Stem Cells Can Restore Movement in Paralyzed Patients

By Pat Anson, PNN Editor

Stem cells derived from body fat can improve sensation and restore movement in patients paralyzed by a severe spinal cord injury, according to a small clinical trial at the Mayo Clinic. One man who was paralyzed from the neck down after a surfing accident is now able to walk again after getting stem cell therapy.

"This study documents the safety and potential benefit of stem cells and regenerative medicine," first author Mohamad Bydon, MD, a Mayo Clinic neurosurgeon, said in a press release. "In spinal cord injury, even a mild improvement can make a significant difference in that patient's quality of life."

The ten patients who participated in the Phase 1 study had adipose (fat) stem calls removed from their abdomen or thigh. After several weeks, 100 million new mesenchymal stem cells (MSCs) grown in a laboratory petri dish were injected into each patient’s lumbar spine. It’s believed the cells then migrate to the injured part of the spine. Participants were regularly followed for the next two years to assess their response to treatment.

The study findings, published in the journal Nature Communications, show that 7 of the 10 patients showed improvement based on the American Spinal Injury Association’s Impairment Scale. Improvements included increased sensation when tested with a pinprick or light touch, increased muscle strength, and the recovery of voluntary bowel function. Three patients showed significant improvement, four had a moderate improvement, and three had no response.

This Mayo Clinic video shows how the process works:

Perhaps the most dramatic improvement was in Chris Barr, a California man who was paralyzed in 2017 while surfing near San Francisco. He broke his neck in eight places when his head hit the ocean floor.

Barr was the first person enrolled in the Mayo study. Eighteen months after the stem cell injection, Barr was able to walk again and continues to show improvement in his mobility and quality of life.

"I never dreamed I would have a recovery like this," Barr told ABC News. "I can feed myself. I can walk around. I can do day-to-day independent activities."  

No serious adverse events were reported from the stem cell treatment. The most common side effects were headaches and musculoskeletal pain that went away after over-the-counter medications were taken.

Since safety is the primary goal of a Phase 1 study, further research will be needed to assess the improvements in movement and sensation. The use of fat-derived stem cells for spinal cord injury is considered experimental by the Food and Drug Administration.

According to the National Spinal Cord Injury Statistical Center, nearly 300,000 Americans currently suffer from a spinal cord injury, costing the healthcare system over $40 billion annually.  The estimated lifetime cost for each patient can reach millions of dollars.

The spinal cord has limited ability to repair itself. Patients who suffer a significant injury typically experience most of their recovery in the first six to 12 months. Improvements generally stop 12 to 24 months after an injury. Only about 5% of people who are paralyzed can expect to regain any feeling or movement.

"For years, treatment of spinal cord injury has been limited to supportive care, more specifically stabilization surgery and physical therapy," Dr. Bydon says. "Many historical textbooks state that this condition does not improve. In recent years, we have seen findings from the medical and scientific community that challenge prior assumptions. This research is a step forward toward the ultimate goal of improving treatments for patients."

Epstein-Barr Virus Emerging As Possible Cause of Chronic Pain

By Dr. Forest Tennant, PNN Columnist 

When most people hear about the Epstein-Barr virus (EBV), they may recall its reputation as the rather harmless "kissing disease" known as mononucleosis.  To the surprise of many, this previously unheralded virus has recently emerged as a cause of some cancers and painful disorders.

It is now clear that EBV must be contained and suppressed in order to relieve the pain and suffering of many persons with chronic pain. This column is an introduction to the critical involvement of EBV with several chronic pain conditions.

The Epstein-Barr virus is named after Drs. Anthony Epstein and Yvonne Barr. In 1964, they discovered the virus after they found it in a cancer common in Africa called Burkitt’s Lymphoma.  Since that time, EBV has been found to cause other cancers including nasopharyngeal, gastric, Hodgkin’s lymphoma, and leukemia.  Some estimate that EBV causes about 200,000 cancers a year.

About three years after Epstein and Barr discovered EBV, it was found to be the cause of infectuous mononucleosis, which is known to trigger autoimmune complications.  Autoimmunity is simply defined as some element in the body that attacks, erodes, and destroys tissue. 

In 1968, this author reported that mononucleosis could cause glomerulonephritis, an autoimmune renal disease.  Over the ensuing decades, EBV has also been associated with other autoimmune disorders, including hepatitis, rheumatoid arthritis, fibromyalgia, systemic lupus, and Sjogren's syndrome.

EPSTEIN-BARR VIRUS

In 2018, a seminal study documented that EBV could cause a number of painful medical conditions by activating specific genes.  Dr. John Harley and colleagues at Cincinnati Children's Hospital Medical Center, with funding from the National Institutes of Health, found that a viral protein called Epstein-Barr nuclear analog 2 (EBNA 2) binds to the deoxyribonucleic acid (DNA) of genes that promote autoimmunity and some chronic pain conditions.

The pain conditions that Harley and his colleagues associated with EBV are multiple sclerosis, rheumatoid arthritis, celiac disease, type 1 diabetes, inflammatory bowel disease, thyroiditis, and juvenile arthritis.  Subsequent studies added Sjogren's syndrome, mixed connective tissue disease, and polymyositis to the list of EBV autoimmune conditions.

The Harley research is compelling.  We urgently need clinical studies of EBV in severe chronic pain patients to help develop new diagnostic, prevention, and treatment measures.  To this end, I've chosen to study the EBV relationship to painful spine and connective tissue diseases, especially adhesive arachnoiditis (AA) and Ehlers-Danlos syndrome (EDS). These conditions are considered intractable pain conditions in clinical pain practice. 

So far, we have collected EBV laboratory test results from over 80 persons with confirmed AA. Every case has demonstrated abnormally high levels of EBV IgG antibodies, which suggests the presence of autoimmunity and the possible invasion of brain and spinal tissue by the virus. 

Every patient with high IgG antibody levels also has herniated discs, and the majority have hypermobile EDS. Prior to developing AA, all had conditions associated with autoimmunity, such as fibromyalgia and small fiber neuropathy. All of them now have intractable pain.

How It Begins

Patients and clinicians concerned about chronic pain need to understand the basics of how EBV causes and aggravates chronic pain conditions. 

EBV is a member of the herpes virus family, which includes the other herpes viruses and cytomegalovirus.  It is a natural, lifelong parasite that usually infects children before the age of two. 

When EBV first enters the body, it is an “active” virus that may cause a cold, sinusitis, bronchitis, or possibly even go unnoticed. Infants and young children often have the “sniffles” and it could be mistaken as a simple cold. Some children who initially become infected with EBV later develop mononucleosis in their teenage or young adult life.  

After the initial infection, EBV settles into one’s lymphocytes and lining of the throat and nasal cavity to remain for life. Under normal physiologic circumstances, it is a latent or dormant parasite that does no harm.

Over 95% of adults will test positive for low levels of IgG antibodies, decades after their initial contact with EBV during childhood. When chronic pain patients are tested, autoimmunity is suspected if IgG antibodies are above normal levels found in the great majority of adults.

Once EBV has settled into lymphocytes or the throat lining and becomes dormant, it is living a harmless, symbiotic, parasitic life with its human host.  It will remain in this state, unless the body undergoes some kind of stress, usually trauma or an infection, that lowers or degrades the body's innate or natural immunologic protection systems. 

At this time, the virus may vacate its dormant or latent state to begin what is called a "lytic" or duplicative state.  The term used to indicate this state is "reactivation," meaning that the virus is again active, and attacking and invading new tissues. 

Once reactivated, EBV may create an autoimmune state by altering genes or by developing what is called an auto-antibody that will attack tissues.  In either case, an autoimmune state has been created that attacks normal tissues to produce inflammation, adhesions, scarring, and pain. 

Lymphocytes infected with reactivated EBV may enter any number of tissues. They may cross the blood brain barrier, enter the spinal cord and brain, and attack tissues such as the cauda equina, arachnoid membrane, intervertebral discs, and glial cells. This is the pathologic process in which EBV reactivation may cause chronic pain.

It is likely that entry and invasion of spinal canal and brain tissues may be responsible for the autoimmune manifestations seen after a stroke, head trauma, or complex regional pain syndrome (CRPS).  EBV may also be a cause of centralized pain that is associated with over-sensitization, hyperalgesia, and intractable pain.  There are reports that such common chronic pain conditions as fibromyalgia, small fiber neuropathy, and some arthropathies are caused by EBV autoimmunity.

This article's major intent is to inform all concerned parties that deal with chronic pain that EBV is not just some virus that causes the "kissing disease." It is a new revelation that compels an understanding and awareness that has the distinct potential to improve the plight of chronic pain patients. 

Laboratories and clinical researchers, including this author, are scurrying to identify more diagnostic, treatment, and preventive measures for EBV-caused autoimmunity. I'm pleased to report that our EBV project has been able to identify some initial testing and treatment measures which appear to be effective and a good start in dealing with EBV autoimmunity.  We will share our findings in future articles.

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 this research should visit the Tennant Foundation’s website, Arachnoiditis Hope. You can subscribe to its bulletins here.

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

Shortage of Primary Care Doctors a ‘Public Health Crisis’

By Lynn Arditi, The Public’s Radio

First, her favorite doctor in Providence, Rhode Island, retired. Then her other doctor at a health center a few miles away left the practice. Now, Piedad Fred has developed a new chronic condition: distrust in the American medical system.

“I don’t know,” she said, her eyes filling with tears. “To go to a doctor that doesn’t know who you are? That doesn’t know what allergies you have, the medicines that make you feel bad? It’s difficult.”

At 71, Fred has never been vaccinated against covid-19. She no longer gets an annual flu shot. And she hasn’t considered whether to be vaccinated against respiratory syncytial virus, or RSV, even though her age and an asthma condition put her at higher risk of severe infection.

“It’s not that I don’t believe in vaccines,” Fred, a Colombian immigrant, said in Spanish at her home last fall. “It’s just that I don’t have faith in doctors.”

The loss of a trusted doctor is never easy, and it’s an experience that is increasingly common.

The stress of the pandemic drove a lot of health care workers to retire or quit. Now, a nationwide shortage of doctors and others who provide primary care is making it hard to find replacements. And as patients are shuffled from one provider to the next, it’s eroding their trust in the health system.

The American Medical Association’s president, Jesse Ehrenfeld, recently called the physician shortage a “public health crisis.”

“It’s an urgent crisis, hitting every corner of this country, urban and rural, with the most direct impact hitting families with high needs and limited means,” Ehrenfeld told reporters in October.

In Fred’s home state of Rhode Island, the percentage of people without a regular source of routine health care increased from 2021 to 2022, though the state’s residents still do better than most Americans.

Hispanic residents and those with less than a high school education are less likely to have a source of routine health care, according to the nonprofit organization Rhode Island Foundation.

Shrinking Workforce

The community health centers known as federally qualified health centers, or FQHCs, are the safety net of last resort, serving the uninsured, the underinsured, and other vulnerable people. There are more than 1,400 community health centers nationwide, and about two-thirds of them lost between 5% and a quarter of their workforce during a six-month period in 2022, according to a report by the National Association of Community Health Centers.

Another 15% of FQHCs reported losing between a quarter and half of their staff. And it’s not just doctors: The most severe shortage, the survey found, was among nurses.

In a domino effect, the shortage of clinicians has placed additional burdens on support staff members such as medical assistants and other unlicensed workers.

Their extra tasks include “sterilizing equipment, keeping more logs, keeping more paperwork, working with larger patient loads,” said Jesse Martin, executive vice president of District 1199 NE of the Service Employees International Union, which represents 29,000 health care workers in Connecticut and Rhode Island.

“When you add that work to the same eight hours’ worth of a day’s work you can’t get everything done,” Martin said.

Last October, scores of SEIU members who work at Providence Community Health Centers, Rhode Island’s largest FQHC, held an informational picket outside the clinics, demanding improvements in staffing, work schedules, and wages.

The marketing and communications director for PCHC, Brett Davey, declined to comment.

Staff discontent has rippled through community health care centers across the country. In Chicago, workers at three health clinics held a two-day strike in November, demanding higher pay, better benefits, and a smaller workload.

Then just before Thanksgiving at Unity Health Care, the largest federally qualified health center in Washington, D.C., doctors and other medical providers voted to unionize. They said they were being pressed to prioritize patient volume over quality of care, leading to job burnout and more staff turnover.

The staffing shortages come as community health centers are caring for more patients. The number of people served by the centers between 2015 and 2022 increased by 24% nationally, and by 32.6% in Rhode Island, according to the Rhode Island Health Center Association, or RIHCA.

“As private practices close or get smaller, we are seeing patient demand go up at the health centers,” said Elena Nicolella, RIHCA’s president and CEO. “Now with the workforce challenges, it’s very difficult to meet that patient demand.”

In Rhode Island, community health centers in 2022 served about 1 in 5 residents, which is more than twice the national average of 1 in 11 people, according to RIHCA.

Job vacancy rates at Rhode Island’s community health centers are 21% for physicians, 18% for physician assistants and nurse practitioners, and 10% for registered nurses, according to six of the state’s eight health centers that responded to a survey conducted by RIHCA for The Public’s Radio, NPR, and KFF Health News.

Pediatricians are also in short supply. Last year, 15 pediatricians left staff positions at the Rhode Island health centers, and seven of them have yet to be replaced.

Research shows that some of the biggest drivers of burnout are workload and job demands.

Community health centers tend to attract clinicians who are mission-driven, said Nelly Burdette, who spent years working in health centers before becoming a senior leader of the nonprofit Care Transformation Collaborative of Rhode Island.

These clinicians often want to give back to the community, she said, and are motivated to practice “a kind of medicine that is maybe less corporate,” and through which they can they develop close relationships with patients and within multigenerational families.

So when workplace pressures make it harder for these clinicians to meet their patients’ needs, they are more likely to burn out, Burdette said.

‘I Can’t Get an Appointment’

When a doctor quits or retires, Carla Martin, a pediatrician and an internist, often gets asked to help. The week before Thanksgiving, she was filling in at two urgent care clinics in Providence.

“We’re seeing a lot of people coming in for things that are really primary care issues, not urgent care issues, just because it’s really hard to get appointments,” Martin said.

One patient recently visited urgent care asking for a refill of her asthma medication. “She said, ‘I ran out of my asthma medicine, I can’t get a hold of my PCP for refill, I keep calling, I can’t get through,’” Martin said.

Stories like that worry Christopher Koller, president of the Milbank Memorial Fund, a nonprofit philanthropy focused on health policy. “When people say, ‘I can’t get an appointment with my doctor,’ that means they don’t have a usual source of care anymore,” Koller said.

Koller points to research showing that having a consistent relationship with a doctor or other primary care clinician is associated with improvements in overall health and fewer emergency room visits.

When that relationship is broken, patients can lose trust in their health care providers.

That’s how it felt to Piedad Fred, the Colombian immigrant who stopped getting vaccinated. Fred used to go to a community health center in Rhode Island, but then accessing care there began to frustrate her.

She described making repeated phone calls for a same-day appointment, only to be told that none were available and that she should try again tomorrow. After one visit, she said, one of her prescriptions never made it to the pharmacy.

And there was another time when she waited 40 minutes in the exam room to consult with a physician assistant — who then said she couldn’t give her a cortisone shot for her knee, as her doctor used to do.

Fred said that she won’t be going back. What will she do the next time she gets sick or injured and needs medical care?

“Well, I’ll be going to a hospital,” she said in Spanish.

But experts warn that more people crowding into hospital emergency rooms will only further strain the health system, and the people who work there.

This article is from a partnership that includes The Public’s Radio, NPR, and KFF Health News, a national newsroom that produces in-depth journalism about health issues.

Does Netflix Trivialize Pain?

By Pat Anson, PNN Editor

Movies and TV shows have long been criticized for the way they depict women, minorities and religions -- either through sensationalism, stereotyped portrayals, or simply omission.

A new analysis of popular programs that aired on Netflix suggests that physical pain is also being ignored, trivialized, or presented in misleading ways.

Researchers in Canada and the UK looked at over a dozen movies and TV series that featured teenage characters. They found that the teens’ pain was almost always the result of violence or accidents – not common medical conditions such as migraine or menstruation. The characters often had minimal reactions to their own pain and observers had “an overwhelming lack of empathy” for them.   

“If we’re not showing the types of pain that adolescents might typically experience like back pain and menstrual pain, then we’re trivializing pain. We’re not doing a great job of enabling them to think about how to manage pain, how to talk about pain and how to show empathy when other people experience pain,” said lead author Abbie Jordan, PhD, a lecturer in the Department of Psychology and Centre for Pain Research at The University of Bath.

“This research matters because if every film and television series shows a boy being a ‘tough guy’ when they experience pain and a girl as a ‘damsel in distress’ in need of saving, they might think they have to be like that in real life. This depiction reinforces old-fashioned ideas about gender and is misleading."

Jordan and her colleagues watched programs such as Sex Education, Stranger Things and Enola Holmes, and found that viewers were exposed to an average of 10 incidents of pain every hour.

The two Netflix shows with the highest number of painful incidents were Outer Banks, a series about teens searching for a hidden treasure, and Spiderman: Homecoming, a movie about a young Peter Parker facing off against a new villain.

Violence (57%) was the most likely cause of pain on the Netflix shows, followed by everyday pain such as headaches (21%) and pain stemming from injuries (20%). Chronic pain or pain resulting from medical procedures were depicted less than one percent of the time.

“‘OUTER BANKS”

Researchers say the Netflix shows often reinforced sexist and patriarchal stereotypes. Boy characters were more likely to experience pain (77%) than girls (23%), and they were also more likely to be criticized or laughed at by other characters. Boys were often portrayed as heroic figures coming to the rescue, while girls were more emotional when reacting to pain.   

The plots and characters are all fictional, but researchers say adolescents watching at home are likely to mirror the behavior themselves.  

“Media is one of the most powerful engines of influence on children’s development and could be harnessed to address pain and suffering in the world. Stories matter. Fictional stories can matter more in some cases than real-life stories. So, let's create stories to reflect the world we want to see: A humane, diverse, inclusive, equitable, compassionate, and caring world,” says co-author Melanie Noel, PhD, an Associate Professor of Clinical Psychology at the University of Calgary.

“I want Netflix to take this seriously and get excited and inspired to directly influence millions of children around the world. They have a monumental opportunity to influence the compassion and humanity we see in our children and our future world.”

The study findings, published in the journal PAIN, echo a previous study that showed pain was trivialized for even younger children (aged 4-6 years). That study also showed that chronic pain in childhood and adolescence was rarely portrayed in popular media.

Physical Activity Can Protect Against Chronic Pain

By Pat Anson, PNN Editor

Chronic pain sufferers are often told that physical activity and exercise can help reduce pain and improve quality of life. Now there is evidence that even light or moderate activity can have a protective effect against pain that lasts for years.

“We found that people who were more active in their free time had a lower chance of having various types of chronic pain 7-8 years later,” says Anders Årnes, a doctoral fellow at The Arctic University of Norway and University Hospital of North Norway.

“This suggests that physical activity increases our ability to tolerate pain and may be one of the ways in which activity helps to reduce the risk of developing severe chronic pain.”

Årnes is the lead author of a study, recently published in the journal PAIN, that found even light physical activity was associated with a 5% lower risk of developing chronic pain that lasts at least three months. More rigorous activity was associated with a 16% reduced risk of widespread moderate-to-severe chronic pain.

The findings are based on data from a large health survey -- the Tromsø Study --- in which over 6,800 Norwegians answered questions about their overall health, pain levels and physical activity, first in 2007-2008 and then again in 2015-2016. The average age of participants was nearly 55. Most reported some form of chronic pain, but only 5% had widespread moderate-to-severe chronic pain.

In a 2023 analysis of the survey data, Årnes and his colleagues found that people who reported vigorous physical activity had significantly more pain tolerance than those with a sedentary lifestyle.

Pain tolerance was assessed by how long they could keep a hand immersed in cold water that was a few degrees above freezing (3 degrees Celsius or 37.4 degrees Fahrenheit).

In their new follow-up study, researchers found that the ability to tolerate pain – or at least cold water -- plays a modest role in the protective effect of physical activity (PA).  

Stina Grønbech/Tromsøundersøkelsen

“We estimate that higher PA levels predict lower risk of chronic pain, with indications of a small mediated effect on this risk through cold pain tolerance for moderate-to-severe chronic pain states,” researchers reported.

Of course, many people with severe chronic pain are unable to exercise or fear that it will only make their pain worse. Previous studies have found that low-impact exercise programs, such as stretching while sitting in a chair, can ease pain from arthritis and other muscle and joint conditions.

“Physical activity is not dangerous in the first place, but people with chronic pain can benefit greatly from having an exercise program adapted to help them balance their effort so that it is not too much or too little,” said Årnes. “A rule of thumb is that there should be no worsening that persists over an extended period of time, but that certain reactions in the time after training can be expected.”

Even moderate physical activity can stimulate the production of endorphins and endocannabinoids – hormones and lipids naturally produced by the body -- which can relieve pain and inflammation. Regular exercise can also help us lose weight, reduce the risk of heart disease, and boost overall health.  

Finding Medical Care Can Be Exhausting for Seniors

By Judith Graham, KFF Health News

Susanne Gilliam, 67, was walking down her driveway to get the mail in January when she slipped and fell on a patch of black ice. Pain shot through her left knee and ankle. After summoning her husband on her phone, with difficulty she made it back to the house.

And then began the run-around that so many people face when they interact with America’s uncoordinated health care system.

Gilliam’s orthopedic surgeon, who managed previous difficulties with her left knee, saw her that afternoon but told her “I don’t do ankles.”

He referred her to an ankle specialist who ordered a new set of X-rays and an MRI. For convenience’s sake, Gilliam asked to get the scans at a hospital near her home in Sudbury, Massachusetts. But the hospital didn’t have the doctor’s order when she called for an appointment. It came through only after several more calls.

Coordinating the care she needs to recover, including physical therapy, became a part-time job for Gilliam. (Therapists work on only one body part per session, so she has needed separate visits for her knee and for her ankle several times a week.)

“The burden of arranging everything I need — it’s huge,” Gilliam told me. “It leaves you with such a sense of mental and physical exhaustion.”

The toll the American health care system extracts is, in some respects, the price of extraordinary progress in medicine. But it’s also evidence of the poor fit between older adults’ capacities and the health care system’s demands.

“The good news is we know so much more and can do so much more for people with various conditions,” said Thomas H. Lee, chief medical officer at Press Ganey, a consulting firm that tracks patients’ experiences with health care. “The bad news is the system has gotten overwhelmingly complex.”

Multiple Doctors Visits

That complexity is compounded by the proliferation of guidelines for separate medical conditions, financial incentives that reward more medical care, and specialization among clinicians, said Ishani Ganguli, an associate professor of medicine at Harvard Medical School.

“It’s not uncommon for older patients to have three or more heart specialists who schedule regular appointments and tests,” she said. If someone has multiple medical problems — say, heart disease, diabetes, and glaucoma — interactions with the health care system multiply.

Ganguli is the author of a new study showing that Medicare patients spend about three weeks a year having medical tests, visiting doctors, undergoing treatments or medical procedures, seeking care in emergency rooms, or spending time in the hospital or rehabilitation facilities. (The data is from 2019, before the covid pandemic disrupted care patterns. If any services were received, that counted as a day of health care contact.)

That study found that slightly more than 1 in 10 seniors, including those recovering from or managing serious illnesses, spent a much larger portion of their lives getting care — at least 50 days a year.

“Some of this may be very beneficial and valuable for people, and some of it may be less essential,” Ganguli said. “We don’t talk enough about what we’re asking older adults to do and whether that’s realistic.”

Victor Montori, a professor of medicine at the Mayo Clinic in Rochester, Minnesota, has for many years raised an alarm about the “treatment burden” that patients experience. In addition to time spent receiving health care, this burden includes arranging appointments, finding transportation to medical visits, getting and taking medications, communicating with insurance companies, paying medical bills, monitoring health at home, and following recommendations such as dietary changes.

Overwhelmed Patients

Four years ago — in a paper titled “Is My Patient Overwhelmed?” — Montori and several colleagues found that 40% of patients with chronic conditions such as asthma, diabetes, and neurological disorders “considered their treatment burden unsustainable.”

When this happens, people stop following medical advice and report having a poorer quality of life, the researchers found. Especially vulnerable are older adults with multiple medical conditions and low levels of education who are economically insecure and socially isolated.

Older patients’ difficulties are compounded by medical practices’ increased use of digital phone systems and electronic patient portals — both frustrating for many seniors to navigate — and the time pressures afflicting physicians.

“It’s harder and harder for patients to gain access to clinicians who can problem-solve with them and answer questions,” Montori said.

Meanwhile, clinicians rarely ask patients about their capacity to perform the work they’re being asked to do.

“We often have little sense of the complexity of our patients’ lives and even less insight into how the treatments we provide (to reach goal-directed guidelines) fit within the web of our patients’ daily experiences,” several physicians wrote in a 2022 paper on reducing treatment burden.

Consider what Jean Hartnett, 53, of Omaha, Nebraska, and her eight siblings went through after their 88-year-old mother had a stroke in February 2021 while shopping at Walmart. At the time, the older woman was looking after Hartnett’s father, who had kidney disease and needed help with daily activities such as showering and going to the bathroom.

During the year after the stroke, both of Hartnett’s parents — fiercely independent farmers who lived in Hubbard, Nebraska — suffered setbacks, and medical crises became common. When a physician changed her mom’s or dad’s plan of care, new medications, supplies, and medical equipment had to be procured, and new rounds of occupational, physical, and speech therapy arranged.

Neither parent could be left alone if the other needed medical attention.

“It wasn’t unusual for me to be bringing one parent home from the hospital or doctor’s visit and passing the ambulance or a family member on the highway taking the other one in,” Hartnett explained. “An incredible amount of coordination needed to happen.”

Hartnett moved in with her parents during the last six weeks of her father’s life, after doctors decided he was too weak to undertake dialysis. He passed away in March 2022. Her mother died months later in July.

Easing the Healthcare Burden

So, what can older adults and family caregivers do to ease the burdens of health care?

To start, be candid with your doctor if you think a treatment plan isn’t feasible and explain why you feel that way, said Elizabeth Rogers, an assistant professor of internal medicine at the University of Minnesota Medical School. 

“Be sure to discuss your health priorities and trade-offs: what you might gain and what you might lose by forgoing certain tests or treatments,” she said. Ask which interventions are most important in terms of keeping you healthy, and which might be expendable.

Doctors can adjust your treatment plan, discontinue medications that aren’t yielding significant benefits, and arrange virtual visits if you can manage the technological requirements. (Many older adults can’t.)

Ask if a social worker or a patient navigator can help you arrange multiple appointments and tests on the same day to minimize the burden of going to and from medical centers. These professionals can also help you connect with community resources, such as transportation services, that might be of help. (Most medical centers have staff of this kind, but physician practices do not.)

If you don’t understand how to do what your doctor wants you to do, ask questions: What will this involve on my part? How much time will this take? What kind of resources will I need to do this? And ask for written materials, such as self-management plans for asthma or diabetes, that can help you understand what’s expected.

“I would ask a clinician, ‘If I chose this treatment option, what does that mean not only for my cancer or heart disease, but also for the time I’ll spend getting care?’” said Ganguli of Harvard. “If they don’t have an answer, ask if they can come up with an estimate.”

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

Keeping Hope Alive

By Mia Maysack, PNN Columnist

In 2022, I was fortunate enough to receive the International Pain Foundation's “Hero of Hope”' award for patient advocacy. I felt and still feel remarkably honored for the recognition, although I am not motivated by any accolade or prestige. I fight for those who can't. I use my voice so others can be heard.

As a patient advocate, I’ve learned the absolute most important thing that I can do is rescue myself – repeatedly. If I don't make it and I'm no longer here, what good can I do or offer to anybody else?

Recently, I've struggled immensely. There have been moments that haven't felt survivable. I sought support, reached out for help, attended therapy, and tried endless lifestyle approaches with little to no progress in how I feel.

It is important for me to express this publicly because I want to drive the point home: An optimistic perspective alone is not enough for survival. You can seek out the bright side, acknowledge how things could always be worse, recognize all your blessings, and be grateful for them -- yet still suffer immensely.

I reached out to someone to vent some of this, in what I'd hoped would be a receptive and safe space. But I was quickly reminded of the extent to which people simply don't know how to navigate others' hardships or struggles.

“I'm having a rough time,” I said.

“Maybe you need to go to counseling,” they replied.

“I tried that again recently. But my medical trauma is extensive. It did not help and actually worsened things for me."

[insert awkward silence here]

"Ordinarily,” I continued, “I’d pour myself into other causes, things, and people. That usually helps, but I am struggling with energy and motivation.”

“Sounds like depression,” they said.

“Depression isn’t new to me,” I explained. “Coping with daily ailments isn’t something that everyone can bear. Depression in these instances occurs by default. It’s an underlying current underneath the symptoms, constantly demanding my attention and effort to accommodate and manage it.”

"I think you need to pour into yourself,” was their reply.

"I have, extensively. But it is as though I'm a cracked cup and it all leaks out,” I said.

[insert another awkward silence]

At this point, I can sense they are uncomfortable, so I rush to ease their pain as mine intensifies. And I’m reminded how there’s just about nowhere for us to turn where we can be adequately received or understood.

“But I will figure it out, I always do,” I declared, tears running down my cheeks.

"Now that's the spirit!” they proclaimed.

I’ve always possessed “spirit” but sometimes it’s not enough. This is why I have such a profound empathy for those who idealize or even follow through on ending life. I see and understand how and to what extent we reach out for help, yet I'm repeatedly reminded that we're ultimately left on our own -- by each other, by our systems, and by society as a whole.

No one wants you to end your existence, yet almost nothing and no one is there to contribute meaningfully to your quality of life.

In observation of this and because I strongly believe in cultivating solutions -- as opposed to fixating on problems – I’m supporting efforts by the American Foundation for Suicide Prevention to raise awareness and talk about how we can prevent suicide and increase access to mental healthcare.

The darkness in me honors yours. It's not only okay, but profoundly necessary to allow that part of ourselves to exist out loud. It’s the only way through to the light. 

I imagine a future where we don't have to beg and plead for basic human needs, and we’re no longer alone in attempting to figure it all out.  This vision keeps me going and keeps the fire of hope alive.

Mia Maysack lives with chronic migraine, cluster headache and fibromyalgia. She is a healthcare reform advocate and founder of Keepin’ Our Heads Up, a support network; Peace & Love, a life coaching practice; and Still We Rise, an organization that seeks to alleviate pain of all kinds.

For anyone thinking about suicide, please contact the 988 Suicide & Crisis Lifeline, available online, via chat, or by dialing “988.”  A comprehensive set of resources can also be found at this link.

Study Finds CBD Ineffective for Chronic Pain

By Pat Anson, PNN Editor

There is little evidence that cannabidiol (CBD) products relieve chronic pain and some could be potentially harmful to patients, according to UK and Canadian researchers.

CBD is one of the chemical compounds found in cannabis, but it doesn’t have the same intoxicating effect as tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana. Often marketed as a pain reliever, CBD can be purchased in edibles, beverages, lotions, oils and other products, usually without a prescription.  

“CBD presents consumers with a big problem,” says lead author Chris Eccleston, PhD, Professor of Pain Science at the University of Bath in the UK. “It’s touted as a cure for all pain but there’s a complete lack of quality evidence that it has any positive effects.

“There should be no excuses for misleading the public, and yet it is likely that the public is being misled and possibly placed in harm’s way.”

Eccleston and his colleagues reviewed the results of 16 high-quality clinical trials of CBD products, involving over 900 participants. Their findings, published in in The Journal of Pain, show that CBD provided little or no pain relief in 15 of the 16 studies. The one small trial that did showed improvement in arthritis pain after two weeks of treatment with a topical CBD lotion.

Just as concerning to researchers is that many CBD products sold directly to consumers have significantly more or less CBD than what their labels indicate. Some CBD products also contain THC, when they weren’t supposed to have any.

“There is no good reason for thinking that CBD relieves pain, but there are good reasons for doubting the contents of CBD products in terms of CBD content and purity,” Eccleston wrote. “Regulatory authorities should also take note of the considerable deficiencies existing in the products sold, especially the incorrect labeling of many products, and possible contamination with psychoactive compounds.”

The researchers say regulators in the US, UK and Canada are often slow to respond to the false medical claims of some CBD manufacturers. The FDA occasionally sends warning letters to companies making unsubstantiated claims about CBD, but it rarely results in fines or disciplinary action.

“What this means is that there are no consumer protections,” said co-author Dr Andrew Moore, Director of Pain Research at the University of Oxford. “And without a countervailing body to keep the CBD sellers in check, it’s unlikely that the false promises being made about the analgesic effects of CBD will slow down in the years ahead.”

In a recent review, the FDA said there was “credible scientific support” for cannabis as a pain reliever and recommended that the DEA reschedule it as a Schedule III controlled substance. Such a move would make it legal under federal law for cannabis to be prescribed for medically approved conditions, but would have no impact on CBD products.

In 2022, FDA Commissioner Dr. Robert Califf asked Congress to give his agency the authority to more closely regulate CBD, but no such legislation has been passed. Eccleston says its part of a pattern in which pain sufferers are neglected and left on their own to find relief.

“It’s almost as if chronic pain patients don’t matter, and that we’re happy for people to trade on hope and despair,” he said.

A Third of Independent Pharmacies May Close

By Pat Anson, PNN Editor

These are tough times for many retail pharmacies and their customers. Big chain pharmacies like CVS, Walgreens and Rite Aid are closing over 1,500 stores, as they grapple with declining sales, higher debt, drug shortages, fallout from opioid litigation, and an overworked, demoralized workforce.

For many patients who had trouble getting their prescriptions filled for opioids and other controlled substances, small independent pharmacies became a welcome refuge from the big chains.

“I'm fortunate to have a compassionate, independent pharmacy that bends over backwards to ensure I have the meds my doctor prescribes. If I was stuck with a chain pharmacy like Walgreens or CVS, my experience would be completely different. Those pharmacies treat pain patients like criminals,” one patient told us.

But now even the independent pharmacies are threatened. About a third of them could close in 2024, according to a dire prediction from the National Community Pharmacists Association (NCPA), a trade group that represents nearly 20,000 independent pharmacy owners in the U.S.

“Nearly a third of independent pharmacy owners may close their stores this year under pressure from plunging prescription reimbursements by big insurance plans and their pharmacy benefit managers,” says B. Douglas Hoey, RPh, NCPA’s CEO.

At issue is a new rule by the Centers for Medicare & Medicaid Services (CMS) that requires insurers and pharmacy benefit managers (PBMs) to implement discounts and price concessions at the point of sale, where a drug is dispensed. The rule is intended to make pricing more transparent for patients, but it’s hurting the bottom line of pharmacies who say the discounts are being unfairly forced on them by insurers.

Part D Prescriptions at Risk

In a recent survey of NCPA members, 32% said they may have to close by the end of the year due to the CMS rule and 93% said they’d consider dropping out of Medicare’s Part D prescription drug program. Most say they are losing money on Part D prescriptions, which don’t compensate the pharmacies for rent, taxes, payroll and other costs of doing business.

“Cash flow for many pharmacies remains in a precarious state, leading to dire concerns for beneficiary access. Our members continue to experience significant harm from egregious Medicare Part D PBM practices,” Hoey wrote in a letter to CMS, which faulted the agency for doing little to stop the PBMs.

Asked which PBMs are causing the most financial stress in the Part D program, almost half the NCPA members identified Express Scripts, with CVS/Caremark coming in at 35 percent.

Hoey says CMS already has the legal authority to change reimbursement practices, but wants Congress to intervene if CMS doesn’t act soon.

“This is an emergency. And if Congress fails to act again, thousands of local pharmacies could be closed within months and millions of patients could be stranded without a pharmacy,” Hoey said in a statement.

NCPA says there are about 2,200 fewer retail pharmacies today than there were four years ago. This has created hundreds of pharmacy “deserts,” primarily in low-income rural and urban areas, where access to a pharmacy is limited or non-existent. Alabama alone has lost 300 pharmacies in recent years.

“With every closure, 5,000 Alabamians are left without a critically important health care provider. This is a major issue for every community in our state, but rural Alabama is hit the hardest. In many cases, that local pharmacy is the only healthcare provider in that rural community,” Alabama State Rep. Phillip Rigsby, a pharmacist, wrote in an op/ed published in AL.com.

“In other businesses, if an operating cost increases, the company’s prices increase to compensate. In pharmacy, that just is not possible. A pharmacy cannot pass on that cost to a patient because the contract doesn’t allow for that.”

Can Naproxen Help You Live Longer?

By Pat Anson, PNN Editor

There may be a hidden benefit to the pain reliever naproxen. The non-steroidal anti-inflammatory drug (NSAID) is primarily used to treat arthritis, muscle aches and joint pain, but might also give a boost to your life expectancy, according to the results of a preliminary study.

An international research team analyzed 12-years of health records for over 500,000 people enrolled in the UK Biobank study to see if prescription drugs taken for at least 3 months were associated with higher or lower death rates. Over 400 medications were studied, with patients who were prescribed the drugs compared to control groups that didn’t take them.

“As expected, most drugs harbor a negative effect on lifespan, probably due to the underlying negative effect of the disease the drug is intended for. Importantly, a few drugs seem to have a beneficial effect on lifespan,” wrote lead author Alejandro Ocampo, PhD, a professor at the University of Lausanne and CEO of Epiterna, a Swiss company studying ways to slow the ageing process.        

Ocampo and his colleagues identified four medications associated with lower death rates:

• Naproxen   

• Atorvastatin (a statin)

• Estradiol (female hormone replacement)

• Sildenafil (Viagra)

Statins have long been known to reduce the risk of heart attack and stroke, while estradiol lowers the risk of osteoporosis and bone fractures in post-menopausal women. Sildenafil is well known for treating erectile dysfunction, but also improves cardiovascular health and may even protect against Alzheimer's disease. It’s easy to see how those drugs might increase life expectancy.

The inclusion of naproxen is a bit of a surprise. The active ingredient in Aleve and other over-the-counter pain relievers, naproxen raises the risk of a heart attack, stroke or internal bleeding when taken in high doses or used long-term. High doses of naproxen in 250mg and 500mg tablets are available by prescription, which is what people in the study were taking.

Even at those high doses, researchers found that naproxen was associated with a 10% lower death rate when compared to people who didn’t take the drug. The protective effect was strongest for men on naproxen, who had mortality rates that were 13% lower.

The findings are preliminary, have not been peer-reviewed, and don’t establish a cause-and-effect relationship. We don’t know why or how naproxen helps people live longer, only that it’s associated with a longer lifespan.  

Interestingly, the research team found that two other pain relievers – morphine and paracetamol (acetaminophen) – are associated with shorter lifespans. Again, this may have more to do with the underlying conditions the drugs were prescribed for, rather than the medications themselves.

Ocampo says more research and clinical studies are needed to get a better understanding of the long-term harms and benefits of medication.

“The benefit on lifespan observed for several drugs in this retrospective study could only be truly determined by performing randomized controlled trials. Such studies would aim at treating a healthy aging population with a drug during a sufficiently long follow-up to be able to observe the effect on all-cause mortality,” Ocampo wrote.

If the life expectancy benefits are proven, researchers say it could result in some drugs being “repurposed” as anti-aging treatments for otherwise healthy older adults.

Naltrexone Shortage Disrupts Addiction Treatment

By Pat Anson, PNN Editor

An inexpensive drug used to manage chronic pain and treat substance use disorders has joined the growing list of medications that are in short supply in the United States.

The Food and Drug Administration and the American Society of Health-System Pharmacists (ASHP) both recently added naltrexone tablets to their drug shortage lists. It’s not clear what caused the shortage, but the ASHP says “there is insufficient supply for usual ordering.”  

Naltrexone is FDA-approved to treat both alcohol and opioid use disorder, and is also used off-label in low doses to treat some chronic pain conditions.

In 50mg doses, naltrexone blocks opioid receptors in the brain and reduces cravings for opiates or alcohol. But in smaller doses of 5mg or less, patients have found low-dose naltrexone (LDN) to be an effective pain reliever for interstitial cystitis, Ehlers-Danlos syndrome, fibromyalgia, and other painful conditions.

LDN advocates believe the drug modulates the immune system, reduces inflammation and stimulates the production of endorphins, the body's natural painkiller. Because it is an opioid antagonist, naltrexone should not be taken with opioid medication.

So far, the shortage only affects 50mg naltrexone tablets. Pain patients usually obtain LDN by prescription from compounding pharmacies, which make the low dose versions in-house.

Several drug makers are reporting short supplies of 50mg tablets, including Accord Healthcare, Major, Elite Laboratories, SpecGx, Sun Pharma, Tagi Pharma, and Avet Pharmaceuticals. The companies didn’t provide the ASHP with a reason for the shortage, but said the tablets are on back order and would be released when they become available.    

The naltrexone shortage comes at an inopportune time, as more people abused alcohol and other substances during the pandemic and sought treatment. The drug that helps them stay sober is now hard to get.

"People are coming in with more cravings," Dr. Aviva Zohar, an addiction medicine provider, told Philly Voice. "Even the feeling of, 'I don't know when my medicine is coming in,' is a huge struggle. It's horrific (and) causing a lot of stress.”

To make up for the shortage, some providers are giving patients Vivitrol, an injectable, extended-release formulation of naltrexone taken once a month. A single Vivitrol injection costs about $1,700, while a month’s supply of 50mg naltrexone tablets costs about $48.

The cheap price of naltrexone may be responsible for the shortage. Most drugs in short supply are low-cost generics with slim profit margins. Some manufacturers have reduced or stopped making generics because they’re not worth the cost of production or the risk of litigation.   

Three generic opioids commonly taken for pain — immediate-release oxycodone, oxycodone-acetaminophen, and hydrocodone-acetaminophen tablets — have been on the ASHP shortage list for nearly a year, with no end in sight.

Can Two Questions Identify ‘High Risk’ Pain Patients?

By Pat Anson, PNN Editor

“Have you ever felt your pain is terrible and it's never going to get any better?”

“Have you ever used an illegal drug or prescription medication for non-medical reasons?”

If you answered yes to both questions, you’d be considered at high risk of a “poor pain outcome” at Duke University’s Health System. You’d also be invited into a specialized pain management program that takes a more holistic approach to pain treatment.

Duke’s Integrated Pain and Wellness (IPW) Program was launched in 2019 to identify and treat pain patients at high risk of long-term opioid use, which can result in more frequent and costly visits to hospitals and emergency rooms. It’s one of several efforts in recent years aimed at identifying high risk patients, such as the controversial analytical software used by NarxCare or the far simpler Opioid Risk Tool survey.

Many pain patients feel stigmatized by these risk assessments, and feel they’ve been weaponized solely to deny them treatment with opioids.   

The IPW program is a little different. Patients are encouraged – but not required – to reduce their use of opioids, try non-opioid treatments, and undergo behavioral health therapies to help them learn how to accept their pain without being obsessed by it.     

“Our goal was to establish a comprehensive, integrated approach to pain management that prioritizes early intervention, reduces the dependency on opioids by providing alternative pain management strategies, and decreases the utilization of acute care resources,” wrote Padma Gulur, MD, a Professor in Anesthesiology and Population Health Sciences at Duke University School of Medicine. 

Gulur and her colleagues assessed how 432 patients at the highest risk of poor pain outcomes did after being enrolled in the IPW program.  

Their findings, published in NEJM Catalyst, show that about half the patients (224) reduced their opioid use within 30 days, while a small number (50) increased their opioid use. 

The average improvement in self-reported pain scores was modest (from 6.56 down to 6.11), as were minor improvements in physical function, anxiety, depression and fatigue.  

There were more robust signs of the IPW program’s success in reducing healthcare utilization, with emergency room visits falling by 26% and hospital admissions declining by 43% among the high-risk patients. 

“This approach led to marked patient improvements in both physical and psychological health outcomes,” Gulur said. "By demonstrating the effectiveness of early identification and intervention for patients at risk of poor pain outcomes, this research can inform the development of new therapies and treatment approaches focused on prevention.” 

One hurdle that remains is getting more patients to participate. Of the 13,561 patients who answered “yes” to both questions in the high-risk assessment, less than 11% accepted a referral into the IPW program. Researchers say many were already being treated at pain clinics outside Duke Health and declined to participate.

Toxic Stress Can Lead to Chronic Illness

By Dr. Lawson Wulsin  

COVID-19 taught most people that the line between tolerable and toxic stress – defined as persistent demands that lead to disease – varies widely. But some people will age faster and die younger from toxic stressors than others.

So how much stress is too much, and what can you do about it?

I’m a psychiatrist specializing in psychosomatic medicine, which is the study and treatment of people who have physical and mental illnesses. My research is focused on people who have psychological conditions and medical illnesses as well as those whose stress exacerbates their health issues.

I’ve spent my career studying mind-body questions and training physicians to treat mental illness in primary care settings. My forthcoming book is titled “Toxic Stress: How Stress is Killing Us and What We Can Do About It.”

A 2023 study of stress and aging over the life span – one of the first studies to confirm this piece of common wisdom – found that four measures of stress all speed up the pace of biological aging in midlife. It also found that persistent high stress ages people in a comparable way to the effects of smoking and low socioeconomic status, two well-established risk factors for accelerated aging.

Good Stress vs. Toxic Stress

Good stress – a demand or challenge you readily cope with – is good for your health. In fact, the rhythm of these daily challenges, including feeding yourself, cleaning up messes, communicating with one another and carrying out your job, helps to regulate your stress response system and keep you fit.

Toxic stress, on the other hand, wears down your stress response system in ways that have lasting effects, as psychiatrist and trauma expert Bessel van der Kolk explains in his bestselling book “The Body Keeps the Score.”

The earliest effects of toxic stress are often persistent symptoms such as headache, fatigue or abdominal pain that interfere with overall functioning. After months of initial symptoms, a full-blown illness with a life of its own – such as migraine headaches, asthma, diabetes or ulcerative colitis – may surface.

When we are healthy, our stress response systems are like an orchestra of organs that miraculously tune themselves and play in unison without our conscious effort – a process called self-regulation. But when we are sick, some parts of this orchestra struggle to regulate themselves, which causes a cascade of stress-related dysregulation that contributes to other conditions.

For instance, in the case of diabetes, the hormonal system struggles to regulate sugar. With obesity, the metabolic system has a difficult time regulating energy intake and consumption. With depression, the central nervous system develops an imbalance in its circuits and neurotransmitters that makes it difficult to regulate mood, thoughts and behaviors.

Though stress neuroscience in recent years has given researchers like me new ways to measure and understand stress, you may have noticed that in your doctor’s office, the management of stress isn’t typically part of your treatment plan.

Most doctors don’t assess the contribution of stress to a patient’s common chronic diseases such as diabetes, heart disease and obesity, partly because stress is complicated to measure and partly because it is difficult to treat. In general, doctors don’t treat what they can’t measure.

1 in 5 Americans Live with Toxic Stress

Stress neuroscience and epidemiology have also taught researchers recently that the chances of developing serious mental and physical illnesses in midlife rise dramatically when people are exposed to trauma or adverse events, especially during vulnerable periods such as childhood.

Over the past 40 years in the U.S., the alarming rise in rates of diabetes, obesity, depression, PTSD, suicide and addictions points to one contributing factor that these different illnesses share: toxic stress.

Toxic stress increases the risk for the onset, progression, complications or early death from these illnesses.

Because the definition of toxic stress varies from one person to another, it’s hard to know how many people struggle with it. One starting point is the fact that about 16% of adults report having been exposed to four or more adverse events in childhood. This is the threshold for higher risk for illnesses in adulthood.

Research dating back to before the COVID-19 pandemic also shows that about 19% of adults in the U.S. have four or more chronic illnesses. If you have even one chronic illness, you can imagine how stressful four must be.

And about 12% of the U.S. population lives in poverty, the epitome of a life in which demands exceed resources every day. For instance, if a person doesn’t know how they will get to work each day, or doesn’t have a way to fix a leaking water pipe or resolve a conflict with their partner, their stress response system can never rest. One or any combination of threats may keep them on high alert or shut them down in a way that prevents them from trying to cope at all.

Add to these overlapping groups all those who struggle with harassing relationships, homelessness, captivity, severe loneliness, living in high-crime neighborhoods or working in or around noise or air pollution. It seems conservative to estimate that about 20% of people in the U.S. live with the effects of toxic stress.

Recognizing and Managing Stress

The first step to managing stress is to recognize it and talk to your primary care clinician about it. The clinician may do an assessment involving a self-reported measure of stress.

The next step is treatment. Research shows that it is possible to retrain a dysregulated stress response system. This approach, called “lifestyle medicine,” focuses on improving health outcomes through changing high-risk health behaviors and adopting daily habits that help the stress response system self-regulate.

Adopting these lifestyle changes is not quick or easy, but it works.

The National Diabetes Prevention Program, the Ornish “UnDo” heart disease program and the U.S. Department of Veterans Affairs PTSD program, for example, all achieve a slowing or reversal of stress-related chronic conditions through weekly support groups and guided daily practice over six to nine months. These programs help teach people how to practice personal regimens of stress management, diet and exercise in ways that build and sustain their new habits.

There is now strong evidence that it is possible to treat toxic stress in ways that improve health outcomes for people with stress-related conditions. The next steps include finding ways to expand the recognition of toxic stress and, for those affected, to expand access to these new and effective approaches to treatment.

Lawson R. Wulsin, MD, is a Professor of Psychiatry and Family Medicine at University of Cincinnati. He also practices psychiatry in primary care settings, specializing in psychosomatic medicine.

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

Experts Say CGRP Drugs Are First-Line Therapies for Migraine Prevention

By Pat Anson, PNN Editor

Migraine medications that block calcitonin gene-related peptides (CGRPs) are “equal to or greater” than other migraine prevention drugs and should be considered first-line therapies, according to a new guideline from the American Headache Society (AHS).

It’s the first time the organization has endorsed CGRP inhibitors for migraine prevention, despite their high cost and limited availability due to insurance requirements. Many insurers have step-therapy policies that require patients to start with cheaper first-line treatments before trying other drugs.

"Moving CGRP-targeting therapies to the first line of treatment could have a transformational impact on the prevention of migraine attacks and their associated burdens," Andrew Charles, MD, AHS president and lead author of the guideline recently published in the journal Headache. 

CGRP inhibitors block a protein that binds to nerve receptors in the brain and trigger migraine pain. Since 2018, the FDA has approved over half a dozen CGRP medications for migraine prevention and/or treatment, the biggest innovation in migraine therapy in decades.   

Older drugs that have long been used for migraine prevention were originally developed for other conditions. They include amitriptyline, a tricyclic antidepressant; simvastatin, which is used to control cholesterol; topiramate (Topamax), an antiseizure medication; and beta-blockers commonly used to control blood pressure.  

The AHS says there is growing “real world” experience that CGRP inhibitors work better than the older, repurposed medications.

“The evidence for the efficacy, tolerability, and safety of CGRP-targeting migraine preventive therapies is substantial, and vastly exceeds that for any other preventive treatment approach,” the AHS said. “The data indicates that the efficacy and tolerability of CGRP-targeting therapies are equal to or greater than those of previous first-line therapies and that serious adverse events associated with CGRP-targeting therapies are rare.”

The biggest problem with CGRP inhibitors is their cost, which can reach tens of thousands of dollars a year. Eight doses of Nurtec, a tablet taken daily, cost over $1,000; while the listed price for Emgality is $706 for a self-injectable syringe used monthly. Prices will vary, depending on insurance and whether a patient qualifies for discounts or patient assistance programs.

By comparison, amitriptyline and simvastatin are bargains. A bottle of 30 simvastatin tablets will cost about $14, while amitriptyline costs about $13 for a supply of 28 tablets. A recent study suggests that amitriptyline and simvastatin work just as well as CGRP inhibitors in reducing the need for medications to treat migraine pain, an indication that they are effective at prevention.

Despite the disparity in cost, the AHS maintains the overall benefits of CGRP inhibitors may justify the price. There are substantial hidden costs to migraine attacks, which can result in lost productivity, income, education, and personal relationships.   

“We recognize that the CGRP-targeting preventive therapies are significantly more expensive on a yearly basis than most of the previously established therapies, and some argue that this expense is a primary consideration in clinical decision-making,” the AHS said. “On the other hand, we argue that it is critically important to consider not only the direct cost of the treatment but also the substantial costs to the individual and society if effective treatment is delayed.”

Migraine affects about 39 million people in the United States and 1.1 billion worldwide. In addition to headache pain, migraine can cause nausea, blurriness, and sensitivity to light or sound. Women are three times more likely to suffer from migraines than men.  

Neurological Conditions Now Leading Cause of Chronic Illness

By Pat Anson, PNN Editor

The number of people living with neurological conditions such as migraine, diabetic neuropathy, epilepsy, stroke and dementia has risen significantly over the past 30 years, making it the leading cause of chronic illness worldwide, according to a new analysis published in The Lancet Neurology.

An international research team estimates that over 3.4 billion people – about 43% of the global population – had a neurological condition in 2021, replacing cardiovascular disease as the leading cause of poor health.

“The worldwide neurological burden is growing very fast and will put even more pressure on health systems in the coming decades,” said co-author Valery Feigin, MD, Director of the National Institute for Stroke and Applied Neuroscience at Auckland University in New Zealand.

“Yet many current strategies for reducing neurological conditions have low effectiveness or are not sufficiently deployed, as is the case with some of the fastest-growing but largely preventable conditions like diabetic neuropathy and neonatal disorders. For many other conditions, there is no cure, underscoring the importance of greater investment and research into novel interventions and potentially modifiable risk factors.”

A total of 37 disorders affecting the brain and nervous system were included in the study. Collectively, the nerve disorders are responsible for 443 million years of healthy life lost due to illness, disability or premature death, known as disability-adjusted life years (DALYs).

Tension-type headaches (about 2 billion cases) and migraines (about 1.1 billion) are the two most common neurological disorders, while diabetic neuropathy is the fastest-growing one. Painful stinging or burning sensations in the nerves of the hands and feet are often the first symptoms of diabetes.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021,” said co-senior author Liane Ong, PhD, from the Institute for Health Metrics and Evaluation at University of Washington. “This is in line with the increase in the global prevalence of diabetes.”

Over 80% of neurological deaths and disability occur in low- and middle-income countries, with western and central sub-Saharan Africa having the highest DALY rates. In contrast, high-income countries in the Asian Pacific and Australasia regions had the lowest rates.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” said co-author Tarun Dua, MD, Unit Head of WHO’s Brain Health unit.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries.”

Medical providers specializing in neurological care are unevenly distributed around the world, with wealthy countries having about 70 times the number of specialists as low-income ones.

Researchers say prevention needs to be a top priority in addressing the growth of neurological conditions. Some disorders, such as stroke and chronic headache, are potentially preventable by lowering risk factors such as high blood pressure, smoking and alcohol use.

The study was funded by the Bill and Melinda Gates Foundation.