Do You Get Adequate Pain Management?

By Victoria Reed, PNN Columnist

For the last few weeks, I’ve been suffering from persistent sinus and dental pain. Sinus pain is not new to me, as I have long-standing allergies which cause swelling in the nasal passages and chronic congestion that sometimes leads to an infection. The medications that I take for my rheumatoid arthritis increase the risk for all types of infections, as they suppress the immune system.  

After seeing a doctor, a sinus infection was diagnosed. Towards the end of a course of antibiotics, I had marked improvement with the sinus symptoms, but was still having considerable pain when chewing, which radiated to my right ear and jaw.  

Initially, I assumed that the pain was related to the sinus infection, but when that didn’t go away after finishing the antibiotics, I made an appointment to see my dentist. He did the usual poking and prodding around my gums and teeth, trying to find the source of the pain, and discovered two areas that could be the culprits. He did a flushing procedure of the gums to try to alleviate the pain. 

However, after the procedure was completed, I had such severe pain that all I could do was hold my head in my hands, while tears seeped out of my eyes. The pain was as bad as the pain I had felt while giving birth without an epidural! 

After more than a few minutes, my face and jaw continued to throb and the pain had not subsided. The dentist could see that I was in quite a bit of distress. He then asked me what the pain level was before I had come in. I replied that it had been a 5, but “now it’s a 10.”  

He sat down beside me and tried to explain what he believed the problem was. It was hard to concentrate, but I was able to understand what he was saying. He told me that he thought a tooth was cracked and that I needed to see an endodontist, a root canal specialist. He also prescribed another antibiotic.  

The dentist then stood up and patted me on the shoulder with compassion. Clearly, he was sorry for having amplified my pain. I appreciated his compassion, but I was ready to leave. At that point, all I wanted was to move on to whichever provider could relieve the awful pain.  

Then, to my surprise, I was offered opioid pain medication! 

This was something I absolutely did not expect. I had root canals for severe infections in the past, but no prescription opioids had been offered and I was sent home with instructions to take over-the-counter pain relievers. The days of getting opioid medication for severe dental pain were over, I assumed.  

However, after my initial shock, I politely declined the prescription. Why? Because I already receive a mild prescription opioid for my chronic pain conditions. Sure, I could have taken the prescription and not said a word about that, but I knew that I should honor the pain management contract I had signed with my doctor.  

While I believed that a stronger medication would have been helpful for my tooth pain, I did not want to risk being ejected from my pain management program. My contract (and nearly all pain management contracts) explicitly states that I am not allowed to receive any additional opioids from any other provider.  

I turned down the possibility of immediate relief of my dental pain so that I wouldn’t lose my regular prescription for chronic pain. I felt that I had no other choice. In addition, I didn’t want to be “red-flagged” by the pharmacy as a drug seeker, even though I did have a legitimate need for the new prescription.  

The pendulum has swung too far in the effort to control opioid overdoses and many people do not receive appropriate medications to treat their pain. I realize that I am one of the lucky ones to still get a prescription opioid, and I feel for those who aren’t as fortunate as me.  

Every patient should advocate for themselves, but if you are unable or afraid to, try having a family member or friend do it for you. Don’t settle for treatment that is less than optimal. If you are unhappy with your treatment or have intolerable side effects, discuss it with your doctor and ask for a different treatment plan. Doctors generally want to help, but some may feel that their hands are tied when it comes to prescribing opioids.  

Unfortunately, chronic pain patients must continue to jump through hoops in order to be treated ethically, fairly and adequately. Many are denied appropriate treatment due to prescribing limits and doctors’ fear of prosecution for prescribing opioids. I am hopeful that with the upcoming revision of the CDC opioid guideline, things will change for the better.  

Victoria Reed lives in Cleveland, Ohio. She suffers from endometriosis, fibromyalgia, degenerative disc disease and rheumatoid arthritis. 

Overdose Crisis Reaches Grim Milestone

By Roger Chriss, PNN Columnist

The CDC announced this week that the U.S. has seen over 100,000 drug overdose deaths in the 12-month period ending May, 2021. This record-high spike in overdoses is thought to be primarily a result of pandemic lockdowns and the continuing spread of illicit fentanyl.

National Institute on Drug Abuse director Nora Volkow, MD, told NPR that the overdoses “are driven both by fentanyl and also by methamphetamines" and predicted that the surge of fatalities would continue because of the spread of more dangerous street drugs.

Connecticut this week warned that fentanyl was found in marijuana and is the suspected cause of several near-fatal overdoses in the state. “This is the first lab-confirmed case of marijuana with fentanyl in Connecticut and possibly the first confirmed case in the United States,” said state public health Commissioner Manisha Juthani, MD.

When asked if there is anything giving hope about the future of the drug crisis, PROP co-founder Andrew Koldony, MD, told Axios, “Uh... not really.”

Public health is often depressing. It is also rarely simple. We are not going to arrest, restrict or treat our way out of the drug crisis. Although harm reduction and improved access to addiction services will help, they will not be sufficient to reverse current trends.

The U.S. does not even have good data on the street drug supply. RAND researcher Bryce Pardo, PhD, looking at better and more current data in Canada, sees designer street drugs becoming even more dangerous.

“There is a recent and alarming trend toward more harmful supply of drugs sold in illegal markets in Canada. Consumers in Ontario, Alberta, and British Columbia buying powder may be at greater risk for exposure to fentanyl mixed with novel benzodiazepines,” Pardo reported in JAMA Psychiatry. “There is a need to improve monitoring and surveillance of drug consumption in the US as markets continue to trend toward more harmful drug mixtures.”

The U.S. also doesn’t have good data on drug deaths. Even the term “overdose” is problematic now. Deaths that are “opioid involved” in toxicological terms are resulting from inadvertent exposure via tainted cocaine and methamphetamine. And although fentanyl and other opioids are still involved in the majority of deaths, there are now more psychostimulant-involved deaths than there were two decades ago.

The U.S. also lacks good data on the people who died, in particular their drug use history, general health status, and other factors thought to affect drug risks and outcomes. It is easy to speculate that the stress and isolation of the pandemic exacerbated existing risks, but it is important to note that suicides did not rise in 2020 when they might have been expected to.

There is no easy policy fix here. Restricting prescription opioids and legalizing cannabis didn’t work. Ideology will not help. Legalizing drugs is a meaningless slogan since neither “drugs” nor “legalization” is well-defined. The same with old narratives and origin stories about the crisis, which may help explain what happened but contribute little about what to do next.

Safe supply is an appealing but problematic notion. There is no obvious way to test illicit substances in human trials. Illicit labs are unlikely to hold back their products any more than illicit cannabis suppliers are going to obey the law. Street drug test kits might help, if only we knew enough about the drugs and their users.

Treatment is similarly challenging. As Kolodny told Axios, “If we really want to see deaths come down in the short run, someone who's opioid addicted has to be able to access treatment more easily than they can buy a bag of heroin or fentanyl.” Though this is an admirable goal, there is no practical way to do it.

And all of this assumes that street users are opioid-addicted. More and more are not, as the increasing levels of death and harm from psychostimulants shows. Further, an increasing number of deaths are “polydrug” deaths involving two or more substances, which makes addressing risks all the more complicated.

But despair is not the appropriate response. The U.S. was facing rapidly rising rates of tobacco-related illness and death for much of the 20th century. But a combination of public health measures has cut the mortality rate from smoking in half since 1990. These measures include stricter laws and regulations, increased costs, and in an unexpected irony, stigmatization of smoking.

Many of the proposed solutions to the drug crisis have been based more on intuition than data. At this point we simply do not know which public health measures are working or how to improve them. What little data we have is often imprecise and years old, and as the crisis accelerates, the importance of granular and timely data grows. Moreover, the measures to date have often been applied piecemeal for short periods, so their real efficacy remains to be determined.

The tragedy of drug deaths cannot be understated, and the potential for far more drug deaths cannot be underestimated. But if the U.S. can improve its understanding of drugs and its response to risks and harms, we needn’t see so many more deaths moving forward.

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. 

Unusual Head-to-Head Migraine Study Pits Emgality vs. Nurtec

By Pat Anson, PNN Editor

Competition has grown intense between pharmaceutical companies in the $2 billion U.S. migraine market.

You’ve probably seen their TV commercials. Eli Lilly hired Olympic athletes to pitch Emgality, an injectable migraine preventative, while reality star Khloé Kardashian is appearing in commercials for Nurtec, an oral medication made by Biohaven Pharamceuticals

Lilly is now taking the competition a step further, with an unusual head-to-head clinical study – rare in the pharmaceutical industry – that pits Emgality against Nurtec. The company is enrolling 700 adults with episodic migraine in a randomized, double-blind, placebo-controlled trial. The so-called CHALLENGE-MIG study will directly compare the efficacy and safety of the two drugs.

“Lilly’s CHALLENGE-MIG study will help us understand how different types of preventive medications may help people achieve the goals that matter most to them. It’s exciting that insights generated in this first-of-its-kind head-to-head trial will be able to spark treatment plan discussions between people with migraine and their health care providers,” Shivang Joshi, MD, a trial investigator at Dent Neurologic Institute, said in a Lilly press release.

Emgality and Nurtec both inhibit calcitonin gene-related peptides (CGRP), a protein that causes migraine pain, but their delivery systems are very different. Emgality is injected once a month, while Nurtec is taken in a pill every other day.

Emgality was one of the first CGRP inhibitors to be approved by the FDA in 2018, while Nurtec is a relative newcomer, first approved in 2020. Nurtec’s label was recently expanded to include both migraine prevention and treatment.

The primary goal of the Lilly study is to see which drug gives patients a greater reduction in monthly headache days, with a secondary goal of measuring quality of life improvements.

“We believe patients should expect more and get more from medications that can help prevent migraine. Therefore, we look forward to sharing the findings from our Emgality versus Nurtec ODT head-to-head trial,” said Anne White, senior vice president of Eli Lilly and president of Lilly Neuroscience.

Biohaven’s CEO welcomes the study and sees it as an affirmation of Nurtec’s growing share of the market. Since it was introduced last year, Nurtec has generated about $200 million in revenue for Biohaven, with over 750,000 prescriptions filled. 

"This new head-to-head trial affirms that Nurtec ODT is perceived as the new standard of care.  The dual-therapy action of Nurtec ODT is unique and provides clear advantages to both treat and prevent migraine attacks.  Since the launch of oral acute CGRP agents, the performance of injectable CGRP (inhibitors) is now negligible to flat,” Vlad Coric, MD, CEO of Biohaven Pharmaceuticals, said in a statement to PNN. 

“Regardless of this Emgality study outcome, the Nurtec ODT value proposition will not be matched. And Nurtec ODT will have an impressive and entrenched market penetration by the completion of the proposed head-to-head study.  We continue to hear from patients, who want oral over needle-based therapies.” 

Regardless of whether it’s a pill or injection, both drugs are expensive. A supply of eight Nurtec tablets costs about $941, depending on insurance coverage. The listed price for Emgality is $627 for a single injection or about $7,524 annually.

If you’d like to know more about the study or possibly enroll in it, call the Lilly Answers Center at 1-800-545-5979.

Exercise Reduces Pain by Increasing Beneficial Bacteria

By Pat Anson, PNN Editor

Regular exercise can benefit people in many different ways, helping us lose weight, reduce the risk of heart disease, and boosting overall health.  

But researchers at the University of Nottingham have found that exercise has an unexpected benefit for people with arthritis. Regular exercise increases levels of beneficial bacteria in their digestive tracts, which reduces pain and inflammation by increasing levels of endocannabinoids – cannabis-like substances naturally produced by the body.

The study, published in the journal Gut Microbes, is believed to be the first to find a potential link between endocannabinoids, exercise and gut microbes.

"Our study clearly shows that exercise increases the body's own cannabis-type substances. Which can have a positive impact on many conditions,” says lead author Amrita Vijay, a Research Fellow at Nottingham’s School of Medicine. "As interest in cannabidiol oil and other supplements increases, it is important to know that simple lifestyle interventions like exercise can modulate endocannabinoids."

Vijay and her colleagues enrolled 78 people in their study. Half of the participants did 15 minutes of muscle strengthening exercises every day for six weeks, and the rest did nothing. Blood and fecal samples were collected from both groups.

At the end of the study, participants who exercised not only had lower pain levels, they also had significantly more Bifidobacteria and Coprococcus 3 -- bacteria that produce anti-inflammatory substances and lower levels of cytokines, which regulate inflammation.

These gut bacteria were particularly adept at raising levels of short chain fatty acids (SCFAs), which increase levels of endocannabinoids. About a third of the anti-inflammatory effects of the gut microbes was due to their ability to raise endocannabinoid levels.

Importantly, the exercise group also had lower levels of Collinsella – a bacteria known to increase inflammation that is strongly associated with processed food and diets low in vegetables.    

“In this study we show that circulating levels of ECs (endocannabinoids) are consistently associated with higher levels of SCFAs, with higher microbiome diversity and with lower levels of the pro-inflammatory genus Collinsella. We also show statistically that the anti-inflammatory effects of SCFAs are up to one third mediated by the EC system,” researchers concluded.

Previous studies have also found an association between gut bacteria and painful conditions. A 2019 study at McGill University found that women with fibromyalgia had 19 different species of bacteria that were present in either greater or lesser quantities than a healthy control group.

Bacteria associated with irritable bowel syndrome, chronic fatigue syndrome and interstitial cystitis were also found to be abundant in the fibromyalgia patients, but not in the control group.    

Having a healthy diet can also affect pain levels for migraine, neuropathy and other types of chronic pain. A recent study funded by the National Institutes of Health found that migraine sufferers who ate more fatty fish and reduced their consumption of polyunsaturated vegetable oils — frequently found in processed foods — had fewer headaches.

FDA Approves First Virtual Reality Device for Chronic Low Back Pain

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has authorized the marketing of the first home-based virtual reality (VR) device for the treatment of chronic lower back pain in adults.

The EaseVRx headset uses guided VR programs to help patients relax, meditate and distract themselves from their pain, using the principles of cognitive behavioral therapy (CBT). The device is made by AppliedVR, a Los Angeles-based company that is developing therapeutic VR programs to help treat pain and other conditions.

"Millions of adults in the United States are living with chronic lower back pain that can affect multiple aspects of their daily life," Christopher Loftus, MD, acting director of the FDA’s Office of Neurological and Physical Medicine Devices, said in a statement. “Today's authorization offers a treatment option for pain reduction that does not include opioid pain medications when used alongside other treatment methods for chronic lower back pain."

Chronic lower back pain is defined as moderate to severe pain in the lower back lasting longer than three months. It is one of the most common chronic pain conditions and a leading cause of disability.

The FDA’s marketing approval is based a clinical study of 179 participants with chronic lower back pain. Half were given an EaseVRx headset to watch immersive 3-D programs daily for 8 weeks. The other half also used the headset, but only watched routine nature scenes as a sham treatment.

APPLIEDVR IMAGE

At the end of treatment, 66% of those who watched VR programs reported at least a 30% reduction in pain, compared to 41% of participants in the sham control group.

Nearly half of those in the EaseVRx group reported at least a 50% reduction in lower back pain.

No serious adverse events were reported during the study. About 20% of participants reported discomfort with the headset and nearly 10% reported motion sickness and nausea.

EaseVRx was given a Breakthrough Device Designation by the FDA in 2020 for treating fibromyalgia and chronic lower back pain. The designation speeds up the development and review of new medical devices.

Marketing approval of EaseVRx – known as a "De Novo pre-market review" – creates a new regulatory classification for VR devices. It clears the way for similar devices with the same intended use to obtain marketing authorization – a significant development for the fledgling virtual reality industry.

"We worked tirelessly over the past few years to build an unmatched body of clinical evidence that demonstrates the power of VR for the treatment of pain, and couldn't be more thrilled to achieve this important milestone," said Josh Sackman, AppliedVR’s co-founder and president. "But, our mission does not stop with this one approval. We're committed to continuing research that validates our efficacy and cost-effectiveness for treating chronic pain and other indications."

EaseVRx will only be available by prescription. Its software programs immerse users in a “virtual” environment where they can swim with dolphins, play games or enjoy beautiful scenery.  The content also incorporates biopsychosocial pain education, diaphragmatic breathing, mindfulness, and relaxation exercises.

AppliedVR headsets are already being used for pain management in over 200 hospitals and healthcare systems. A company spokesman told PNN that EaseVRx will be available on a limited basis through select providers toward the middle of 2022, with a full commercial launch expected in 2023. AppliedVR's is currently building a distribution network and working with insurers -- Medicare, Medicaid and commercial -- to establish reimbursement levels. No pricing plans have been announced for its VR headset or programs.

OHSU Focused on Opioid Tapering, but at What Cost to Patients?

By Pat Anson, PNN Editor

An internal medicine clinic at Oregon Health & Science University has significantly reduced the use of opioid pain medication through the use of a review board that oversees whether prescriptions are in line with federal and state guidelines, according to a new study.

“The question was, how do clinics actually implement those guidelines in practice?” co-author Jonathan Robbins, MD, assistant professor of medicine at the OHSU School of Medicine, said in a press release. “The opioid review board was a way to turn high-level recommendations into action steps we can take in our clinic to treat patients and create a culture of safe prescribing.”

The study highlights the declining use of high dose opioids at the clinic since 2017, along with increased prescriptions for the addiction treatment drug Suboxone (buprenorphine). But critics say the research failed to address whether pain relief and quality of life improved for patients or if they suffered side effects when they were tapered to lower doses or prescribed buprenorphine.

“This is a frustratingly vague account of a practice that could have serious implications for treating a large number of people with chronic pain,” said Bob Twillman, PhD, former Executive Director of the Academy of Integrative Pain Management. 

“The summary statistics presented give us some idea about how frequently people are being tapered, and how often they are being transitioned to buprenorphine, but we really could use some better data analysis, especially with respect to outcomes,” Twillman wrote in an email. “The article continues a trend in the literature, in which an output of these interventions (i.e., the change in prescribing) is confused with an outcome (i.e., what happens to the patient as a result). Basically, the article says, ‘We decided to do this, and we think it's great.’ But there are no data presented to back that up.”

“We’ll let the article stand for itself,” is the response PNN received from Erik Robinson, a senior communications specialist at OHSU. Robinson declined a request to speak with the authors of the study and to identify members of the review board.

“The article published in the Annals of Family Medicine describes a clinical practice in general terms, and we will not engage questions about specific patient outcomes and clinical discussions among physicians,” Robinson said in an email.

‘High-Risk Cases’ Reviewed

What can be gleaned from the article is that patients with more than 6 opioid prescriptions in a 9-month period had their cases reviewed, along with those on high daily doses that exceed 90 MME (morphine milligram equivalent) or those co-prescribed benzodiazepines. The 90 MME threshold is based on a recommendation in the 2016 CDC opioid guideline.

“We combed through 14,000 patients in our clinic and developed a registry about who we’re chronically treating with opioids,” co-author Mary Pickett, MD, associate professor of medicine in the OHSU School of Medicine, said in the press release. “We picked out high-risk cases to review and invited those patients’ primary care doctors to consult with us.”

The review board initially identified 664 patients on chronic opioid therapy (COT). Three years later, there were only 458 COT patients at the clinic, the number of high-dose opioid prescriptions was reduced significantly, and buprenorphine prescriptions increased over 300 percent.  

But there is no information on how many patients experienced withdrawal, whether their pain levels and quality of life improved, or if patients were satisfied with their treatment. The study only notes that “a subset of patients have had adverse response to tapering.” Those cases were reviewed a second time, but again there are no details about patient outcomes or if the tapering was stopped..

The FDA warned in 2019 that rapid tapering or abrupt discontinuation of opioid therapy could result in serious harm to patients, including withdrawal, uncontrolled pain, psychological distress and suicide. A recent study found that tapered patients were 68% more likely to be hospitalized for withdrawal, overdose or alcohol intoxication, and twice as likely to have a mental health crisis such as depression, anxiety or suicide attempt.  

“We’re coaching primary care providers to approach this carefully, and, when necessary, slowly taper their patients,” Robbins says in the OHSU press release. “We don’t do anything abruptly, and patients have supported this careful process.”

But Twillman wonders if the tapering was voluntary and if patients agreed to have their cases reviewed. The press release mentions a waiver being signed by patients, but the study does not.

“That detail is missing from the scientific publication, and it raises a concern about the extent to which that signature is truly voluntary, or if it is coerced by a threat to stop prescribing if the waiver is not signed. What is the consequence for patients who don't sign the waiver?” asked Twillman.

“And what happens if tapering or transition to buprenorphine is recommended, and the patient doesn't agree? We've seen the dangers of involuntary tapers in several studies now, so is any tapering that happens truly voluntary, and supported appropriately with ancillary services? In sum, this article raises more questions than it answers.”

Patient Urged to Taper

“In my experience, they care more about de-prescribing than they do about their patients' individual needs,” says Emma, a patient at OHSU’s Comprehensive Pain Center who lives with an intractable pain condition. She asked that we not use her real name because she fears retaliation or being discharged from the pain clinic.

Emma gets opioids from her primary care provider, but can’t get any from the pain clinic, which she says has a strict policy against prescribing opioids at any dose.

Emma says she is constantly urged to taper by her OHSU doctor. The pain clinic emphasizes non-opioid alternative treatments such as physical therapy, acupuncture, yoga, massage and psychotherapy. 

“I’m getting pretty damn fed up with OHSU’s total lack of concern for my wellbeing. They’ve all but eliminated individualized care when it comes to the treatment of pain.”

— OHSU patient

“I told them that I had spent years trying every possible alternative, and had become suicidal due to severe untreated pain. That was when my primary doc asked me to at least consider opioids as an alternative to taking my own life. I did try them, and they gave me my functionality back,” she told PNN.

“I'm getting pretty damn fed up with OHSU's total lack of concern for my wellbeing. They've all but eliminated individualized care when it comes to the treatment of pain. And how they can label the Comprehensive Pain Center a ‘pain management clinic’ while completely eliminating an entire class of effective medications is beyond me.”

Roger Chou’s Role

Patients at OHSU’s Comprehensive Pain Center were apparently not included in the study on tapering. But they too have their cases regularly reviewed by a panel of pain management experts.

One of the experts is Roger Chou, MD, a prolific researcher and longtime critic of opioid prescribing who heads OHSU’s Pacific Northwest Evidence-based Practice Center (EPC). According to the website GovTribe, over the last five years OHSU has been awarded over $2 billion in federal grants – much of it going to the EPC to support Chou’s medical research.

In addition to his research, Chou co-authored the CDC’s 2016 opioid guideline and has collaborated on several occasions with members of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid advocacy group.

In 2019, Chou co-authored an op/ed with PROP President Dr. Jane Ballantyne and PROP board member Dr. Anna Lembke that encourages doctors to consider tapering “every patient receiving long term opioid therapy.” He also served on a state task force that supported a rigid opioid tapering policy for Medicaid patients in Oregon.

Emma considers Chou “a major player behind all of OHSU’s anti-opioid policies” and is concerned that guidelines that he helped write are being used to justify tapering.

“It’s concerning to me that they’re justifying these actions by stating that they’re ‘in alignment with the guidelines.’ So essentially, they are both creating and enforcing their own set of guidelines with no transparency and no real oversight,” she said.

Last year, the American Medical Association called for a major overhaul of the CDC guideline, saying it was clear the agency’s recommendations “harmed many patients” by setting arbitrary limits on opioids.

The CDC is currently in the process of revising and possibly expanding the guideline, with the goal of releasing a new version next year. One of the authors drafting the revised guideline is Roger Chou.

Experimental Injection Could Reverse Spinal Cord Injuries

By Pat Anson, PNN Editor

An experimental injection therapy that uses synthetic nanofibers to stimulate nerve cells could be used someday to reverse paralysis and repair damaged spinal cord tissues, according to a new study by researchers at Northwestern University.

In experiments on laboratory animals, the therapy successfully regenerated spinal cord nerves, reduced scar tissue and triggered the formation of new blood vessels. After a single injection, paralyzed mice regained the ability to walk within four weeks.

“Our research aims to find a therapy that can prevent individuals from becoming paralyzed after major trauma or disease,” said lead author Samuel Stupp, PhD, an expert in regenerative medicine and founding director of the Simpson Querrey Institute for BioNanotechnology (SQI) at Northwestern.

“For decades, this has remained a major challenge for scientists because our body’s central nervous system, which includes the brain and spinal cord, does not have any significant capacity to repair itself after injury or after the onset of a degenerative disease. We are going straight to the FDA to start the process of getting this new therapy approved for use in human patients, who currently have very few treatment options.”

Stupp and his colleagues used nanotechnology to develop synthetic nanofibers that mimic the natural environment around the spinal cord. Intensifying the motion of molecules within the nanofibers promotes the repair and regeneration of myelin, the insulating layer of axons that help nerve cells transmit electrical signals.

Researchers say the nanofibers biodegrade into nutrients for nerve cells within 12 weeks and completely disappear from the body without noticeable side effects. Their study, published in the journal Science, is the first in which researchers controlled the motion of molecules through changes in chemical structure to increase a therapy’s efficacy.

Nearly 300,000 people are currently living with a spinal cord injury in the United States. About 30% are hospitalized at least once a year after the initial injury and less than 3% of those with a severe injury ever recover basic physical functions. Life expectancy for patients with spinal cord injuries is significantly lower than healthy people and has not improved since the 1980s.

“Currently, there are no therapeutics that trigger spinal cord regeneration,” Stupp said in a news release. “I wanted to make a difference on the outcomes of spinal cord injury and to tackle this problem, given the tremendous impact it could have on the lives of patients.” 

The key behind Stupp’s breakthrough therapy is fine tuning the motion of molecules so that they can find and constantly engage with moving cellular receptors with bioactive signals. Injected as a liquid, the “dancing molecules” immediately form a gel in a complex network of nanofibers that mimic the extracellular matrix of the spinal cord.

“Receptors in neurons and other cells constantly move around,” Stupp said. “The key innovation in our research, which has never been done before, is to control the collective motion of more than 100,000 molecules within our nanofibers. By making the molecules move, ‘dance’ or even leap temporarily out of these structures, known as supramolecular polymers, they are able to connect more effectively with receptors.”

Stupp and his team found that fine-tuning the molecules’ motion within the nanofibers makes them more agile and results in greater therapeutic effect in paralyzed mice. They also confirmed that formulations of their therapy performed successfully in vitro tests with human cells, indicating increased bioactivity and cellular signaling.

Once connected to the nerve receptors, the dancing molecules trigger two cascading signals, both of which are critical to spinal cord repair. One signal induces myelin to rebuild around axons, which improves how nerve cells communicate with the brain. The second signal helps neurons survive after injury by promoting the regrowth of lost blood vessels that feed neurons and other cells for tissue repair. The therapy also reduces glial scarring, which acts as a physical barrier that prevents the spinal cord from healing. 

“The signals used in the study mimic the natural proteins that are needed to induce the desired biological responses. However, proteins have extremely short half-lives and are expensive to produce,” said first author Zaida Álvarez, a former research assistant in Stupp’s laboratory who is now a researcher scholar at SQI. “Our synthetic signals are short, modified peptides that — when bonded together by the thousands — will survive for weeks to deliver bioactivity. The end result is a therapy that is less expensive to produce and lasts much longer.”

While the new therapy could be used to treat paralysis after a major spinal cord injury, Stupp believes it could also be used to as a therapy for neurodegenerative diseases and strokes.

“The central nervous system tissues we have successfully regenerated in the injured spinal cord are similar to those in the brain affected by stroke and neurodegenerative diseases, such as ALS, Parkinson’s disease and Alzheimer’s disease,” Stupp said. “Beyond that, our fundamental discovery about controlling the motion of molecular assemblies to enhance cell signaling could be applied universally across biomedical targets.”

You can learn more about Stupp’s research in this podcast and by watching this video:

Recent research at Yale University and Sapporo Medical University in Japan found that injections of mesenchymal stem cells (MSCs) in patients paralyzed by spinal cord injuries led to significant improvement in their motor functions. In a small study, more than half of the paralyzed patients showed substantial improvements in function within weeks of being injected with autologous MSCs derived from their own bone marrow.

Guidelines Urge More Caution in Use of Invasive Neck Procedures

By Pat Anson, PNN Editor

Invasive procedures such as steroid injections, nerve blocks and radiofrequency ablation should be used more cautiously when treating chronic neck pain, according to new guidelines adopted by the American Academy of Pain Medicine and American Society of Regional Anesthesia and Pain Medicine.

The two medical societies formed a joint guidelines committee in 2020 to look into cervical spine joint procedures, which are increasingly used despite questions about their effectiveness and safety. The use of radiofrequency ablation -- heat from an electric current used to burn painful nerve endings — has increased by 112% in the U.S. over the past decade.

Spine pain in the neck or lower back is the leading cause of disability worldwide, with nearly half of adults likely to be affected at some point in their lives. The cervical facet joints, which allow the neck and back to tilt forwards, backwards and to rotate, are the primary source of pain in about 40% of patients with chronic neck pain and over half of those with neck pain after whiplash injury.

"It is precisely because neck pain and cervical spine procedures are so common, and there is so little high-quality evidence to guide care, that consensus guidelines are needed,” says lead author Steven Cohen, MD, a professor of anesthesiology at Johns Hopkins Hospital and co-chair of the guidelines committee.

The new guidelines, published online in the journal Regional Anesthesia & Pain Medicine, are based on over 400 publications and clinical studies of cervical spine procedures. Reviewers also looked at clinical signs and imaging used to select patients for particular procedures; the diagnostic and prognostic value of procedures; and several aspects of radiofrequency ablation (RFA), including how to reduce the risk of complications from the procedure and whether it should be repeated.

Because acute neck pain often resolves by itself, the guidelines recommend 6 weeks of conservative management, such as non-opioid painkillers and physical therapy, before opting for RFA or nerve blocks.

The reviewers found that RFA may be helpful for easing chronic neck pain, but only in patients whose pain corresponds to the joints being treated; those whose symptoms don’t emanate from a nerve root; and those who obtain meaningful pain relief from diagnostic nerve blocks, which are typically performed before RFA. 

Many insurance carriers require two nerve blocks, but the evidence indicates that doubling up will result in a significant number of unnecessary procedures and higher costs. Reviewers say the evidence for performing only a single block is much stronger for the neck than for the lower back.

The guidelines also recommend against stringent patient selection criteria, such as requiring nearly total pain relief from diagnostic blocks, because it might exclude patients who might benefit from radiofrequency ablation. None of the clinical studies that were reviewed support using pain relief thresholds above 50 percent.

Physicians should warn patients about the common side effects of RFA, such as tingling and burning sensations, numbness, dizziness, and loss of balance and coordination, which can last from a few days to a few weeks after the procedure. Patients also need to be told that RFA won’t cure them, and that pain relief typically lasts between 6 and 14 months. 

While most patients who have the procedure repeated will get pain relief, the benefits may wane over several years. RFA shouldn’t be repeated more than twice a year, the guidelines recommend.

Other key recommendations include:

• Use only soluble, short-acting steroids when injecting into the upper neck joints

• Use fluoroscopy imaging before spinal injections to avoid inadvertent needle placement

• Use smaller needles and electrodes than those used for the lower back

• Use nerve and muscle stimulation to improve effectiveness and reduce the risk of complications

• Take steps to minimize interference with implanted electrical devices such as pacemakers

“Clinical trials evaluating cervical facet blocks and RFA are characterized by widely disparate outcomes, and there is enormous variation in selecting patients and performing procedures. These multi-society guidelines have been developed to serve as a roadmap to improve outcomes, enhance safety, and minimize unnecessary tests and procedures,” the reviewers concluded.

Fearing DEA, Many Pharmacies Stop Dispensing Addiction Medication

By Aneri Pattani, Kaiser Health News

When Martin Njoku saw opioid addiction devastate his West Virginia community, he felt compelled to help. This was the place he’d called home for three decades, where he’d raised his two girls and turned his dream of owning a pharmacy into reality.

In 2016, after flooding displaced people in nearby counties, Njoku began dispensing buprenorphine to them and to local customers at his Oak Hill Hometown Pharmacy in Fayette County.

Buprenorphine, a controlled substance sold under the brand names Subutex and Suboxone, is a medication to treat opioid use disorder. Research shows it halves the risk of overdose and doubles people’s chances of entering long-term recovery.

“I thought I was doing what was righteous for people who have illness,” Njoku said.

But a few years later, the Drug Enforcement Administration raided Njoku’s pharmacy and accused the facility of contributing to the opioid epidemic rather than curbing it. The agency revoked the pharmacy’s registration to dispense controlled substances, claiming it posed an “imminent danger to public health and safety.” Although two judges separately ruled in Njoku’s favor, the DEA’s actions effectively shuttered his business.

“I lost everything that I worked for,” Njoku said.

Lawyers, pharmacists, harm-reduction advocates and a former DEA employee say Njoku’s case is emblematic of the DEA’s aggressive stance on buprenorphine. An opioid itself, the medication can be misused, so the DEA works to limit its diversion to the streets. But many say the agency’s policies are exacerbating the opioid epidemic by scaring pharmacies away from dispensing this medication when it’s desperately needed.

Drug overdose deaths hit record highs last year, and despite medical experts considering medications like buprenorphine the gold standard, less than 20% of people with opioid use disorder typically receive them. The federal government has taken steps to increase the number of clinicians who prescribe buprenorphine, but many patients struggle to get those prescriptions filled. A recent study found that 1 in 5 U.S. pharmacies do not provide buprenorphine.

“Pharmacies are terrified they’re going to lose their DEA registration and go out of business,” said Charles “Buck” Selby, a former inspector and chief compliance officer for the West Virginia Board of Pharmacy, who retired in 2018.

The ramifications can be particularly acute in rural areas, where a dearth of addiction treatment providers, lack of transportation and stigma against these medications already create barriers. If pharmacies decline to provide buprenorphine too, patients will have few options left, Selby said.

The DEA did not respond to requests for comment.

Buprenorphine Misuse

Like many other prescription drugs, buprenorphine can be found illegally on the street. There are unscrupulous doctors who hand out prescriptions and pharmacists who fill them. Subutex, which consists of buprenorphine alone, is easier to misuse and typically has higher street value than Suboxone, a combination of buprenorphine and the overdose-reversal drug naloxone.

In the case against Njoku’s pharmacy, an assistant U.S. attorney explained that the DEA “got slapped hard for being asleep at the switch as the opioid crisis ramped up. … They’re trying to make sure that Subutex doesn’t become the next problem,” according to court transcripts.

But recent research suggests that buprenorphine misuse has decreased in recent years even as prescribing has increased, and that most people who use diverted buprenorphine do so to avoid withdrawal symptoms and because they can’t get a prescription.

Misuse rates for buprenorphine are twice as high as misuse rates for hydrocodone, oxycodone and other opioid medications, but buprenorphine is less likely to cause overdoses because its effects taper off at higher doses, said Dr. Aaron Wohl, medical director of the Florida-based coalition Project Opioid.

In Njoku’s case, the DEA said in court documents that several “red flags” had suggested the pharmacy’s actions were irresponsible. First, many of the prescriptions it filled were for Subutex instead of Suboxone. Patients also traveled – sometimes out of state – to get prescriptions, drove long distances within West Virginia to reach Njoku’s pharmacy, and often paid in cash.

In traditional prescription drug cases, these are all markers of trouble. But — as Njoku’s lawyers argued and two judges later agreed — they can also reflect the difficulty of getting addiction treatment, which is sometimes more challenging than obtaining illicit drugs.

“The practical reality and context of West Virginia turn these additional flags from red to yellow,” U.S. District Judge Joseph Goodwin wrote in his opinion. Patients may go out of their way for the drug because there aren’t enough nearby doctors who prescribe it or pharmacies that stock it, he wrote. They might pay cash because they’re uninsured or Medicaid won’t cover prescriptions written by an out-of-network doctor. And they might prefer Subutex because it’s often cheaper than Suboxone.

By 2020, Goodwin and an administrative law judge at the DEA had both ruled in Njoku’s favor. But several insurers and drug suppliers had already stopped doing business with him. Njoku closed the pharmacy in April 2021. 

‘Prescribing Cliff’

Across the country, when a pharmacy stops providing buprenorphine, the ripple effects can be far-reaching.

Trish Mashburn works at two independent pharmacies in western North Carolina. When a nearby pharmacy stopped dispensing buprenorphine, she began getting five calls a day from prospective customers trying to get their prescriptions filled, she said. Although both her employers stock buprenorphine, they order only a set amount, so Mashburn often must turn patients away.

Research in North Carolina and Kentucky has found that many pharmacists worry that ordering more buprenorphine will trigger a DEA investigation. The DEA does not specify thresholds for controlled substances, but it requires wholesalers to flag suspicious orders. In turn, wholesalers limit how much a pharmacy can buy or create algorithms to detect orders that exceed projected need.

They base these limits, in part, on the DEA’s enforcement actions, said Larry Cote, a former DEA attorney who now advises wholesalers, pharmacies and other clients on regulatory compliance. Since pharmacies are not typically privy to how these limits are set, many simply order small batches of buprenorphine out of caution.

That creates a “prescribing cliff,” said Bayla Ostrach, lead author of a paper studying this issue in North Carolina. Doctors may prescribe buprenorphine to more patients, but pharmacies order enough for only a certain number of customers. Since many people stay on buprenorphine for years, once the pharmacy hits its self-established quota, it may rarely have openings for new patients.

A Lee County, Florida, man thought he was one of the lucky ones. James, 34, had been filling his Subutex prescription at the supermarket chain Publix for seven years. In that time, he held steady jobs and cared for his wife and children. (James asked KHN to withhold his last name so future employers wouldn’t judge him on his addiction history.)

Then, last year, James said, he went to get his prescription refilled and was told Publix no longer stocks Subutex — the medication the DEA considered a “red flag” in Njoku’s case. Publix did not respond to requests for comment.

A decade ago, when James began the medication, he chose Subutex because it was cheaper than Suboxone. Today, most insurance plans cover Suboxone, and the price difference has narrowed somewhat.

James was not eager to change to a potentially pricier medication. And he worried a different drug might disrupt his recovery — a common sentiment among patients in long-term recovery, said Dr. Nathan Mullins, director of addiction medicine fellowship at Mountain Area Health Education Center in North Carolina. Changing their medication is unnecessary and can cause needless anxiety, Mullins said.

Luckily, James found an independent pharmacy that provides Subutex. It’s more expensive, since the new place doesn’t accept his insurance, he said. He pays about $40 a week, compared with $40 a month previously.

But James said it’s worth it.

“I’ve been in 10 rehabs and a million detoxes, and the only thing that has worked for me was one sublingual tablet,” James said. Along with therapy, “this saved my life.”

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

Oklahoma Supreme Court Reverses Landmark Opioid Ruling

By Pat Anson, PNN Editor

Oklahoma’s Supreme Court has reversed a landmark court ruling that found opioid drug makers created a public nuisance and were responsible for the state’s opioid crisis. It was the second major victory this month for the pharmaceutical industry, as it fights back against a tsunami of opioid litigation around the country.

The 5-1 decision by Oklahoma’s highest court throws out a $465 million verdict by Judge Thad Balkman against Johnson & Johnson. Former Oklahoma Attorney General Mike Hunter alleged that J&J and two other drug makers fueled the opioid crisis by flooding the state with painkillers. But the court said J&J can’t be held liable for the actions of others with legally prescribed opioids.

"We hold the opioid manufacturer's actions did not create a public nuisance. The district court erred in extending the public nuisance statute to the manufacturing, marketing, and selling of prescription opioids," the ruling states.

The decision is very similar to a ruling by a California judge last week, who said that J&J and three other drug makers can’t be held responsible for “adverse downstream consequences flowing from medically appropriate prescriptions.”

Like the California judge, Oklahoma’s high court acknowledged that an opioid epidemic exists and that it has caused the overdose deaths of thousands. While illicit use of prescription opioids led to many of those deaths, the court said few deaths occurred when individuals used opioids as prescribed.

“J&J had no control of its products through the multiple levels of distribution, including after it sold the opioids to distributors and wholesalers, which were then dispersed to pharmacies, hospitals, and physicians' offices, and then prescribed by doctors to patients. J&J also had no control over the laws and regulations that govern the disbursement of its prescription opioids or whether prescribers follow the laws,” the court said.

“We also cannot disregard that chronic pain affects millions of Americans. It is a persistent and costly health condition, and opioids are currently a vital treatment option for pain. The U.S. Food and Drug Administration has endorsed properly managed medical use of opioids (taken as prescribed) as safe, effective pain management, and rarely addictive.”

An Oklahoma patient advocate told PNN the court’s ruling was the “only logical outcome” because the state failed to prove its case.

“Their evidence never proved that bad marketing caused excess prescriptions nor the overdose crisis,” said Tamera Lynn Stewart, Policy Director for the P3 Political Action Alliance. “Looking at the totality of the evidence and data available from state and federal sources, it is clear that this crisis was always caused by attempts to fuel the drug war. If this use of public nuisance was allowed to stand, it would open up Pandora's box to future use against any company that produces a product for public use.”

Possible Impact on Other Cases

Plaintiff law firms representing state and local governments have filed over 3,000 lawsuits against drug makers, opioid distributors and pharmacies for their role in the opioid crisis. If successful, the law firms stand to make billions of dollars in contingency fees.

“Coming on the heels of a verdict in favor of opioid manufacturers in California, this news really casts significant doubt on similar cases that are still underway. I haven't read the ruling in this case yet, but the fact that the decision was 5-1, and that the lone dissenter agreed with the premise of the court's majority, but only wanted a different procedural outcome, means that the Oklahoma Supreme Court was not the least bit swayed by the state's case,” said Bob Twillman, PhD, former Executive Director of the Academy of Integrative Pain Management.

“It will be interesting to see if this court picked up on the same issues identified by the judge in California, namely, that the plaintiffs' presentation missed the mark with respect to an accurate and non-hyperbolic presentation of the facts. It's worth noting that much of the hyperbole came from ‘expert’ witnesses such as Andrew Kolodny.”

The state’s star witness in the Oklahoma trial was Kolodny, an addiction treatment specialist who founded Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group. Dr. Kolodny claimed that J&J and other drug makers operated an “opioid mafia” that funded patient groups and professional medical organizations that promoted the use of opioids.

“I don’t believe physicians should be helping drug companies market their products,” Kolodny testified in 2019. “It’s very easy to fool yourself when it’s profitable to fool yourself.”

Kolodny admitted under questioning that he was being paid $725 an hour to testify by the law firm of Nix Patterson & Roach and stood to make up to $500,000 for his services in Oklahoma. He also acknowledged that he was paid a similarly high hourly rate as a consultant for at least one other law firm involved in opioid litigation. Other PROP board members have also been paid witnesses in opioid litigation cases.

“It looks like the half-million dollars (or more) paid to him and to others is an indication of just how invested the plaintiffs are in the bill of goods they have been sold,” Twillman said in an email. “Meanwhile, while fully recognizing the toll taken by opioid use disorder, we need to keep reminding people of the harm caused by the pursuit of cases such as these -- the harm suffered by people with chronic pain who rely on opioid medications for pain relief, but whose access to those medications has been severely limited by the money-grab inherent in these cases. If there really is a public nuisance here, it may be that these cases are that nuisance.”

Purdue Pharma and Teva Pharmaceuticals settled out-of-court with Oklahoma before the case even went to trial, for $270 million and $85 million respectively. Several other drug companies have also settled out of court or are contemplating settlements rather than risk protracted and expensive litigation. The California and Oklahoma rulings are no doubt giving them second thoughts.

According to the CDC, the U.S. saw over 96,000 fatal overdoses in the 12 month period ending in March, 2021. Most of the deaths involve illicit fentanyl and other street drugs, not prescription opioids.

Most Americans Believe Opioids Necessary for Pain After Surgery

By Pat Anson, PNN Editor

Nearly 8 out of 10 U.S. adults believe opioids are sometimes necessary to manage pain after a surgery, according to a new survey that found most people are more worried about treating post-operative pain than they are about becoming addicted to opioids.

The online survey of over 2,000 adults was conducted last month by The Harris Poll on behalf of MediaSource and Orlando Health, a large Florida-based healthcare system. The survey comes at a time when many hospitals around the nation have adopted policies that discourage or eliminate the use of opioids after many common surgeries.

A recent study of nearly half a million surgeries performed at U.S. hospitals found that the number of opioid pills prescribed to patients decreased by 50% since 2017. Instead of opioids, hospitals are giving patients acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), gabapentinoids and other non-opioid medications.  

“It's very important for us to keep in mind that people do have pain and people do need pain control. The solution is not to just pull opioids away from people and leave them to fend for themselves,” said Luke Elms, MD, a general surgeon at Orlando Health’s Dr. P. Phillips Hospital. “That is a real problem after surgery that needs to be addressed in a compassionate manner.”

Dr. Elms has implemented a protocol that uses over-the-counter drugs like acetaminophen, ibuprofen and muscle relaxers. He says they are safer medications than opioids and help surgical patients recover faster without side effects such as nausea, dizziness and constipation.

“When I talk to patients and reassure them that we're going to be replacing opioids with a much more effective and safe method, and really talk to them about the risks of opioids that have become much more evident with the research that's come out recently, most patients are very open to the idea,” Elms said in a press release.

But that is not how most U.S. adults feel, according to the survey findings. When asked a series of questions about post-surgical pain, many said they have a strong preference for opioids:

• 78% Believe opioid pain medication after surgery is sometimes necessary

• 67% Expect to receive opioids to manage pain after surgery

• 65% Are more concerned about pain relief after surgery than opioid addiction

• 60% Prefer strong prescription painkillers over OTC pain relievers like ibuprofen

At the same time, over two-thirds of respondents (68%) said they are open to the idea of using non-opioid pain relievers and would be willing to try them. Adults who are employed, have high incomes and those with college degrees are more likely to prefer sticking to opioids.

Opioid addiction is actually quite rare after surgery.  A large 2016 study found that less than one percent of older adults were still taking opioids a year after major surgery.  Another large study in 2018 found less than 1% of patients prescribed opioids for post-operative pain were later diagnosed with opioid dependence, abuse or had a non-fatal overdose.

A recent Mayo Clinic study found that hospital guidelines are useful in reducing the number of opioid pills prescribed after surgery, but sometimes go too far. While most patients were satisfied with their pain control, about 10 percent were not.  

Poorly controlled post-operative pain is associated with increased morbidity, less function and quality-of-life, delayed recovery time, and higher health-care costs. The intensity of acute pain during or after surgery is also predictive of developing of chronic pain.

Integrative and Comprehensive Pain Management Provide Only Small Benefits

By Pat Anson, PNN Editor

As concerns rose in recent years about opioid addiction and overdoses, it became trendy for healthcare providers to offer “comprehensive” or “integrative” pain management programs to patients – usually a combination of medication, physical and behavioral therapy, lifestyle changes and alternative treatments such as massage and acupuncture.

But a new study commissioned by the Agency for Healthcare Research and Quality (AHRQ) found that integrative and comprehensive pain management provide only small improvements in pain and function for people with chronic pain.   

Researchers at Oregon Health & Science University (OHSU) reviewed 57 “fair quality” clinical studies, most involving patients with moderate chronic pain caused by fibromyalgia, osteoarthritis and musculoskeletal conditions. Although the improvements in pain and function were small and the evidence limited, researchers concluded that integrative (IPMP) and comprehensive (CPMP) pain management programs worked about as well as individual treatments.

“Our review suggested that IPMPs and CPMPs may provide small to moderate improvements in function and small improvements in pain for patients with chronic pain compared with usual care and may be more effective than some medications alone. The average improvements in function and pain in our review were consistent with those reported for other therapies for pain, including opioids for chronic pain, nonpharmacologic treatments, and surgery,” researchers found.

One of the problems researchers encountered was the mish-mash of terms used to define integrative and comprehensive pain management – such as multimodal, multidisciplinary, interdisciplinary and biopsychosocial – the meaning of which often varies from provider to provider. Researchers said there was “no firm consensus on their definition or use,” which made it harder to evaluate their effectiveness. Only a few of the reviewed studies compared treatments head-to-head and many were of poor quality.

Although none of the trials specifically included Medicare patients, researchers concluded that IPMPs and CPMPs should be more widely used to address pain in the Medicare population.   

“To the extent that programs are tailored to patients’ needs, our findings are potentially applicable to the Medicare population. Programs that address a range of biopsychosocial aspects of pain, tailor components to patient need, and coordinate care may be of particular importance in this population,” they said. 

“Although use of selected individual treatments may serve some patients, a broader range of therapies that address the full scope of biopsychosocial concerns available in formal programs may benefit others. Research in the Medicare population and in patients with a broader range of pain conditions is needed as is research on the impact of program structures, coordination methods, and components on patient outcomes. Additional evidence from primary care-based programs is particularly needed.” 

One of the co-authors of the AHRQ study is Dr. Roger Chou, a primary care physician who heads the Pacific Northwest Evidence-based Practice Center at OHSU.  Chou, who co-authored the 2016 CDC opioid guideline, is a prolific researcher who has collaborated on several occasions with members of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid advocacy group.

PROP Vice President Gary Franklin, MD, “provided input” on the AHRQ study, as well as others.

In July, Chou declared a conflict of interest and recused himself from a meeting of the CDC’s Board of Scientific Counselors, which is evaluating a revision and possible expansion of the agency’s controversial guideline. Chou’s recusal apparently applied only to that meeting, as he is one of the co-authors of the revised opioid guideline — which has yet to be released publicly — and continues his involvement in federally funded pain research. 

OHSU researchers have conducted a series of reviews on a wide variety of pain therapies for the AHRQ. According to the website GovTribe, over the last five years OHSU has been awarded over $2 billion in federal grants for medical research. 

A group of patient advocates and researchers recently called for a congressional or DOJ investigation of the CDC opioid guideline, due to Chou’s significant role in writing it and his then-undeclared conflicts of interest.

Study Finds ‘Urgent Need’ for Regulation of Stem Cell Industry

By Pat Anson, PNN Editor

Over 2,750 businesses and clinics in the U.S. are selling stem cell products – four times as many as in 2016 – most of them offering treatments for pain and orthopedic conditions that are not approved by the Food and Drug Administration, according to a new analysis.

The only stem cell products that are currently approved by the FDA are used to treat sickle cell disease and some cancers. Despite FDA threats to crackdown on “unproven” stem cell products, clinics have proliferated around the country, marketing stem cell therapies for chronic pain, arthritis and other medical conditions. California, Texas and Florida lead the nation with over 300 stem cell clinics in each state.

"One of the most troubling features of this marketplace is that businesses selling unproven and non-FDA-approved stem cell products often use marketing misrepresentations and aggressive sales tactics to exploit the hope, suffering, fear or desperation of patients," says lead author Leigh Turner, PhD, a professor of health, society and behavior at the University of California, Irvine.

Using Google Maps and other online search tools, Turner and his colleagues spent five years compiling data on stem cell businesses. Their findings are published online in the journal Cell Stem Cell.

Turner's analysis found that the most common types of stem cell treatments being offered were for pain (85%), orthopedic diseases and injuries (46%), and sports-related injuries (22%). Most companies did not disclose on their websites how much their therapies cost, but of those that do, the average price was $5,118. Stem cell injections and infusions are usually not covered by insurance.

"Many of these 'clinics' are promoting unlicensed and unproven stem cell products and claim their interventions do not require FDA approval," Turner said. "However, that couldn't be further from the truth. I found that there is widespread promotion of products that do, in fact, require premarketing authorization by the FDA. In many cases, these clinics are using misleading advertising and predatory marketing techniques."

Most stem cell businesses offer “autologous” stem cell products derived from a patient’s own body tissue – such as fat or bone marrow -- which the companies don’t consider a “drug” that falls under FDA jurisdiction.

The FDA has been slow to take action against unlicensed stem cell operators, due in part to a grace period the agency adopted in 2017 to give them more time to submit new drug applications for FDA review. That grace period recently ended, with no indication that many stem cell providers took the agency up on its offer.      

Turner acknowledges there have been “some encouraging results” from studies on stem cell treatments for osteoarthritis and orthopedic conditions, but said there was not enough research yet to justify commercializing them. He worries the stem cell industry has grown so quickly that the FDA can’t provide adequate regulation without substantial increases in enforcement activity.

“There is an urgent need for better oversight of this marketplace. Regrettably, marketing claims by some businesses also question the legitimacy and trustworthiness of regulatory bodies,” he wrote.

Turner’s research was funded by The Pew Charitable Trusts, which released its own report in June that was highly critical of the stem cell industry. Like the Pew report, Turner cites cases where patients suffered injuries after receiving unapproved stem cell treatments, without pointing out that the number pales in comparison to over 250,000 Americans who die every year from medical errors linked to “proven” treatments.   

Why Oral Opioids Can Give Poor Pain Relief

By Forest Tennant, PNN Columnist

Every day, our Research and Education Projects hear from persons with a serious pain problem who can’t obtain enough relief. There are multiple reasons, but a major one is that they are trying to relieve their pain with oral opioids. It appears to us that there is a gross misunderstanding and ignorance about the inability of oral opioids to ever provide good pain relief in many persons who have Intractable Pain Syndrome (IPS).

A person who has constant pain from adhesive arachnoiditis, Ehlers-Danlos Syndrome (EDS), Reflex Sympathetic Dystrophy (CRPS/RSD), cervical neck neuropathy, or another disease that causes constant pain with cardiovascular and endocrine abnormalities will often have impairment of the stomach and intestine. This affects their ability to properly dissolve, digest and place enough opioid into the bloodstream to get pain relief. This occurrence is technically called “opioid malabsorption” or “opioid maldigestion.”

All the conditions listed above cause dysfunction of the many nerves that go from the spinal cord to the stomach and intestine. The nerves carry the bioelectricity that activates the stomach and intestines so that the acids and enzymes from them will fully dissolve and digest tablets, capsules and liquids. EDS, diabetes and autoimmune diseases may also erode or degenerate the collagen matrix of the small intestine, so it won’t properly function, which impedes digestion.

Stomach and intestinal malfunction due to many severe painful diseases may manifest differently at different times. For example, on some days function will be good, and on others, almost non-existent. Another example is “maximal ability.” In this case, the impaired stomach and intestine will allow only a maximal amount of opioid to be digested. For example, 4 tablets will provide some relief, but 6 or 8 won’t do any better.

Review your situation. Do you have some days when you got relief, but not others? Does increasing your oral dose give you no more relief?

If you have IPS, don’t always count on oral opioids to give you the pain relief you need. Start looking into opioid injections, suppositories, patches, topicals, sublingual (under-the-tongue), or buccal (inside the mouth-upper cheek). Also, start probiotics and/or intestinal enzyme preparations, as they sometimes help oral opioids do their job.

Injectable and Suppository Opioids

Why aren’t injectable and opioid suppositories the standard care for severe pain flares? They used to be. For example, the 1956 Merck Manual (9th Edition) states “more severe pain requires the oral or subcutaneous use of narcotics.”

Today, most doctors somehow have the irrational and false idea that injectable opioids always cause overdoses and/or will be diverted into illegal channels. Most doctors are hardly aware that opioid suppositories are available from the local pharmacy and that they are far more effective for flares or breakthrough pain than oral opioids.

At best, an oral opioid will need 30 to 60 minutes to provide pain relief. Opioids administered by injection or suppository work much faster, bypassing the stomach, intestines and liver, and going right to the blood brain barrier.  Pain relief will usually occur within 5 to 10 minutes. Pain relief is also much better, even at a fraction of the oral dose, because the entire dosage reaches the endorphin receptors without being filtered by the stomach, intestines and liver.

Opioid injections and suppositories help patients remain below the CDC guideline’s recommended daily limit of 90 morphine milligram equivalent (MME).

Injectable opioids are used subcutaneously or intramuscularly, not intravenously, for at home use. Injectable
opioids should only be used for flares.

Our enthusiasm for injectable opioids has been enhanced by the development of compounded hydromorphone. This innovation allows a micro dose of only .1cc (5mg), which can be taken subcutaneously with a small needle.

Opioid injections have traditionally been prescribed by local primary care practitioners who know the patient is responsible, and not a street person or substance abuser. Patients and their families should also be trained and warned to keep the injectable away from children, pets and guests. We are not aware of a single case of injectable opioid reaching the street or causing an overdose death in a bona fide IPS patient who was trained with their family.

IPS patients and families can inquire at their local pharmacy as to which injections and suppositories are available. Then approach your personal MD, DO, or NP about starting an opioid injection or suppository for pain flares. 

Every IPS patient needs to achieve some pain free hours so they can walk, physically exercise their arms and
legs, do activities of daily living, and be able to mentally concentrate enough to be able to read and write. These hours of zero or very little pain help strengthen the cardiovascular and endocrine systems so some tissue regeneration can occur and permanently reduce their constant pain. Injectable opioids provide the best opportunity at achieving some pain free hours.

Forest Tennant, MD, DrPH, 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 gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.     

If Covid Vaccines Are So Effective, Why Do I Need a Booster Shot?

By Julie Appleby, Kaiser Health News

The politicization of covid vaccines — and just about everything else having to do with the pandemic — has led to confusion, if not utter fatigue.

And some posts circulating on social media — like this slickly edited piece on YouTube — seem to build on these feelings, attempting to cast doubt on the effectiveness of the vaccines.

The video intersperses comments from White House medical adviser Dr. Anthony Fauci extolling their protectiveness with screenshots of news headlines, starting with those citing 100% effectiveness, then moving through others reporting sharply lower percentages. Set to the rapidly increasing tempo of the orchestral piece “In the Hall of the Mountain King,” the video ends with headlines about drug company profits.

But slowing the video to parse the headlines reveals more complexity. Some are reporting on studies that looked only at infection rates; others, more serious outcomes, including hospitalization and death. Some are about vaccines not offered in the U.S. In short, the video fosters misperceptions by mixing together dissimilar data points and leaving out key details.

Still, one can’t help but wonder what’s really going on with effectiveness — and is any of it a surprise?

If you don’t read any further, know this: No vaccine is 100% effective against any disease. The covid shots are no exception. Effectiveness in preventing infection — defined as a positive test result — appears in some studies to wane sharply the more time that goes by after completing the one- or two-shot regimen.

But on key measures — prevention of serious illness, hospitalization and death — real-world studies from the U.S. and abroad generally show protection weakening slightly, particularly in older or sicker people, but remaining strong overall, even with the rise of the more infectious delta variant of the covid virus.

The bottom line? Getting vaccinated with any of the three vaccines available in the U.S. reduces the chance of getting infected in the first place, and significantly cuts the risk of hospitalization or death if you do contract covid-19. The Centers for Disease Control and Prevention recently published a study showing fully vaccinated people were more than 10 times less likely to die or be hospitalized than the unvaccinated.

“When it comes to what matters, vaccines hold up really well,” said Dr. Amesh Adalja, an infectious-disease physician and senior scholar at the Johns Hopkins Center for Health Security. “They were designed to tame the virus.”

What do “efficacy” and “effectiveness” really mean?

Before a drug or vaccine is greenlighted by federal regulators, it is tested on volunteers randomly assigned to get either the product or a placebo. Then researchers compare how the groups fare. In the case of a vaccine, they look at how well it prevents infection, and whether it protects against serious illness, hospitalization or death. Those clinical trial results are often referred to as efficacy measures.

In the real world, however, a drug or vaccine’s performance is affected by numerous factors, including a much larger population receiving it, some of whom have underlying conditions or socioeconomic circumstances different from those in the clinical trial. That real-world performance measure is called effectiveness.

When authorized for emergency use following clinical trials, both the Pfizer-BioNTech and Moderna two-dose vaccines reported efficacy against symptomatic illness in the mid-90% range. The Johnson & Johnson single-dose shot — which was tested later, when there were more variants — reported overall efficacy in the high 60% range.

So, all three vaccines exceeded the 50% threshold health officials sought as a minimum for efficacy. Keep in mind, also, that the annual influenza vaccine’s real-world effectiveness is often 40% to 50%.

Another point: 95% effectiveness doesn’t mean 95% of vaccinated people will never get infected. What it means is that a fully vaccinated person exposed to the virus faces only 5% of the risk of infection compared with an unvaccinated person.

Have the effectiveness numbers changed?

Yes, decline in effectiveness against infection is seen in some studies. A few have also raised concerns that protection against serious illness may also be diminished, particularly in older people and patients with underlying medical conditions.

Reasons for the decline vary. First, when the vaccines were authorized, much of the U.S. was under tighter pandemic-related stay-at-home rules. Nearly a year later, restrictions — including mask rules — have loosened in many areas. More people are traveling and going into situations they would have avoided a year ago. So, exposure to the virus is higher.

Some studies from the U.S. and abroad show that time elapsed since vaccination also plays a role. The Lancet recently published a study of more than 3.4 million Kaiser Permanente members, both vaccinated and not, reviewing the effectiveness of the Pfizer vaccine. It showed an overall average 73% effectiveness against infection during the six months after inoculations, and an overall 90% effectiveness against hospitalization.

But protection against infection declined from 88% in the month after full vaccination to 47% at five to six months. Time since vaccination played a larger role than any changes in the virus itself, the researchers concluded.

“It shows vaccines are highly effective over time against severe outcomes,” said lead author Sara Tartof, an epidemiologist with the Department of Research and Evaluation for Kaiser Permanente Southern California. “Against infection, it does decline over time, something that is not unexpected. We have boosters for many other vaccines.”

The virus, too, has mutated.

“Along came delta,” said Dr. William Schaffner, a professor of preventive medicine at Vanderbilt University School of Medicine. “Because this virus was so highly contagious, it changed the outcomes slightly.”

And some vaccinated people can fall seriously ill with covid, or even die, especially if they have an underlying medical problem, as was the case with Gen. Colin Powell. He died of covid complications even though he was fully vaccinated — likely because he also had a blood cancer called multiple myeloma, which can lower the body’s response to an invading virus as well as to vaccination.

Why are they recommending booster shots?

Most scientists, researchers and physicians say the vaccines are working remarkably well, especially at preventing serious illness or death. But it’s not unusual to need more than one dose.

Vaccines for shingles and measles both require two shots, while people need to be revaccinated against tetanus every 10 years. Because influenza varies each year, flu shots are annual.

Immune response is often better when vaccines are spaced apart by a few months. But during the rollout of the covid vaccines, so many people were falling ill and dying of covid each day that the Food and Drug Administration and CDC decided not to delay, but to authorize the first and second doses within about a month of each other.

“We learn as we go along,” said Schaffner. “It was always anticipated there might have to be follow-up doses.”

Now, the recommendations call for a second dose for anyone who received a J&J shot at least two months prior. For those who received the two-dose Pfizer or Moderna vaccine, the recommendation is to wait six months after the second dose to get a booster, which is currently recommended for those who are 65 and older; have any of a variety of underlying health conditions; live in congregate settings, such as nursing homes; or have jobs that put them at higher risk. The booster recommendations may expand in the coming months.

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