It’s Time for People in Pain To Be Heard

By Carol Levy, PNN Columnist

I just had my second “there's an issue with filling your codeine prescription” incident.

I have been on codeine, on and off, for over 30 years. Initially, I was allowed refills. When that was no longer permitted, my doctor gave me a new prescription, each and every month, for 120 pills.

When my trigeminal neuralgia pain became somewhat better as a result of various surgeries, I often took only 1 or 2 pills per day.

I am now about 90% housebound. Part of it is due to Covid, but mostly it’s because I do not want to go out and make the baseline pain worse. As a result, some days I take no codeine at all. My last prescription was for 120 pills. It was a month’s supply that lasted for 9 months.

The first incident was last year, when my pain management doctor decided, without discussing it with me, that he was no longer writing scripts for 120 codeine pills a month. Instead, he changed it to 10 pills a month.

I was told he didn’t like me having extra pills, a nonsensical excuse as I had no history of giving them away or taking too many. Prescriptions for 120 pills just made it easier for everyone, including the insurance company, since they would be paying less for fewer doctor appointments.

Fortunately, I was able to go to my family doctor, who had no problem writing for 120 pills. They trusted me there, knowing I would not abuse them.

But when I took the script to the pharmacy, I was told, “We can only fill a 7-day supply per your insurance company.”

The worst part about that was not that I would have to repeatedly go back to the pharmacy, but that the cost for each 7-day supply was much more for me out-of-pocket than if they just filled the whole prescription at once.

My Physician Assistant called the insurance company to ask for a pre-authorization. This would allow the pharmacy to fill the entire amount at one time. They immediately allowed it for the next 12 months, which seemed odd.

If they think I should only be getting a 7-day supply, then why allow the whole script to be filled for an entire year? Either I am untrustworthy or I'm not.

I am lucky. I don’t rely on daily opioids to get me out of bed, go to the store or be able to work. So many of us have no other option but to take them. My annoyance is tame compared to what other patients go through, who have been unable to get what they need due to restrictions on prescribing.

Physicians for Responsible Opioid Prescribing (PROP) recently sent a letter to the AMA saying the organization shouldn’t be calling for changes in the CDC opioid guideline, even though far more people are dying from street drugs than prescription opioids.

“Medically prescribed opioids remain a common gateway to illicit opioid use and are themselves frequent causes of opioid addiction and overdose, even if illicit opioids currently cause the greater number of deaths,” PROP said.

PROP founder Dr. Andrew Kolodny even said that prescriptions “still have a very long way to go” and should be reduced even further.

PROP’s reach is loud and strong. We complain so much to each other, patient support groups, Twitter and other social media about how awful this is, how unfair and inhumane.

A number of people have started online petitions to send to the FDA or CDC, asking that the guidelines be changed so they stop hurting chronic pain patients. Many say, “This is a great idea.” Yet few actually sign.

Nothing will change if we don’t band together and make our voices heard. The call keeps going out, “Something must be done!” But too often the answer is, “Oh yes, somebody must do something. But I'm too busy.”

Whispering in the wind won’t help. It is long past time for us to become a true force, with a voice that is louder and stronger than PROP’s. 

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

New European Guideline Says Opioids ‘Do Not Work’ for Many Types of Chronic Pain

By Pat Anson, PNN Editor

Calling opioid medication a “two edged sword,” the European Pain Federation (EFIC) has released new guidelines that strongly recommend against using opioids to treat fibromyalgia, low back pain, migraine, irritable bowel syndrome and other types of chronic non-cancer pain.

“The new recommendations advise that opioids should not be prescribed for people with chronic primary pain as they do not work for these patients,” the EFIC said in a statement.

However, the guideline states that low doses of opioids may be suitable for treating “secondary pain syndromes” caused by surgery, trauma, disease or nerve damage, but only after exercise, meditation and other non-pharmacological therapies are tried first.

“Opioids should neither be embraced as a cure‐all nor shunned as universally dangerous and inappropriate for chronic noncancer pain. They should only be used for some selected chronic noncancer pain syndromes if established non‐pharmacological and pharmacological treatment options have failed,” the guideline states. “In this context alone, opioid therapy can be a useful tool in achieving and maintaining an optimal level of pain control in some patients.”

Opioid pain relievers are not as widely used in Europe as they are in the United States or Canada. The EFIC said it was trying to “allay concerns over an opioid crisis” developing in Europe, as it has in North America.       

“As the leading pain science organisation in Europe, it is crucial that EFIC sets the agenda on issues such as opioids, where there are growing societal concerns. These recommendations clarify what role opioids should play in chronic pain management,” EFIC President Brona Fullen said in a statement.

The guideline’s lead author, Professor Winfried Häuser, said he and his colleagues tried to strike a middle ground on the use of opioids.

“The debate on opioid-prescribing for chronic non-cancer pain has become polarized: opioids are either seen as a dangerous risk for all patients, leading to addiction and deaths, or they are promoted as most potent pain killers for any type of pain,” said Häuser, who is an internal medicine specialist in Germany.

“Opioids are still important in the management of chronic non-cancer pain – but only in some selected chronic pain syndromes and only if established non-pharmacological and non-opioids analgesics have failed or are not tolerated.”

PROP Consulted for European Guideline

The guideline was developed by a 17-member task force composed of European experts in pain management, including 9 delegates selected by EFIC’s board “who advocate and who are critical with the use of opioids.” Only one delegate from Pain Alliance Europe represented patients.

The recommendations developed by the task force were reviewed by five outside experts, including Drs. Jane Ballantyne and Mark Sullivan, who belong to Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group in the U.S.  Ballantyne is PROP’s President, while Sullivan is a PROP board member. Several changes suggested by the outside experts were adopted.

Coincidentally, Ballantyne, Sullivan and three other PROP board members were involved in the drafting of the opioid guideline released in 2016 by the U.S. Centers for Disease Control and Prevention. That controversial guideline is now being rewritten by the CDC after voluminous complaints from patients and doctors that the recommendations led to forced tapering, withdrawal, uncontrolled pain and suicides.

Sullivan and two other PROP board members were also involved in drafting Canada’s 2017 opioid guideline, which was modeled after the CDC’s and provoked similar complaints from Canadian pain patients.

90 MME Recommended Limit

The CDC and Canadian opioid guidelines appear to have been used as resources by the EFIC task force, which adopted many of the same recommendations, even while acknowledging the low quality of evidence used to support them.   

One recommendation is straight out of the CDC guideline, advising European doctors to “start low and go slow.” Prescribers are urged to start patients on low doses of 50 morphine milligram equivalents (MME) or less a day and to avoid increasing the dosage above 90 MME/day.

One significant difference with the North American guidelines is that the EFIC recommends that opioids not be prescribed for fibromyalgia, migraines and other chronic “primary pain” conditions for which there is no known cause – suggesting those disorders have an emotional or psychological element that will lead to opioid abuse.

“Prescription of high doses of opioids to patients with primary pain syndromes might have been a factor driving the opioid crisis in North America,” the EFIC guideline warns.

“This was further compounded by patient characteristics that included physical and psychological trauma, social disadvantage and hopelessness that served as a trigger for reports of pain intensity prompting prescriptions of more opioids.”

Secondary pain conditions for which opioids “can be considered“ include multiple sclerosis, stroke, restless leg syndrome, Parkinson’s disease, rheumatoid arthritis, phantom limb pain, non-diabetic neuropathy, spinal cord injuries and Complex Regional Pain Syndrome (CRPS). 

Unlike the North American guidelines, the EFIC acknowledges that there are physical and genetic differences between patients. Some patients who are rapid metabolizers “might require higher dosages of opioids than the ones recommended by the guidelines.“

EFIC GRAPHIC

The EFIC also warns that its guideline should not be used to justify abruptly tapering or discontinuing opioids for anyone already prescribed at higher dosages. The recommendations are also not intended for the management of short-term acute pain, sickle cell disease or end-of-life care.

Individualized Pain Care After Surgery Raises Patient Satisfaction

By Pat Anson, PNN Editor

An opioid prescribing guideline tailored to a patient’s specific needs – that doesn’t take a one-size-fits-all approach – resulted in high patient satisfaction rates and reduced the use of opioids after surgery.

The post-operative pain management guideline was developed by surgeons at Dartmouth-Hitchcock Medical Center in New Hampshire, who based the number of opioid pills sent home with patients on how many they needed the day before they were discharged from the hospital. Other guidelines typically base the number of pills on the type of operation that was performed and do not take into account a patient’s individual needs.

“In this new prospective study we found that 93 percent of patients had their post-surgery opioid needs satisfied,” said lead author Richard Barth Jr., MD, section chief of general surgery. “This finding means that this guideline can be used for a wide variety of operations to guide surgeons on how many opioids to prescribe when sending patients home after surgery.”

Barth and his colleagues enrolled 229 patients in the study who had elective general surgery, including colorectal, gynecological, thoracic and urological operations. Upon discharge, patients received prescriptions for acetaminophen and ibuprofen, as well as opioids, based on the guideline.

If they needed no opioids the day before discharge, they were sent home with the morphine milligram equivalent (MME) of five oxycodone 5mg pills. If they took one or three pills, they were given a prescription for 15 more. And if they needed four or more pills, they were given a prescription for 30 pills.  

Patient satisfaction was highest among those who needed the fewest number of pills. Despite being given an opioid prescription, 73 percent of the patients who were prescribed five pills used no opioids at home, and 85 percent used two pills or less.

In all, 60 percent of patients in the study had leftover opioid pills, according to findings published in the Journal of the American College of Surgeons. They were given instruction on how to dispose of them safely.

Barth says surgeons played a pivotal role in minimizing opioid use by talking to patients before surgery and setting their expectations for pain management. They told patients they were likely to be discharged with either no opioids or a small amount based on their opioid use in the hospital.

“The other part of that discussion involves letting patients know that they should expect some pain, that our goal isn’t to get rid of every last bit of their pain,” Barth said. “That was something that surgeons tried to accomplish years ago, but that’s not what we’re aiming for now. A low level of discomfort is acceptable, and patients need to have that expectation.”

That process also including prescribing, not just recommending, over-the-counter pain relievers.  

“By prescribing non-opioid analgesics, the surgeon sets the expectation that they should be used,” he said. “It’s a big difference if a surgeon prescribes non-opioid analgesics compared with just recommending that a patient take acetaminophen or ibuprofen that they might have at home.” 

In recent years, many U.S. hospitals have adopted policies that reduce or completely eliminate the use of opioids after surgery. Those policies unfairly leave some patients in pain, according to a recent study presented at the annual meeting of the American College of Surgeons. Researchers found that about half of patients need opioid medication after major surgeries.

“Our goal is to give them the exact right amount so that we limit the number of un-used opioids in our community while also making sure we don’t reduce it down too far and then leave them in pain,” said lead author Cornelius Thiels, DO, a surgical oncology fellow at Memorial Sloan Kettering Cancer Center.

“The right answer may be more non-opioid based pain medications, better patient education and setting of expectations, or in some cases patients may actually require slightly more opioid medications, and that is OK.”

Medical Cannabis Linked to Rebound Headaches

By Pat Anson, PNN Editor

Medication overuse headache, also known as “rebound” headache, is a common problem for people who frequently use pain medication to relieve headaches and migraine.

According to the American Migraine Foundation, rebound headaches can be triggered by a wide assortment of analgesics, from aspirin and triptans to acetaminophen and opioids. Even caffeine can cause a rebound headache if you consume more than 200mg a day – about two cups of coffee.     

So perhaps it’s not surprising that medical cannabis is also associated with medication overuse headache, according to a preliminary study by researchers at Stanford University School of Medicine.

“Many people with chronic migraine are already self-medicating with cannabis, and there is some evidence that cannabis can help treat other types of chronic pain,” said study author Niushen Zhang, MD, a neurologist who is director of Stanford’s Headache Fellowship Program.

“However, we found that people who were using cannabis had significantly increased odds of also having medication overuse headache, or rebound headache, compared to people who were not using cannabis.”

Zhang and her colleagues looked at the medical records of 368 people who had chronic migraine -- which is 15 or more headache days per month. Less than half were using medical cannabis

Researchers found the cannabis users were six times more likely to have rebound headaches than those who did not use cannabis. People who used cannabis were also more likely to take opioids.  Previous research has found that opioids and cannabis can both influence the part of the brain called the periaqueductal gray, which has been linked to migraine.

Zhang’s study will be presented at the American Academy of Neurology’s annual meeting next month.

Medical cannabis has become a trendy alternative to pharmaceuticals for treating migraine, with research showing that both inhaled and ingested cannabis can reduce migraine pain. 

A recent study of nearly 10,000 people in the U.S. and Canada who used a migraine tracking app found that 82 percent who used cannabis believed it was an effective pain reliever.    

A 2017 study conducted in Israel found that combining THC and CBD in an oral dose was just as effective in treating migraine pain as amitriptyline – a tricyclic antidepressant commonly prescribed for migraine.

And a 2016 study at the University of Colorado found that cannabis significantly reduced the number of migraine headaches. Inhalation appeared to provide the fastest results, while edible cannabis took longer to provide pain relief.

About a billion people worldwide suffer from migraine headaches, which affect three times as many women as men. Over 37 million people in the United States live with migraines, according to the American Migraine Foundation.

Don't Get Picky: All Three Covid Vaccines Highly Effective

By Arthur Allen and Liz Szabo, Kaiser Health News

When getting vaccinated against Covid-19, there’s no sense being picky. You should take the first authorized vaccine that’s offered, experts say.

The newest Covid vaccine on the horizon, from Johnson & Johnson, is probably a little less effective at preventing sickness than the two shots already being administered around the U.S., from Pfizer-BioNTech and Moderna.

The Food and Drug Administration authorized the Johnson & Johnson vaccine after reporting it showed about 66% effectiveness at preventing Covid illness in a 45,000-person trial. No one who received the vaccine was hospitalized with or died of the disease, according to the data released by the company and FDA. As many as 4 million doses could be shipped out of J&J’s warehouses beginning this week.

The J&J vaccine is similar to the shots from Moderna and Pfizer-BioNTech, but uses a different strategy for transporting genetic code into human cells to stimulate immunity to the disease. The Moderna and Pfizer-BioNTech vaccines were found in trials last fall to be 94% effective in preventing illness caused by Covid. They also prevented nearly all severe cases.

But the difference in those efficacy numbers may be deceptive. The vaccines were tested in different locations and at different phases of the pandemic. And J&J gave subjects in its trial only one dose of the vaccine, while Moderna and Pfizer have two-dose schedules, separated by 28 and 21 days, respectively. The bottom line, however, is that all three do a good job at preventing serious Covid.

“It’s a bit like, do you want a Lamborghini or a Chevy to get to work?” said Dr. Gregory Poland, director of the Mayo Clinic’s Vaccine Research Group, who was a paid consultant in the J&J study. “Ultimately, I just need to get to work. If a Chevy is available, sign me up.”

“From a personal and public health perspective, the best advice for now is to get whatever you can as soon as you can get it, because the sooner we all get vaccinated the better off we all are,” said Dr. Norman Hearst, a family doctor and epidemiologist at the University of California-San Francisco.

Of the 10 people who got severe disease in the Pfizer trial, nine had received a placebo, or fake vaccine; none of the 30 severe cases in the Moderna trial occurred in people who got the true vaccine. A month after receiving the Johnson & Johnson shot there were no deaths or hospitalizations in those who had been vaccinated.

“The real goal is to keep people out of the hospital and the ICU and the morgue,” said Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia. “This vaccine will do that well.”

J&J Vaccine Tested Against Variants

The data that Moderna and Pfizer-BioNTech presented to the FDA for their vaccines came from large clinical trials that took place over the summer and early fall in the United States. At the time, none of the new variants of Covid — some of which may be better at evading the immune responses produced by vaccines — were circulating here.

In contrast, the J&J trial began in September and was put into the arms of people in South America, South Africa and the United States. The J&J vaccine was 72% effective against moderate to severe Covid in the U.S. part of the trial, compared with 57% in South Africa, where a more contagious mutant virus is the dominant strain.

The Moderna and Pfizer-BioNTech vaccines might not have gotten the same sparkling results had they been tested more recently — or in South Africa.

“This vaccine was tested in the pandemic here and now,” said Dr. Dan Barouch, a Harvard Medical School professor whose lab at the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston developed the J&J vaccine. “The pandemic is a much more complex pandemic than it was several months ago.”

The J&J vaccine appears to have some other advantages. First, it seems to cause fewer serious side effects like the fever and malaise suffered by some Pfizer-BioNTech and Moderna vaccine recipients. High fever and dehydration are particular concerns in fragile elderly people who “have one foot on the banana peel,” said Dr. Kathryn Edwards, scientific director of the Vanderbilt Vaccine Research Program. The J&J vaccine “may be a better vaccine for the infirm.”

Many people may prefer the J&J shot because “it’s one and done.” It’s easier for administrators too: just one appointment to schedule.

The J&J vaccine can also be stored in regular refrigerators, while the Pfizer and Moderna vaccines have to be stored in freezers and must be used or discarded within six hours after the vial is opened. Vials of the J&J vaccine can be restored in a refrigerator for later use if doses remain.

“Right now we have mass immunization clinics that are open but have no vaccine,” said Offit. “Here you have a single-dose regime with easy storage and handling.”

Ultimately, a person’s address — not their personal preference — may determine which vaccine they receive, said E. John Wherry, director of the Institute for Immunology at the University of Pennsylvania’s Perelman School of Medicine. He pointed out that the Johnson & Johnson vaccine is a simpler choice for rural areas.

“A vaccine doesn’t have to be 95% effective to be an incredible leap forward,” said Wherry. “When we get to the point where we have choices about which vaccine to give, it will be a luxury to have to struggle with that question.”

Kaiser Health News is a nonprofit news service covering health issues. It is not affiliated with Kaiser Permanente.

What COVID-19 Teaches Us About Rare Diseases

By Roger Chriss, PNN Columnist

Sunday, February 28th is Rare Disease Day -- a day created to recognize and increase awareness of rare diseases that affect millions of people worldwide. This year that includes the effects of Covid-19 on the rare disease community.

The National Organization of Rare Disorders reports that there are over 7,000 rare diseases. A disease is considered rare in the U.S. if it affects fewer than 200,000 people; while in Europe a disease is classified as rare if it affects fewer than 1 in 2,000 people. Although each disease is rare, there are so many conditions that roughly 1 in 17 people are affected by a rare disease.

Rare Disease Day 2021 is occurring amid a pandemic. Covid-19 has increased awareness of medical problems like anosmia, a loss of sense of smell. In it congenital form, anosmia affects only 1 in 10,000 people, but now it is seen in millions infected with the coronavirus. For most, the loss of smell is temporary, but for some Covid patients it persists long after the initial infection.

“One might think that it is not important to be able to smell nature, trees, forests,” Evan Cesa told AP News. “But when you lose the sense of smell, you realize how truly lucky we are to be able to smell these things.”

Long Haul Covid

In a recent study, University of Washington researchers monitored 300 recovering Covid patients in the Seattle area and found that 30% reported worse health and quality of life in the wake of the illness. Some were unable to perform simple chores, lift heavy objects or walk for more than a short distance.

Chronic Covid syndrome (CSS), also known as long-haul Covid, seems to occur in about 10% of infected people. In addition to loss of smell, long haulers often have disabling fatigue, headache, shortness of breath, weakness and brain fog – symptoms that are strikingly similar to chronic fatigue syndrome (CFS/ME).

Research on how to manage long-haul Covid is looking at treatments already used for rare disorders. A clinical trial of low-dose naltrexone (LDN) is underway. LDN is sometimes used to treat refractory chronic pain conditions, and is being explored for lupus and obsessive-compulsive disorder.

The pandemic has created new challenges for the rare disease community. Accessing medical care amid a pandemic has been tricky, in particular for people whose immune function is compromised. And the handful of deaths associated with Covid vaccines has raised questions for people with severe thrombocytopenia (ITP), a rare platelet disorder.

Covid-19 is revealing what living with a rare disease is like. Some people with long-haul Covid are reluctant to disclose their condition, much as people with rare disorders often struggle with when and how to share information about their diagnoses.  

People with long haul Covid are struggling to gain recognition for their disability. As NPR reports, long haulers have asked the federal government for disability coverage, rights and protections -- but it's unclear if they qualify under the Americans with Disability Act.

While Covid-19 has increased awareness of rare diseases, it’s also slowing rare disease research and complicating care. This year, many Rare Disease Day events are being held online due to the pandemic.

Hopefully, Rare Disease Day in 2022 will take place in a post-Covid world.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

Who Develops Intractable Pain Syndrome?

By Forest Tennant, PNN Columnist

It is clear that a small percentage of chronic pain patients can develop Intractable Pain Syndrome (IPS), which is constant, incurable pain that has cardiovascular and endocrine complications. But which unfortunate chronic pain patients will succumb to this fate?

To this end, we have been surveying persons with IPS to understand who they are and how they developed the syndrome. Without knowledge as to “who” and “how” IPS occurs, it will be impossible to either prevent the condition, identify it in early stages or stop its progression.

In a survey of persons with IPS, we found that many were older and primarily female. Out of 28 patients surveyed, 20 were female and 8 were male, and their ages ranged from 34 to 77 years. The average age was 56 years.

In addition, these individuals had been ill and experienced chronic pain for many years. Only two of the 28 patients surveyed reported pain of less than five years duration. The majority could actually recall the day, month and year that their chronic pain shifted to IPS. 

Almost all reported three major manifestations:

• 100% Physical function declined

• 86% Needed medication to sleep

• 82% Mental functions declined

Key laboratory tests were frequently abnormal:

• 71% Hormone abnormality

• 53% High inflammatory markers 

• 32% High glucose levels 

The 28 patients surveyed were asked what medical conditions caused their IPS. Surprisingly, the majority said they had multiple diagnoses, which are listed below by condition:

• 20 Adhesive Arachnoiditis

• 9 Ehlers-Danlos Syndrome

• 7 Cervical Neck Neuropathy

• 5 Osteoarthritis

• 2 Reflex Sympathetic Dystrophy (CRPS)

• 2 Interstitial Cystitis

• 2 Traumatic Brain Injury

• 1 Rheumatoid Arthritis

• 1 Stroke

These findings show that IPS can develop from a relatively small number of painful conditions, with Adhesive Arachnoiditis and Ehlers-Danlos Syndrome the most common ones reported. Persons with IPS almost all report severe insomnia and declines in their physical and mental abilities. And laboratory tests validate the abnormal physiological impact of their non-stop constant pain.

In a separate clinical analysis of 40 persons with IPS, we found that over 60% had symptomatic characteristics in common, from constant pain and difficulty sleeping to sugar cravings and cold hands and feet. For a list of over two dozen IPS symptoms, click here.

Our mission forward as the IPS Research and Education Project is to bring recognition and treatment of IPS to every community across the globe. This presents a great challenge for us; to instruct and inform all concerned parties in acknowledging that IPS is a serious syndrome, and that it is exceedingly different from what is commonly known as chronic pain.

Forest Tennant is retired from clinical practice but continues his research on intractable pain and arachnoiditis. This column is adapted from newsletters recently issued by the IPS Research and Education Project of the Tennant Foundation. Readers interested in subscribing to the newsletter can sign up by clicking here.

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

Abuse of Rx Opioid Painkillers Unchanged During Pandemic

By Pat Anson, PNN Editor

An alarming spike in U.S. overdose deaths during the COVID-19 pandemic does not appear to be fueled by increased abuse of opioid painkillers, according to a new nationwide analysis of urine drug tests.

The Drug Enforcement Administration approved an exemption last year allowing patients to connect with doctors via telehealth – without a physical examination -- to get prescriptions for opioids and other controlled substances. While the relaxed rules made it easier for patients to get pain medication during the pandemic, they have not resulted in more diversion or abuse of oxycodone and hydrocodone, according to the Millennium Health Signals Report. Urine positivity rates for the two opioids remained flat during 2020.

“Despite the hardships faced during the pandemic, it is encouraging to see that positivity rates for non-prescribed use of hydrocodone and oxycodone have not changed,” said Michael Parr, MD, an addiction treatment specialist and consultant to Millennium.

“Patients requiring opioids for the treatment of pain have faced difficulty obtaining medications, as well as stigma, before the pandemic. Perhaps this data will reassure clinicians who have taken additional steps to safely prescribe these medications during the pandemic.”

There was an uptick in positivity rates for non-prescribed tramadol, a weaker opioid, particularly in Ohio, Tennessee and Kentucky. Millennium said there were more cases of people with substance use disorders using tramadol as their “drug of preference.”

Millennium researchers also found that positivity rates for non-prescribed gabapentin (Neurontin) showed little change in 2020 – but they remain at levels nearly three times higher than positivity rates for oxycodone, hydrocodone and tramadol. The abuse of non-prescribed gabapentin did rise significantly in Ohio and Virginia.

POSITIVITY RATES FOR NON-PRESCRIBED PAIN MEDICATIONS

SOURCE: MILLENNIUM HEALTH

The abuse of gabapentin has been going on for years, but with little public attention. Gabapentin is a non-opioid nerve medication increasingly prescribed for pain, despite the fact many patients say it doesn’t help and has too many side effects. Drug abusers, however, have found that gabapentin can heighten the effect of heroin and other street drugs.

While positivity rates for non-prescribed pain medication were mostly unchanged during the pandemic, they soared for illicit fentanyl and methamphetamine, increasing 78% and 29%, respectively.

After initially increasing in the early stages of the COVID-19 crisis, Millennium found that positivity rates for cocaine and heroin soon returned to pre-pandemic levels.

Another encouraging sign is that positivity rates for carfentanil, a deadly fentanyl analogue, have flatlined to nearly zero. It is unclear why carfentanil abuse has fallen so sharply, but Millennium said it may be because the pandemic has disrupted manufacturing and supply routes from China.     

Home-Based Virtual Reality Reduces Chronic Low Back Pain

By Pat Anson, PNN Editor

A new clinical study has found that home-based virtual reality (VR) therapy can significantly reduce pain levels in people suffering from chronic lower back pain. Patients who watched VR programs also reported better mood, reduced stress and that pain interfered less with their sleep.

The study, published in the Journal of Medical Internet Research, is the first controlled trial to compare home-based VR therapy to a “sham” or placebo treatment for chronic pain. The research was funded by AppliedVR, a Los Angeles-based company that is developing therapeutic VR content to help treat pain and other conditions.

Eighty-nine people used the company’s EaseVRx headset daily for eight weeks, immersing themselves in relaxing and meditative VR programs designed to make their pain seem less important, similar to cognitive behavioral therapy. A control group received the sham treatment, watching routine nature scenes with the headset. All participants had chronic low back pain for at least six months.   

By the end of the study, 87 percent of people in the VR group reported less pain intensity, with nearly two-thirds experiencing at least a 30% reduction in pain compared to the control group. There were also significant improvements in sleep, mood and stress in the VR group.

Importantly, the improvements in pain and other symptoms were cumulative over time – meaning the relief was long-lasting and not just when people were watching VR programs.

“If you look at the results graph, you’re able to see the trajectory of pain and pain intensity very reliably declining over the course of the eight weeks. It’s a really strong time trend. It’s not just a random effect,” explained Beth Darnall, PhD, AppliedVR’s chief science advisor.

You can see the graph below. Over the course of 56 days, average pain intensity fell by 43% in patients using the EaseVRx headset, compared to 23% in the control or sham group.

JOURNAL OF MEDICAL INTERNET RESEARCH

Most of the research to date on VR therapy has focused on treating acute pain in hospitalized patients. AppliedVR is trying to demonstrate that virtual reality can also be used to treat chronic pain at home. A small study released last summer showed that home-based VR therapy reduced pain in people with fibromyalgia and chronic low back pain.

Darnall was hesitant to say if there were any pain conditions that VR therapy might not useful for.

“At the end of the day, pain is pain,” said Darnall, who is a pain psychologist at Stanford University. “This basic approach, in which we’re equipping people with self-regulatory skills, is going to be beneficial and broadly applicable for every pain condition.

“We have multiple studies in progress that are testing this device on different populations. It’s really going to be an exciting year, because there’s going to be an explosion of research that’s really going to inform our understanding of how this may help people across different disease conditions.”   

AppliedVR’s headset received breakthrough device designation from the Food and Drug Administration last year. The company hopes to get clearance from the FDA later this year to begin selling the devices. Due to a recent decision by Medicare to start covering breakthrough medical devices, the company is hopeful that private insurers will also start paying for VR therapy. 

Study Finds Regular Exercise Reduces Migraine Triggers

By Pat Anson, PNN Editor

Two-and-a-half hours of moderate to vigorous exercise a week can significantly reduce migraine triggers like stress, depression and poor sleep, according to a new survey that found more than two-thirds of migraine sufferers do not get enough exercise.

“Migraine is a disabling condition that affects millions of people in the United States, and yet regular exercise may be an effective way to reduce the frequency and intensity of some migraines,” says lead author Mason Dyess, DO, a Senior Fellow at the University of Washington School of Medicine.

“Exercise releases natural pain killers called endorphins, helps people sleep better and reduces stress. But if people with migraine are not exercising, they may not be reaping these benefits.”

The survey involved 4,647 people diagnosed with migraine. About three-fourths of participants had chronic migraine, meaning 15 or more migraines a month. The others had episodic migraine, or up to 14 a month.

Participants completed a questionnaire about their migraines, sleep, depression, stress, anxiety and the amount of exercise they get each week.

Researchers then divided them into five groups based on their level of exercise: those who did not exercise; people who exercised up to 30 minutes per week; those who exercised 31 to 90 minutes; people who exercised 91 to 150 minutes; and participants who exercised more than 150 minutes per week.

Types of exercise that qualified as moderate to vigorous included jogging, very brisk walking, playing a sport, heavy cleaning and bicycling.

Researchers found that only 1,270 participants – about 27 percent -- reported the highest level of exercise. Those who got less than 150 minutes of exercise had increased rates of depression, anxiety and sleep problems:

• Depression was reported by nearly half of people who got no exercise, compared to 25% of those that exercised the most.

• Anxiety was reported by 39% of people in the no exercise group, compared to 28% of people in the high exercise group.

• Sleep problems were reported by 77% of people in the no exercise group, compared to 61% in the high exercise group.

Researchers also found an association between exercise and increased frequency of migraines. Among people in the no exercise group, nearly half had 25 or more headache days per month. That compares to only 28% of people in the high exercise group.

“There are new therapeutics available for migraine, but they are very expensive. People with migraine should consider incorporating more exercise into their daily life because it may be a safe and low-cost way to manage and minimize some of the other problems that often accompany migraine,” said Dyess.

Two-and-a-half hours a week of moderate to vigorous exercise, or 150 minutes, is the minimum amount recommended by the World Health Organization.

The study findings, which will be presented at the annual meeting of the American Academy of Neurology in April, have not yet been peer-reviewed or published. One weakness of the study was that participants self-reported their exercise minutes, rather than having their activity monitored with a device. It also only shows an association between exercise and migraines, and does not prove cause and effect. 

Stem Cells Restore Function in Patients Paralyzed by Spinal Cord Injuries

By Pat Anson, PNN Editor

Intravenous injection of mesenchymal stem cells (MSCs) in patients paralyzed by spinal cord injuries led to significant improvement in their motor functions, according to a team of researchers at Yale University and Sapporo Medical University in Japan.

The study findings, published in the Journal of Clinical Neurology and Neurosurgery, focused on 13 patients who suffered spinal cord injuries (SCIs) after falls or trauma. Some lost the ability to use their arms and legs, while others suffered coordination and sensory loss, or experienced bowel and bladder dysfunction.

For more than half of the patients, substantial improvements in motor function were observed within weeks of being injected with autologous MSCs derived from their own bone marrow. Although this was a small observational Phase 2 study, researchers are excited by the findings.

"The idea that we may be able to restore function after injury to the brain and spinal cord using the patient's own stem cells has intrigued us for years," said senior author Stephen Waxman, MD, a professor of neurology, neuroscience and pharmacology at Yale. "Now we have a hint, in humans, that it may be possible."

One of the patients profiled was a 34-year-old man who was left partially paralyzed and bedridden after a fall. He received an intravenous injection of MSCs 47 days after his injury. Two weeks after the infusion, voluntary movement was restored to his lower extremities and he was walking with the support of a walker.

In another case, a 47-year-old man left bedridden after a diving accident showed rapid improvement after a stem cell infusion. He was able to drive a wheelchair the next day, walk and climb stairs after two weeks, and eat independently after eight weeks.

Other patients paralyzed after similar injuries were able to breath again without assistance, regain control of their bowel functions, and perform independent living tasks such as dressing and grooming.

“Although this initial case study was unblinded and uncontrolled, the SCI patients appeared to demonstrate a tendency of relatively rapid improvement of neurological function that was often apparent within a few days following infusion of MSCs,” researchers said.

“We would emphasize that this case series describes an early study on a small number of patients. In addition to being unblinded and uncontrolled, this study has a number of limitations. We cannot rule out observer bias nor a contribution of surgical intervention to recovery in cases where this intervention occurred, or spontaneous recovery.”

Other case studies have also shown that stem cells can restore motor and sensory function in patients paralyzed by spinal cord injuries.

The Mayo Clinic reported in 2019 that a California man paralyzed from the neck down in a surfing accident was able to walk again after being injected with his own stem cells. Researchers emphasized the man was a “super-responder” and that other paralyzed patients injected with stem cells don’t have such a dramatic recovery.

According to the National Spinal Cord Injury Statistical Center, over 17,000 Americans suffer spinal cord injuries each year. Chronic pain is a serious problem that can result from SCI, affecting about two-thirds of patients, with one out of three reporting their pain as severe.

Opioid Promotion Cited in FDA Warning Was Stopped in 2019

By Pat Anson, PNN Editor

A California pharmaceutical company that received a warning letter from the Food and Drug Administration over its promotion of a controversial opioid painkiller stopped using the marketing material over a year ago.

The FDA sent the warning letter to AcelRx Pharmaceuticals last week. The agency told the company to stop making “false and misleading claims” about Dsuvia, a potent opioid tablet used to relieve acute pain in hospital settings.

The “Tongue and Done” banner ads and tabletop displays emphasized how easy Dsuvia is to administer by using a plastic applicator that releases a single tablet directly into a patient’s mouth. The FDA said the promotions were misleading and dangerous.

“AcelRx has disseminated promotional communications that undermine key prescribing conditions required for the safe use of this opioid product. Dsuvia was approved with special restrictions requiring that it only be prescribed in a certified medically supervised setting by health care practitioners trained to properly administer it,” the FDA said in a statement.

“This promotion dangerously undercuts FDA-required conditions on the proper administration of the drug, which requires particular diligence to minimize the risk of serious or even fatal adverse events.”

The letter warns AcelRx to either stop using the marketing material or cease distributing Dsuvia. It gave the company 15 days to respond or face “further regulatory action.”    

ACELRX PROMOTION

But in a filing with the Securities and Exchange Commission, AcelRx said it could “easily address” the FDA’s concerns because it stopped using the “Tongue and Done” promotions in late 2019.

“The Company intends to respond to the FDA within the timeframe requested in the Letter and seek guidance and clarification from the FDA on the concerns raised in the Letter,” the SEC filing states. “The Company cannot give any assurances, however, that the FDA will be satisfied with its response to the Letter or that such response will resolve the issues identified in the Letter.”

Few Adverse Events Involve Dsuvia

The FDA approved the use of Dsuvia in 2018 over the objections of anti-opioid activists who said it was a “dangerously unnecessary opioid medication" that would be diverted, abused and lead to more overdoses. There is little evidence any of that has occurred.

Dsuvia contains sufentanil, an opioid 10 times stronger than fentanyl. It was developed to fulfill an unmet need in military and civilian hospitals, where patients need quick relief from acute trauma pain and can’t wait for opioids to be administered intravenously. Each Dsuvia tablet comes in a single dose applicator. The tablets quickly dissolve under the tongue and are not available for home use.

Those safety measures appear to be working. The FDA’s Adverse Events Reporting System lists only six cases involving Dsuvia in 2019 and 2020. There were no deaths and none of the cases were considered serious.

AcelRx recently published the results of a clinical study that showed surgery patients treated with Dsuvia used significantly fewer opioids than those treated with traditional IV opioids. They were also discharged sooner.

The FDA’s belated warning letter to AcelRx about its Dsuvia marketing comes as the agency faces renewed scrutiny for its regulation of opioids.

Acting FDA Commissioner Dr. Janet Woodcock is reportedly under consideration by President Biden for a formal nomination to the job, which has drawn the ire of some anti-opioid activists. A letter sent to the Acting Secretary of Health and Human Services accuses Woodcock of “dereliction of duty” for failing to address the opioid crisis by halting the approval of new opioids. Woodcock has been Director of the FDA’s Center for Drug Evaluation and Research for over 25 years.

Would Drug Legalization Reduce Overdoses?

By Roger Chriss, PNN Columnist

As the overdose crisis worsens, public health data and biostatistics become more important. Debates about opioid prescribing and drug legalization often center on two key concepts: incidence and prevalence as applied to drug use, substance use disorder (SUD) and overdoses.

Brandeis University researcher Andrew Kolodny, MD, recently argued against drug legalization on Twitter.

“Some critics of reducing Rx opioids don't believe that repeated use of highly addictive drugs cause addiction and/or they believe all drugs, including heroin & cocaine should be available over the counter. They don't believe that easy access can increase prevalence of SUD,” said Kolodny, who founded Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.

Conversely, Columbia University professor Carl Hart, the author of “Drug Use for Grown-Ups,” believes legalizing recreational drugs would help reduce overdoses by making the drug supply safer.

“A large proportion of these deaths are caused by adulterated substances purchased on the illicit market. A regulated market, with uniform quality standards, would virtually put an end to contaminated drug consumption and greatly reduce fatal accidental drug overdoses,” Hart told Columbia Magazine.

Both claims hinge on a proper understanding of incidence and prevalence. In epidemiology, incidence is the rate of new-onset diagnosis of a medical condition. It is measured over a given period of time -- typically a year -- though sometimes the time period is shortened to a week for an urgent problem, such as a viral pathogen like the coronavirus.

By contrast, prevalence measures the total number of people in a population who have a specific medical condition. For prevalence, the duration of the condition is important. For an infectious disease, it may be brief. But for cancer, SUD and many other chronic conditions, it may last a lifetime.

For instance, the incidence of opioid use disorder (OUD) among people who are on long-term opioid therapy is 8-12%, according to the National Institutes of Health. But unlike claims frequently made by PROP, only a small fraction of patients who abuse prescription opioids start using heroin, less than 4% over a five-year period. So, making a clear distinction between OUD involving prescription opioids versus heroin becomes important.

The prevalence of OUD is a cumulative total of all people with OUD over time. This is because OUD and other substance use disorder diagnoses are lifetime diagnoses that remain on a person’s medical records forever. When we count people with OUD, we are counting everyone ever diagnosed with the condition, though in practice sometimes the OUD diagnosis is dropped due to administrative error, poor record-keeping or deliberate obfuscation.

This means that OUD prevalence can go up over time even when the incidence of OUD is going down. In fact, that is what is happening at present.

A recent report from the Substance Abuse and Mental Health Services Association showed modest declines for both prescription opioid misuse and heroin use. This came at a time when U.S. drug deaths were rising, fueled primarily by overdoses involving illicit fentanyl.

These counterintuitive trends make for intense debate about the success or failure of the 2016 CDC opioid guideline and state laws restricting prescription opioid use. A recent study from Indiana University concluded that limits on legal opioid prescribing may have actually driven more people to illicit drugs.

"Our work reveals the unintended and negative consequences of policies designed to reduce the supply of opioids in the population for overdose. We believe that policy goals should be shifted from easy solutions such as dose reduction to more difficult fundamental ones, focusing on improving social conditions that create demand for opioids and other illicit drugs," said co-author Brea Perry, PhD, a professor of sociology at Indiana University.

Even if drug legalization were to reduce drug risks, an increase in the number of drug users could lead to more harms. For instance, if an illicit drug harms 10% of users and there are 1 million users, that results in 100,000 people harmed. If that drug is then legalized and made safer, harming only 1% of users, that seems like an improvement. But if the number of users rises to 15 million, then 150,000 people would be harmed.

Since we don’t know how these numbers would change under a legalized drug regime, any claims about changes in incidence or prevalence are speculative at best.

What is counted and how it is expressed are very important in debates about the role of prescription opioids or drugs in general in SUD and overdose deaths. A failure to be specific about methodology or using data that is not well-founded can result in specious or even deceptive claims. And counterintuitive results are possible, as we are seeing at present in the ever-evolving overdose crisis.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

Latina and Asian Women at Significantly Higher Risk from Lupus

By Pat Anson, PNN Editor

Asians and Latinos diagnosed with systemic lupus erythematosus (SLE) are significantly more likely to die from the disease than other racial groups, according to a new analysis by the Centers for Disease Control and Prevention. The CDC set up half dozen state registries over a decade ago to help track the illness.

SLE is the most common form of lupus, a condition in which the body's immune system attacks its own healthy tissues, especially joints and skin, causing flare-ups of pain and fatigue that keep nearly half of adult patients from working.

In an effort to better understand why the disease disproportionately affects women and people of color, CDC researchers analyzed a database of over 800 SLE patients in San Francisco from 2007 to 2017. About 90 percent of them were female. Mortality rates were highest in racial and ethnic minorities who died during the study period,

“Asian females with SLE were four times more likely to die than were Asian females without SLE in the general San Francisco County population, and Hispanic/Latina females with SLE were six times more likely to die than were persons in the corresponding general populations,” researchers reported. “Higher mortality within these populations might be the result of more severe outcomes and manifestations of SLE, as previously demonstrated, or possibly less access to care.”

The mean age at death for people with SLE was 62 years. On average, Black persons died 6.8 years earlier than White people with SLE, while people of Hispanic/Latino ethnicity died 9.5 years earlier.

A recent study published in the journal Arthritis and Rheumatology estimated that over 200,000 Americans suffer from SLE, a number that comes statistically close to officially reclassifying the illness as a rare disease. The Rare Diseases Act of 2002 classifies conditions as rare when they affect 200,000 or fewer Americans. Until now, SLE disease estimates were larger but unverified.

“Our study potentially redefines systemic lupus erythematosus as a rare disease in the United States and lays the groundwork for where we need to focus our efforts to reduce the burden of this disease on Americans,” said lead investigator and rheumatologist Peter Izmirly, MD, an associate professor in the Department of Medicine at NYU Langone Health.

Rare-disease classification could, according to Izmirly, significantly improve efforts to study and treat SLE by reducing the number of participants needed for clinical trials.

Current treatments for lupus include steroids or other anti-inflammatory and immunosuppressing medications, including newer biologic drugs made from living cells.

A Flawed Person's Drug Problem Isn't a Moral Failing

By Dr. Lynn Webster, PNN Columnist

Rush Limbaugh was as controversial as he was politically influential. In fact, Nicole Hemmer, a research scholar at Columbia University, called Limbaugh "the man who created Donald Trump" and opined that Limbaugh created the political foundation that catapulted Trump to power.

In 2020, President Trump returned the favor by awarding Limbaugh the Medal of Freedom, our highest civilian honor, for his "decades of tireless devotion to our country."

But the Independent points out that Limbaugh also left behind a legacy of "divisiveness, cruelty, racism, homophobia, bigotry, and sexism." And Rolling Stone said the radio host "trafficked in bigotry and cruelty."

RUSH LIMBAUGH

It's hard to argue with either of those statements. To me, Limbaugh was a deeply flawed human being who caused harm. But some statements about him go too far.

When Limbaugh died this week after a lengthy battle with lung cancer, Mark Frauenfelder, editor of The Magnet, tweeted: "Rush Limbaugh, the sex tourist and drug addict whose four marriages, mockery of people after their deaths, and overt racism and misogyny made him a beloved icon of American conservatism, is dead at 70." 

That statement is troubling. Overt racism and misogyny are character flaws. Drug addiction, however, is not. It's unfortunate to see Limbaugh's detractors point to his well-documented problems with painkillers as moral failings. This supports my firm belief that our culture holds deeply negative views of people with addiction.  

History of Back Pain and Drug Use 

Limbaugh began abusing prescription painkillers after his spinal surgery in the 1990s. He was eventually arrested on drug charges — specifically, charges of fraud to conceal information to obtain prescriptions, also known as "doctor shopping." In exchange for having the charges dropped, Limbaugh agreed to undergo drug treatment and pay $30,000 in court costs. He posted $3,000 bail and was released.

I wrote about Limbaugh's prescription drug problem in my book, "Avoiding Opioid Abuse While Managing Pain." What we knew about Limbaugh's problem, as I said at the time, was that he abused large quantities of prescription opioids for several years; kept his abuse secret from family, friends and colleagues; entered a rehabilitation program twice, but relapsed each time; remained successful without a visible reduction in functioning while he used drugs; and was suspected of buying drugs illegally. 

What we didn't know, and perhaps now can never ascertain, is whether Limbaugh had an addiction or an undiagnosed psychiatric disorder (although some may argue his professional conduct was evidence of a disturbed personality). We also can't know whether his main motivation for using drugs was to control physical pain, to mask emotional pain or stress, to seek a "high," or some combination of those reasons.  

The answers to these questions — about his history of drug abuse, mental health and motivation — would have told us whether his opioid use disorder (OUD) was treatable with better pain control or, tragically, was an incurable disease.  

Limbaugh exemplifies the type of patient most physicians face when treating serious pain conditions. Sometimes, opioids fail to provide adequate relief for them. And, increasingly, patients cannot access the opioids they need due to misguided polices and regulations.   

How Society Views Addiction 

Some people may agree with Limbaugh's political and social views, and others may not. But conflating his drug abuse and associated illegal activities with the opinions he expressed about social issues harms people who suffer from the disease of addiction. It also makes it more difficult for people with severe pain to receive the care they deserve, whether their abuse is caused by addiction or, as is often the case, a symptom of undertreated pain. 

Many of those with addiction may not have the power or influence to bail themselves out of prison or pay tens of thousands of dollars in court costs. They may remain in prison for years and suffer the loss of their careers, reputations, homes and even their families.  

Generally, our society views people with addiction as flawed, weak and hopeless. We distance ourselves from those who have the disease, and we allow the criminal justice system to have jurisdiction over them, making it difficult or even impossible for them to receive treatment.  

We may never know why Rush Limbaugh made the choices he did. But, just as we would never think of berating him for falling victim to lung cancer, we also shouldn't chastise him for misusing painkillers. We may have a right to judge Limbaugh's behavior, but we cannot, in decency, judge his disease. 

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book The Painful Truth, and co-producer of the documentary It Hurts Until You Die. Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences. You can find Lynn on Twitter: @LynnRWebsterMD.