Stem Cell Discovery Could Revolutionize Spine and Cancer Care

By Pat Anson, PNN Editor

The discovery of a new type of stem cell could revolutionize the treatment of spine disorders and slow the progression of some cancers, according to a groundbreaking study published in Nature.

Researchers from Hospital for Special Surgery (HSS) and Weill Cornell Medicine say the vertebral stem cells they found in human spines appear to play a key role in spinal health and in the metastasis of cancerous tumors as they spread through the body.

“There are two big takeaway discoveries that were made here. One is that we have discovered a stem cell that forms the spine and maintains the spine throughout life. This cell makes all the other cells that mineralize the spine,” said lead investigator Matthew Greenblatt, MD, associate professor of pathology and laboratory medicine at Weill Cornell Medicine.

“The second discovery here is that we found that this stem cell drives tumors. Breast cancer is what we focused on here, but likely also prostate cancer.”

Cancer experts have long believed that tumors metastasize to other parts of the body simply through blood flow. But Greenblat and his colleagues found that vertebral stem cells essentially attract cancer cells to the spine. That could explain why some cancers are first detected in the spine after they have metastasized from the breast, prostate and lung.

“Because we found that molecular ‘come here’ signal that's made by this spine stem cell, that gives us the ability to block that signal therapeutically. And that's something we're working on to try to prevent or treat established spine metastases,” Greenblatt told PNN.

Boosting Bone Health

Researchers say their discovery could also lead to breakthroughs in spinal health, by giving physicians a way to speed up recovery from spinal injuries and slow the progression of degenerative conditions such as osteoporosis, a disease that makes bones thinner, less dense and more likely to fracture.

For example, someone with degenerative disc disease could have their vertebral stem cells harvested, reproduced in a laboratory, and then reinjected to stimulate the growth of new bone. In animal tests, human vertebral stem cells helped laboratory mice form new bones in their spines.

“We can show that they formed basically little vertebral bones when those patient cells are put into mice, which really tells us that we found the right cell. And we can work with the cell transplant and retain stability to make new bone,” said co-author Sravisht Iyer, MD, a spine surgeon at HSS.

“I think kind of figuring out how to recruit the cells or how to how to encourage them to form more bone is going to be an important area or avenue of investigation for us, as a way to help people and protect people against what is a very morbid condition for them.”

Iyer says early treatment with vertebral stem cells could help someone with osteoporosis or a spine fracture, but wouldn’t necessarily benefit patients suffering from more advanced cases of bone loss.

“By the time people are presenting to us with spine pain, they usually have some element of compressive pathology or a degree of degeneration, which will likely require some intervention, whether that's surgery or epidural injection,” Iyer said.

“Where this work I think can really help push us forward is once you get those at-risk patients, they probably will need a surgery because a lot of degeneration is asymptomatic, and by the time they get to you they probably need something, but maybe you can prevent the second, third or fourth operation or intervention.”

More research and human studies are needed before the stem cells can be used in clinical settings to improve bone health and slow the metastasis of cancer cells. But researchers are excited by what they’ve learn so far.    

“We predict this discovery will lead to the targeting of these cells to disrupt the function and ultimately reduce the spread of cancer to the spine," said Greenblatt.

Lyme Disease: How a Bacteria Plays Havoc with Immune Systems

By Dr. Jenny Wachter, University of Saskatchewan

Lyme disease is the leading vector-borne disease — meaning diseases that are transmitted to humans from another organism like a tick or mosquito — in North America and Europe.

New human cases are estimated at over 400,000 in the United States each year. Canada has experienced a drastic increase in human cases, from 266 cases in 2011 to 3,147 in 2021, as the habitat of its vector, a tick, expands north.

The initial symptoms of human Lyme disease can be vague, such as fever, headache, fatigue and often rash. It is a potentially serious condition that can affect multiple systems in the body — including the heart, nervous system and joints — and can become a chronic illness.

Lyme disease is caused by a unique, spiral-shaped (spirochete) bacterium called Borrelia burgdorferi. B. burgdorferi cannot survive in the environment on its own. For survival and transmission, it requires susceptible hosts (usually small mammals or birds) and a specific vector: the black-legged tick, also called the deer tick.

Evading the Immune System

B. burgdorferi must survive extremely diverse conditions over the course of its transmission and infection cycle: from host to tick vector, and then into new hosts.

This bacterium senses and responds to its surroundings, most notably by modifying its appearance by changing the proteins on its outer surface to help it survive in either the tick or the host.

When a tick infected by B. burgdorferi bites and feeds on a vertebrate host, it provides a signal for the bacteria to switch its proteins to those required to infect the host, and to begin migrating through the tick and into the bite site. This process takes between 36 and 72 hours.

However, many of these proteins are recognized by the host as foreign, and the host’s immune system works to try to clear the infection. This includes a strong, antibody response targeted against B. burgdorferi.

Despite these immune responses, B. burgdorferi is able to cause long-term infections. In natural host reservoirs — the animals that the bacterium usually finds itself in via tick bites, such as small rodents — these infections do not cause diseases like those seen in humans and other non-natural reservoirs.

In fact, the bacteria itself does not produce any products that would be toxic to its hosts, either natural or non-natural. Yet chronic infection in humans can lead to Lyme neuroborreliosis, carditis and Lyme arthritis.

How then, are these bacteria able to cause such a devastating disease in humans and other animals, but not in their natural host reservoirs?

While there is still much to learn about B. burgdorferi, we know of several factors that play a role in the range of disease it causes. These include:

• its genetic make-up,

• its ability to access various tissues (such as the joints, heart and nervous system) due to its ability to move around (motility), and

• the immune response of the host.

Apart from motility, B. burgdorferi also protects itself from the strong B. burgdorferi-specific targeted antibody response of its host’s immune system by changing the appearance of the main outer surface protein expressed during persistent infection in a process called antigenic variation.

In addition to antigenic variation, B. burgdorferi bacteria can also change their DNA by exchanging genetic information, a process also known as gene transfer. This process allows these bacteria to further alter their appearance during infection to avoid the host immune system.

This process works so well that these B. burgdorferi bacteria appear different enough to allow re-infection or even co-infection (where multiple strains of B. burgdorferi infect a single host at the same time) of a vertebrate host, like a mouse or a human, despite the presence of specific antibodies to fight the bacterium.

In fact, in nature, the majority of host reservoirs and the ticks that carry the bacterium are infected with multiple strains of B. burgdorferi. The ability of B. burgdorferi to reinfect and co-infect both ticks and hosts increases the spread of the bacteria in the environment as well as the chances that humans will encounter Lyme disease.

Human Cases of Lyme Disease Are Increasing

As a vector-borne pathogen, B. burgdorferi only infects individuals that are bitten by an infected tick. It is not transmitted from person to person.

Environments that support black-legged/deer ticks are at risk of harbouring B. burgdorferi. In North America, these species of ticks are widely distributed throughout the eastern and midwestern United States. Recent geographic expansion to the north is increasing the prevalence of Lyme disease in Canada.

The increase of human Lyme disease cases highlights the failure of existing preventive strategies — such as minimizing exposure to tick habitats, performing diligent tick checks, and wearing suitable clothing when performing activities in known tick habitats — and emphasizes the need for an effective human vaccine.

At Vaccine and Infectious Disease Organization at the University of Saskatchewan, we are taking a One Health approach by recognizing that human health is closely related to the health of animals and the shared environment. We are investigating the role of B. burgdorferi, ticks, and susceptible animals on the spread and survival of the Lyme disease bacterium.

It is important to mimic the natural infectious cycle as much as possible when identifying potential vaccine and drug targets. This is because the way host animals are infected (for example, artificial needle infection or natural tick bite) can produce drastic differences in the resulting infection.

Additionally, despite the prevalence of this disease, there are still many aspects of the infectious cycle that remain unknown due to the uniqueness of B. burgdorferi and a lack of knowledge about the tick vector.

For example, we recently learned that a B. burgdorferi protein is responsible for regulating the components necessary for the bacterium to infect vertebrates, including humans. The absence of this protein, among other things, leads to the death of B. burgdorferi in ticks, making it an exciting target for research investigation.

By learning more about the molecular mechanisms that change or reduce the severity of the disease caused by this bacterium, we can identify new targets for the prevention of human Lyme disease. 

Jenny Wachter, PhD, is a research scientist and adjunct professor at University of Saskatchewan.

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

Millions Disabled by Chronic Pain, Anxiety and Depression

By Pat Anson, PNN Editor

About 12 million people in the United States – nearly 5% of the adult population – have chronic pain that is accompanied by anxiety or depression so severe that it limits their ability to work, socialize and complete daily tasks, according to a new study.

The co-occurrence of chronic pain with anxiety and/or depression (A/D) is well known, but little research has been conducted on its prevalence or impact. To see how often the symptoms occur, researchers at the University of Arizona Health Sciences analyzed responses from nearly 32,000 people who participated in the 2019 National Health Interview Survey.

Their findings, published in in the journal PAIN, show that adults with chronic pain are about five times more likely to report anxiety or depression than those without chronic pain. The risk is even higher in adults with “high impact pain” – pain severe enough to limit daily life and work activities -- who are eight times more likely to have A/D.

"The study's findings highlight an underappreciated population and health care need -- the interdependency between mental health and chronic pain," said lead author Jennifer De La Rosa, PhD, director of strategy for the UArizona Health Sciences Comprehensive Pain and Addiction Center.

De La Rosa and her colleagues found that adults with co-occurring symptoms of pain, anxiety and depression had a significantly more disability compared to those with either chronic pain alone or A/D symptoms alone. Nearly 70% reported that their work was limited, about 44% had difficulty doing errands alone, and over half (56%) had problems participating in social activities.

"I was surprised by the magnitude of the effect with functional limitations," said De La Rosa. "Across all domains of functional activity in life, we saw an enormous jump among people who are living with both conditions. These are people who are at a high risk for functional limitation, which will disturb their quality of life."

Like pain, anxiety and depression are difficult to measure and clinicians have to rely on patients self-reporting their symptoms. Making a diagnosis is also difficult because chronic pain and A/D are interconnected neurologically, affecting the same parts of the brain that control cognition and emotional function. Anxiety and depression can heighten the perception of pain and may increase the likelihood of acute, short-term pain becoming chronic.

"When someone is experiencing both chronic pain and anxiety or depression symptoms, achieving positive health outcomes can become more challenging," said senior author Todd Vanderah, PhD, director of the Comprehensive Pain and Addiction Center. "This study gives us another avenue to explore in our continuing effort to find new ways to treat chronic pain."

Researchers say further studies are needed to see if people receiving pain treatment are also getting mental health care, and whether that care is helping with their symptoms.

A recent study found that anxiety, depression and other mood disorders often precede the development of fibromyalgia, irritable bowel syndrome (IBS), and chronic fatigue syndrome (CFS).

Unions Threaten Strike Against Kaiser Permanente

By Bernard J. Wolfson, KFF Health News

Kaiser Permanente and union representatives pledged to continue negotiating a new contract up until the last minute as the threat of the nation’s latest large-scale strike looms next month.

Unless a deal is struck, more than 75,000 health workers will walk out for three days from Oct. 4-7, disrupting care for KP patients in California, Colorado, Oregon, Virginia, Washington, and Washington, D.C. The unions represent a wide range of KP health workers, including lab technicians, phlebotomists, pharmacists, optometrists, social workers, orderlies, and support staff.

A strike, if it occurs, would affect most of Kaiser Permanente’s 39 hospitals and 622 medical offices across the U.S., and would disrupt care for many of its nearly 13 million patients. If workers walk off their jobs, “it will start to impact patient care right away,” said John August, director of health care and partner programs at Cornell University’s Scheinman Institute on Conflict Resolution, who is a former head of the union coalition currently negotiating with KP.

“You are immediately subject to problems with not being able to get patients in and out of the hospital. You risk problems with infection control. You’re not going to get meals,” August said.

Arlene Peasnall, Kaiser Permanente’s senior vice president for human resources, said the Oakland, California-based health care giant’s goal is “to reach a mutually beneficial agreement before any work stoppage occurs.” But she also said the nonprofit has plans in place to blunt the impact of a walkout.

“We will be bargaining with Kaiser up until the day we go on strike,” said Caroline Lucas, executive director of the Coalition of Kaiser Permanente Unions, which represents about 40% of KP’s workforce. “Our front-line health care workers are fed up, and we really need Kaiser executives to seize the initiative and move forward on resolving the contract.”

The current contract expires Sept. 30 and, after months of talks, the two sides still disagree over pay and staffing. The coalition wants a $25-an-hour minimum wage across the company. KP executives agree there should be an organization-wide floor, but they’ve proposed $21.

KP prefers varying wage increases across regions, since the cost of living can vary sharply. The coalition, which is pushing for uniform wage increases across all regions, contends that management’s proposal is part of a “divide-and-conquer strategy.” Peasnall said the union’s stance “would prevent us from addressing fair market wages where we need to pay more to attract and retain the best people.”

The unions say their lowest-paid workers can barely make ends meet in the face of soaring prices for food, gasoline, and other essentials. And, they say, KP hospitals and clinics are severely understaffed, forcing workers to put in long hours and fill multiple roles. They argue that management is not moving quickly enough to fill positions and that the quality of care has suffered as patients, some with serious illnesses, often wait months for appointments, face extremely long waits in the emergency room, and experience delays in hospital admissions.

Healthcare Labor Shortage

An industrywide labor shortage hangs heavily over the contract talks. The pandemic was particularly brutal for health care workers who often worked long hours in grueling conditions, as colleagues fell ill, died, or quit. Workers say many of the positions that became vacant during the pandemic still have not been filled.

Miriam De La Paz, a secretary in the labor and delivery department of KP’s Downey Medical Center in Southern California and a union steward, said when she is alone on a shift, she is responsible for two labor and delivery stations as well as triage, where patients are prioritized based on the acuity of their cases.

“Imagine if I’m putting this baby in the system and your wife shows up in pain, crying, but I’m not there to register her,” De La Paz said. “I can’t break myself in two.”

Unions want KP to invest more in education, training, and recruitment to fill current openings and create a pipeline of future workers. KP says it is doing so.

Peasnall said KP has already filled more than 9,700 out of 10,000 new coalition-represented jobs the two sides had agreed to create this year. And she said KP’s turnover rate is one-third the industry rate, in part because of “excellent pay and benefits.”

Earlier this month, California lawmakers passed legislation to gradually raise the minimum wage for health care workers in the state to $25 an hour. If Democratic Gov. Gavin Newsom signs the bill into law, KP will have to comply. And nearly 80% of workers represented by the coalition in the current contract talks are in California.

On Sept. 22, as bargaining continued in San Francisco, the unions announced that more than 75,000 of the 85,000 workers they represent would stage the three-day walkout if there’s no deal. Federal law requires 10 days’ notice of strikes at health care facilities. The coalition said it is “prepared to engage in another longer, stronger strike in November,” if no agreement is reached by then.

A coalition spokesperson, Betsy Twitchell, said workers would welcome the Biden administration’s involvement in the talks “because of the importance of these negotiations to millions of patients and 75,000 frontline healthcare workers.”

The unions say KP can afford to be more generous, citing its robust financial health.

Although KP reported a net loss of almost $4.5 billion in 2022, it generated a cumulative net income of nearly $22 billion over the three preceding years — both results driven largely by investment performance. In the first half of this year, KP posted profits of over $3 billion. And it is in a strong position to manage its debt, according to a report earlier this year by Fitch Ratings.

The unions note that Kaiser Permanente’s CEO, Greg Adams, received almost $16 million in compensation in 2021 and that dozens of others in KP management made more than $1 million, according to a KP filing with the IRS.

Peasnall said the compensation of KP’s senior management is less than that of their peers at other health care companies.

A KP walkout would be the latest in a string of worker movements. Strikes have hit Hollywood, hotels, auto manufacturers, and other industries. Public approval of unions is at a nearly 60-year high, according to a Gallup Poll released in August 2022.

Health workers are increasingly engaged, too. Several hospital groups have been hit by strikes, including Cedars-Sinai Medical Center in Los Angeles and numerous facilities belonging to Sutter Health in Northern California, as well as health care organizations in other states.

“There is an atmosphere in the country: It’s labor summer, it’s strike summer, it’s all that,” August said. “That definitely has an influence on union leadership that says, ‘We need to be a part of that.’”

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

Sens. Manchin and Markey Want Opioid Research Stopped

By Pat Anson, PNN Editor

Seven years ago, Sens. Ed Markey (D-MA) and Joe Manchin (D-WV) wrote a letter to the acting administrator of the Drug Enforcement Administration, asking for stricter limits on the production of opioid pain medication. They joined with over a dozen of their colleagues with another letter in 2017, asking for the same thing.

The letters said too many Americans were becoming addicted to opioids and that there was “insufficient research body about the effectiveness of opioids when used long term.”

The letters and a personal meeting with the DEA administrator had an impact. The agency embarked on a years-long campaign to slash production quotas for opioid manufacturers, which now stand at their lowest levels in two decades. Since their peak, DEA production quotas have fallen by 65% for oxycodone and 73% for hydrocodone. And the U.S. now has chronic shortages of opioid medication.    

Flash forward to 2023, and Sens. Markey and Manchin are at it again, but in a different way.  

In a new letter --- this time to the Food and Drug Administration – the senators called on the agency to scrap plans for a new clinical trial that could help prove whether opioids are effective long term – the very thing the senators said there was “insufficient research” on just a few years ago.

“Other studies have already evaluated prolonged opioid use,” Markey and Manchin wrote in their letter, which was first reported by STAT.

SENS. JOE MANCHIN AND ED MARKEY

At issue is an FDA plan to use a research design known as enriched enrollment randomized withdrawal (EERW) to study the use of opioids by patients with chronic pain – persistent pain that lasts for over three months.  Such a study would require patients on extended-release morphine to either continue taking the medication or be unwittingly switched to a placebo – which would essentially amount to a rapid taper with no pain relief.  

Markey and Manchin say such a study is biased in favor of opioids and would “needlessly expose” patients on morphine to the risk of addiction. They also make the dubious claim that long-term clinical studies of opioids are no longer needed, citing a controversial Australian study – known as the OPAL study -- that found low dose opioids gave little relief to patients with back and neck pain.

“A recent randomized placebo-controlled study found that prolonged opioid use was ineffective for acute back and neck pain. The study found that after six weeks, there was no significant difference in pain scores for the patients taking opioids compared to those who took a placebo,” the senators wrote.

Critics were quick to note the OPAL study has a number of flaws, the most obvious one being that the treatment period only lasted six weeks. OPAL was a short-term study of opioids for acute pain – not “prolonged opioid use” as Manchin and Markey claimed.   

“The letter by Markey and Manchin is a phenomenon of misinformation and lack of understanding of the opioid crises,” said Stephen Nadeau, MD, a Professor of Neurology at the University of Florida College of Medicine.

“The OPAL study indisputably examined only ACUTE neck and back pain; it is completely inappropriate to apply its results to chronic pain,” said Chad Kollas, MD, a palliative care physician and pain policy expert.

Kollas posted a long thread on Twitter (now known as X) debunking other aspects of the OPAL study, saying its findings were “overstated & oversimplified to support the policy agenda of opioid reductionists.”

“I believe Manchin and Markey are being influenced to shut down any public funding of research that would demonstrate positive benefits for the long-term use of opioids -- of which, enriched enrollment trials are a prime example. By whom, I do not know,” says patient advocate Richard “Red” Lawhern.   

The “whom” in this case appears to be Dr. Andrew Kolodny, the president and founder of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group that is funded by dark money. Several PROP members, including Kolodny, have repeatedly failed to disclose their conflicts of interest and enriched themselves by testifying as paid expert witnesses in opioid litigation cases.  

Kolodny has worked previously with Manchin on anti-opioid legislation and is apparently doing so again. Manchin is co-sponsoring a bill that would require the FDA to review the use of EERW studies on opioids. Kolodny is quoted in a recent Manchin press release promoting the senator’s bill. 

“The FDA has been putting new painkillers on the market based on improper studies that skew results in favor of approval. The methodology they're using was cooked up in private meetings with drug makers. The time for outside experts to examine the use of enriched enrollment randomized withdrawal is long overdue,” said Kolodny, who is Medical Director of Opioid Policy Research at Brandeis University.  

Coincidentally, when the OPAL study was published in The Lancet medical journal, it was accompanied by an invited commentary from two other PROP members, Drs. Jane Ballantyne and Mark Sullivan, who said the study “raises serious questions about the use of opioid therapy for acute low back and neck pain.”

More Opioid Studies Needed

Although opioids have been used for thousands of years for pain relief, there are surprisingly few placebo-controlled clinical studies of their long-term effectiveness. That is mainly due to the ethical issues involved in giving a placebo to someone in pain. Few pain patients would want to participate in a long-term study in which there’s a good chance they don’t get any pain relief. And few studies duplicate the real world experiences of pain sufferers.

“Depriving patients of benefits they might gain from receiving LTOT (long term opioid therapy) ethically precludes using randomized controlled studies (RCTs) as a research method in studying LTOT. This necessitates using other types of research, including the type of research that the senators seek to eliminate,” Kollas told PNN.

“The reason that RCTs of opioids for chronic pain have failed is very simple:  the trial design is fundamentally flawed. It is simply not adequate to address the scientific question at hand,” says Nadeau. “EERW trials have shown promise, and certainly more evidence of efficacy then the conventionally designed trials, but they have their problems.” 

Nadeau and other have proposed that EERW studies be modified so that patients on opioids are gradually tapered, not just suddenly switched to a placebo. 

“What is glaringly evident is that the gold standard of randomized double-blind trials cannot be applied with opioids because of very high failure rates in the placebo arm, due to breakthrough pain,” said Lawhern. “Moreover, even short-term trials are invalidated by protocols that do not remotely resemble actual clinical use of these medications.”  

As flawed as they might be, EERW studies may be a way to fill in some of the missing gaps in opioid research. Do opioids work long-term? Do they inevitably lead to addiction?  Are chronic pain patients helped or harmed by using opioids? Those are simple questions we still don’t have definitive answers to – and may never know if politicians dictate health policy and try to block much needed pain research. 

“We ask the FDA not to permit the use of EERW to determine the long-term efficacy and tolerability of opioids in chronic pain patients. We also urge you to reject EERW study designs for any future new drug applications for opioids and reconsider past opioid approval decisions using EERW,” Manchin and Markey wrote.

Understanding the Difference Between Chronic Pain and Intractable Pain

By Dr. Forest Tennant, PNN Columnist  

The difference between simple chronic pain and intractable pain (IP) is what is known as pathologic sympathetic overdrive. This major medical complication is characterized by excessive electrical activity in the body's sympathetic nervous system. Excess electricity causes hyperarousal and pathologic overactivity of the sympathetic nervous system, which controls the body’s stress response. A comprehensive grasp of this complication is crucial for effective treatment.

Pathologic complication is the root cause of the disability, profound suffering and shortened lifespan often caused by intractable pain. Even though I recognized and published the difference between chronic and intractable pain in the Western Journal of Medicine over 20 years ago, it is still poorly understood in the mainstream medical practices of today. This contributes greatly to the undertreatment and mistreatment of IP patients.

The severe, constant and disabling pain of IP causes anatomical defects in the brain, which leads the cells in the brain to generate excess electricity. This is how pathologic sympathetic overdrive (PSO) starts. The brain must get rid of the excess electricity to prevent damage from the “burning” of brain tissue.

The brain rids itself of excess electricity by sending it into the sympathetic nervous system. This system is comprised of nerves that connect the brain to the heart, blood vessels, skin, lung and gastrointestinal system. The best-known neural connection in the network that connects the brain to bodily organs is the vagus nerve, but there are less known nerve connections in and along the spinal cord.

The “overdrive” of excess electricity produces a typical set of easily recognized symptoms and physical signs. These include an elevated pulse rate (tachycardia), high blood pressure, cold extremities (sometimes exhibiting a bluish hue), goosebumps, dilated pupils, and hyperactive reflexes. Another common symptom is temperature spikes and flushing, often followed by chills.

Amazingly, while the nation persistently clamors about the importance of controlling blood pressure, making Americans very aware that hypertension leads to serious medical conditions and is one of the leading causes of death in the U.S., I cannot identify a single lay magazine or medical journal that even refers to the undeniable correlation between severe, unmanaged pain and high blood pressure.  Strangely, there is also a conspicuous absence of discussions even in medical publications about the necessity of adequate pain management to reduce blood pressure.

Complications Caused by Intractable Pain

PSO interferes with normal respiratory function. The lungs may not expand and bring in the normal level of oxygen, and carbon dioxide may elevate in the blood. Inadequate oxygenation may lead to lethargy, fatigue, poor motivation, muscle weakness and mental impairment.

An IP patient’s ability to sleep, and especially achieving adequate REM sleep, is greatly reduced by PSO.  The hazards of inadequate sleep are well-known: fatigue, depression, amotivation, poor mental activity, and hormone imbalances. A tragic misunderstanding is the belief that somehow a lack of sleep is better than taking a bedtime sedative. This notion lacks any scientific merit.

There are lesser known but other serious and debilitating sequalae of PSO. The gastrointestinal system becomes so impaired by PSO to the point that loss of appetite, malabsorption (nutrients do not assimilate) and malnutrition is present in essentially all IP patients. The disturbed nutritional metabolic deficits can lead to either significant weight gain or loss. Constipation and diarrhea will often alternate, while stomach pain and bloating are routine. Patients are often misdiagnosed as having irritable bowel syndrome (IBS), with treatment that gives no consideration that bowel symptoms will persist without control of the underlying IP.

PSO has a significant impact on the endocrine system, similar to the body's "fight or flight" response during moments of stress. With IP the stress is constant. This physiological response involves an increase in adrenaline and cortisone levels in the bloodstream. Normally, this response to stress is temporary, allowing the adrenal and pituitary glands to recover and remain intact. But with the constant pain and electrical overdrive of IP, the glands hypertrophy (enlarge abnormally) trying to keep up their hormonal output to protect the body.

Unfortunately, the glands will often deplete. IP patients have died due to adrenal failure as the glands could not produce enough cortisone and adrenaline to maintain life. PSO tends to especially cause the pituitary gland to enlarge. Some uninformed surgeons have “removed the pituitary tumor” without understanding the root cause of the enlargement, or the imperative need to manage pain.

If PSO goes on long enough, and the pituitary and adrenal glands exhaust or wear out, testosterone and estradiol will deplete. While most people are aware of the impact of such depletion on libido and menstrual functions, what many medical practitioners miss is the critical role these hormones play in tissue healing, pain reduction, and various mental functions.

Since PSO raises cortisone for as long as one has IP, calcium is extracted from bones and teeth. Osteoporosis may develop and teeth may deteriorate. Sudden loss of a tooth is common in IP as is chronic dental cavities.

PSO in an adult IP patient will often cause some level of adult attention deficit disorder (ADD/ADHD), which is the exact clinical syndrome that occurs in a child with hyperactivity or attention deficit disorder. Furthermore, when the IP patient develops the same “attention deficits,” they will need the same medications that a child does to normalize attention span, carry out the 3R’s (“reading, riting, rithmetic”), and activities of daily living.

The mental aberrations caused by IP, unless treated with today’s hyperactivity medications (Ritalin, Adderall), can be so debilitating that the IP patient can become a lonely, despondent invalid, who becomes expensive to care for and totally dependent on family and society. The medical profession’s rejection or dismissal of ADD/ADHD in IP patients can only be classified as blatant professional oversight.

Diagnosing Intractable Pain

It is essential to point out that a medical practitioner who understands PSO can distinguish an IP patient from a simple chronic pain patient with a 5-to-10-minute physical examination. For starters, the IP patient with PSO will show some abnormality of pulse-rate, blood pressure, temperature or breathing rate. Some reflexes will be hyperactive, and the pupil may be dilated.  Hands and feet will be cold to touch and may show a blue discoloration. Teeth will be missing and/or show a lot of decay. Mental activity and speech may be slow and deliberate. Movement also may be slow.

These physical signs correlated with the history and symptoms provided by the patient and family will easily and quickly nail down the presence of IP and PSO, without the need for blood tests or brain scans.

This essay is a call for all parties concerned to fully understand the difference between chronic pain and intractable pain with PSO. Every IP patient, family and medical practitioner must fully understand that PSO will cause dire complications. IP patients and their families need to recognize them and record their PSO manifestations and present them to their medical practitioners.

Sadly, this author cannot identify a single education effort by a recognized medical publication, organization or academic institution that has or is currently trying to educate on the obvious and blatant clinical manifestations of the sympathetic pathological complications of IP. Like most things in medical science and practice today, the demand and education must “start at the bottom and work up.”

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain. To help patients and clinicians better understand intractable pain, the Tennant Foundation has launched a new website, IntractablePain.Org, where you can learn more about the conditions that cause intractable pain and their many complications.

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

How Technology Could Improve Healthcare in Underserved Communities

By Barby Ingle, PNN Columnist 

This year I was fortunate to visit all 15 counties in Arizona, from large cities and rural areas to those considered “frontier” and tribal reservations. I talked to patients, providers and caregivers about the stress points in their access to healthcare. I was in towns with no EMS, no hospital, and no specialists.

Seeing these disparities in healthcare closeup was an eye-opener for me. Imagine being injured or needing surgery, and you must take a helicopter to get immediate care. It’s like living on another planet.  

We can ensure that underserved communities have equal access to healthcare services, regardless of location, by providing remote and rural areas with access to telemedicine. Although the ability to access the internet is still difficult in some areas, services like Elon Musk's Star Link are being utilized to improve healthcare no matter where you live. 

With the recent pandemic, we were able to utilize telemedicine more often and see advancements in digital health solutions. Healthcare professionals can now remotely diagnose, treat and monitor patients from a distance. But will relaxed telehealth rules continue in the same form now that the pandemic has ended? Many of the details are still being worked out.

Mobile applications and wearable devices enable patients to monitor their vital signs and share the data with providers, allowing for remote monitoring and proactive intervention. They can also empower patients to more closely monitor their own health, receive medical advice, and manage chronic conditions from their homes.

With the increased availability of internet connectivity and mobile networks, technology has the potential to revolutionize healthcare delivery and improve health outcomes in remote and underserved regions. Several steps can be taken to address the digital divide in healthcare between urban and rural areas.

First, it is crucial to educate individuals about the benefits of technology and digital health tools. Technology can reduce transportation barriers, provide on-demand health advice, and minimize the risk of exposure to infectious diseases by enabling patients to stay at home.

Second, partnerships between stakeholders, such as academia, the private sector and government can help narrow the digital divide by leveraging resources to place healthcare technology where it is most needed. By building awareness, partnerships and targeting resources, it will be possible to bridge the digital divide and ensure that all communities have access to healthcare technology.

Here are some specific steps that can be taken:

• Conduct a comprehensive needs assessment in underserved communities to understand their unique healthcare challenges, cultural context and technological requirements. A needs assessment can involve surveys, interviews and focus group discussions with community members, healthcare providers and other stakeholders.

• Engage community members, healthcare professionals, and technology experts in a co-design approach. This means collaborating with the community to design and develop healthcare technology solutions that align with its needs, preferences and capabilities.  

• Adopt a user-centered design approach to make sure healthcare technology is user friendly.  Involve people from underserved communities in testing and interface design to ensure the technology is accessible, culturally appropriate and easy to operate.

• Consider the affordability and sustainability of healthcare technology by addressing cost barriers. ensuring compatibility with low-resource settings, and developing tools that can operate with limited infrastructure or connectivity.

• Provide training and support for people to utilize healthcare technology effectively. The training should include digital literacy programs, capacity-building workshops, and ongoing technical assistance.  

By involving underserved communities in the design process, healthcare technology can be tailored to their specific needs, leading to increased adoption and improved healthcare outcomes. It is crucial to prioritize the needs of these communities to ensure that they are included in the design and development of healthcare technology. By doing so, we can create more effective and sustainable solutions that genuinely address the healthcare challenges faced by underserved communities.

I am grateful for the opportunity to talk to patients, providers and caregivers in Arizona, thanks to a grant from HealtheVoices, Respond & Rescue, KB Companies and the International Pain Foundation. I look forward to continuing to gather feedback from underserved communities nationwide. By listening to patients and understanding their unique healthcare challenges, we can work towards creating meaningful solutions that improve access to care and overall health outcomes. 

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. You can follow Barby at www.barbyingle.com. 

FDA Recalls Abbott Stimulators for Technical Malfunction

By Pat Anson, PNN Editor

After receiving reports of dozens of injuries, the Food and Drug Administration has issued a Class I recall for two models of implantable neurostimulators due to a technical malfunction. The recall affects over 155,000 of Abbott’s Proclaim and Infinity devices, which are primarily used in spinal cord and deep brain stimulation.

Although Class I recalls are the most serious type of recall because they may result in injuries or death, patients are not being advised at this time to have the devices surgically removed. The stimulators were implanted in some patients as far back as 2015.

The malfunction occurs when the devices are temporarily turned off when a patient is having magnetic resonance imaging (MRI). There have been 186 complaints of patients being unable to turn the devices back on once the MRI ends, resulting in a loss of therapy and 73 injuries. No deaths have been reported.

In July, Abbott sent an “urgent medical device correction” letter to healthcare providers who install the devices, to clarify instructions on how to exit MRI mode.

The letter also advises providers to tell patients not to delete their device controller’s connection to Bluetooth if a malfunction occurs, and to update their systems and consult with a physician before having an MRI scan.   

ABBOTT IMAGE

Abbott estimates that only about 0.06% of the recalled devices malfunctioned, with 0.03% of them resulting in loss of therapy and additional surgery.   

The following devices are included in the recall:

• Proclaim XR 5 IPG Model 3660 (previously known as the ‘Proclaim 5 Elite IPG Model 3660’)

• Proclaim XR 7 IPG Model 3662 (Previously known as the ‘Proclaim 7 Elite IPG Model 3662’)

• Proclaim Plus 5 IPG Model 3670

• Proclaim Plus 7 IPG Model 3672

• Proclaim DRG IPG Model 3664

• Infinity 5 IPG Model 6660

• Infinity 7 IPG Model 6662

Implantable neurostimulators are an invasive treatment of last resort for people with chronic back, leg or head pain. The devices are surgically implanted near the spine or brain, and emit low-level electrical impulses to block pain signals.

About 50,000 spinal cord stimulators (SCSs) are implanted annually in the U.S. and their use is growing – in part because of the belief they’ll reduce the need for opioids and other pain therapies. A recent study found that many patients with stimulators did not reduce their use of opioids, epidurals, corticosteroid injections or radiofrequency ablation; and about one in five had complications so severe the devices had to be removed or revised.

A 2018 study found that SCSs have some of the worst safety records of medical devices tracked by the FDA. An FDA review of adverse events involving stimulators found that nearly a third were reports of poor pain relief. The review also identified nearly 500 deaths linked to the devices, along with nearly 78,000 injuries and 30,000 malfunctions.

‘A Devil’s Bargain’: Why Pharmacy Benefit Managers Are Sticking with Humira

By Arthur Allen, KFF Health News

Tennessee last year spent $48 million on a single drug, Humira — about $62,000 for each of the 775 patients who were covered by its employee health insurance program and receiving the treatment. So when nine Humira knockoffs, known as biosimilars, hit the market for as little as $995 a month, the opportunity for savings appeared ample and immediate.

But it isn’t here yet. Makers of biosimilars must still work within a health care system in which basic economics rarely seems to hold sway.

For real competition to take hold, the big pharmacy benefit managers, or PBMs, the companies that negotiate prices and set the prescription drug menu for 80% of insured patients in the United States, would have to position the new drugs favorably in health plans.

They haven’t, though the logic for doing so seems plain.

Humira has enjoyed high-priced U.S. exclusivity for 20 years. Its challengers could save the health care system $9 billion and herald savings from the whole class of drugs called biosimilars — a windfall akin to the hundreds of billions saved each year through the purchase of generic drugs.

The biosimilars work the same way as Humira, an injectable treatment for rheumatoid arthritis and other autoimmune diseases. And countries such as the United Kingdom, Denmark, and Poland have moved more than 90% of their Humira patients to the rival drugs since they launched in Europe in 2018.

Kaiser Permanente, which oversees medical care for 12 million people in eight U.S. states, switched most of its patients to a biosimilar in February and expects to save $300 million this year alone.

Biosimilars Are Cheaper

Biologics — both the brand-name drugs and their imitators, or biosimilars — are made with living cells, such as yeast or bacteria. With dozens of biologics nearing the end of their patent protection in the next two decades, biosimilars could generate much higher savings than generics, said Paul Holmes, a partner at Williams Barber Morel who works with self-insured health plans. That’s because biologics are much more expensive than pills and other formulations made through simpler chemical processes.

For example, after the first generics for the blockbuster anti-reflux drug Nexium hit the market in 2015, they cost around $10 a month, compared with Nexium’s $100 price tag. Coherus BioSciences launched its Humira biosimilar, Yusimry, in July at $995 per two-syringe carton, compared with Humira’s $6,600 list price for a nearly identical product.

“The percentage savings might be similar, but the total dollar savings are much bigger,” Holmes said, “as long as the plan sponsors, the employers, realize the opportunity.”

That’s a big if.

While a manufacturer may need to spend a few million dollars to get a generic pill ready to market, makers of biosimilars say their development can require up to eight years and $200 million. The business won’t work unless they gain significant market share, they say.

The biggest hitch seems to be the PBMs. Express Scripts and Optum Rx, two of the three giant PBMs, have put biosimilars on their formularies, but at the same price as Humira. That gives doctors and patients little incentive to switch. So Humira remains dominant for now.

“We’re not seeing a lot of takeup of the biosimilar,” said Keith Athow, pharmacy director for Tennessee’s group insurance program, which covers 292,000 state and local employees and their dependents.

The ongoing saga of Humira — its peculiar appeal to drug middlemen and insurers, the patients who’ve benefited, the patients who’ve suffered as its list price jumped sixfold since 2003 — exemplifies the convoluted U.S. health care system, whose prescription drug coverage can be spotty and expenditures far more unequal than in other advanced economies.

Biologics like Humira occupy a growing share of U.S. health care spending, with their costs increasing 12.5% annually over the past five years. The drugs are increasingly important in treating cancers and autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease, that afflict about 1 in 10 Americans.

Humira’s $200 billion in global sales make it the best-selling drug in history. Its manufacturer, AbbVie, has aggressively defended the drug, filing more than 240 patents and deploying legal threats and tweaks to the product to keep patent protections and competitors at bay.

The company’s fight for Humira didn’t stop when the biosimilars finally appeared. The drugmaker has told investors it doesn’t expect to lose much market share through 2024. “We are competing very effectively with the various biosimilar offerings,” AbbVie CEO Richard Gonzalez said during an earnings call.

How AbbVie Maintains Market Share

One of AbbVie’s strategies was to warn health plans that if they recommended biosimilars over Humira they would lose rebates on purchases of Skyrizi and Rinvoq, two drugs with no generic imitators that are each listed at about $120,000 a year, according to PBM officials. In other words, dropping one AbbVie drug would lead to higher costs for others.

Industry sources also say the PBMs persuaded AbbVie to increase its Humira rebates — the end-of-the-year payments, based on total use of the drug, which are mostly passed along by the PBMs to the health plan sponsors. Although rebate numbers are kept secret and vary widely, some reportedly jumped this year by 40% to 60% of the drug’s list price.

The leading PBMs — Express Scripts, Optum, and CVS Caremark — are powerful players, each part of a giant health conglomerate that includes a leading insurer, specialty pharmacies, doctors’ offices, and other businesses, some of them based overseas for tax advantages.

Yet challenges to PBM practices are mounting. The Federal Trade Commission began a major probe of the companies last year. Kroger canceled its pharmacy contract with Express Scripts last fall, saying it had no bargaining power in the arrangement, and, on Aug. 17, the insurer Blue Shield of California announced it was severing most of its business with CVS Caremark for similar reasons.

Critics of the top PBMs see the Humira biosimilars as a potential turning point for the secretive business processes that have contributed to stunningly high drug prices.

Although list prices for Humira are many times higher than those of the new biosimilars, discounts and rebates offered by AbbVie make its drug more competitive. But even if health plans were paying only, say, half of the net amount they pay for Humira now — and if several biosimilar makers charged as little as a sixth of the gross price — the costs could fall by around $30,000 a year per patient, said Greg Baker, CEO of AffirmedRx, a smaller PBM that is challenging the big companies.

Multiplied by the 313,000 patients currently prescribed Humira, that comes to about $9 billion in annual savings — a not inconsequential 1.4% of total national spending on pharmaceuticals in 2022.

The launch of the biosimilar Yusimry, which is being sold through Mark Cuban’s Cost Plus Drugs pharmacy and elsewhere, “should send off alarms to the employers,” said Juliana Reed, executive director of the Biosimilars Forum, an industry group. “They are going to ask, ‘Time out, why are you charging me 85% more, Mr. PBM, than what Mark Cuban is offering? What is going on in this system?’”

Cheaper drugs could make it easier for patients to pay for their drugs and presumably make them healthier. A KFF survey in 2022 found that nearly a fifth of adults reported not filling a prescription because of the cost. Reports of Humira patients quitting the drug for its cost are rife.

Inflated Sticker Prices

When Sue Lee of suburban Louisville, Kentucky, retired as an insurance claims reviewer and went on Medicare in 2017, she learned that her monthly copay for Humira, which she took to treat painful plaque psoriasis, was rising from $60 to $8,000 a year.

It was a particularly bitter experience for Lee, now 81, because AbbVie had paid her for the previous three years to proselytize for the drug by chatting up dermatology nurses at fancy AbbVie-sponsored dinners. Casting about for a way to stay on the drug, Lee asked the company for help, but her income at the time was too high to qualify her for its assistance program.

“They were done with me,” she said. Lee went off the drug, and within a few weeks the psoriasis came back with a vengeance. Sores covered her calves, torso, and even the tips of her ears. Months later she got relief by entering a clinical trial for another drug.

Health plans are motivated to keep Humira as a preferred choice out of convenience, inertia, and fear. While such data is secret, one Midwestern firm with 2,500 employees told KFF Health News that AbbVie had effectively lowered Humira’s net cost to the company by 40% after July 1, the day most of the biosimilars launched.

One of the top three PBMs, CVS Caremark, announced in August that it was creating a partnership with drugmaker Sandoz to market its own cut-rate version of Humira, called Hyrimoz, in 2024. But Caremark didn’t appear to be fully embracing even its own biosimilar. Officials from the PBM notified customers that Hyrimoz will be on the same tier as Humira to “maximize rebates” from AbbVie, Tennessee’s Athow said.

Most of the rebates are passed along to health plans, the PBMs say. But if the state of Tennessee received a check for, say, $20 million at the end of last year, it was merely getting back some of the $48 million it already spent.

“It’s a devil’s bargain,” said Michael Thompson, president and CEO of the National Alliance of Healthcare Purchaser Coalitions. “The happiest day of a benefit executive’s year is walking into the CFO’s office with a several-million-dollar check and saying, ‘Look what I got you!’”

Executives from the leading PBMs have said their clients prefer high-priced, high-rebate drugs, but that’s not the whole story. Some of the fees and other payments that PBMs, distributors, consultants, and wholesalers earn are calculated based on a drug’s price, which gives them equally misplaced incentives, said Antonio Ciaccia, CEO of 46Brooklyn, a nonprofit that researches the drug supply chain.

“The large intermediaries are wedded to inflated sticker prices,” said Ciaccia.

AbbVie has warned some PBMs that if Humira isn’t offered on the same tier as biosimilars it will stop paying rebates for the drug, according to Alex Jung, a forensic accountant who consults with the Midwest Business Group on Health.

AbbVie did not respond to requests for comment.

One of the low-cost Humira biosimilars, Organon’s Hadlima, has made it onto several formularies, the ranked lists of drugs that health plans offer patients, since launching in February, but “access alone does not guarantee success” and doesn’t mean patients will get the product, Kevin Ali, Organon’s CEO, said in an earnings call in August.

If the biosimilars are priced no lower than Humira on health plan formularies, rheumatologists will lack an incentive to prescribe them. When PBMs put drugs on the same “tier” on a formulary, the patient’s copay is generally the same.

In an emailed statement, Optum Rx said that by adding several biosimilars to its formularies at the same price as Humira, “we are fostering competition while ensuring the broadest possible choice and access for those we serve.”

Switching a patient involves administrative costs for the patient, health plan, pharmacy, and doctor, said Marcus Snow, chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

Doctors Reluctant to Switch

Doctors seem reluctant to move patients off Humira. After years of struggling with insurance, the biggest concern of the patient and the rheumatologist, Snow said, is “forced switching by the insurer. If the patient is doing well, any change is concerning to them.” Still, the American College of Rheumatology recently distributed a video informing patients of the availability of biosimilars, and “the data is there that there’s virtually no difference,” Snow said. “We know the cost of health care is exploding. But at the same time, my job is to make my patient better. That trumps everything.”

“All things being equal, I like to keep the patient on the same drug,” said Madelaine Feldman, a New Orleans rheumatologist.

Gastrointestinal specialists, who often prescribe Humira for inflammatory bowel disease, seem similarly conflicted. American Gastroenterological Association spokesperson Rachel Shubert said the group’s policy guidance “opposes nonmedical switching” by an insurer, unless the decision is shared by provider and patient. But Siddharth Singh, chair of the group’s clinical guidelines committee, said he would not hesitate to switch a new patient to a biosimilar, although “these decisions are largely insurance-driven.”

HealthTrust, a company that procures drugs for about 2 million people, has had only five patients switch from Humira this year, said Cora Opsahl, director of the Service Employees International Union’s 32BJ Health Fund, a New York state plan that procures drugs through HealthTrust.

But the biosimilar companies hope to slowly gain market footholds. Companies like Coherus will have a niche and “they might be on the front end of a wave,” said Ciaccia, given employers’ growing demands for change in the system.

The $2,000 out-of-pocket cap on Medicare drug spending that goes into effect in 2025 under the Inflation Reduction Act could spur more interest in biosimilars. With insurers on the hook for more of a drug’s cost, they should be looking for cheaper options.

For Kaiser Permanente, the move to biosimilars was obvious once the company determined they were safe and effective, said Mary Beth Lang, KP’s chief pharmacy officer. The first Humira biosimilar, Amjevita, was 55% cheaper than the original drug, and she indicated that KP was paying even less since more drastically discounted biosimilars launched. Switched patients pay less for their medication than before, she said, and very few have tried to get back on Humira.

Prescryptive, a small PBM that promises transparent policies, switched 100% of its patients after most of the other biosimilars entered the market July 1 “with absolutely no interruption of therapy, no complaints, and no changes,” said Rich Lieblich, the company’s vice president for clinical services and industry relations.

AbbVie declined to respond to him with a competitive price, he said.

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

Moderation – Not Prohibition – Is Key to Treating ER Patients With Opioids

By Pat Anson, PNN Editor

Over the years many people living with pain have told us that they avoid going emergency rooms because they fear their pain will be ignored and that they’ll be treated as an addict if they ask for opioids.  

“Going to the ER terrifies me and I am an RN,” one patient said. “I was recently there on 2 separate episodes for kidney stones. Over a three-day period they gave me absolutely nothing for pain!” 

“I can't and won't return to an ER even if I am dying because I won't accept being treated like an addict ever again,” said a 60-year-old disabled woman.  

“It took me 12 hours and a staged public fit to get any pain relief at my local ER when I went in with a pinched nerve,” another patient told us. 

“Called suicide hotline and was told to go to ER,” said a woman suffering from a severe flare from rheumatoid arthritis. “Well, that was a waste. Told I was drug seeking and received a hefty bill to pile on top of all the others.”

A new study suggests that moderation – not prohibition -- is the key to treating pain in the ER with opioids. Researchers in Canada found that half of patients discharged from an emergency department needed only a handful of opioid tablets to control their pain.

“Patients are often prescribed too many opioid tablets and that means unused tablets are available for misuse,” Raoul Daoust, MD, a professor of Family and Emergency at University of Montreal, said in a press release. “On the other hand, since the opioid crisis, the tendency in the USA is to not prescribe opioids at all, leaving some patient in agonising pain.

“With this research I wanted to provide a tailored approach to prescribing opioids so that patients have enough to manage their pain but almost no unused tablets available for misuse.”

Daoust and his colleagues surveyed 2,240 adult patients who were treated for acute pain at one of six hospital emergency departments in Canada. All were discharged with an opioid prescription and were asked to complete a pain diary for two weeks.

Their findings, presented over the weekend at the European Emergency Medicine Congress in Spain, showed five or fewer morphine tablets (5mg) were adequate for about half the patients. The rest needed more tablets, depending on their condition. For example, patients suffering from renal colic or abdominal pain needed eight tablets, while a patient with broken bones needed 24 tablets. 

Daoust says emergency room physicians need to recognize that morphine can be “very beneficial” for patients. The key is to individualize treatment and prescribe the right amount to minimize the risk of addiction.

“Our findings make it possible to adapt the quantity of opioids we prescribe according to patient need. We could ask the pharmacist to also provide opioids in small portions, such as five tablets initially, because for half of patients that would be enough to last them for two weeks,” said Daoust.

The researchers plan to apply their findings in a clinical setting to evaluate whether they can reduce the long-term use and misuse of opioids. 

“This study shows how opioid prescriptions could be adapted to specific acute pain conditions, and how they could be dispensed in relatively small numbers at the pharmacy to lower the chance of misuse. This research could provide a safer way to prescribe opioids that could be applied in emergency departments anywhere in the world,” said Youri Yordanov, MD, an emergency physician at Saint-Antoine Hospital in Paris, who was not involved in the research.

A large 2017 study found that the risk of long-term opioid use is lower for ER patients than it is for patients treated in other medical settings. Researchers found that only 1.1% percent of ER patients taking opioids for the first time progressed to long term use. That compares to 2% of patients in non-emergency settings.

Virtual Reality Has Long-Term Benefits for Patients with Back Pain

By Pat Anson, PNN Editor

A novel treatment that combines virtual reality with cognitive behavioral therapy significantly reduced pain levels and other symptoms in patients with chronic back or neck pain, according to results of a new study presented at the annual meeting of the Congress of Neurological Surgeons.

Unlike other therapies using virtual reality (VR) – which temporarily distract people from their pain – patients in this study had long term reductions in their pain, anxiety and depression. This suggests that combining VR with cognitive behavioral therapy (CBT) induces neuroplasticity, a “rewiring” of the brain and nervous system that reduces the impact of physical and emotional trauma.    

“What we found is it actually creates new neural pathways to form, what's called neuroplastic reprogramming or neuroplastic change, and that actually creates a more resilient patient,” said co-author Gerry Stanley, MD, Chief Medical Officer of Harvard MedTech, a medical device company that offers VR therapy.

“The patient who may be thinking about their pain 22 hours a day, and their pain (level) has always been eight or nine, now thinks about their pain one or two hours a day and their pain (level) is a three or four, because the brain is no longer fixating on it. So it allows for, I don't want to say permanent distraction, it’s really neuroplastic reprogramming.”

Stanley and his colleagues enrolled 145 patients with non-operative degenerative neck or back pain in Harvard MedTech’s Vx Therapy program, which included daily virtual reality sessions for 14 weeks and weekly telephone calls with a therapist trained in CBT.  

Unlike other VR therapies, which encourage physical activity, participants sat stationary in a chair while watching and listening to prerecorded programs with a headset and earphones. The VR programs come in four categories that emphasize education, meditation, distraction or entertainment, depending on the patient’s needs and goals.

HARVARD MEDTECH IMAGE

After 14 weeks, results showed that Vx Therapy reduced pain and anxiety during sessions by an average of 33% and 46%, respectively. The duration of pain relief also increased over time, from 2.5 hours in the first weeks of treatment to 4.5 hours in the final weeks.

The study has not been peer-reviewed or published yet, but Stanley says the findings mirror what his company has learned after treating about 4,000 patients. The benefits of Vx Therapy continue long after the treatment ends, with many patients still reporting improvement after two years.  

“They're often reporting the same level of resiliency. I think a lot of it is they start getting into better sleep patterns,” he told PNN.  “And they really get good at meditation. Most people fail in meditation because of distractions. But when they're doing it in the virtual reality, they get very good at it. So they really develop some nice, I'm going to say muscle memory, even though I know it's cognitive. But they do develop a little bit of muscle memory around the meditation.”

Because Vx Therapy is done remotely, it’s available to any patient regardless of location, as long as they have a prescription. Some worker compensation insurers cover the treatment.   

Previous studies have also suggested that virtual reality therapy has long-term benefits for people with chronic back pain. A 2022 study showed that people with moderate lower back pain reported improvements in pain, function, mood and sleep six months after treatment ended.  

Stimulants Involved in Growing Number of Fentanyl Overdoses

By Pat Anson, PNN Editor

The number of drug deaths involving both fentanyl and stimulants has soared in recent years, according to a new UCLA study that highlights the complex and changing nature of the U.S. overdose crisis.

Stimulants such as cocaine and methamphetamine are now involved in nearly a third of fentanyl-related overdoses, the most of any other drug class. Fentanyl is a synthetic opioid up to 100 times more potent than morphine and 50 times as potent as heroin.

In 2010, researchers say there were only 235 fatal overdoses in the U.S. involving illicit fentanyl and stimulants. In 2021, there were 34,429 drug deaths linked to fentanyl and stimulants, a 14,550% increase in a little over a decade.

"We're now seeing that the use of fentanyl together with stimulants is rapidly becoming the dominant force in the US overdose crisis," said lead author Joseph Friedman, PhD, an addiction researcher at the David Geffen School of Medicine at UCLA. "Fentanyl has ushered in a polysubstance overdose crisis, meaning that people are mixing fentanyl with other drugs, like stimulants, but also countless other synthetic substances. This poses many health risks and new challenges for health care providers.

“We have data and medical expertise about treating opioid use disorders, but comparatively little experience with the combination of opioids and stimulants together, or opioids mixed with other drugs. This makes it hard to stabilize people medically who are withdrawing from polysubstance use."

People who overdose on stimulants and other non-opioid substances mixed with fentanyl may not be as responsive to naloxone, which only works as an antidote to opioids.

The study findings, published in the journal Addiction, highlight the four “waves” of the overdose crisis, which began with an increase in deaths from prescription opioids (Wave 1) in the early 2000s, followed by a rise in heroin deaths (Wave 2) in 2010, and fentanyl-related overdoses in 2013 (Wave 3). The fourth wave — overdoses from fentanyl and stimulants — began in 2015 and continues to escalate.

The Four Waves of Overdose Crisis

SOURCE: ADDICTION

Since cocaine, methamphetamine and other stimulants are not opioids, the findings undercut the long-held theory that the overdose crisis started with prescription opioids and is still being fueled by people addicted to them. Deaths involving prescription opioids and heroin have been in decline for several years.

Researchers found that fentanyl/stimulant deaths disproportionately affect African Americans and Native Americans. There are also geographical patterns to fentanyl/stimulant use. In the northeast US, fentanyl is usually combined with cocaine, while in the south and western US, fentanyl is most commonly found with methamphetamine.

"We suspect this pattern reflects the rising availability of, and preference for, low-cost, high-purity methamphetamine throughout the US, and the fact that the Northeast has a well-entrenched pattern of illicit cocaine use that has so far resisted the complete takeover by methamphetamine seen elsewhere in the country," Friedman said.

In addition to its low cost, drug users say methamphetamine helps prolong fentanyl’s “high” and delays the onset of withdrawal symptoms.  

Counterfeit pills laced with fentanyl – which are frequently made to look like oxycodone or alprazolam (Xanax) – represent about a quarter of all illicit fentanyl seizures. Researchers say it is difficult to track deaths involving counterfeit pills because they are often mistaken for legitimate medication, so the data is not completely reliable.

In its most recent update on the overdose crisis, the CDC estimates there were a record 111,355 drug deaths in the 12-month period ending April 2023 -- about a thousand more deaths than the year before. Fentanyl and its analogues were involved in nearly 70% of the overdoses, stimulants were linked to about a third of them, and cocaine was involved in about a quarter of the drug deaths.

CDC Recommends New Covid Boosters

By Arthur Allen, KFF Health News

Everyone over the age of 6 months should get the latest covid-19 booster, a federal expert panel recommended Tuesday after hearing an estimate that universal vaccination could prevent 100,000 more hospitalizations each year than if only the elderly were vaccinated.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted 13-1 for the motion after months of debate about whether to limit its recommendation to high-risk groups. A day earlier, the FDA approved the new booster, stating it was safe and effective at protecting against the covid variants currently circulating in the U.S.

After the last booster was released, in 2022, only 17% of the U.S. population got it — compared with the roughly half of the nation who got the first booster after it became available in fall 2021. Broader uptake was hurt by pandemic weariness and evidence the shots don’t always prevent covid infections. But those who did get the shot were far less likely to get very sick or die, according to data presented at Tuesday’s meeting.

The virus sometimes causes severe illness even in those without underlying conditions, causing more deaths in children than other vaccine-preventable diseases, as chickenpox did before vaccines against those pathogens were universally recommended.

The number of hospitalized patients with covid has ticked up modestly in recent weeks, CDC data shows, and infectious disease experts anticipate a surge in the late fall and winter.

The shots are made by Moderna and by Pfizer and its German partner, BioNTech, which have decided to charge up to $130 a shot. They have launched national marketing campaigns to encourage vaccination. The advisory committee deferred a decision on a third booster, produced by Novavax, because the FDA hasn’t yet approved it. Here’s what to know:

Who Should Get a Booster Shot?

The CDC advises that everyone over 6 months old should, for the broader benefit of all. Those at highest risk of serious disease include babies and toddlers, the elderly, pregnant women, and people with chronic health conditions including obesity. The risks are lower — though not zero — for everyone else. The vaccines, we’ve learned, tend to prevent infection in most people for only a few months. But they do a good job of preventing hospitalization and death, and by at least diminishing infections they may slow spread of the disease to the vulnerable, whose immune systems may be too weak to generate a good response to the vaccine.

Pablo Sánchez, a pediatrics professor at The Ohio State University who was the lone dissenter on the CDC panel, said he was worried the boosters hadn’t been tested enough, especially in kids. The vaccine strain in the new boosters was approved only in June, so nearly all the tests were done in mice or monkeys. However, nearly identical vaccines have been given safely to billions of people worldwide.

When Should You Get It?

The vaccine makers say they’ll begin rolling out the vaccine this week. If you’re in a high-risk group and haven’t been vaccinated or been sick with covid in the past two months, you could get it right away, says John Moore, an immunology expert at Weill Cornell Medical College. If you plan to travel this holiday season, as he does, Moore said, it would make sense to push your shot to late October or early November, to maximize the period in which protection induced by the vaccine is still high.

Who Pays For It?

When the ACIP recommends a vaccine for children, the government is legally obligated to guarantee kids free coverage, and the same holds for commercial insurance coverage of adult vaccines.

For the 25 to 30 million uninsured adults, the federal government created the Bridge Access Program. It will pay for rural and community health centers, as well as Walgreens, CVS, and some independent pharmacies, to provide covid shots for free. Manufacturers have agreed to donate some of the doses, CDC officials said.

Will New Booster Work Against Current Variants?

It should. More than 90% of currently circulating strains are closely related to the variant selected for the booster earlier this year, and studies showed the vaccines produced ample antibodies against most of them. The shots also appeared to produce a good immune response against a divergent strain that initially worried people, called BA.2.86. That strain represents fewer than 1% of cases currently. Moore calls it a “nothingburger.”

Why Are People Still Skeptical About Vaccines?

Experience with the covid vaccines has shown that their protection against hospitalization and death lasts longer than their protection against illness, which wanes relatively quickly, and this has created widespread skepticism.

Most people in the U.S. have been ill with covid and most have been vaccinated at least once, which together are generally enough to prevent grave illness, if not infection — in most people. Many doctors think the focus should be on vaccinating those truly at risk.

What About Getting Other Vaccines?

People tend to get sick in the late fall because they’re inside more and may be traveling and gathering in large family groups. This fall, for the first time, there’s a vaccine — for older adults — against respiratory syncytial virus. Kathryn Edwards, a 75-year-old Vanderbilt University pediatrician, plans to get all three shots but “probably won’t get them all together,” she said.

Covid “can have a punch” and some of the RSV vaccines and the flu shot that’s recommended for people 65 and older also can cause sore arms and, sometimes, fever or other symptoms. A hint emerged from data earlier this year that people who got flu and covid shots together might be at slightly higher risk of stroke. That linkage seems to have faded after further study, but it still might be safer not to get them together.

Pfizer and Moderna are both testing combination vaccines, with the first flu-covid shot to be available as early as next year. Although Pfizer’s shot has been approved in the European Union, Japan, and South Korea, and Moderna has won approval in Japan and Canada. Rollouts will start in the U.S. and other countries this week.

Unlike in earlier periods of the pandemic, mandates for the booster are unlikely. But “it’s important for people to have access to the vaccine if they want it,” said panel member Beth Bell, a professor of public health at the University of Washington.

“Having said that, it’s clear the risk is not equal, and the messaging needs to clarify that a lot of older people and people with underlying conditions are dying, and they really need to get a booster,” she said.

ACIP member Sarah Long, a pediatrician at Children’s Hospital of Philadelphia, voted for a universal recommendation but said she worried it was not enough. “I think we’ll recommend it and nobody will get it,” she said. “The people who need it most won’t get it.”

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

ChatGPT Is Replacing Dr. Google

By Andrew Leonard, KFF Health News

As a fourth-year ophthalmology resident at Emory University School of Medicine, Riley Lyons’ biggest responsibilities include triage: When a patient comes in with an eye-related complaint, Lyons must make an immediate assessment of its urgency.

He often finds patients have already turned to “Dr. Google.” Online, Lyons said, they are likely to find that “any number of terrible things could be going on based on the symptoms that they’re experiencing.”

So, when two of Lyons’ fellow ophthalmologists at Emory came to him and suggested evaluating the accuracy of the AI chatbot ChatGPT in diagnosing eye-related complaints, he jumped at the chance.

In June, Lyons and his colleagues reported in medRxiv, an online publisher of health science preprints, that ChatGPT compared quite well to human doctors who reviewed the same symptoms — and performed vastly better than the symptom checker on the popular health website WebMD.

And despite the much-publicized “hallucination” problem known to afflict ChatGPT — its habit of occasionally making outright false statements — the Emory study reported that the most recent version of ChatGPT made zero “grossly inaccurate” statements when presented with a standard set of eye complaints.

The relative proficiency of ChatGPT, which debuted in November 2022, was a surprise to Lyons and his co-authors. The artificial intelligence engine “is definitely an improvement over just putting something into a Google search bar and seeing what you find,” said co-author Nieraj Jain, an assistant professor at the Emory Eye Center who specializes in vitreoretinal surgery and disease.

But the findings underscore a challenge facing the health care industry as it assesses the promise and pitfalls of generative AI, the type of artificial intelligence used by ChatGPT: The accuracy of chatbot-delivered medical information may represent an improvement over Dr. Google, but there are still many questions about how to integrate this new technology into health care systems with the same safeguards historically applied to the introduction of new drugs or medical devices.

The smooth syntax, authoritative tone, and dexterity of generative AI have drawn extraordinary attention from all sectors of society, with some comparing its future impact to that of the internet itself. In health care, companies are working feverishly to implement generative AI in areas such as radiology and medical records.

When it comes to consumer chatbots, though, there is still caution, even though the technology is already widely available — and better than many alternatives. Many doctors believe AI-based medical tools should undergo an approval process similar to the FDA’s regime for drugs, but that would be years away. It’s unclear how such a regime might apply to general-purpose AIs like ChatGPT.

“There’s no question we have issues with access to care, and whether or not it is a good idea to deploy ChatGPT to cover the holes or fill the gaps in access, it’s going to happen and it’s happening already,” said Jain. “People have already discovered its utility. So, we need to understand the potential advantages and the pitfalls.”

The Emory study is not alone in ratifying the relative accuracy of the new generation of AI chatbots. A report published in Nature in early July by a group led by Google computer scientists said answers generated by Med-PaLM, an AI chatbot the company built specifically for medical use, “compare favorably with answers given by clinicians.”

AI may also have better bedside manner. Another study, published in April by researchers from the University of California-San Diego and other institutions, even noted that health care professionals rated ChatGPT answers as more empathetic than responses from human doctors.

Indeed, a number of companies are exploring how chatbots could be used for mental health therapy, and some investors in the companies are betting that healthy people might also enjoy chatting and even bonding with an AI “friend.” The company behind Replika, one of the most advanced of that genre, markets its chatbot as, “The AI companion who cares. Always here to listen and talk. Always on your side.”

“We need physicians to start realizing that these new tools are here to stay and they’re offering new capabilities both to physicians and patients,” said James Benoit, an AI consultant. While a postdoctoral fellow in nursing at the University of Alberta in Canada, he published a study in February reporting that ChatGPT significantly outperformed online symptom checkers in evaluating a set of medical scenarios. “They are accurate enough at this point to start meriting some consideration,” he said.

A ’Band-Aid’ Solution

Still, even the researchers who have demonstrated ChatGPT’s relative reliability are cautious about recommending that patients put their full trust in the current state of AI. For many medical professionals, AI chatbots are an invitation to trouble: They cite a host of issues relating to privacy, safety, bias, liability, transparency, and the current absence of regulatory oversight.

The proposition that AI should be embraced because it represents a marginal improvement over Dr. Google is unconvincing, these critics say.

“That’s a little bit of a disappointing bar to set, isn’t it?” said Mason Marks, a professor and MD who specializes in health law at Florida State University. He recently wrote an opinion piece on AI chatbots and privacy in the Journal of the American Medical Association.

“I don’t know how helpful it is to say, ‘Well, let’s just throw this conversational AI on as a band-aid to make up for these deeper systemic issues,’” he said to KFF Health News.

The biggest danger, in his view, is the likelihood that market incentives will result in AI interfaces designed to steer patients to particular drugs or medical services. “Companies might want to push a particular product over another,” said Marks. “The potential for exploitation of people and the commercialization of data is unprecedented.”

OpenAI, the company that developed ChatGPT, also urged caution.

“OpenAI’s models are not fine-tuned to provide medical information,” a company spokesperson said. “You should never use our models to provide diagnostic or treatment services for serious medical conditions.”

John Ayers, a computational epidemiologist who was the lead author of the UCSD study, said that as with other medical interventions, the focus should be on patient outcomes.

“If regulators came out and said that if you want to provide patient services using a chatbot, you have to demonstrate that chatbots improve patient outcomes, then randomized controlled trials would be registered tomorrow for a host of outcomes,” Ayers said.

He would like to see a more urgent stance from regulators.

“One hundred million people have ChatGPT on their phone,” said Ayers, “and are asking questions right now. People are going to use chatbots with or without us.”

At present, though, there are few signs that rigorous testing of AIs for safety and effectiveness is imminent. In May, Robert Califf, the commissioner of the FDA, described “the regulation of large language models as critical to our future,” but aside from recommending that regulators be “nimble” in their approach, he offered few details.

In the meantime, the race is on. In July, The Wall Street Journal reported that the Mayo Clinic was partnering with Google to integrate the Med-PaLM 2 chatbot into its system. In June, WebMD announced it was partnering with a Pasadena, California-based startup, HIA Technologies Inc., to provide interactive “digital health assistants.” And the ongoing integration of AI into both Microsoft’s Bing and Google Search suggests that Dr. Google is already well on its way to being replaced by Dr. Chatbot.

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

The National Opioid Settlement Is Causing Drug Shortages

By Pat Irving, Guest Columnist

I am a retired nurse with over 40 years of healthcare experience. The principal focus of my career was on healthcare regulations, risk management and patient safety.  My most recent position was as National Leader for Risk and Patient Safety for Kaiser Permanente. 

As a pain patient myself and the victim of a mandatory opioid taper, I was motivated to understand the reasons behind the many difficulties patients have getting opioids, anti-anxiety medications and other controlled substances. 

The goal of my research over the last several months is to help patients and their families understand the drastic changes in pain management that have occurred in recent years. While much of it is due to the CDC opioid guideline and the law enforcement crackdown on prescribers, the fallout from opioid litigation now plays a major role in our inability to get prescriptions filled.

As early as 2017, acting on the incorrect premise that prescription opioids were the primary cause for the opioid crisis, the National Association of Attorneys General began a legal assault on entities they believed were responsible for the “opioid crisis.”  This included opioid manufacturers, big chain pharmacies, and the three biggest wholesale distributors -- AmerisourceBergen, Cardinal Health, and McKesson.

On July 21, 2021, the Attorneys General announced that they had reached a $26 billion settlement with the three distributors and Johnson & Johnson, who agreed to make major changes in how they do business.  The intent was to improve the safety and oversight of prescription opioids, but the unintended consequences of the settlement have caused incalculable harm to patients with chronic pain and mental health disorders.

In addition to the monetary settlement, the three distributors agreed to substantially increase measures to identity suspicious orders from pharmacies for ten years.  The distributors, collectively known as “Injunctive Relief Distributors,” also established an independent clearinghouse to keep track of every shipment of opioids and other controlled substances to pharmacies.

Red Flags and Suspicious Orders

For reference, the 571-page settlement can be found at this link.  The most important section (Exhibit “P”) begins on page 478.  Among other things, it requires the distributors to collect from each pharmacy a list of their top prescribers for opioids and other “Highly Diverted Controlled Substances,” the number of prescriptions and doses they wrote, their DEA registration number, address and medical specialty.

You may notice several other things.  Many of the restrictions came directly out of DEA regulations.  For example, there is language about “Red Flags” and “Suspicious Orders,” the latter being “orders of unusual size, orders deviating substantially from a normal pattern, and orders of unusual frequency.”

Other potential red flags include patients paying for a prescription in cash and “out-of-area” patients with prescribing doctors from a zip code that’s 50 miles or more from the pharmacy. 

If a pharmacy customer has an excessive number of suspicious orders or “unresolved Red Flag activity,” it risks being “terminated” from receiving further controlled substances – which would effectively put the pharmacy out of business: 

“In the event that an Injunctive Relief Distributor identifies one or more unresolved Red Flags or other information indicative of potential diversion of Controlled Substances through the onboarding process or otherwise, the Injunctive Relief Distributor shall refrain from selling Controlled Substances to the potential Customer pending additional due diligence.”

It is easy to see why the settlement has made pharmacists more hesitant, even fearful, about filling orders that might be suspicious. 

Under federal law, pharmacists already had a “corresponding authority” to decide whether a prescription is suspicious and if it should be filled. Whereas before a pharmacist might call a prescriber to double check on a prescription and the reasons for it, under the settlement a pharmacist may err on the side of caution and not fill the prescription at all.

To make the situation worse, the definitions of “suspicious orders” are purposely vague, and may be interpreted in the strictest way possible.  For example, since the CDC guideline recommends that physicians “should carefully evaluate” increasing doses above 50 morphine milligram equivalents (MME), the distributor or pharmacy may see that as hard limit, not a suggestion.  

And because the CDC guideline urges caution when prescribing opioids and benzodiazepines together, that may be another hard stop on a prescription, regardless of how long or how safely a patient was managed on these medications. There may be serious consequences for the prescribing physician as well, who could be reported to state authorities and the DEA if they have too many suspicious prescriptions.

Medication Thresholds 

The injunction also brought with it medication “thresholds.”  Unlike the annual DEA production quotas which are imposed on drug makers nationwide, the settlement thresholds are very specific to each pharmacy or pharmacy chain. It limits the total volume of a controlled substance that a pharmacy may receive in any given month, quarter and year.  These threshold limits, are developed by the distributor using a statistical algorithm of their own design. 

Once a pharmacy has exceeded its particular threshold, it is unable to obtain additional medication in that drug category. Physicians and patients have no way of knowing if they are the unlucky ones to have exceeded a pharmacy’s threshold.  For many patients, this means being cutoff cold turkey, waiting another month, or having a prescription only partially filled – essentially a forced taper.

Many health plans talk about their concern for patient safety, but there is often a lack of information given to patients about the known risks of tapering, especially for “legacy” patients who have been on prescribed opioids for an extended period, and who were stable and doing well. There is often no discussion with the tapered patient on the possibility of withdrawal, suicidal thoughts, anxiety, depression, and unmanaged pain. 

The patient population most affected by the distributors’ settlement are either disabled, seniors or both.  This is the very population that has difficulty accessing alternative pain therapies such as acupuncture or injections, and in many cases are alone and homebound. It has been almost impossible to get attention for this segment of the population that needs the most support. 

There has been no strong response to the settlement and resulting drug shortages from the Health and Human Services Administration, DEA, CDC, or FDA.  There has also been a lack of a coordinated response from Medicare/CMS to patients being forcibly tapered. 

It is likewise unclear what position state medical and pharmacy boards are taking on the ruptured drug supply chain. Many patients with legitimate prescriptions now have to wait weeks for their medications to become available or are forced to travel to other pharmacies to get their prescriptions filled. Worst of all, the suffering imposed on these patients has done nothing to reduce the number of drug overdose deaths.

Our government must wake up to the fact that the injunction portion of the settlement must be modified.  There are sections of the settlement that allow for “potential adjustments” and “modifications” in the event of a national or state emergency “to meet the critical needs of the supply chain.” Such an emergency now exists.

Future efforts by stakeholders must focus attention on these sections and the need for changes. It is possible to have a safe and well monitored drug supply chain that also allows legitimate patients to have the medical treatment they deserve. As it stands now, patients are needlessly suffering due to the unreasonable restrictions imposed by the national opioid settlement.

Pat Irving, RN, lives with Complex Regional Pain Syndrome (now in remission) and piriformis syndrome, a type of sciatica. Pat wishes to thank Monty Goddard, a patient advocate, for his contributions to her research.