What Doctors Should Ask Patients in Pain

By Carol Levy, PNN Columnist

I learned in childhood to keep my mouth shut if I had pain or was feeling sick. My siblings would say, "Stop your whining. Just go to your room if you're feeling so bad, so we don't have to hear about it!"

I learned to say nothing, no matter how bad I felt.

That is how I still handle it today. When I see a doctor about my trigeminal neuralgia pain or some other pain, they’ll often say, “Your pain can't be as bad as you say. You don't act like you're in pain.”

I was at the neurosurgeon's office. One of his residents wanted to touch the left side of my face and I wasn't sure why. Maybe to see what I would do? He knew any touch to the affected area would set off horrible, terrible pain.

“Are you ready?” he asked before touching me. His finger hit the mark and I instinctively jumped back, but didn't make a sound. The resident looked at me; like he was waiting for a cry, scream, wail, or any normal vocalization of pain. Instead, I was silent.

“Are you okay?” he asked, somewhat warily. He didn't realize I was literally unable to answer. My childhood lesson not to speak about pain had morphed into mute silence as an adult. I was speechless; my larynx unable to produce a sound.

I cleared my throat a few times in an effort to speak, while raising a finger in the universal sign of “wait.” After a few minutes, I was finally able to speak, but my words would not come out clearly.  Once triggered, the pain takes its own sweet time before it settles down.

My words were interspersed with more throat-clearing: “I can't, hahahem, speak when the, hahahem, pain is triggered.” 

Others who have chronic pain usually say the opposite: “When a doctor sets off my pain or I am in pain, I have no choice. I scream, I cry or I curse. I make faces and grimace.”

It is an automatic response. And often the doctor's reply in words or facial expression is, ”I don't believe this act you're putting on."

So what's a pain patient to do? What's a doctor to do?

For us, it's simple. If the doctor says, “It really isn't necessary to be so loud and to use profanity, or to wail and scream. In fact, it makes me think you're being overly dramatic.”

We need to reply in a way that says, “Doctor, this is what I do to express my pain. It may be unusual to you, too loud, or too unpleasant. But it is the only way I know how to express it.”

The doctor on the other hand? He doesn't know unless he asks a key question: “How do you let others know if you are in pain or what your level of pain is? Do you express it by crying or with grimaces? Or do you become silent?”

It comes down to one of my favorite sayings: You don't know what you don't know. And if you don't know what you don't know, you don't know what to ask. Our doctors need to ask.

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.

A Little Extra Weight Is Okay for Older Adults

By Judith Graham, Kaiser Health News

Millions of people enter later life carrying an extra 10 to 15 pounds, weight they’ve gained after having children, developing joint problems, becoming less active, or making meals the center of their social lives.

Should they lose this modest extra weight to optimize their health? This question has come to the fore with a new category of diabetes and weight loss drugs giving people hope they can shed excess pounds.

For years, experts have debated what to advise older adults in this situation. On one hand, weight gain is associated with the accumulation of fat. And that can have serious adverse health consequences, contributing to heart disease, diabetes, arthritis, and a host of other medical conditions.

On the other hand, numerous studies suggest that carrying some extra weight can sometimes be protective in later life. For people who fall, fat can serve as padding, guarding against fractures. And for people who become seriously ill with conditions such as cancer or advanced kidney disease, that padding can be a source of energy, helping them tolerate demanding therapies.

Of course, it depends on how heavy someone is to begin with. People who are already obese (with a body mass index of 30 or over) and who put on extra pounds are at greater risk than those who weigh less. And rapid weight gain in later life is always a cause for concern.

Making sense of scientific evidence and expert opinion surrounding weight issues in older adults isn’t easy. Here’s what I learned from reviewing dozens of studies and talking with nearly two dozen obesity physicians and researchers.

Bodies Change with Age 

As we grow older, our body composition changes. We lose muscle mass — a process that starts in our 30s and accelerates in our 60s and beyond — and gain fat. This is true even when our weight remains constant.

Also, less fat accumulates under the skin while more is distributed within the middle of the body. This abdominal fat is associated with inflammation and insulin resistance and a higher risk of cardiovascular disease, diabetes and stroke, among other medical conditions.

“The distribution of fat plays a major role in determining how deleterious added weight in the form of fat is,” said Mitchell Lazar, director of the Institute for Diabetes, Obesity and Metabolism at the University of Pennsylvania’s Perelman School of Medicine. “It’s visceral [abdominal] fat [around the waist], rather than peripheral fat [in the hips and buttocks] that we’re really concerned about.”

Activity Diminishes

Also, with advancing age, people tend to become less active. When older adults maintain the same eating habits (energy intake) while cutting back on activity (energy expenditure), they’re going to gain weight.

According to the Centers for Disease Control and Prevention, 27% of 65- to 74-year-olds are physically inactive outside of work; that rises to 35% for people 75 or older.

For older adults, the health agency recommends at least 150 minutes a week of moderately intense activity, such as brisk walking, as well as muscle-strengthening activities such as lifting weights at least twice weekly. Only 27% to 44% of older adults meet these guidelines, according to various surveys.

Experts are more concerned about a lack of activity in older adults who are overweight or mildly obese (a body mass index in the low 30s) than about weight loss.

With minimal or no activity, muscle mass deteriorates and strength decreases, which “raises the risk of developing a disability or a functional impairment” that can interfere with independence, said John Batsis, an obesity researcher and associate professor of medicine at the University of North Carolina School of Medicine in Chapel Hill.

Weight loss contributes to inadequate muscle mass, insofar as muscle is lost along with fat. For every pound shed, 25% comes from muscle and 75% from fat, on average.

Since older adults have less muscle to begin with, “if they want to lose weight, they need to be willing at the same time to increase physical activity.” said Anne Newman, director of the Center for Aging and Population Health at the University of Pittsburgh School of Public Health.

Ideal BMI Higher for Older Adults

Epidemiologic research suggests that the ideal body mass index (BMI) might be higher for older adults than younger adults. BMI is a measure of a person’s weight, in kilograms or pounds, divided by the square of their height, in meters or feet.

One large, well-regarded study found that older adults at either end of the BMI spectrum — those with low BMIs (under 22) and those with high BMIs (over 33) — were at greater risk of dying earlier than those with BMIs in the middle range (22 to 32.9).

Older adults with the lowest risk of earlier deaths had BMIs of 27 to 27.9. According to World Health Organization standards, this falls in the “overweight” range (25 to 29.9) and above the “healthy weight” BMI range (18.5 to 24.9). Also, many older adults that the study found to be at highest mortality risk — those with BMIs under 22 — would be classified as having “healthy weight” by the WHO.

The study’s conclusion: “The WHO healthy weight range may not be suitable for older adults.” Instead, being overweight may be beneficial for older adults, while being notably thin can be problematic, contributing to the potential for frailty.

Indeed, an optimal BMI for older adults may be in the range of 24 to 29, Carl Lavie, a well-known obesity researcher, suggested in a separate study reviewing the evidence surrounding obesity in older adults.

Lavie is the medical director of cardiac rehabilitation and prevention at Ochsner Health, a large health care system based in New Orleans, and author of “The Obesity Paradox,” a book that explores weight issues in older adults. Lavie and other experts say maintaining fitness and muscle mass is more important than losing weight for many older adults.

“Is losing a few extra pounds going to dramatically improve their health? I don’t think the evidence shows that,” Lavie said.

Unintentional weight loss is associated with several serious illnesses and is a danger signal that should always be attended to. “See your doctor if you’re losing weight without trying to,” said Newman of the University of Pittsburgh. She’s the co-author of a new paper finding that “unanticipated weight loss even among adults with obesity is associated with increased mortality” risk.

Maintain Healthy Diet

Ensuring diet quality is essential. “Older adults are at risk for vitamin deficiencies and other nutritional deficits, and if you’re not consuming enough protein, that’s a problem,” said Batsis of the University of North Carolina.

“I tell all my older patients to take a multivitamin,” said Dinesh Edem, director of the Medical Weight Management program at the University of Arkansas for Medical Sciences.

Losing weight is more important for older adults who have a lot of fat around their middle (an apple shape) than it is for people who are heavier lower down (a pear shape). “For patients with a high waist circumference, we’re more aggressive in reducing calories or increasing exercise,” said Dennis Kerrigan, director of weight management at Henry Ford Health in Michigan.

Maintaining weight stability is a good goal for healthy older adults who are carrying extra weight but who don’t have moderate or severe obesity (BMIs of 35 or higher). By definition, “healthy” means people don’t have serious metabolic issues (overly high cholesterol, blood sugar, blood pressure, and triglycerides), obesity-related disabilities (problems with mobility are common), or serious obesity-related illnesses such as diabetes or heart disease.

“No great gains and no great losses — that’s what I recommend,” said Katie Dodd, a geriatric dietitian who writes a blog about nutrition.

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

Veterans Say Cannabis Reduces Drug Use and Improves Quality of Life

By Pat Anson, PNN Editor

The U.S. Department of Veterans Affairs (VA) and the Department of Defense (DoD) have long taken a dim view of medical cannabis. VA providers are not allowed to recommend or prescribe cannabis, and veterans who admit using cannabis will have it recorded in their VA medical records, which could potentially lead to drug testing or “adjustments” in their treatment plans.

Despite those barriers, cannabis use among U.S. military veterans is growing. In a 2019-2020 survey, nearly 12% of veterans reported using cannabis, with younger veterans (20.2%) and those with psychiatric conditions (24%) even more likely to be cannabis users.

A new study helps explain the popularity of cannabis among veterans. In an anonymous survey of 510 veterans who use medical cannabis, 91 percent said it improved their quality of life and nearly half said it helped them reduce their use of over-the-counter and prescription drugs, including opioids, anti-depressants, muscle relaxers and anti-inflammatory medication.

Veterans who were Black, female, served in combat, and those with chronic pain were most likely to report a desire to reduce their use of “unwanted” medications.

“Many of the respondents reported that medicinal cannabis treatment helped them to experience a greater quality of life, fewer psychological symptoms, fewer physical symptoms, and to use less alcohol, fewer medications, less tobacco, and fewer opioids,” researchers reported in the journal Clinical Therapeutics.

“These findings should inform clinicians who work with the veteran population, as cannabis may be an effective means of helping veterans, especially women and racially minoritized members of this population, to reduce unwanted medication use.”

Previous research has suggested that medical cannabis may play a “harm reduction role” by helping people reduce or even stop their use of opioid pain medication. But a recent study found otherwise. In an analysis of prescription data for over 150,000 chronic pain patients, researchers found that opioid prescribing declined only slightly in states after medical marijuana was legalized.

The VA is also holding the line against using cannabis as a treatment for post-traumatic stress disorder (PTSD).  While many veterans use cannabis to relieve symptoms of PTSD and several states consider PTSD an approved use of medical cannabis, the VA maintains that “cannabis can be harmful,” especially when used long-term, and is “not recommended for the treatment of PTSD.”

Tylenol on Trial: Does Acetaminophen Cause Autism and ADHD?

By Teresa Carr, Undark Magazine

More than 100 families of children with autism and attention deficit hyperactivity disorder are suing companies that market acetaminophen, the pain reliever in Tylenol and an array of other medications. Tylenol-maker Johnson & Johnson, as well as major retailers that use acetaminophen in their store-brand products, knew about research linking prenatal use of acetaminophen to neurodevelopmental disorders in children, the families claim, and should have included warnings on product labels.

The court filings reveal mothers wracked with guilt, convinced that by taking an over-the-counter pain reliever, they caused their child’s disability. In case after case, these women say that if they had thought acetaminophen could possibly harm their baby, they would have minimized their use of the drug — or not taken it at all.

It’s hardly an open-and-shut case. Most of what is known about acetaminophen and pregnancy comes from a type of study that sifts through data looking for correlations between prenatal exposures and developmental disorders. Scientists have been fighting amongst themselves over how much weight to give these studies, which were not designed to prove that a given factor — in this case, acetaminophen — caused ADHD or autism.

The debate reached a boiling point in 2021, when a group of international scientists declared that the current research, limited as it is, warrants stronger warnings about the use of acetaminophen during pregnancy. In a consensus statement published in Nature Reviews Endocrinology, the scientists called for “precautionary action” through focused research and increased awareness of the drug’s potential risks. Ninety-one scientists, clinicians, and public health professionals from around the world signed on.

That statement was the “galvanizing incident” for the lawsuits, said Ashley Keller, a founding partner at the legal firm Keller Postman LLC and one of the lawsuits’ lead attorneys.

‘An Outlier Opinion’

But there’s a hitch: The consensus statement does not, in fact, reflect the views of many experts or of any major medical organization. The same Nature journal published three rebuttals signed by numerous professional groups as well as individual researchers and clinicians. These critics wrote that the consensus statement used flawed data to exaggerate potential harms of acetaminophen and downplayed the drug’s essential role for treating fever and pain.

Johnson & Johnson has seized on those criticisms in its defense. The consensus statement “is an outlier opinion of a small group whose position has been rejected by their own medical organizations and every regulatory body to address the issue,” company spokesperson Melissa Witt told Undark in an email. Giving credence to theories not based in sound science, she said, could harm millions of pregnant women.

This debate over how to interpret the acetaminophen science lies at the heart of the lawsuits, and the answer has profound implications, both for individuals and for public health. Acetaminophen is one of the most common drugs in the world, and in the United States, up to 65 percent of all expectant mothers use it. The cases have been consolidated in the Southern District of New York. If the litigation proceeds to trial, attorneys expect tens to hundreds of thousands of families to join in.

It’s a shame that questions linger about the safety of a drug that’s been around for 70 years, said Christina Chambers, a professor of pediatrics at the University of California, San Diego and lead investigator for a series of studies on exposures during pregnancy for the Organization of Teratology Information Specialists, a professional society that provides advice on using medications during pregnancy and breastfeeding.

In an interview with Undark, Chambers expressed doubts about the consensus statement, saying that if acetaminophen has any effect on fetal development, that effect is likely to be modest. Still, she added, “What this accumulated data calls for is to do better study.”

Top Selling Pain Reliever

Acetaminophen was discovered in 1878, according to an FDA history of groundbreaking medications. But it wasn’t until the early 1950s that researchers demonstrated that the compound worked as well as the two popular pain relievers of the time — aspirin and acetanilide — with fewer side effects. In 1955, drugmaker McNeil gained FDA approval and launched Tylenol Elixir for Children, advertising it “for little hotheads.”

Four years later Johnson & Johnson acquired McNeil, and, in 1975, began aggressively marketing an “extra strength” 500-milligram version of the drug to adults. By the early 1980s, Tylenol was the top-selling pain reliever in the U.S.

Acetaminophen is now used in more than 600 over-the-counter and prescription medications, including combination products for sleep, cough, cold, and allergy.

Acetaminophen is one of the most common drugs in the world, and in the United States, up to 65 percent of all expectant mothers use it.

Today, new medications typically undergo toxicity testing in animals before researchers study their safety and effectiveness in humans, but like many older drugs, acetaminophen didn’t undergo as thorough of a process. “Back in ’55 we weren’t doing preclinical testing for reproductive safety,” said Chambers.

Scientists do know that, in most cases, acetaminophen is the safest way for pregnant women to relieve fever and pain. “Not treating a fever — especially a high fever — can have consequences,” continued Chambers.

Strong data from lab animal and human studies have associated a high fever at certain points in pregnancy with an increased risk of birth defects and other fetal abnormalities. And, while it’s an understudied area, she said, chronic pain is associated with depressive symptoms, insomnia, and other harms to the mother and could adversely affect her pregnancy.

Some common over-the-counter drugs treat both fever and pain, such as nonsteroidal anti-inflammatory drugs like aspirin, ibuprofen (Advil), and naproxen (Aleve), but the FDA warns against using any of these after 20 weeks of pregnancy because these drugs can damage the unborn babies’ kidneys.

Meanwhile, other painkillers have their own drawbacks. Babies exposed to opioids during the first trimester of pregnancy are at increased risk for birth defects of the brain, spine, and spinal cord. In addition, studies show that regular use of opioids during pregnancy increases the risk of poor fetal growth, preterm delivery, stillbirth, and neonatal opioid withdrawal syndrome.

Medicinal cannabis may address pain, and some women might think of it as a natural and, therefore, safe alternative. But there’s very little data available on short- and long-term outcomes for mothers and babies exposed to the potent products available today, said Chambers. Recent studies suggest that cannabis increases the risk of preterm birth and smaller babies, but it’s hard to tease out the effects from other factors. She described the drug’s legalization and increased societal acceptance as “a huge experiment happening now.”

“So, what are you left with?” she asked.

In 1975, Johnson & Johnson began aggressively marketing extra-strength Tylenol to adults. In this 1983 commercial, the product is touted as the most potent pain reliever that can be bought without a prescription:

Rising Rates of Autism and ADHD  

For pregnant people experiencing fever or pain, acetaminophen is widely viewed as the best option. But can it also harm the fetus?

To begin answering this question, researchers have analyzed preexisting datasets of health information, looking for associations between acetaminophen use during pregnancy and neurodevelopmental problems in children. Such research is referred to as observational, and while it can be useful, this approach can’t typically prove causality.

Autism rates have climbed steadily since the Diagnostic and Statistical Manual of Mental Disorders, or DSM, first established it as a distinct disorder in 1980. In 2000, 1 in 150 children were diagnosed with autism by the age of eight according to the Centers for Disease Control and Prevention; by 2020, the number had risen to 1 in 36.

ADHD rates increased as well, though not as sharply. In 2019, 6 million children between the ages of 3 and 17 (9.8 percent) had received a diagnosis of ADHD, compared to 4.4 million children in 2003, according to CDC data from a national survey of parents.

Many experts attribute the bulk of that increase to greater awareness and broadening definitions of the disorders. Factors such as improved survival for premature infants and a trend toward starting families later may also play a role, as both prematurity and older parents are associated with increased risk for neurodevelopmental disorders.

In the early 2010s researchers additionally became interested in whether acetaminophen, so commonly used by pregnant people, could affect fetal development.

In 2014, after a couple of observational studies suggested a possible link, the Food and Drug Administration began a formal process to track data on the issue. The findings from the agency’s initial review of the evidence, based on limited and contradictory data, were inconclusive according to a Drug Safety Communication published the following year.

Since then, researchers from several countries, including the U.S., have published a steady stream of observational research. In 2021, an international group of researchers came together to review the evidence and craft a consensus.

“We all sat down and said, it’s time to put all this together; we’ve done reviews, there’s more and more evidence,” said lead author Ann Bauer, an epidemiologist at the University of Massachusetts Lowell. “We all felt that it was time for women to have this information.”

Of the 29 observational studies involving 220,000 mother-child pairs, 26 linked prenatal use of acetaminophen to neurodevelopmental disorders including ADHD, autism, language delays, lower IQ, and cerebral palsy among others. Sixteen studies showed a more-pronounced effect with longer-term use of the drug.

Bauer pointed out that a handful of observational studies published after the consensus statement also suggest an association.

The group conceded that the observational data is imperfect. The positive association could stem from other factors, such as heredity or the condition that prompted the woman to take the drug. Still, the researchers concluded that the combined weight of the data was strong enough to warrant warning labels on acetaminophen and for health care professional to caution women against indiscriminate use of the drug. Society should act now, they wrote, “not wait unequivocal proof that a chemical is causing harm to our children.”

In science, it’s always possible to find something wrong with individual studies, said David Møbjerg Kristensen, a professor of molecular biology at Roskilde University in Denmark, one of the consensus authors. “But it’s more when you have all the studies lining up that you begin to be concerned,” he said.

‘Irresponsibly Published’

But other experts say that it’s misleading to stack up profoundly limited data and conclude that, as a whole, it carries more weight.

The paper from Bauer’s team was “irresponsibly published,” said Nathaniel DeNicola, an obstetrician-gynecologist based in Orange County, California, who helped review the evidence for the American College of Obstetricians and Gynecologists. “It did not reflect the preponderance and overall weight of the data, and it did not reflect the clinical context.”

DeNicola, who has expertise in environmental exposures and health policy, pointed out that consensus authors didn’t include numerous reviews, including those from major medical organizations, that drew different conclusions. Both ACOG and the Society for Maternal-Fetal Medicine, for example, found no clear evidence that acetaminophen causes fetal developmental issues and no reason to change current medical advice and practice.

In the end, neither did the FDA. In 2018, the agency brought the issue before its Medical Policy and Program Review Council, which provides oversight and direction of policies. The council found the available data didn’t warrant changes on acetaminophen labels or updates to the existing safety communication, wrote FDA press officer Charlie Kohler in an email to Undark.

While the agency continues to monitor the issue, it closed the formal tracking process in 2020 said Kohler, because extensive reviews failed to turn up solid evidence of a link between the drug and neurodevelopmental issues.

The gold standard for understanding the effect of a medication is to randomly assign one group to take the drug and another to get a placebo, with neither researchers nor participants knowing who got what until the end of the study. However, those randomized clinical trials rarely include pregnant women because of potential risks to the fetus. As a result, acetaminophen researchers rely on observational studies and laboratory experiments, including those that test the effects of the drug on experimental animals.

It can be difficult, however, to study neurodevelopmental problems in these animals. For one, researchers wouldn’t diagnose ADHD or autism in a mouse, though some research finds that mice exposed to acetaminophen in the womb are more likely to have problems with learning, memory, motor skills, and social behavior. Additionally, the biological mechanisms that lead to a diagnosis in humans are complex and not well understood, said Kristensen, so researchers don’t know what to exactly look for when they study the brains of laboratory animals.

Research in test tubes and lab animals does show that acetaminophen affects several chemical systems involved in brain development. “The compound is doing multiple different things during development at specific time points when the fetus is vulnerable,” said Kristensen. But whether these factors contribute to neurodevelopmental problems, he added, is unclear. Kristensen said that he expects to publish data within the next year or so that could help clarify the connection.

It’s also hard to know what to make of the observational research, which has numerous limitations, according to DeNicola. Many of the studies rely on women’s recall of having taken acetaminophen, which can be faulty weeks and even months later, he said. And instead of a clinical diagnosis of a child’s developmental or behavior disorder, studies often depend on assessments by parents and teachers, which sometimes differ.

One of the biggest issues with the observational research is failing to adequately control for other factors that cause autism and ADHD, particularly heredity, said Per Damkier, head of research in clinical pharmacology at the University of Southern Denmark and a co-author of a consensus rebuttal by the European Network of Teratology Information Services. (Teratology is the study of diseases and conditions that are congenital, or present at birth.) Based on data from Western countries, researchers estimate that up to 80 percent of autism and up to 90 percent of ADHD results from genes children inherited from their parents. If you don’t account for that huge factor, he said, “you inevitably will come up with misleading results.”

For example, a 2017 Pediatrics study included in the original consensus review found that the father’s use of acetaminophen increased a child’s risk of ADHD just as much as the mother’s use during pregnancy. While the researchers theorize that acetaminophen could have altered how the fathers’ genes work, Damkier said that the more likely explanation is that the analysis didn’t sufficiently adjust for heredity.

The pain or illness that prompts a woman to take a pain reliever may also skew the data. In their consensus rebuttal, authors from the Organization of Teratology Information Specialists point to the OTIS’ long-running MotherToBaby study, which found that compared to pregnant women who use acetaminophen for short periods, those who take it longer term report having more mental health conditions, including depression and anxiety, and are more likely to take antidepressants — all factors studies suggest are associated with ADHD and autism in children.

In a 2020 study, epidemiologist Reem Masarwa, then a postdoctoral fellow at McGill University in Montreal, and colleagues explored whether confounding factors such as heredity and maternal illness could be biasing acetaminophen research.

The group reanalyzed data from a meta-analysis Masarwa had published two years earlier, which had found a 35 percent increased risk of ADHD in children exposed to prenatal acetaminophen. This time the researchers stringently adjusted for parental ADHD and migraines in the mother.  The ADHD risk nearly disappeared.

‘There’s Something Biological Going On’

The consensus authors cite two studies that overcome the limitation of relying on a mother’s memory of acetaminophen use. The first, a 2019 study, tested umbilical cord blood for traces of acetaminophen and the second, published in 2020, measured acetaminophen in babies’ first bowel movement. Both found that the higher the prenatal exposure to acetaminophen, the greater the chance of a child receiving a physician diagnosis of a neurodevelopmental disorder.

“The beautiful thing about the new studies coming out is that the better the study, the stronger the associations,” said Kristensen. “Suddenly, you can see dose response, which is something we always look for because that argues that there’s something biological going on.”

However, both of those studies have drawbacks as well. Acetaminophen only lingers in the blood for a few hours, so the implication of the cord-blood study is that a single dose right before birth could have a dramatic effect on a child’s brain. Many experts find that result implausible.

Testing a newborn’s bowel movement may be a better measure as it is thought to reflect the mother’s use of acetaminophen during the last two trimesters of pregnancy. But as with some other observational studies, the researchers didn’t account for why the mother took the drug in the first place.

Plaintiff attorney Ashley Keller said that his first responsibility is to help his clients win compensation. In addition, he said, there’s also a public health issue at stake in that the women need full information to make informed decisions.

In April, U.S. District Judge Denise Cote, who is presiding over the pre-trial proceedings, took the unusual step of inviting federal regulators to provide an opinion on whether the science warrants adding a warning to acetaminophen labels about an association between prenatal exposure and ADHD and autism.

The FDA declined to comment on whether the agency would weigh in by the end of July as requested by Judge Cote.

Claiming that FDA regulations and federal laws prevent them from changing Tylenol labels, Johnson & Johnson is pushing for a dismissal. The company continues to evaluate the science and has not seen any evidence that acetaminophen use during pregnancy causes fetal development issues, Witt, the company spokesperson, wrote in an email. “Leading medical organizations agree with the current product label which clearly states, ‘If pregnant or breast-feeding, ask a health professional before use.’”

Bauer said the lawsuits are helping get the word out about the accumulating research on acetaminophen’s risks. Up until now, she said, a lot of women have viewed the drug as “completely innocuous,” something to take “whenever they are in discomfort.” Others disagree. DeNicola said that the women he sees in his practice are conscientious about using acetaminophen.

One thing everyone agrees on is the recommendations for acetaminophen use, said DeNicola: “Use it only where indicated in the lowest dose for the shortest duration.” So, for pain or fever that means taking one pill, one time, to see if symptoms ease, he said.

Another point of real consensus is the need for more research. Bauer said that several groups are looking at possible mechanisms for how acetaminophen could affect development. “As far as the epidemiology, there’s a pretty perfect study that could be done,” she said, pointing out that, with smartphones, women can easily record what they take and why. “But it’s going to take us many, many years is the problem.”

“Something that is potentially this important for, not just fetal, but for childhood brain development should be studied,” DeNicola said. “And it should be studied in a real way.” For example, he would like to see studies that use blood tests and other measures throughout pregnancy to accurately track exposures not just to acetaminophen, but also to environmental substances of greater concern to fetal development, such as industrial chemicals. And, since a baby’s brain continues to develop after birth, studies should account for use of acetaminophen in childhood — a glaring omission from most of the current research, said DeNicola.

At the moment, no one is conducting exactly that type of study on acetaminophen.

However, FDA spokesperson Charlie Kohler said that agency is conducting a small study to see how people’s bodies absorb, metabolize, and excrete the drug. The agency is also planning a toxicology study in 2024, pending approval of funding.

And Chambers said that she is coordinating a study funded by the National Institutes of Health of about 8,000 mother-child pairs in 25 sites across the U.S. The Healthy Brain and Child Development Study will capture information on prenatal exposures, including to acetaminophen, and use brain imaging and standardized assessments to track brain development in children. Researchers will release data annually, so information on prenatal exposure to acetaminophen will begin to emerge in the next couple of years, she said.

If there’s anything good to come out of the controversy, it’s that every drug, over the counter or not, deserves rigorous research on safety, said Chambers — and society hasn’t invested in systematically doing that type of research. She pointed out that while the FDA requires new drugs to be assessed for safety during pregnancy, nobody has the resources of motivation to do that for old drugs like acetaminophen.

“And we need to stop that,” said Chambers. “We need to turn that wheel around, pay attention and do the work that needs to be done.”

This article was originally published by Undark, a non-profit, editorially independent online magazine covering the complicated and often fractious intersection of science and society. You can read the original article here.

‘Take Care of Maya’: The High Cost of a Mother’s Love

By Cynthia Toussaint, PNN Columnist

Netflix’s top-notch documentary, Take Care of Maya, was excruciatingly painful for me to watch because it hit so close to home. I related on many levels: the disease, maltreatment from healthcare professionals, being labeled crazy, the family breakdown, and the pursuit of justice. But the dagger to my heart was the price paid for a mother’s love.

Like me, the protagonist, Maya Kowalski, has Complex Regional Pain Syndrome (CRPS), but the over-riding message of the film is about something far more insidious. It lays out the abusive extremes some health and social care systems take to make a buck at the cost of patients and their families. Sometimes that price can be unimaginable.

In Maya’s case, her parents were falsely accused of child abuse, specifically making their daughter ill for their own gain, a disorder known as Munchausen by Proxy. This misguided allegation led to Maya being kidnapped by hospital administrators, who then barred her from seeing her family, all while the 10-year-old’s physical and emotional pain became increasingly worse.

It was horrifying to watch Maya’s family unravel under the strain of this prolonged nightmare, in particular her bold and unflinching mother Beata’s relentless confrontations with the powers that be.

After multiple failed attempts to reverse matters in the courts, Beata, the focus of the abuse allegations and the target of the hospital’s ire (***spoiler alert***), became increasingly despondent to the point that she hanged herself to give her daughter the best chance of getting back home.

‘They’re Killing My Daughter’

I’m guessing that many who watched the documentary found its facts too fantastic to be true – and there was a time when I might have agreed with them. But I’ve lived too much of this story to question it now.

In my early 20’s, when it was clear that my still unnamed disease wasn’t going away, my mother became progressively distraught over watching my life slip down the rabbit hole. It’s fair to say my recovery came to be her over-riding obsession.

Mom wrote 200+ searing letters, sometimes demanding, at other times begging my HMO to diagnose and treat me. She spent large swaths of those years on the phone in desperate attempts to get me, as she coined them, “no-care” appointments, all in the hope that a compassionate physician or administrator would at last hear her pleas and change my course.

My poor mother became more and more unglued and unwell from the abuse, aimed first at me and then toward her, from this evil empire. She developed life-threatening heart problems and her legs, addled by aching varicose veins, went from bad to worse from constantly lifting me. Perhaps my most distressing memory of those dark days was when I’d hear her full-volume moans emanating from out-of-control sadness.  

One day after my HMO dropped the ball on an appointment we’d driven miles to attend, Mom snapped with rage. With super human strength, she hoisted my 50-pound wheelchair in the parking lot and smashed it into her car. As I cried in fear, she repeatedly bashed away.

“They don’t care about my daughter!” she screamed. “She’s dying! They’re killing my daughter!”

During this time, I was terrified for my mother’s life. Though it never crossed my mind she would take her own, I was hounded incessantly with the thought that she would succumb to a stroke or heart attack.

Maya’s mother made the ultimate sacrifice by taking her own life to save her daughter’s. Some might say that was tragically misguided, but I’m certain Beata’s intentions were true and real. My mother said to me on more occasions than I care to remember, “If cutting off my arm would make you well, I’d do it.” I never doubted her.

After fighting my HMO for nearly a decade with no tangible results, not even a diagnosis, my mom pulled up stakes, but in a different way than Beata. Mom moved to New York to pursue her long-delayed acting career. When I confronted her about feeling abandoned, she explained her reasoning. “Maybe if I go, you’ll get better by doing more for yourself,” she told me. It didn’t have to be logical.

In Beata and my mother’s desperation to somehow, someway fix impossibly tragic situations for their daughters, both made questionable choices out of love. It’s true, the path to hell is paved with good intentions, especially where chaos and heartbreak intersect.

Like Maya, I couldn’t just fold tent and walk away from the institution that did me wrong. Sure, I wanted justice for me, but also for my mom. I became a spokesperson and a whistle-blower for HMO reform in California, hell bent on exposing all of their atrocities. I did get a number of licks in, multiple high-profile media stories that helped change public opinion, which helped pave the way to sweeping legislative reform.

In retrospect, something I think of quite a bit these days, the cost was too high. I’m harassed by this entity to this day and they were successful in killing much of my most important work. In short, the fallout from my justice-seeking made me sicker and sadder over the decades, taking away more than it gave.

When I see Maya seeking justice in her mother’s name, I have great respect for her, but also concern. This young woman is now in remission and, going forward, my prayer is that she puts her health front and center. After poignantly telling her story on a world stage and prevailing in the courts (which I believe will mercifully happen soon), I hope Maya will step away with the knowledge that she’s done enough, and never looks back. It’s time to save herself.     

It’s also time to grieve, maybe more than anything, the loss of a mother’s love.    

Cynthia Toussaint is the founder and spokesperson at For Grace, a non-profit dedicated to bettering the lives of women in pain. She has lived with Complex Regional Pain Syndrome (CRPS) and 19 co-morbidities for four decades, and has been battling cancer since 2020. Cynthia is the author of “Battle for Grace: A Memoir of Pain, Redemption and Impossible Love.”

5 Lessons I’ve Learned About Chronic Pain

By Barby Ingle, PNN Columnist

Do you ever feel like your time, energy and hope are running out due to chronic pain or illness? That you aren’t living life to the fullest and may never be able to?

Many people who live with painful disabling conditions have that kind of fear and self-doubt. If you are struggling with similar thoughts, read along while I dive into the five most meaningful lessons I’ve learned about chronic pain.

I wish I had known these things when my journey through the American healthcare system began. I strive to be healthier and wonder if my wellness would be further along if I had known better from the start.

The good news is that changing today can affect your tomorrow. It is never too late to make improvements in your life. Whether you are a longtime chronic pain patient or just starting on your pain journey, these five insights may help save you some heartache and frustration. 

1.  Keep good medical records 

I have long been a proponent of keeping and updating your medical records.  Use technology to your advantage. Advances in health information technology make it easy to store and retrieve data, and facilitates the rapid exchange of patient information. This can help you file insurance appeals and when seeking prior authorizations.

When a provider closes down unexpectedly, having medical records from your patient portal either printed or downloaded in PDF form can also help you find a new provider. This is something I faced this year when my ketamine provider abruptly shut down.  

2.  Not all providers are equal 

Learn everything you can about your illness and keep learning. It is also essential to seek specialists who know about your complex medical condition.

People often look up to their doctors and put total faith in them. However, most doctors are educated and trained in only one specialty in the practice of medicine. Just because a doctor is a neurologist doesn’t mean they can treat diabetic neuropathy, multiple sclerosis or Lyme disease. 

Providers may have expertise in treating one or two conditions, and know only a little about others. With thousands of diseases, conditions and treatments, no provider can know them all in-depth. Learn about your provider's experience and limitations, and encourage them to seek additional knowledge from their peers to help you. Communication is the key to improving trust and faith in your treating doctors.

3.  Your diagnosis does not define you 

In medicine, a diagnosis refers to a specific disease or illness, but not the characteristics of each patient. A condition may present itself and progress differently, depending on the patient’s genetics, lifestyle and environment.

I was once given a diagnosis of thoracic outlet syndrome (TOS) when I was exhausted, over-treated, and scared. It turned out that was an incorrect diagnosis and that the TOS-like symptoms I was having were secondary to the real cause: Reflex Sympathetic Dystrophy (RSD).  

We need to be careful not to jump to easy conclusions. I also realized I had to stop comparing my symptoms and outcomes to others with the same condition. I turned my focus on creating the best me I could be. 

4.  If something is too challenging, break it into smaller pieces 

Do the more manageable actions first, and then see what is left to conquer.

Tackling one problem – like organizing medical records from a single provider -- can give you the positive momentum to take on the more challenging ones. If you find yourself having difficulty -- stop, take a break and work on something else. Get that feeling of success (and the endorphins that come with it), and return to the challenge when you are ready for it. 

5.  Share your journey 

Each of our journeys are unique, but hearing someone else’s experience can offer us hope, options, and ideas that we can use to improve our own lives.

For example, I’ve found that hydration is super essential for coping with RSD. My primary care doctor said I should drink water regularly to help regulate my body temperature, keep my joints lubricated, prevent infections, replace nutrients in my cells, and to keep my organs functioning correctly.

He was right. I learned that when I consistently drink 60-70 oz. of water daily, take my medications on time, and do light stretching, my sleep, cognition and mood also improve.

Continue to share and cultivate habits that support your long-term health and happiness. The more we know, the better our decisions will be. I’ve dedicated my life to helping people with chronic conditions have happier and more meaningful lives. The key is to believe in yourself while building the life that you want. After helping thousands of people worldwide and reading countless success stories, I am confident that you can do that.

Barby Ingle is a reality TV personality living with multiple rare and chronic diseases. She is a chronic pain educator, patient advocate, motivational speaker, and best-selling author on pain topics. Barby has received over 25 awards for her advocacy efforts. You can follow her at www.barbyingle.com.    

Arthritis Pain Varies Widely Across States

By Pat Anson, PNN Editor

People living in West Virginia are three times more likely to have moderate or severe joint pain from arthritis than those in Minnesota, according to a comprehensive new study that highlights how disparities in education and access to social services contribute to chronic pain.

“Very little research has examined the geography of chronic pain, and virtually none has examined the role of state-level policies in shaping pain prevalence,” says co-author Hanna Grol-Prokopczyk, PhD, an associate professor of sociology at the University of Buffalo. “We were excited to identify state characteristics that reduce residents’ risk of pain.”

Grol-Prokopczyk and her colleagues looked at data for over 400,000 adults who participated in the 2017 Behavioral Risk Factor Surveillance System, along with data from all 50 states on social assistance and anti-poverty programs such as the Earned Income Tax Credit, Medicaid and Supplemental Nutrition Assistance Program (SNAP), more commonly known as food stamps.

Their findings, published in the journal PAIN,  show the risk of joint pain was significantly higher in states in Appalachia, the Mississippi Valley and the South, compared to states in the Upper Midwest and West.

Nearly one in four adults in West Virginia (23.1%), Alabama (21.6%) and Arkansas (21.4%) had moderate to severe joint pain. States with the lowest risk of joint pain are Minnesota (6.9%), Hawaii (7.5%) and Utah (7.7%).

SOURCE: PAIN

Digging deeper into the data, researchers found that educational disparities are also associated with pain frequency. People who did not complete high school in West Virginia (31.1%), Arkansas (29.7%) and Alabama (28.3%) were far more likely to have joint pain compared to those with bachelor degrees in California (8.8%), Nevada (9.8%) and Utah (10.1%).

People with less education are more likely to have blue-collar jobs requiring manual labor that may contribute to joint pain. They also have lower incomes and less access to healthcare.

“Education can function as a ‘personal firewall’ that protects more highly educated people from undesirable state-level contexts, while increasing the vulnerability of less educated individuals,” said first author Rui Huang, a sociology PhD student in the UB College of Arts and Sciences.

Researchers also found that states with higher levels of SNAP benefits, social support and community health services had lower levels of pain frequency.

“The increase in the generosity of SNAP benefits could potentially alleviate pain by promoting healthier eating habits and alleviating the life stress associated with food insecurity,” says Huang. “Social factors such as conflict, isolation and devaluation are also among the ‘social threats’ that can lead to physical reactions such as inflammation and immune system changes.”

Previous studies at the University of Buffalo have found that gender, poverty and education play a role in pain frequency and that the overall prevalence of pain is increasing in the United States, affecting virtually every age group, sex, ethnicity and demographic.

Should Suboxone Be Used to Treat Kratom Addiction?

By Pat Anson, PNN Editor

A man with a history of substance abuse – including addiction to kratom – has been successfully treated with buprenorphine/naloxone (Suboxone), according to a case study published in the journal Cureus.  Suboxone is a medication that is normally used to treat opioid use disorder.

Kratom is not derived from the opium poppy and is not an opioid. It’s an herbal supplement that comes from the leaves of a tree in southeast Asia, where it has been used for centuries as a stimulant and pain reliever. In recent years, millions of Americans have discovered kratom and use it to self-treat their pain, anxiety, depression and addiction.

The unidentified patient in the case study has a history of using cocaine, marijuana and alcohol, and suffers from anxiety and depression. He was introduced to kratom 12 years ago by his brother for stress relief and as a substitute for oxycodone. Over the years, the patient used more and more kratom, at one point spending up to $600 a week on kratom supplements.

After several failed attempts to wean himself off kratom, which resulted in severe withdrawal symptoms, the patient went to see his primary care physician, Dr. Paul Remick, one of the study’s co-authors. It was Remick who suggested that Suboxone might help him quit kratom.

“He’d been struggling with depression, anxiety, all these various issues. He was pretty reluctant to try therapy like Alcoholics Anonymous or trying to speak to a therapist,” explained lead author Martin Arhin, a medical student at the University of North Carolina at Chapel Hill. “Dr. Remick suggested Suboxone, since kratom has some like opioid-like properties. He felt like it could potentially work. And fortunately, it did.”

After 23 weeks of using Suboxone, the patient’s withdrawal symptoms subsided and he stopped using kratom. He’s also been successfully tapered off Suboxone, a drug that many people wind up taking for life.   

Suboxone is only approved for opioid use disorder and there is no clinical evidence that it can treat kratom addiction. Such a use, while legal, would be considered “off-label” by the FDA. But based on this one anecdotal case, Arhin and his co-authors say Suboxone could be a treatment for kratom dependence.

“Currently, there is no established evidence-based consensus for the treatment of kratom addiction and withdrawal, leaving individual providers to decide on the appropriate course of action,” they wrote. “We recognized the patient's dependency on kratom and subsequently implemented a treatment plan utilizing buprenorphine/naloxone, which effectively alleviated withdrawal symptoms and supported the patient's abstinence from kratom. We suggest that this drug combination may be a potential treatment for kratom addiction.”

‘Kratom Saved My Life’

Ironically, many people use kratom as an alternative to Suboxone. In a 2016 PNN survey of over 6,100 kratom users, nearly ten percent said they used kratom primarily as a treatment for opioid addiction. Most said it was very effective (91%) in easing their withdrawal symptoms and worked better than Suboxone, with fewer side effects.

“Kratom saved my life. I tried every other type of treatment for drug addiction over the past 10 years. Subutex, methadone, total abstinence and the 12 step program. Each time I failed. After 2 years of Suboxone, I stopped treatment and began using kratom,” one respondent told us.

“Because of kratom, I no longer have to worry about heroin (or methadone or Suboxone) making me sick. I've been clean for 2 years. I can hold a job now, and I only use it when I need pain relief or need to relax,” another respondent wrote.

“I became hooked on oxycodone and had to take Suboxone to get off it. The problem is Suboxone withdrawals were nearly as bad, so I used kratom to cure that,” another patient said.

“Kratom truly saved my life. I've always suffered from extreme anxiety, but it has decreased drastically since taking it. Withdrawals from opiates and Suboxone are awful. I would not have been able to get clean without kratom. I'm confident in saying that if you make kratom illegal, the number of overdoses will rise,” wrote another kratom user.

The DEA and FDA have tried to make kratom illegal by having it declared a Schedule I controlled substance. So far, those efforts have failed due to a public backlash.

Kratom is sold legally in most U.S. states, but a handful of states and cities have banned it over concerns about addiction and overdoses.  About 100 deaths nationwide have been linked to kratom use, but in the vast majority of cases other drugs and illicit substances were involved.

About two million Americans use kratom, primarily to treat chronic pain. A 2020 study funded by the National Institute on Drug Abuse concluded that kratom is an effective treatment for pain, helps users reduce their use of opioids, and has a low risk of adverse effects.

Although many people use kratom to self-treat opioid addiction and ease withdrawal symptoms, the FDA won’t allow kratom vendors to advertise or promote kratom for addiction treatment or any other medical purpose. This month, the FDA sent a warning letter to the Sunshine Trading Company in Colorado, warning it to stop promoting its kratom products for “opiate withdrawal.”

“You market kratom products for the treatment or cure of opioid addiction and withdrawal symptoms. However, these products have not been determined by FDA to be safe and effective for these (or any other) uses. Further, the unproven treatments could cause patients to forego or delay FDA-approved treatments for opioid addiction or withdrawal,” the FDA said.

In recent years, several other kratom vendors have received similar warning letters from the agency..

Home Delivery of Rx Opioids Would Help Chronic Pain Patients

By Pat Anson, PNN Editor

We hear almost every day from people in pain who say they can’t get an opioid prescription filled because their pharmacy is out of stock. Often, the pharmacist has no idea when the next shipment of pain medication is coming.

“Walgreens cannot fill my prescription. They say the drug is on back order with no ship date available,” a patient recently told us.

“20 years on the same Rx for Vicodin and now CVS says they are out of stock and no idea when it will be available,” another patient wrote.

“Just talked to a pharmacist today that said they are out of Percocet, Vicodin and morphine. They said that their supplier, Cardinal Health, wasn't sure when they would get more,” said another patient.

Now imagine, if you will, what it would be like to have a pharmacy that delivers opioid medication directly to your home. No more standing in line at the pharmacy. No more dirty looks from the pharmacist. No more excuses about being out of stock.

For about 1,000 patients in the Philadelphia area, most of them chronic pain sufferers, that fantasy is a reality. They are customers of a boutique pharmacy in the Delaware Valley that specializes in home deliveries of controlled substances – including high dose opioids.  Prescriptions and refills are delivered on a carefully managed schedule before a patient runs out, becomes disabled by uncontrolled pain, and goes into withdrawal.

“We hand deliver directly to the patient. I have a whole delivery team. They're our own drivers, our own vehicles,” says Brian Dunleavy, CEO of PMC Pharmacy. “Our customers get notified when their delivery is anticipated to arrive at their home. And then every patient has to sign for it. They have to be present or we can't leave it there. Or it has to be an adult that's been authorized to receive the medication.”

I first heard of PMC Pharmacy when it sent out a news release last month to address difficulties that some patients have getting opioids and other controlled medications from other pharmacies in the Delaware Valley. PMC said it could help those patients avoid gaps in drug therapy and was committed to keeping them “on schedule, at home, and independent.”

“We should really have every chronic pain management patient in the Delaware Valley under our care because of the way our program works,” Dunleavy told PNN.

While big chain pharmacies and their wholesale drug suppliers are under increased scrutiny from law enforcement and regulators, PMC flies under the radar because its customers’ medical conditions, prescriptions and insurance claims are carefully documented – reducing the risk of diversion or misuse.     

“We won't take patients from a typical primary care practice, we're only working with chronic pain specialists who give us (patient) chart notes and supporting documentation to satisfy our wholesalers’ desires that we're doing due diligence on all these doctors and all these patients, and making sure that there's a legitimate need for the medication,” Dunleavy explained. “The diversion isn't coming from the people that are legitimate chronic pain patients. Those people hold onto that medication as if it's their lifeline.”

Trifecta of Problems

The supply of opioids and other controlled substances is tight because of a trifecta of problems that have hamstrung the pharmaceutical industry.

First, the Drug Enforcement Administration has been aggressively cutting opioid production quotas for nearly a decade, reducing the supply of oxycodone by 65% and hydrocodone by 73% since 2013.

Second is the fallout from opioid litigation. The nation’s three largest drug wholesalers reached a $21 billion settlement with 46 states, requiring them to impose strict limits on opioid shipments to pharmacies. CVS, Walgreens and other pharmacy chains have also paid tens of billions of dollars to settle lawsuits that alleged they helped fuel the overdose crisis by dispensing too many opioids.  

The third reason for tight supplies is a retooling of the generic drug industry. There’s little money to be made in selling most opioids and there’s a risk of further liability, so drug makers are cutting back production of many generic opioids.  One of the world’s largest manufacturers of generics, Teva Pharmaceutical, recently notified the FDA that it was discontinuing production of oxycodone.

It all adds up to an increasing number of drug shortages, involving not just opioids, but medications used to treat cancer, anxiety and attention deficit disorder. Dunleavy thinks the shortages are a direct result of regulatory overreach.

“You have all these things going on and everybody's like, ‘Oh well, there's a shortage of oxycodone out there.’ And in actuality, there isn't. It's a regulatory created shortage, which is why there's a discrepancy between what we're hearing from patients versus what we see at the on the wholesalers’ shelves,” he explained. “The pharmacies can't get those drugs because they're quantity restricted by the wholesalers, based on the programs that the wholesalers have implemented to police the pharmacies.”

Dunleavy says PMC would like to add more patients to its customer base, provided they live in its delivery area in southeastern Pennsylvania and parts of New Jersey and Delaware that border Philadelphia. He’s confident he’ll be able to get the additional medication from suppliers.

“You're not going to have a better adherence and compliance program from a pharmacy than ours,” he said. “Because our program is pain management specific, once we start working with a practice, we start getting quite a few referrals. So it's very easy for us to start growing.”

Could PMC’s business model be adopted by other pharmacies? With pain management under so much scrutiny, Dunleavy says home deliveries to selected patients make sense.

“There's a legitimate need for a pharmacy that puts in a little bit more effort, that's a little bit more specialized. Because the regulatory environment requires it, the patients require it, and the physicians require it,” he said.

“This is a very interesting concept. It almost sounds too good to be true, but if it really works it would be tremendously helpful to many chronically ill people,” says Kristen Ogden, a patient advocate in Virginia. “I think this concept may be really helpful to house-bound patients and persons with limited access to transportation, especially those who don't have an engaged family member helping them.”  

For many years, Kristen and her husband Louis have traveled to California to get the high dose opioids he needs to treat severe pain from arachnoiditis and Ehlers-Danlos Syndrome. Not having to make that monthly cross-country trip for refills would be a welcome relief to the Ogdens.  

“It would be great to think this sort of service would be available to us as we get older, especially since we have no children and no other family members who live in our area to assist us. This could certainly be a big factor in enabling older adults to continue living in their own homes if that's what they prefer to do,” Kristen said. 

The American Society of Health-System Pharmacists put immediate release oxycodone on its list of drug shortages in March and added hydrocodone/acetaminophen tablets to the list in May.  Neither shortage has yet to be recognized by the FDA, although many patients are already well aware that both medications are in short supply. 

“I've been waiting for over a week for oxycodone to come in. Over the last weekend, I went to over 25 different pharmacies searching, until I couldn't drive anymore. It's not fair to any of us!” a pain patient recently told PNN

Patients Squeezed in Fight Over Costly Infusion Drugs

By Samantha Liss, KFF Health News

Health insurers and medical providers are battling over who should supply high-cost infusion drugs for patients, with the tussle over profits now spilling into statehouses across the country.

The issue is that some insurers are bypassing hospital pharmacies and physician offices and instead sending more complex drugs through third-party pharmacies. Those pharmacies then send the medications directly to the medical provider or facility for outpatient infusing, which is called “white bagging,” or, more rarely, to patients, in what is called “brown bagging.” That shifts who gets to buy and bill for these complex medications, including pricey chemotherapy drugs.

Insurers say the policies are needed because hospital markups are too high. But hospitals argue that adding an intermediary results in unnecessary risks and delays, and they say some insurers have their own or affiliated pharmacy companies, creating financial motives for controlling the source of the medications. The patients, meanwhile, are left to deal with the red tape.

Paula Bruton Shepard in Bolivar, Missouri, is among those caught in the middle. Flares of lupus, an autoimmune disease, rob Shepard of her mobility by attacking her joints. She relies on monthly infusions to treat her symptoms.

PAULA SHEPARD

But at times, she said, her treatments were delayed due to UnitedHealthcare’s white bagging infusion policy. And interruptions to her treatments exacerbated her symptoms.

“I once had to use a toilet lift and it was kind of demoralizing to say, ‘I’m a 50-year-old woman and I have to use a toilet lift,’” Shepard said of the medication delays.

This is a tug of war over profits between insurers and medical providers, said Ge Bai, a professor of accounting and health policy at Johns Hopkins University. While insurers claim the arrangement reduces costs, she said, that doesn’t mean insurers pass along savings to patients.

“I don’t think we should have more sympathy toward one party or the other,” Bai said. “Nobody is better than the other. They’re all trying to make money.”

The savings from white bagging can be significant for expensive infusion drugs, according to a report from the Massachusetts Health Policy Commission. For example, Remicade, used to treat a variety of inflammatory diseases, including Crohn’s, cost on average $1,106 per unit in 2015 under hospitals’ traditional buy-and-bill system, the commission found in its review of state claims data. That same drug cost an average of $975 per unit under white bagging, a 12% savings.

But the report also found patients, on average, faced higher cost sharing — what they are responsible for paying — for Remicade and other drugs when white bagging was used. While some patients had only modest increases to their costs under the policy, such as $12 more for a medication, the review found it could mean much greater cost sharing for some patients, such as those on Medicare.

Delays in Care

At Citizens Memorial Hospital in rural Bolivar, more than 1 in 4 patients who receive regular infusions are being forced to use an outside pharmacy, said Mariah Hollabaugh, the hospital’s pharmacy director. Shepard was among them.

Even if the hospital has the exact drug on the shelf, patients must wait for a separate shipment, Hollabaugh said, potentially interrupting care. Their shipped drugs may sometimes be unusable when the doctor needs to change the dosage. Or the medicine comes in a nondescript package that doesn’t get immediately flagged for the pharmacy, potentially subjecting the drugs to damaging temperature fluctuations. For patients, that can mean delays in care.

“They’re in pain, they’re uncomfortable,” Hollabaugh said. “They may be having symptoms that don’t allow them to go to work.”

Siteman Cancer Center, led by physicians from Washington University School of Medicine in St. Louis, has confronted the same issue. But the cancer center’s size has helped it largely avoid such insurer policies.

John DiPersio, a Siteman oncologist and researcher who led the university’s oncology division for more than two decades, said Siteman reluctantly allows white bagging for simple injectables but refuses to accept it for complicated chemotherapies. It does not accept brown bagging. Occasionally, he said, that means turning patients away.

“You’re talking about cancer patients that are getting life-threatening treatments,” DiPersio said, referring to the dangers of chemo drugs, which he said can be fatal if used improperly. “It doesn’t make any sense to me. It’s all stupid. It’s all lunacy.”

At least 21 states, including Missouri, introduced some form of white or brown bagging legislation during the most recent legislative session, according to the American Society of Health-System Pharmacists. And in the past two years, the trade group said, at least 13 states have already enacted restrictions on white bagging, including Arkansas, Louisiana, and Virginia.

ASHP has created model legislation to limit insurers from requiring the practices as a condition of coverage.

“This is a major issue,” said Tom Kraus, a vice president at the trade group. “We see this as central to our ability to coordinate patient care.”

At the heart of the tension is an often-litigated federal program that allows certain hospitals and the clinics they own to purchase drugs at deep discounts. The 340B program, named for a section of the law that created it, allows hospitals to buy certain drugs for much less — sometimes for a total cost of a single penny — than what they are later paid for those drugs. Hospitals are not required to pass along 340B savings to patients.

The program was intended to help hospitals spread scarce resources further to treat patients in poor and vulnerable communities, but it has morphed into a means of enriching hospitals and their affiliated clinics, researchers said in a 2014 Health Affairs report. Hollabaugh said many rural facilities such as Citizens rely on the revenue generated from the 340B drugs to subsidize infusions that have no profit margin.

The number of participating hospitals and their affiliated outpatient clinics has increased significantly since the 340B program was created in 1992. More than 2,600 of the nation’s roughly 6,100 hospitals were participating in the 340B program as of January 2023. That gives them access to discounts that can knock off as much as 50% of a drug’s cost, according to the Health Resources & Services Administration, which oversees the program.

‘People Got Greedy’

The insurance industry argues that hospital markups, especially when made on top of those discounts, have gotten out of control.

“The fact is, people got greedy,” Shannon Cooper, a lobbyist for Blue Cross and Blue Shield of Kansas City, said during a Missouri state Senate hearing in March.

Markups are not unique to 340B hospitals, said Sean Dickson, who helps lead pharmaceutical policy for AHIP, a trade group formerly known as America’s Health Insurance Plans. The markups thrusted on commercial plans are “widely out of line” with what Medicare will pay, he said, and that is driving up costs without providing additional value.

Legislation that targets white bagging hinders an insurer’s ability to rein in such costs, Dickson said, especially when an area lacks competition.

“What we're really trying to focus on here is putting pressure on those markups that are not related to cost or safety,” Dickson said.

Anthem Blue Cross and Blue Shield lobbyist David Smith testified during the March hearing in Missouri that even the idea of white bagging elicited a quick response and that almost every major hospital system in the state said they would drop their prices and come back to the negotiation table.

For now, Citizens Memorial Hospital and other Missouri medical facilities will have to continue to tango with the insurers: Legislation to limit white and brown bagging did not pass during the Missouri General Assembly’s recent session.

Shepard, though, won’t need such legislation.

UnitedHealthcare had been sending her lupus infusion through other pharmacies on and off since 2021, unwilling to cover the drugs if they came from Citizens’ in-house pharmacy. Shepard had to authorize each shipment before it was sent. If she missed the monthly call, she said, it was a “bureaucratic mess” trying to get the medication shipped.

“We are driving unnecessary costs out of the health care system to help make care more affordable, while also maintaining drug safety, effectiveness and quality of care,” UnitedHealthcare spokesperson Tony Marusic wrote.

But after KFF Health News inquired about Shepard’s case, Marusic said UnitedHealthcare stopped white bagging Shepard’s medication to “prevent potential delays in shipping.” And during her latest infusion in June, her hospital was again able to supply Shepard’s medication directly.

“I'm just so relieved,” Shepard said. “I don't have to take phone calls. I don't have to reply to emails. I just show up.”

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

Millions of People Worldwide Are ‘Left Behind in Pain’

By Pat Anson, PNN Editor

A new report by the World Health Organization (WHO) warns that limited access to morphine and other opioids is leaving millions of people in many parts of the world suffering in preventable pain.

The report, “Left Behind in Pain,” calls morphine a low cost, essential medicine for relieving moderate to severe pain. But access to morphine and other opioids is inadequate in many low and middle-income countries, with consumption patterns in wealthier nations that don’t correspond to medical need. Over 95% of the world’s supply of opioids is distributed in wealthy countries, with only 0.03% distributed in low-income ones.

“Leaving people in pain when effective medicines are available for pain management, especially in the context of end-of-life care, should be a cause of serious concern for policy-makers,” says Yukiko Nakatani, MD, WHO Assistant Director-General for Medicines and Health Products. “We must urgently advocate for safe and timely access to morphine for those in medical need through balanced policy, everywhere.”

The report calls for expanded access to morphine through local and regional distribution centers, changes in restrictive laws and guidelines, and reduced stigma surrounding opioid use.

“Some historical events, cultural beliefs, misinformation and disinformation about pain, and social stigma related to opioid use are known to have caused mistrust of opioids and contributed to fear of using them,” the report found.

Lawsuits and regulatory controls on the pharmaceutical industry are so strong in some countries that drug makers have stopped manufacturing morphine because the profit is low and risk of liability is high.

That may have played a role in Mundipharma’s recent decision to discontinue supplying Ordine, a liquid formulation of morphine, to Australia. Mundipharma is owned by the Sackler family, which has been enmeshed in opioid litigation over its role in the opioid crisis in the U.S. through its operation of Purdue Pharma.

A Mundipharma spokesperson told the Australia Broadcasting Corporation that the company’s third-party manufacturer decided to stop producing Ordine and that "sourcing another manufacturer would not be commercially viable."

Evolving Stance on Opioids

WHO’s position on opioids has evolved over the years. WHO’s guidelines for treating chronic pain, for example, used to say that opioids “are known to be safe and there is no need to fear accidental death or dependence.”

That changed in 2019, after two U.S. congressmen – without any real evidence -- accused WHO of being “corruptly influenced” by opioid manufactures. WHO withdrew the guidelines a month later, citing “new scientific evidence” – although critics said caved in to political pressure and threats to withdraw U.S. funding of WHO.

In 2021, WHO backpedaled further, recommending that morphine only be given to sick children when they are dying. Physical therapy and “biopsychosocial” treatments such as cognitive behavioral therapy were suggested as alternatives for children who are in pain, but expected to live.

WHO’s latest report recognizes the potential harms of opioids, couched in language about the world facing two opioid crises.

“The world is facing two crises related to the use of opioids. In the first, inappropriate use and over-prescription combined with the wide availability of illicit unregulated opioids, such as fentanyl, in some countries is causing significant harm and loss of life. In the second, a lack of access to opioids such as morphine in many parts of the world means that millions of people continue to suffer preventable pain,” said Nakatani.

About 80% of the world’s morphine supply was consumed in North America in 2021, primarily in the United States, although the rest of the developed world is catching up. Opioid consumption in the U.S. has fallen so sharply in recent years that Canada, Australia and several European countries have become the highest consumers of opioid analgesics, according to a 2022 study that ranked the U.S. as being 8th in per capita opioid sales.

Long Covid May Not Be Caused by Covid-19 Virus

By Pat Anson, PNN Editor

An immune system response to the COVID-19 virus has been suspected as a possible cause of Long Covid, a poorly understood disorder that causes chronic fatigue, brain fog, insomnia, chest pain and other symptoms long after the initial infection.  

But a small new study in the UK suggests that Long Covid may not be an inflammatory immune reaction to the SARS-CoV-2 virus. Instead, the body appears to be responding to the activation of dormant viruses many of us already have in our systems.

"Long Covid occurs in one out of 10 COVID-19 cases, but we still don't understand what causes it,” said Laura Rivino, PhD, Senior Lecturer at the University of Bristol's School of Cellular and Molecular Medicine. “Several theories proposed include whether it might be triggered by an inflammatory immune response towards the virus that is still persisting in our body, sending our immune system into overdrive or the reactivation of latent viruses such as human cytomegalovirus (CMV) and Epstein Barr virus (EBV)."

Rivino and her colleagues collected and analyzed blood samples from 63 Covid patients with mild, moderate or severe symptoms who were hospitalized at the start of the pandemic -- before vaccines were available – and tested them again 3, 8 and 12 months after their admission.  

Their findings, published in the journal eLife, show that patients with severe symptoms had significant dysfunction in their T-cell profiles after three months. T-cells are white blood cells released by the immune system to fight bacteria and viruses.

Further analysis showed there was no rapid increase in immune cells targeting SARS-CoV-2, but there was an increase in T-cells targeting CMV -- a common virus that is usually harmless but can stay in the body for life once you’re infected with it. That suggests that the prolonged T-cell activation observed at three months in severe patients may not be driven by SARS-CoV-2, but instead may be "bystander driven" by dormant viruses that were reactivated.  

"Our findings suggest that prolonged immune activation and long COVID may correlate independently with severe COVID-19. Larger studies should be conducted looking at both a larger number of patients, including if possible vaccinated and non-vaccinated COVID-19 patients,” said Rivino. "Understanding whether inflammation and immune activation associate with long COVID would allow us to understand whether targeting these factors may be a useful therapy for this debilitating condition."

The good news for Covid long haulers is that after 12 months, the T-cell levels of patients with severe Covid symptoms were similar to those of patients who experienced mild and moderate symptoms – suggesting that severe cases can resolve over time.

Medical Marijuana Laws Had Little Impact on Opioid Prescribing

By Pat Anson, PNN Editor

The cannabis industry and advocates in the U.S. have long claimed that state laws legalizing medical marijuana could help solve the opioid crisis by reducing demand for prescription opioids.

Various studies have suggested that may be true, like a recent one in New York state that found patients on high-dose opioids significantly reduced their opioid use once they started using medical cannabis. A similar study in 2021 found that cannabis was so effective in reducing chronic pain that most patients were able to reduce or completely stop their use of opioids.

But a large new study of commercially insured adults with chronic non-cancer pain found that the legalization of medical cannabis in 12 states (Arkansas, Connecticut, Florida, Louisiana, Maryland, Minnesota, North Dakota, New Hampshire, New York, Oklahoma, Ohio, Pennsylvania) had little to no effect on opioid prescribing.  

“Some research suggests that perhaps medical cannabis laws reduce opioid prescribing for chronic non-cancer pain because some people may substitute cannabis,” said lead author Beth McGinty, PhD, chief of the Division of Health Policy and Economics at Weill Cornell Medicine. “We found no effects of these laws on opioid prescribing or any types of treatment for chronic non-cancer pain that we looked at.”

McGinty and her colleagues looked at prescription data for over 150,000 chronic pain patients in the four years prior to state legalization and compared it to their medication use in the three years after medical marijuana laws were adopted. That data was then compared to prescription data for over 430,000 pain patients in 17 other states without medical marijuana laws, who served as a control group   

The study findings, published in Annals of Internal Medicine, show that opioid prescribing for chronic pain fell only slightly in states with medical marijuana laws, leading to tiny decreases in the average supply of opioids (0.35 fewer days) and for daily doses in morphine milligram equivalents (0.42 less MME). Small reductions were also noted in the prescribing of non-opioid pain relievers and in treatments such as physical therapy.

Importantly, the decreases were not substantially different than the data from states where medical marijuana remained illegal.

“Medical cannabis laws do not appear to be associated with changes in the prescription opioid or other non-cannabis, non-opioid treatments for chronic non-cancer pain,” McGinty said. “Policy makers trying to curb excess opioid prescribing and overdoses should focus on other strategies.”

Researchers say the minimal impact of medical cannabis on opioid prescribing may be due to the slow implementation of medical marijuana laws. Surveys show that most doctors are reluctant to discuss cannabis with their patients, and have doubts about its safety and effectiveness.

Doctors may not approve, but nearly a third of U.S. adults with chronic pain have used cannabis as a pain reliever and over half of them have reduced their use of pain medication. Many had no choice but to look for alternatives. Nationwide, opioid prescribing for commercially insured adults has fallen by 51% since 2011.

Hydrogel Shows Promise as Treatment for Arthritic Joints

By Pat Anson, PNN Editor

An experimental hydrogel that helps regenerate bone and cartilage tissue is showing promise as a treatment for arthritic joints, according to new research by Chinese and Canadian scientists. The gel is biodegradable and mimics the articular cartilage found in knee and hip joints.

In tests on laboratory animals, researchers say the gel showed signs of repairing articular cartilage 12 weeks after being implanted in rabbits, with no gel remaining and no rejection by the animals’ immune systems, according to findings published in the journal Nature.

Further animal testing is needed, but if the hydrogel proves useful in human trials, it could be used someday as an alternative to knee and hip replacement surgery. About one in four adults in the United States have some form of arthritis, which causes thinning of cartilage and progressive joint damage. Many resort to risky joint repair and replacement procedures.

“Cartilage is tricky,” says senior author Dr. Hongbin Li, a professor in the University of British Columbia’s department of chemistry. “Articular cartilage repair represents an important medical challenge because naturally speaking, it doesn’t repair itself.”

A delicate balance is needed to make biodegradable cartilage implants tough and stiff enough to support muscle-bearing tissues. They can’t be too stiff, or they’ll break when bent too far. Conversely, if they are too soft, they may not be useful in a joint.

In animal studies, researchers say a stiffer version of the gel had better results than a softer version, because it formed a scaffold that was more compatible with bone and cartilage tissue. That provided a physical cue to the body for tissue regeneration.

Dr. Linglan Fu holding the hydrogel

“This just shows how complex this area of research is, and the need to take into account the many different physical and biochemical cues and factors when designing these scaffolds,” says co-author Dr. Qing Jiang, a professor and surgeon at Nanjing University.

The research team used a new approach to stiffen biomaterials in the gel without sacrificing toughness, by physically entangling the chains of a protein.

“These entangled chains can move, which allows energy, for instance, the impact from jumping, to be dissipated, just like shock absorbers in bikes. In addition, we combined this with an existing method of folding and unfolding proteins, which also allows for energy dissipation,” says first author Dr. Linglan Fu, who conducted the research as a doctoral student at UBC’s department of chemistry.

The resulting gel is tough, able to resist slicing with a scalpel, and is more stiff than other protein-based hydrogels. Its ability to resist compression was among the highest achieved by any such gel, according to researchers, who say it compared favorably with actual articular cartilage. The gel was also able to rapidly recover its original shape after compression, as real cartilage does.

Researchers at Duke University are also working on an experimental hydrogel to replace damaged knee cartilage. The gel is made with thin sheets of cellulose fibers infused with a water absorbing polymer, creating a Jello-like material that is surprisingly strong. The cellulose fibers act like the collagen in natural cartilage, giving the gel strength when pulled or stretched.  

Restoring Safe Supply of Rx Opioids Would Reduce Overdoses

By Pat Anson, PNN Editor

A decade long effort to reduce the supply of opioid pain medication in the U.S. has contributed to a surge in overdose deaths and made the illicit drug supply more toxic, according to a new study.

“A big reason that we have such a problem with addiction in this country is because people can't access legitimate pain medication,” said lead author Grant Victor, PhD, an assistant professor at Rutgers University School of Social Work. “Our findings support a change in policy.”

Victor and his colleagues analyzed toxicology data from nearly 2,700 accidental overdose deaths in the Indianapolis metropolitan area (Marion County, Indiana) from 2016 to 2021, comparing them to patient records in the state’s prescription drug monitoring program (PDMP).

Their findings, published in the Journal of Substance Use and Addiction Treatment, show that less than half the people who overdosed (43.3%) had any kind of PDMP record, meaning they were never prescribed an opioid pain reliever or buprenorphine (Suboxone), a medication used to treat opioid use disorder.

Most of the decedents who did have a prescription for an opioid analgesic or buprenorphine had not filled one in the 30 days prior to their deaths, indicating that prescription opioids are not driving overdose deaths in Marion County. Overdoses there increasingly involve illicit fentanyl, a synthetic opioid 100 times more potent than morphine, which accounts for nearly 90% of the county’s overdoses.  

There were 637 drug deaths in Marion County in 2021, nearly twice the number that died in 2016. During that period, opioid prescriptions in the county fell by nearly a third.

MARION COUNTY PUBLIC HEALTH DEPT.

Toxic Drug Market

Victor says many of the overdose deaths could have been prevented if a safer supply of prescription opioids was still accessible – both to legitimate patients and those who misuse the drugs.

“There was a wave of policy initiatives that effectively tamped down on the diversion of prescription opioids, but did so primarily by increasing surveillance of prescribing practices for opioids. And through a number of mechanisms, that made it more difficult for individuals with legitimate pain concerns to access these types of medications,” Victor told PNN.

“When you remove a certain class of drugs that is federally regulated and can be monitored and dosed appropriately, it leaves folks with few options. Options that are currently available are illicit and the potency of these drugs is highly variable. The drug market in general, as we know it today, is very toxic and that is one of the main drivers in the overdose crisis.”

Victor says some of his own family members have chronic pain and after years of taking opioids safely, they’ve been cutoff and told to take Tylenol. He said it’s rare for a pain patient to die from an overdose and few meet the diagnostic criteria for substance use disorder.   

“There are a number of researchers who are trying to drive this point home and hope to reverse some of the policy initiatives that have unfolded over the last few years that have been perhaps unintentionally harmful to public health and to chronic pain patients,” he said.

“We've been swept up in this kind of frenzy about prescription opioids. They're still making movies about the Sackler’s (owners of Purdue Pharma). My opinion of them is not all that high, but I think it is a convenient kind of scapegoat to portray pharmaceutical companies as the evil here, when they’re not a primary concern. When you're looking at public health and what's currently driving overdose deaths, it’s not prescription opioids.”

Few previous studies have compared overdose deaths directly to prescription drug data, which would seem to be an obvious way to get to the bottom of what’s causing the overdose crisis.  One such study looked at opioid overdoses in Massachusetts, finding that only 1.3% of those who died had an active prescription for opioids.