t solve anything. It will, however, drive people to street drugs or to self-medicate with alcohol and other substances. 

If doctors actually want to help patients, they should still be prescribing low-dose opioids, which are relatively safe. And they should prescribe high-dose opioids to people who really need them, just at realistic intervals.

Purdue Pharma’s sins were real – but letting that justify complete bans on pain treatment only results in more suffering, not less.

Dose and Type of Opioid May Increase Risk of Constipation  

By Pat Anson

Constipation is one of the most common – yet least talked about – side effects of opioid pain medication. About 80% of patients on daily opioid therapy experience constipation, even when taking laxatives, which can severely impact quality of life and sleep.

But talking about constipation brings little sympathy and often starts a round of potty jokes. When AstraZeneca aired a commercial during the 2016 Super Bowl promoting its opioid induced constipation (OIC) drug, the ad was greeted with derision..

“The Super Bowl is known for inspiring lots of eating and lavish spreads of food. So why would advertisers pay millions to air ads focusing on constipation?” asked Eric Deggans of National Public Radio.

“Was that really an ad for junkies who can’t sh**? America, I luv ya but I just can’t keep up,” comedian Bill Maher wrote on Twitter.  

All jokes aside, constipation really is a health problem. Which makes a new study at the UK’s University of Manchester all the more valuable because it identifies which opioid painkillers are most likely to be associated with constipation and which ones are not.

"Constipation is a frequent adverse event associated with opioid medications that can have a considerable impact on patients' quality of life,” says lead author Meghna Jani, PhD, an epidemiologist and Senior Clinical Lecturer at The University of Manchester. “Opioid-induced constipation has also been associated with longer hospital stays, higher hospital costs, and increased emergency department visits."

Jani and her colleagues analyzed hospital health records for over 80,000 non-cancer patients on opioids in England between 2009 and 2020. About 8% suffered from constipation severe enough to require an enema or suppository.

The study findings, recently published in BMC Medicine, show that morphine, oxycodone, fentanyl and combination opioids were associated with a significantly higher risk of severe constipation compared to codeine. Tramadol and buprenorphine had the least amount of constipation risk.

Tramadol and buprenorphine have different mechanisms of action than other opioids, which may explain their lower risk, while codeine and tramadol are considered less potent opioids.

The risk of constipation was also found to be dose-dependent. Patients taking less than 50 morphine milligram equivalents (MME) a day had the lowest risk of constipation, while those taking 50 to 120 MME daily had a risk twice as high. Fifty MME per day is roughly equal to taking either 50mg of morphine or 33 mg of oxycodone each day.

The Faculty of Pain Medicine of the Royal College of Anaesthetists says the dose above which opioid harms likely outweigh their benefits is 120 MME per day. Guidance in the U.S. and Canada is more cautious, recommending that opioid doses be kept at or below 90 MME.

This is believed to be largest study of its kind to evaluate constipation risk based on types of opioids, and one of the first to assess the impact of doses. Researchers say previous estimates of constipation rates probably under-represent their true prevalence, because constipation is often not seen as a serious issue and may not be coded in medical records. Patients may also be reluctant to openly talk about their bowel habits with a healthcare provider.

"Previously, we didn't know enough about the risk associated with specific opioids, given the different ways they act on the body, as well as the effect of daily dose,” said Jani. "This study will allow clinical prescribers and patients to make better shared decisions about what pain relief is best for them, to minimize the risks of this side effect of opioids, and thus improve patients' quality of life.

"If patients need to be on opioids, we urge prescribers to be cautious with opioid dosing, and aim for the lowest effective dose to manage pain while mitigating the risk of constipation and other side effects."

A Non-Alcoholic Drink Can Help You Relax, Socialize and May Even Relieve Pain

By Madora Pennington

I am going for a month without drinking, not because I have a problem with alcohol or because alcohol is interfering with my life. I don't and it isn't.

I just got back from a long vacation, which included an 8-day all-inclusive cruise. We wanted to get our money’s worth. After weeks of drinking every day, it seemed only sensible to take a full break from alcohol. No one would argue that so much drinking is healthy.

I am not alone. You may have heard about the “sober curious” — those who abstain to see what socializing, stress, and life itself is like without alcohol. Young adults, overall, are drinking less alcohol. These trends are fueling the demand for non-alcoholic, yet interesting drinks that seem sophisticated or reminiscent of a cocktail.

But is there a non-alcoholic drink that also helps you relax and socialize? I found a company, Sentia Spirits, that makes beverages that enhance your body’s production of GABA

Don’t confuse GABA (gamma-aminobutyric acid) with the nerve pain medication gabapentin (Neurontin). GABA is a naturally occurring neurotransmitter that sends signals in the brain and spinal cord, while gabapentin is a synthetic variation of GABA. The medication acts similarly as GABA, but tends to cause many unwanted side effects. Benzodiazepines, SSRI antidepressants, muscle relaxers, and other drugs also affect GABA in the body.

Sentia’s beverages contain herbs and botanicals that improve mood, focus, calmness, and energy. Their concoctions taste more like bitters than a mocktail, but certainly provide an interesting experience for the palate.

I found them to be subtly relaxing, without the impairment of an alcohol-induced buzz.

GABA itself is also available in supplements that people take to relax and improve sleep. It may also help relieve pain. When GABA binds to pain receptors, it reduces the transmission of pain signals, potentially providing relief from various types of physical discomfort.

SENTIA SPIRITS

Research has found that low levels of GABA make it harder to keep negative emotions such as fear, anxiety and depression in check, and may also worsen chronic pain. As PNN has reported, Dr. Forest Tennant recommends GABA supplements for patients with intractable pain "to force damaged nerve tissue to correctly function and relieve pain.”  

As far as reasons for abstaining, alcohol worsens depression. And people with alcohol use disorder often have chronic pain, which means they could be self-medicating.

Using supplemental GABA or medications that promote it could be a useful strategy in managing the spiral of chronic pain on the body and brain. Many sources suggest taking GABA on an empty stomach to give it a better chance of reaching the brain.

Limiting alcohol intake might also be a wise choice for anyone. Certainly, finding ways to diminish stress and improve sleep should be part of pain management.

Sentia costs about $40 for a 500ml bottle, which is enough for 20 shot-sized servings. If you don't want it straight or want to make it look like a cocktail, you can mix it with tonic water.

Talk to your healthcare provider about your pain control regimen and how to improve it before taking GABA or any supplement.

I enjoyed my time of sobriety very much. I thought I would miss drinking, but did not. The sleepiness and haziness from a glass of wine is stronger than I realized, and it doesn’t make socializing more fun for me. I ended my sober curious time with a resolve to drink less overall.

Will FDA’s New Review Process Sell Drug Approvals to the Highest Bidder? 

By Crystal Lindell

The U.S. Food and Drug Administration has launched a new speedy review process for new medications, dubbed the Commissioner’s National Priority Voucher (CNPV) program. 

The FDA claims the program will speed up the approval process for pharmaceutical companies looking to get a new drug on the market – but it remains unclear whether it is based on a need for the drug, its effectiveness, or how much companies are willing to pay for the privilege of early approval..

The FDA said the CNPV program will shorten the review time to 1-2 months, compared to the typical 10-12 months it usually takes after a company’s final drug application.

They’ll accomplish this by allowing for a “team-based review.” This differs from the current process, where a drug application is “sent to numerous FDA offices” to give them a chance to weigh-in.

The program will even allow companies to submit the lion’s share of the drug application before a clinical trial is complete, according to FDA Commissioner Marty Makary, MD.

“Using a common-sense approach, the national priority review program will allow companies to submit the lion’s share of the drug application before a clinical trial is complete so that we can reduce inefficiencies. The ultimate goal is to bring more cures and meaningful treatments to the American public,” Makary said. 

Neither the FDA press release about the new program or its "Frequently Asked Questions" page specify how much this new program will cost companies interested in participating. 

We can gain some frame of reference by looking at what the existing Priority Review and Priority Review Voucher costs for companies, as well as what their true value is. 

While the FDA charges companies about $2.5 million for those vouchers, according to the General Accounting Office (GAO) they have been resold on the secondary market for as much as $350 million. The GAO found that of the 31 vouchers awarded by the FDA between 2009 and 2019, over half (17) were sold to another drug company.

The new vouchers cannot be transferred to other companies as of now, but with so much money at stake, you have to wonder if there will be a valuable aftermarket for them.

Even if the new vouchers themselves are reasonably priced, my guess is that they will be more likely to go to companies that donate money to elected officials or are politically favored. 

The FDA says that in the first year of the program it will give a limited number of vouchers to companies “aligned with U.S. national priorities,” which include “unmet public health needs” and increased domestic drug manufacturing. But then they also say the vouchers “can be applied to drugs in any area of medicine.”

In other words, basically any medication would qualify. There’s not much else to explain just how vague the criteria is for receiving the vouchers.  

And if any medication would qualify for the new vouchers, it makes sense that the ultimate qualification would be what companies are willing to pay to get them. 

Under the current voucher system, the GAO found there is “no obligation to make the approved drug available at an affordable price,” so companies are free to limit access and charge whatever they want. The new voucher system also has no requirement that new drugs will be affordable or accessible. 

While I do understand the need for more efficiencies in the drug review process, when those efficiencies are applied unevenly, it inevitably invites corruption. And the last thing we need when it comes to prescription medications and healthcare in our country is more corruption. 

My concern is that the drugs getting speedy review won’t actually be the ones that are in the public’s best interests, but rather the ones that best serve the interests of our elected officials and the drug companies themselves. 

And when it comes to prescription medications, we all know that what’s best for politicians and the pharmaceutical industry is not what’s best for patients.

A Pained Life: Stop Torturing Us

By Carol Levy

For many chronic pain conditions, such as Complex Regional Pain Syndrome, trigeminal neuralgia and Ehlers Danlos Syndrome, a major aspect is the spontaneity of pain attacks. They can come at any time and without warning.

Not being able to anticipate a pain flare may sound familiar to you. It causes psychological stress, keeping you in a constant state of fear and anxiety. The lack of predictability deprives a person of any sense of normalcy or control over their situation, causing helplessness and despair.

That often leads to other health problems and interrupts the sleep cycle, causing fatigue, disorientation and even cognitive decline. 

Where did this description of chronic pain come from?

It is actually a description (with some word modification) of torture and how disruptive it can be to a person. It’s striking how similar chronic pain and torture can be.

Having chronic pain is torture to me in an abstract way: I have pain. I can't find a way to stop it. I suffer as a result.

Like pain, torture is worse when it arrives unexpectedly and you have no way to stop it. You may be feeling okay, when suddenly a blitzkrieg of pain invades. You have no control or defense, and have no choice but to wait it out, cowering under the covers waiting for it to pass.

The Center for Victims of Torture writes this about using unpredictability as a torture technique:

“Randomizing torture makes it even more psychologically damaging and ethically problematic, as it deprives the victim of any control or predictability.”

Too often doctors miss the ethical implications of the effect of the pain on us, much less when one aspect of it is the unpredictability. The need for them to understand it is a necessary component of taking care of us and our needs --- what a physician, in the truest sense of the word, should do.

Too many of them, even those who claim “pain management” as their specialty, seem to get tired of listening as we explain the various ways our pain manifests. Most pain conditions don’t have a nice clean orderly way of detail.

It can be torturous to deal with the medical profession and its reluctance to accept our stories about living with chronic pain. It is harder still when a patient has the additional spontaneity of pain, being repeatedly physically and psychologically bombarded by it, and their defenses on the verge of being destroyed.

Doctors don’t seem to be able to understand this on their own. We may come to them psychologically tattered because of the pain. Those of us with spontaneous pain may come to them appearing very emotionally fragile.

As hard as it is, as difficult our lives already are due to the pain, we may have to be the ones to teach them, to help them to understand why we are so torn and battered. At the end of the day we need to tell them: “Please, listen to me. Understand me. Please, don’t be another level of torture.”

Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.”  Carol is the moderator of the Facebook support group “Women in Pain Awareness.” Her blog “The Pained Life” can be found here.