Can Two Questions Identify ‘High Risk’ Pain Patients?

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

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

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

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

Is Your Personal Health Data For Sale?

By Pat Anson, PNN Editor

Many U.S. consumers believe their personal health information is protected under the Health Insurance Portability and Accountability Act (HIPPA), a federal law that requires healthcare providers and insurers not to share a patient’s sensitive health information without their consent or knowledge.

A new study on consumer data brokers and a federal complaint against a popular drug discount service show otherwise, with patient names, social security numbers, email addresses, prescription drug use and other personal information routinely being sold to third parties.

The Duke University study on data brokers focused only on mental health records, but gives you a good idea of what’s available on the open market. When researcher Joanne Kim contacted 37 data brokers asking to buy mental health data on millions of patients, 11 of them offered to sell her the requested data, which included information about whether an individual was being treated for depression, anxiety or insomnia, and if they were prescribed drugs such as Prozac or Zoloft.

The asking price for the information was relatively cheap, with one broker offering data on 10,000 aggregated patient records for $2,000 – or 20 cents per record. The cost was even cheaper if the data was ordered in volume; 435,780 records were available for 6 cents each.

Many of the brokers did not provide Kim with a full explanation about their data or where it came from, making it difficult to determine whether the company was offering “deidentified” information. Some firms openly advertised data that included individual names, addresses, phone numbers and emails. One broker even offered to sell her the IP addresses and browser history of patients.

“This research highlights a largely unregulated data brokerage ecosystem that sells sensitive mental health data in large quantities, with either vague or entirely nonexistent privacy protections,” Kim wrote in her report. “Data brokers are collecting, aggregating, analyzing, circulating, and selling sensitive mental health data on individuals. This comes as a great concern, especially since the firms seem either unaware of or loosely concerned about providing comprehensive privacy protections.”

Due to the stigma associated with mental health problems, Kim says the easy availability of personal health data puts millions of patients at risk of discrimination from employers and insurers, or even theft from scammers who prey on vulnerable populations.

“The nation is in dire need of a comprehensive federal privacy law, and this report recommends that the federal government should also consider generally banning the sale of mental health data on the open market,” she wrote. “Such a law should include provisions that allow consumers to opt out of the collection of their data, gain access to their information, and correct any discrepancies. Furthermore, data brokers should be obligated to be more transparent about their use and exchange of data, as well as have more controls in place for client management.”

One potential “client” that Kim doesn’t mention is law enforcement. In 2020, the Drug Enforcement Administration asked data brokers to submit bids on a potential contract for a surveillance program that would track at least 85% of U.S. prescriptions for opioids and other controlled substances. The DEA was seeking “unlimited access” to this prescription data, including the names of prescribers and pharmacists, types of medication, quantity, dose, refills and forms of payment.

While the contract was never awarded, it remains unclear what the DEA planned to do with the information or if it has found other ways to collect the data.

GoodRx Settlement

Where and how is personal health data collected? It could be as simple as a consumer trying to save money on medications.

The Federal Trade Commission recently reached a $1.5 million settlement with prescription drug discount provider GoodRx for failing to notify consumers that it was selling their information to Facebook, Google and other third parties for advertising purposes.

GoodRx offers considerable savings to patients who enroll in its free drug discount program, and makes money by selling their health and contact information to third parties. For example, according to the FTC complaint, GoodRx shared patient health data with Facebook, which then targeted them with advertisements for specific drugs to treat their health conditions.

“GoodRx’s sharing of personal and health information has revealed highly sensitive and private details about its users, most of whom suffer from chronic health conditions. This has led to the unauthorized disclosure of facts about individuals’ chronic physical or mental health conditions, medical treatments and treatment choices, life expectancy, disability status, parental status, substance addiction, sexual and reproductive health, and sexual orientation, as well as other information,” the FTC said.

“Disclosure of this information without authorization is likely to cause GoodRx users stigma, embarrassment, or emotional distress, and may also affect their ability to obtain or retain employment, housing, health insurance, disability insurance, or other services.”

In a press release, GoodRx said the FTC was focusing on an “old issue” that it addressed and corrected three years ago. “Millions of Americans use GoodRx to save on their healthcare, and we take strong measures to ensure they can trust us with their information,” the company said.

Data mining isn’t limited to healthcare providers, advertisers, internet companies or law enforcement. Medical researchers also use it, to track and evaluate patient conditions and the effectiveness of treatments. Some would also like to use data to predict patient outcomes.

In a new study, researchers at the University of Alberta said they had devised a form of artificial intelligence -- based on patient health data -- that can predict with 90% accuracy whether a patient is at risk of an adverse outcome from opioid prescriptions. Researchers say their model could be used someday to warn doctors about high-risk patients, so they can prescribe another drug or give smaller doses.

Experimental Blood Test Could Improve Fibromyalgia Treatment

By Pat Anson, PNN Editor 

Finding effective treatment for fibromyalgia has always been problematic. The Food and Drug Administration has approved three drugs for fibromyalgia, but many patients find pregabalin (Lyrica), duloxetine (Cymbalta) and milnacipran (Savella) ineffective in treating the widespread body pain, fatigue, depression and “brain fog” that are common symptoms of fibromyalgia.  

A small pilot study suggests an experimental blood test for fibromyalgia – called FibroGENE -- could be used to determine which drug works best for each patient. Researchers at AMPEL BioSolutions and Duke University Medical Center found genetic biomarkers in the blood cells of 18 lupus patients with fibromyalgia-like symptoms. Their findings, published in the journal Lupus Science and Medicine, could lead to patients getting more effective, personalized treatment through genetic profiling.

“The bottom line is that we found the driving pathways for fibromyalgia that can be targeted by drugs that are already on the market,” said Amrie Grammer, PhD, Ampel’s co-founder and President.

“This is a disease management tool. This is meant for patients who know they have fibromyalgia, either on its own or in the context of another disease, such as lupus, and will be a game changer because treatment is often by trial and error. The doctor says, ‘Try this, let me know if it doesn’t work and try that.’ It often takes years, if ever, to get on a medication or medications that relieve the brain fog, the pain, etc.”  

Lupus is an autoimmune disease in which the body attacks its own tissues and organs, causing pain and inflammation. Like fibromyalgia, lupus is difficult to diagnose because its symptoms mimic those of other pain conditions. Genetic profiling of patients helps reduce the guesswork in treatment.

“The gene expression profiles of patients with fibromyalgia or type 2 lupus with fibromyalgia suggest both available drugs and new drugs that might be tested in patients with extensive pain and fatigue,” says study co-author David Pisetsky, MD, Rheumatologist and Professor of Medicine at Duke.

“Moreover, the gene expression profiles suggest a means to match patients with specific drugs. This opens a novel area of precision therapeutics for each individual patient rather than the trial and error approach currently employed.”

Larger studies are needed to prove the viability of Ampel’s blood test, but the company’s goal is to make FibroGENE commercially available by 2024 or 2025. Ampel is currently looking for fibromyalgia patients to participate in its clinical trials.

Green Eyeglasses Improve Anxiety and Wellness in Fibromyalgia Patients

By Pat Anson, PNN Editor

Fibromyalgia is well known as one of the most difficult chronic pain conditions to treat. The Food and Drug Administration has approved a handful of medications for fibromyalgia, but many patients find them ineffective in treating the muscles aches, joint pain, fatigue, anxiety and other symptoms that are common in fibromyalgia.  

Researchers at Duke University may have found an easy way to reduce some of those symptoms without the use of drugs. In a small study of fibromyalgia patients being treated with opioids, those who wore eyeglasses with specially tinted green lenses reported a significant improvement in their anxiety and overall sense of wellness. And while their pain levels were unchanged, their use of opioids declined.

“My research has been focused heavily on finding alternatives to opioids for pain management,” says lead author Padma Gulur, MD, Executive Vice Chair of the Department of Anesthesiology at Duke University. “One of the things we discovered early on was that there were visually mediated triggers for pain. We definitely could see that with headaches, but also that it could actually impact pain itself, the pain pathways. While we still don’t fully understand the mechanism of how pathways for pain get activated with visual mediation, it definitely does happen.

“We narrowed it down over some years to the hypothesis that with green light, particularly in the green spectrum, there was an opportunity where it was influencing pain, both chronic pain and acute pain.”

Previous research has found that green light therapy has a calming effect on the brain and is useful in treating fibromyalgia and migraines. But in those studies, participants were confined to a room where they were immersed in green light and told to avoid activities like watching TV or using their cellphones.

Gulur thought there must be an easier way to experience the benefits of green light.

“People want pain relief, but they also want to live their lives. And spending hours and hours in a room or exposure takes away from that quality of life,” she told PNN. “On the other hand, wearing eyeglasses is something we’re all very comfortable doing and, thankfully these days, colored eyeglasses are all the thing.”

Gulur and her colleagues studied 34 fibromyalgia patients who were randomly selected to wear various shades of eyeglasses at least four hours a day for two weeks: 10 patients wore blue eyeglasses, 12 wore clear eyeglasses and 12 wore green eyeglasses.

DUKE UNIVERSITY

Their findings, presented this week at the annual meeting of the American Society of Anesthesiologists, showed that participants who wore green eyeglasses were four times more likely to have reduced anxiety than those in the other two groups, who reported no reduction in anxiety. They also reported feeling better.

“We found that although their pain scores remained the same, those who wore the green eyeglasses used fewer opioids, demonstrating that their pain was adequately controlled,” said Gulur, who noted that patients who wore the green eyeglasses asked if they could keep them at the end of the study.

“They didn’t want to give them back. We had no trouble getting the blue and the clear back, but none of them wanted to return the green glasses.”

Unfortunately, they had to give them back. The eyeglasses are specially formulated to filter a specific wavelength on the green light spectrum and were needed for further study. You can’t buy the glasses online or at your local drug store. At least not yet.

Gulur and her team are planning further studies with green eyeglasses on patients with diabetic neuropathy and chronic back pain.

Experimental Gel Could Replace Damaged Knee Cartilage

By Pat Anson, PNN Editor

Clinical trials on humans may begin as soon as next year on an experimental hydrogel designed to replace damaged cartilage in arthritic knees, according to researchers at Duke University, who say the gel is up to three times stronger than natural cartilage.   

Implants made of the material are currently being tested on sheep by Sparta Biomedical, a medical device company that is developing a line of synthetic cartilage.

“If everything goes according to plan, the clinical trial should start as soon as April 2023,”  Benjamin Wiley, PhD, Sparta’s chief technology officer and a Duke chemistry professor, said in a press release. “I think this will be a dramatic change in treatment for people.”

Wiley says hydrogel implants could someday be used as an alternative to total knee replacement surgery, one of the fastest growing elective procedures in the United States. About one in six adults suffer from knee osteoarthritis, a painful disorder that leads to thinning of cartilage and progressive joint damage.

Often considered the treatment of last resort, knee replacement surgery can be problematic. Studies have found that about a third of the patients who have their knees replaced continue to experience chronic pain. The artificial joints also have a limited life span and sometimes need to be replaced after a few years.   

“There's just not very good options out there,” said Wiley.

To make the hydrogel, Wiley and his team took thin sheets of cellulose fibers and infused them with a water absorbing polymer, creating a Jello-like material that is surprisingly strong. The cellulose fibers act like the collagen in natural cartilage, giving the gel strength when pulled or stretched.

Natural cartilage can withstand up to 8,500 pounds per inch of tugging and squishing before reaching a breaking point. The hydrogel can handle even more pressure and is 66% stronger than cartilage when compressed, the equivalent of parking a car on a postage stamp.

“It’s really off the charts in terms of hydrogel strength,” Wiley says.

Duke researchers first reported in 2020 that they had developed a hydrogel strong enough for knees, but using it to replace cartilage presented some design challenges. Hydrogels are difficult to attach directly to bone or cartilage to keep them from breaking loose or sliding off during intense activities.

They got around that problem by cementing and clamping the hydrogel to a titanium base, which is then anchored into a small hole where the damaged cartilage used to be. Tests showed the design stays fastened 68% more firmly than natural cartilage on bone.

In wear tests, the researchers took the hydrogel and natural cartilage and spun them against each other a million times, with a pressure similar to what the knee experiences during walking. Using high-resolution X-ray imaging, they found that the artificial cartilage held up three times better than the real thing.

DUKE UNIVERSITY IMAGE

And because the hydrogel mimics the smooth and cushiony nature of real cartilage, it protects other joint surfaces from being damaged as they slide against the implant. Other researchers have tried replacing cartilage with implants made of metal or polyethylene, but because those materials are stiffer than cartilage, they can chafe against other parts of the knee.

The research study, published in the journal Advanced Functional Materials, was funded by Sparta Biomedical and Duke University.

An experimental gel also shows promise as a treatment for low back pain caused by degenerative disc disease, according to a recent small study. Hydrafil – an injectable gel developed by ReGelTec – fills in cracks and tears in damaged discs, restoring the disc’s structural integrity. The injection procedure is minimally invasive and only takes about 30 minutes.

U.S. Ranked Poorly in End-of-Life Care

By Pat Anson, PNN Editor

The U.S. healthcare system barely gets a passing grade in caring for dying patients, ranking well behind most developed countries and even some third world nations, according to a new analysis of end-of-life care around the world.

The United Kingdom earned the highest ranking in the study, followed by Ireland, Taiwan, Australia, South Korea and Costa Rica, which all earned A grades. The U.S. earned a C grade, ranking 43rd of the 81 countries evaluated. Nigeria, Guatemala, Botswana, Romania, Mongolia and several other low-income countries had higher grades than the U.S.  

“Many individuals in both the developed and developing world die very badly – not at their place of choice, without dignity, or compassion, with a limited understanding about their illness, after spending down much of their savings, and often with regret about their course of treatment. These things are very common,” lead author Eric Finkelstein, PhD, a palliative care expert and professor at Duke University’s Global Health Institute, said in a news release.

Top 10 Countries on Quality of Death Index

SOURCE: LIEN FOUNDATION

The study findings, recently published in the Journal of Pain and Symptom Management, are based on a survey of 181 palliative care experts around the world who were asked how well their own countries provided for the physical and emotional wellbeing of dying patients.

Over a dozen health factors were evaluated, including pain management, being treated kindly, affordability, spiritual and emotional needs, and providing patients with a clean and safe space. Treatments that address quality of life, rather than just extending life, were also an important consideration.          

“Perhaps the main conclusion from this important exercise is that most people in the world die badly -- many through no treatment at all and many through excessive often futile treatment that increases suffering,” says Richard Smith, a palliative care expert and former editor of the British Medical Journal.

It’s no surprise that most developed countries with well-funded healthcare systems rated highly in end-of-life care, while poorer countries fared worse.

“The overwhelming need for palliative care is in low and middle-income countries, where less than a third of services exist,” said co-author Stephen Connor, executive director of the Worldwide Hospice Palliative Care Alliance.

The obvious exception to that is the United States’ lackluster rating. Researchers say that’s because healthcare decisions in the U.S. are often based on last-ditch efforts to extend life, rather than ensuring comfort and quality of life in a patient’s final days.  

“We spend so much money trying to get people to live longer, but we don’t spend enough money in helping people die better,” says Finkelstein, who is also the director of the Lien Centre for Palliative Care at Duke-NUS.

The study was funded by the Lien Foundation, a Singapore-based nonprofit focused on improving quality of life. Previous surveys of palliative care experts by the foundation ranked the U.S. 9th on the “Quality of Death” index in 2010 and in 2015.

Finkelstein says the covid pandemic has opened a window into end-of-life care, with millions of patients spending their dying moments alone, often separated from their families and without emotional support.

“Generally, people don’t talk about death. COVID has made it less taboo. We have an opportunity to continue this discussion and not just help COVID patients, but to help everyone have a better end-of-life experience,” he said.

Finkelstein hopes the study will spur action from policymakers to improve conditions for dying patients, such as loosening restrictions on pain medication. A recent study in Oregon found that overzealous enforcement of opioid guidelines led to a significant decrease in opioid prescribing to patients being admitted to hospice, resulting in some terminally ill patients suffering needlessly.

Finkelstein urges people to ensure a better end-of-life experience for themselves and their loved ones by making an end-of-life plan and discussing it with family and friends.

“Do an advanced care plan or at least express your wishes to friends and family,” Finkelstein says. “Don’t wait. By the time you fall ill, it may be too late and folks may not know what you want.”

Old Cancer Drug May Have New Purpose Treating Chronic Pain

By Pat Anson, PNN Editor

Over the years, several drugs that were developed to treat medical conditions such as epilepsy and depression have been repurposed as treatments for chronic pain — often with mixed results. Pregabalin (Lyrica) and duloxetine (Cymbalta) are just two examples.

A team of researchers at Duke University may have found a new pain medication while looking through what they call the “junkyard of cancer drugs.” They analyzed over 1,000 compounds contained in Compound Libraries at the National Cancer Institute, looking for drugs that reset genetic switches that control neurotransmission. Their goal was to find a drug that doesn’t just temporarily block pain signals, but changes the underlying mechanism that causes pain sensation.  

“Because chronic pain, like many chronic diseases, has an important root in genetic switches being reprogrammed in a bad way, a disease modifying treatment for chronic pain should reset the genetic switches, not just cover up the pain, as with opioid and aspirin/Tylenol-like painkillers." said Wolfgang Liedtke, MD, an adjunct professor of neurobiology at Duke and an executive scientist at Regeneron Pharmaceuticals.

Liedtke and his colleagues identified four promising compounds. Among them was kenpaullone, a drug developed over 20 years ago that inhibits neurotransmission by activating a gene called Kcc2. When Kcc2 is enhanced, it reduces chloride levels in nerve cells and silences pain signals.

In laboratory mice, Liedtke's team found that kenpaullone significantly reduced pain caused by nerve injury and bone cancer. The pain relief was long-lasting, which is consistent with the drug stopping pain signals through gene regulation.

"At this stage, we knew we had met the basic requirement of our screen of shelved cancer drugs, namely identified Kcc2 gene expression-enhancers, and demonstrated that they are analgesics in valid preclinical pain models,” Liedtke explained in a university press release.

Encouraged by their findings, Liedtke's team assessed whether kenpaullone affects spinal cord processing of pain and whether kenpaullone treatment can reduce chloride levels in pain-relaying neurons. Both sets of experiments on laboratory mice produced positive results.

The research findings, published in the journal Nature Communications, suggest that kenpaullone and gene therapy both have the potential to become treatments for chronic refractory pain conditions, such as neuropathy, cancer bone pain, trigeminal neuralgia, and other forms of chronic pain associated with poor Kcc2 function.

Controlling pain through experimental gene therapy is in its early stages, but has produced some intriguing results. In a study earlier this year, researchers at the University of California San Diego used a gene editing tool to alter a gene that senses pain in mice. The suppressed gene increased pain tolerance, lowered pain sensitivity and provided months of pain relief without the use of drugs.