Blood Pressure Meds May Help Treat Osteoarthritis

By Pat Anson, PNN Editor

People who suffer from osteoarthritis have few pain-relieving options outside of surgery and joint replacement. Opioids are usually not prescribed for osteoarthritis (OA) and over-the-counter drugs such as acetaminophen provide only mild relief or may have side effects if taken too often.

Some OA patients may have another treatment option already sitting in their medicine cabinets: blood pressure medication.

In a retrospective study, researchers at the University of Nottingham analyzed health data for over 223,000 people in the UK and found that patients taking two beta-blockers commonly prescribed for high blood pressure -- propranolol and atenolol -- made fewer trips to the doctor to be treated for knee and hip pain compared to those who don’t use the drugs. When patients stopped taking propranolol and atenolol, they had more office visits for joint pain.

The findings, recently published in the journal Rheumatology, suggest that beta-blockers have analgesic properties and may even slow the progression of osteoarthritis, a joint disorder that leads to thinning of cartilage in the knees, hips, fingers and spine. About 10% of men and 18% of women over age 60 have some form of osteoarthritis. .  

"Our findings suggest that atenolol could be considered for people with osteoarthritis and comorbidities for which beta blockers are indicated," co-authors Georgina Nakafero, PhD, and Abhishek Abhishek, PhD, said in a news release. "Similarly, propranolol may be a suitable analgesic for people with OA and comorbid anxiety.

"If these findings are confirmed in independent studies, and in a confirmatory randomized controlled trial, it may change clinical practice."

Previous research has suggested that beta-blockers have antinociceptive effects that help block pain signals. A 2017 study found the drugs lowered pain scores and reduced opioid use in 873 patients with OA. But a larger study failed to confirm those findings.

Two FDA advisory committees recently voted against recommending tanezumab, an experimental non-opioid pain reliever, as a treatment for osteoarthritis due to possible side effects. The agency has yet to make a final decision on the drug. If approved, tanezumab would be the first new class of medication for osteoarthritis in well over a decade.

Positive Results From Stem Cell Trial for Knee Osteoarthritis

By Pat Anson, PNN Editor

A California stem cell company has announced positive results from a small, early-stage clinical trial of an experimental stem cell therapy for knee osteoarthritis.  

The Phase 1/2a trial conducted by Personalized Stem Cells (PSC) involved 39 patients with knee osteoarthritis who were given a single injection of autologous mesenchymal stem cells derived from their own body fat. Safety was the primary objective of the trial and there were no serious adverse events reported by the company.

The secondary objective of the trial was to assess the effectiveness of the therapy with the Knee Injury and Osteoarthritis Outcome Score (KOOS), a survey that asks patients about their pain, other symptoms, daily function, quality of life, and recreational activities. Nearly 80% of study participants improved above the “minimal important change” (MIC), with an average improvement over baseline of 2.2 times the MIC.

Osteoarthritis is a progressive joint disorder caused by painful inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine.

Results from the PSC study have been submitted to the FDA for review. The company hopes to get approval for a larger, Phase 2 randomized study of its stem cell therapy later this year.  

“We are pleased at the strong safety profile and efficacy results in this FDA-approved clinical study of stem cell therapy for knee osteoarthritis,” said PSC founder and CEO, Dr. Bob Harman. “We are proud to have reached this milestone in our first FDA approved clinical trial. This data supports our progress in the larger placebo-controlled clinical study.”

Veterinarians Already Using Stem Cells

While the FDA has approved hundreds of clinical trials of stem cells, it has not approved a single stem cell product as a treatment for arthritis or any orthopedic condition. That hasn’t stopped stem cell clinics from offering regenerative medicine to patients or veterinarians from using it on animals.

VetStem Biopharma, the parent company of PSC, pioneered the use of adipose derived stem cells in veterinary medicine. Its laboratory has processed stem cells for nearly 14,000 dogs, cats, horses and other animals for use by veterinarians in the U.S. and Canada.

“The 15 years of veterinary experience with adipose derived stem cell therapy of our parent company, VetStem Biopharma, provided the basis for our FDA study submission and approval and provided valuable insights into the study design and conduct,” said Harman.

In addition to the Phase 2 trial for osteoarthritis, PSC plans to pursue FDA approval for a stem cell trial to treat traumatic brain injuries in humans. A clinical study using PSC’s stem cell platform to treat respiratory distress syndrome in COVID-19 patients is currently underway.

FDA Panels Say New Arthritis Drug Too Risky

By Pat Anson, PNN Editor

Two FDA advisory committees have voted against recommending an experimental non-opioid pain reliever as a new treatment for osteoarthritis, dealing a potential death blow to a drug that’s been under development for 15 years.

On a nearly unanimous 19 to 1 vote, the FDA’s Arthritis Advisory Commitee and Drug Safety and Risk Management Advisory Committee decided that the benefits of tanezumab do not outweigh its possible safety risks, which include the acceleration of osteoarthritis in some patients.  Advisory committee recommendations are not binding on the FDA, but they are likely to carry a good deal of weight when the agency makes a final decision on tanezumab.

Pfizer and Eli Lilly are jointly developing tanezumab, an injectable humanized monoclonal antibody that targets nerve growth factor (NGF), a protein that increases in the body due to injury, inflammation or chronic pain. Tanezumab binds to NGF and inhibits pain signals from muscles, skin and organs from reaching the brain.

FDA reviewers released a report this week saying tanezumab works as a pain reliever, but the effect “is modest, and there is no convincing evidence of a superior efficacy” over non-steroidal anti-inflammatory drugs (NSAIDs), the current standard treatment for osteoarthritis.

More concerning are the potential side effects of tanezumab, the most serious being rapidly progressing osteoarthritis that is so severe some patients need total joint replacements. Investigators say tanezumab also appears to affect healthy joints and causes “abnormal peripheral sensation” similar to carpal tunnel syndrome.

The side effects of tanezumab have been known for over a decade. The FDA slowed the development of tanezumab and other NGF inhibitors in 2010 because of concerns they make osteoarthritis worse in some patients.

Under pressure to approve more non-opioid pain relievers, the FDA allowed clinical studies of tanezumab to resume in 2015 and two years later gave it “fast track” designation to help speed its development.

Pfizer and Eli Lilly have conducted dozens of clinical trials evaluating the safety and efficacy of tanezumab on more than 18,000 patients. The companies at one time considered, but then abandoned plans to develop tanezumab as a treatment for chronic low back pain after 10% of patients given high doses developed joint pain and other side effects.

Critics say its time to finally throw in the towel on tanezumab.

“The drug is unsafe. It accelerates the underlying joint disease. And according to the FDA, even if you stop the drug early on, there’s evidence you can still progress to having these joint problems,” Michael Carome, director of Public Citizen’s Health Research Group, told PNN.  “The decision here is clear cut. The drug should not be approved. And in our view, no further studies on this drug should be done. Because it would be unethical to continue to expose people to this drug where the harm is clear and there’s no real benefit.”

A Pfizer spokesman said the company would continue to seek approval for tanezumab, despite the committees’ recommendation.

“While we are disappointed in today’s outcome, we continue to believe that the clinical data presented for tanezumab supports its benefit-risk profile,” Jim Rusnak, chief development officer for Pfizer, said in a statement. “The patients whom we aim to help with tanezumab are suffering from significant, debilitating osteoarthritis pain and have exhausted available medical therapies and are hopeful for new, non-opioid treatments. We will continue to work with the FDA to determine next steps.”

Osteoarthritis is a progressive joint disorder caused by painful inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine. The World Health Organization estimates that about 10% of men and 18% of women over age 60 have some form of osteoarthritis.

Injections of Tiny Particles Reduce Osteoarthritis Knee Pain

By Pat Anson, PNN Editor

A minimally invasive procedure significantly reduces pain and inflammation caused by knee osteoarthritis, according to preliminary research being presented this week at the annual meeting of the Society of Interventional Radiology.

Geniculate artery embolization (GAE) is a relatively new procedure in which thousands of microscopic particles are injected into arthritic knees. The particles reduce inflammation by disrupting the abnormal flow of blood caused by osteoarthritis (OA), a joint disorder that causes thinning of cartilage and progressive joint damage. As the cartilage breaks down, it releases enzymes that cause inflammation and pain.

GAE takes about one to two hours, and many patients with knee OA report significant improvement in pain and physical function that can last up to a year.

"Prior to treatment, patients' knee pain had taken over their whole life," said lead researcher Siddharth Padia, MD, a professor of radiology at UCLA Health. "But after treatment, patients who initially could walk only three or four blocks were walking three miles. Some were able to do away with walking aids, such as canes, while others reported being in a better mood now that they were living without pain."

For their Phase 2 study, Padia and his colleagues enrolled 40 patients with knee OA who were not candidates for total knee replacement, and who failed to benefit from pain relievers, joint injections and physical therapy.

Catheters were inserted into arteries leading to the knees through pinhole incisions in the patients’ hips. The microscopic particles — called Embozene microspheres — were then slowly injected through the catheter into the knees. Each patient was evaluated for pain and adverse events at one week; one, three and six months; and one year after the treatment.

Researchers say patients saw benefits as soon as three days after the procedure. Average pain levels decreased from 8 out of 10 before GAE to 3 out of 10 within the first week. Most patients reported more than 50% reduction in their pain levels at the one-year follow up.

Adverse events, such as skin ulceration and small bone infarction – the death of bone tissue due to reduced blood supply -- were reported by 9 patients, but resolved without treatment.

Embozene microspheres are made by Boston Scientific and are currently used in the treatment of vascular tumors, uterine fibroids and arterial malformations. They must be carefully injected into affected tissue to prevent them from circulating in the blood and reaching healthy tissue and organs.

“This prospective trial demonstrates that GAE is highly effective and durable in reducing symptoms due to moderate to severe knee OA that is refractory to other conservative therapy, and has an acceptably low toxicity profile,” researchers concluded.

The UCLA researchers plan to conduct a larger, randomized trial to determine which patients may benefit most from GAE and the impact it has on slowing the progression of arthritis.

Results from other studies on the use of GAE are also being presented at the meeting of the Society of Interventional Radiology. One review found that GAE can be effective for patients who don't respond well to conservative treatments for knee OA, but cautioned that “definitive conclusions can't be made on the true efficacy of GAE until studies are done with longer follow up and larger patient numbers.”

Latina and Asian Women at Significantly Higher Risk from Lupus  

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

Antidepressants Ineffective for Back Pain and Osteoarthritis

By Pat Anson, PNN Editor

Antidepressants like duloxetine (Cymbalta) are increasingly being prescribed to treat various types of pain, but a new study shows the medications are largely ineffective for people suffering from chronic back pain or osteoarthritis and may even cause harm.

Many clinical guidelines recommend using antidepressants as pain relievers – even when depression is not involved -- yet evidence supporting that use is uncertain. To address that knowledge gap, researchers at the University of Sydney reviewed data from 33 controlled trials involving more than 5,000 adults who took antidepressants for low back or neck pain, sciatica, or hip or knee osteoarthritis.

Their findings, published in The BMJ, show that for people with back pain the effects of antidepressants were too small to be worthwhile, but for those with osteoarthritis there may be a small beneficial effect.

“The use of antidepressants to treat people with chronic back pain and osteoarthritis is increasing worldwide, but prior to our work, it was not clear whether antidepressants relieved pain or were safe,” said lead author Dr. Giovanni Ferreira, PhD, a postdoctoral research fellow at the Institute for Musculoskeletal Health at the University of Sydney. 

“We conducted a review of all randomised clinical trials evaluating the efficacy of antidepressants for people with back pain or knee osteoarthritis and found that for back pain the antidepressants were either ineffective or provided a very small effect, which was unlikely to be perceived as worthwhile by most patients. For people with osteoarthritis, effects were still small, but could be potentially perceived as worthwhile by some patients” 

Ferreira and his colleagues reviewed six classes of antidepressants: serotonin-noradrenaline reuptake inhibitors (SNRIs); selective serotonin reuptake inhibitors (SSRIs); noradrenaline-dopamine reuptake inhibitors (NDRIs); tricyclic antidepressants; and tetracyclic antidepressants. 

Results showed that SNRIs such as duloxetine reduced back pain after three months, but the benefits were so small they were unlikely to be considered clinically important to most patients. SNRIs had a slightly stronger effect on sciatica and osteoarthritis pain. 

Tricyclic antidepressants were ineffective for back pain, but might reduce pain in people with sciatica, although the evidence for that was weak.  

Industry Funded Studies 

Importantly, about two-thirds of people taking SNRI antidepressants experienced an adverse event such as nausea, fatigue, mood swings and weight gain.

“Many people are being treated with these medications that may not be helping their pain and may be doing them harm,” said Ferreira, adding that doctors need to be upfront with patients about possible side effects.

Researchers say the long-term effects of antidepressants prescribed for chronic pain are not well known and many of the studies that do exist were sponsored by industry, raising the risk of bias. 

Many people are being treated with these medications that may not be helping their pain and may be doing them harm.
— Dr. Giovanni Ferreira

“Large, definitive trials free of industry ties are urgently needed to evaluate the efficacy of antidepressants,” Ferreira said. “There needs to be more transparency about how evidence coming from those trials is appraised by guideline panels. A good starting point would be to consider all industry-funded trials to be at high risk of bias, and downgrade the strength of recommendations where industry-sponsored trials represent an important part of the available evidence.”

The Food and Drug Administration recently approved duloxetine as a treatment for fibromyalgia in pediatric patients, largely on the basis of a small trial conducted by Eli Lilly, Cymbalta’s manufacturer. Children enrolled in the study did show a modest improvement in pain, but several of them had serious adverse events, including two attempted suicides, suicidal thoughts, an intentional drug overdose, depression and hallucinations.

In their published findings in the journal Pediatric Rheumatology, Eli Lilly researchers downplayed the adverse events associated with duloxetine, saying they were not drug related or “not significantly different” than those of children on placebo. The two attempted suicides aren’t even mentioned.

A common complaint of patients who take duloxetine is how quickly they become dependent and what happens when they stop taking the drug. Many complain of severe withdrawal symptoms, including electric-like sensations called “brain zaps.”

Duloxetine’s checkered history is well known at the FDA. The agency’s adverse events reporting system has recorded nearly 35,000 cases involving duloxetine since 2007, most of them classified as psychiatric disorders. Over 4,000 of those adverse events resulted in death.

Weather App Provides Personalized Pain Forecast

By Pat Anson, PNN Editor

Like many people who live with arthritis, Dave Richtor noticed that cold and wet weather made his joints ache more than usual.

“I’ve always just been stiffer and slower on grey days,” says Richtor, who lives in the seaside city of Brighton, south of London. “I’m in bed for ten hours a day. When I’m waking up and stiff, there’s obviously been in the night a temperature change.

“My grandma used to know when a storm was coming 20 minutes before it happened. She’d say, ‘Oh, a storm is coming. I’m getting a headache.’”

Feeling “under the weather” is more than just family folklore. Richtor was intrigued by a recent University of Manchester study called Cloudy With a Chance of Pain, which analyzed data from over 10,000 UK residents who recorded their daily pain levels on a smartphone app. The GPS location of their phones was then compared to local weather conditions.

The study found a modest association between weather and pain, with people more likely to feel muscle aches and joint pain on days with low barometric pressure – and the wet and windy weather that usually comes with it.

The study not only gave credibility to a link between weather and pain, it gave Richtor an idea. Why not create an app that gives users a personalized pain forecast? Many apps track the weather and some keep track of pain levels, but there were no apps that married the two.  

“I’ve done extensive research into it, and can’t see those two things matching up,” Richtor told PNN. “Most people I know in this field have been like, ‘Why hasn’t anyone done this before?’”

That’s the inspiration behind Weather Flare, a free health app designed to help people with chronic pain anticipate changes in the weather and their pain levels. Users create a personal profile of their conditions, medications and symptoms, which are then compared to weather conditions provided by AccuWeather. The app “learns” from user input and develops a customized forecast to help people prepare for changes in their symptoms. 

Richtor is currently holding a Crowdfunding campaign to raise money for further upgrades to the Weather Flare app.

Weather Flare is not just for pain sufferers. Richtor says people with asthma, allergies and other health conditions can benefit from knowing about weather conditions such as air quality and pollen counts.

He’s also working with a professor at the University of Sussex to develop a database to warn of drug interactions caused by the weather. For example, people with psoriasis who take methotrexate can be sensitive to prolonged sunlight.

“We’re incredibly excited to have the University of Sussex onboard to assist us with further developments for our app, making Weather Flare even more supportive for sufferers,” says Richtor. “The positive thing about me just having this crazy idea in my head, is that I can help other people manage their own conditions. If it just makes 1% of difference to someone’s day, then I’ve achieved what I set out to do.” 

The app is still in beta stage – meaning the developers are still working out some technical issues. When I downloaded the app, it was unable to recognize my location despite repeated attempts.

Weather Flare is not just for people in the UK. Because AccuWeather provides forecasts and weather conditions around the world, it can be used anywhere. To download the app, click here.

Migraine and Arthritis Patients Report More Pain During Pandemic

By Pat Anson, PNN Editor

Two new surveys are opening a window into how migraine and arthritis patients are managing their pain and getting treatment during the coronavirus pandemic. Many remain fearful about visiting a provider and want insurers to make access to medication easier.

The first survey, conducted by the Headache & Migraine Policy Forum, found a significant increase in stress and migraine attacks in over 1,000 U.S. migraine patients who were surveyed over the summer.

Asked how COVID-19 had impacted their health and treatment, over two-thirds (69%) of patients said they were experiencing an increase in monthly migraines. Eight out of ten (84%) said they felt more stress managing their disease (84%) and over half (57%) said their overall health had worsened.

“Treating a debilitating condition like migraine disease during a global pandemic can increase stress for patients, many of whom already struggle with day-to-day activities. Added stress can mean more frequent attacks, resulting in more visits to see a health care provider or even costly ER visits,” the Policy Forum said.

But while the frequency of migraine attacks increased, many patients were reluctant about seeing a provider and potentially exposing themselves to COVID-19. Six out of ten (61%) said they were afraid to seek care at a doctor’s office or hospital, and 74% were hesitant to visit an emergency room when having an acute migraine attack.

Some insurers have relaxed rules about prior authorization and step therapy to make access to medication easier during the pandemic. But most migraine patients say their own insurers need to be more flexible.

  • 72% had difficulty managing their migraine because they couldn’t get a longer supply of medication

  • 73% said insurers did not allow them to get more medication per pharmacy fill

  • 70% said insurers did not reduce barriers like prior authorization

  • 76% said insurers did not stop requiring step therapy

While migraine patients were often unhappy with their insurers, most were delighted with telehealth. The vast majority (83%) said they hoped their providers continued using telehealth after the pandemic ends.

“COVID has introduced a host of new challenges for people living with migraine disease. Telemedicine clearly provides an important link to care, but patients are looking for insurance providers to do more to facilitate care, including cutting red tape and ending delay tactics,” Lindsay Videnieks, Executive Director of the Headache & Migraine Policy Forum said in a statement.

Arthritis Patients Want New Treatments

The second survey of nearly 2,000 adults suffering from osteoarthritis had similar findings. Over a third of respondents (37%) told the Arthritis Foundation that they had missed or cancelled a doctor’s appointment due to fear of COVID-19 infection. Only 15% said their osteoarthritis is well managed.

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. No disease-modifying drugs are currently available to treat OA, and over the counter pain relievers have only mild to moderate effects on OA pain.

"Pain is debilitating. My back and hip pain are so bad that I have trouble getting out of bed," said one survey respondent. "Each step is excruciating, and I wonder how much longer I can deal with the pain."

"You spend a lot of time & effort trying not to think about it because what you focus on magnifies," another patient wrote. "You hate pain scales because how do you rate something that is always there? Oftentimes it's not the pain's intensity but rather the duration."

Nearly two-thirds (65%) of patients said they use non-steroidal anti-inflammatory drugs (NSAIDs) or topical medication to manage their pain, 29% use physical therapy or massage, and another 29% said total joint replacement helped.

The primary change OA patients want is for insurers to increase coverage of new arthritis treatments, though more than half said they were only interested in a new treatment for pain if it didn't also increase their joint damage.

The Arthritis Foundation recently joined with 30 other healthcare organizations in asking the Food and Drug Administration and National Institutes of Health to make the development and availability of pain treatments a higher priority within the agencies.

Lancet Study Calls for Improvements in Pediatric Pain Care

By Pat Anson, PNN Editor

An international study by The Lancet has found that childhood pain often goes untreated, unrecognized and poorly managed, leading to chronic pain, disability and other negative consequences in adulthood.

The report by the Lancet Child and Adolescent Health Commission, led by the Centre for Pain Research at the University of Bath, found that too many children live with pain — even in developed countries — and calls for improvements in pediatric pain care, including diagnosis, pain management, social support and psychological treatment.

"Among health-care professionals, it is easy to agree that no child should experience pain if that pain can and should be prevented, avoided, or successfully treated,” said lead author Emma Fisher, PhD, a Versus Arthritis fellow at the University of Bath.

“In practice, however, we know there is ample evidence that children frequently experience preventable pain, and that in high-income settings, with advanced health-care systems and highly educated and regulated health professionals, children and young people experience pain that often goes unnoticed, unreported, or is not responded to, across healthcare including in the Emergency Department, post-surgical care, and in tertiary care.”

Childhood Pain ‘Swept Under the Carpet’

The report provides several examples of childhood pain not being recognized or treated adequately, such as what happened to Caitriona Roberts of Belfast, Northern Ireland. At age 12, she went to her doctor with pain and swelling in her ankle. Initially written-off as 'just a sprain' that would go away, she would spend the next six months living in almost constant pain, until she was referred to a specialist who diagnosed her with juvenile idiopathic arthritis, an autoimmune condition.

Now 28, Roberts has learned how to live and manage the disease. She helped researchers prepare The Lancet report.

"I think this issue has been swept under the carpet for too long. Still today, over 15 years on from my diagnosis with arthritis, I find people, including medical professionals, unaware of the condition or its effects on my day-to-day life. And when I speak to other young people, I find that sadly, very little seems to have changed in terms of how they experience pain or the support they receive,” Roberts said.

Researchers say up to 10% of young people experience chronic pain into early adulthood, with conditions such as arthritis, other types of musculoskeletal pain, recurring abdominal pain, and headaches.  

"This really matters, both for those experiencing pain and those around them but also across wider society. We know that chronic pain experienced in childhood is likely to feed through to adulthood and this has long-term health and economic costs associated,” said Fisher.

She called on providers and policymakers “to sit up and listen to the fact that too many of our young people are in pain and need help."

Myths About Opioids

One obstacle to getting that help is the stigma associated with opioid pain medication, particularly in the United States and Canada, where researchers say guidelines intended to control opioid use in adults are being “inappropriately applied to young people.”

“Substance use disorders and pain medication are both conflated in policy and in the media's portrayal of the North American opioid crisis,” the report found. “Through this media, public views have been influenced to consider opioids as drugs of addiction rather than pain medicine.  

“Health-care professionals, young people, and parents continue to hold misconceptions and believe myths about opioid use in pediatric patients, whereby the media depicts opioids as the villain and the underlying reason for substance misuse. Opioids have their place in pediatric pain medicine. In the context of the oversupply of opioids, childhood pain can usefully be considered a risk factor for long-term harmful exposure to opioids.”

More Than Growing Pains

The report found that improvements in pediatric pain care have come slowly. The last major intervention in the field came in the 1980’s, when it was recognized for the first time that babies experienced pain. Up until that point, a number of routine and major operations, including heart surgery, were carried out on babies without anesthetics.

"Parents tell us about the struggle they have convincing their GP that their child's illness is more than growing pains,” said Zoe Chivers, Head of Services at Versus Arthritis, which funded the report. “While the focus, attention, and dedication in providing quality services to children is consistently in place for conditions like cancer it's woefully absent for childhood arthritis and chronic pain.

"As a society we need to understand that dismissal of arthritis comes at high price and that adults and children living in pain with the condition should no longer be expected to pay it."

The study has four key goals: to make childhood pain matter, to make it understood, to make it visible, and to make it better. One recommendation is to make routine vaccinations less painful and stressful for children, such as allowing parents to be present during the injections and using topical analgesics.

"For many parents and children, a trip to the doctors for routine inoculations will be a stressful and painful experience. This does not have to be the case - we know how we can make the experience less painful for young people, but we're not doing it. This is just another example of how pain has been accepted as an everyday feature of growing up," said Fisher.

COVID-19 Lockdown Made Symptoms Worse for Pain Patients

By Pat Anson, PNN Editor

A new survey is providing some insight into how patients suffering from arthritis, fibromyalgia and other types of joint and muscle pain fared during the early stages of the coronavirus pandemic.

In late April, researchers at the University of East Anglia (UEA) surveyed 678 patients in the UK with musculoskeletal pain, asking how the pandemic impacted their well-being and access to healthcare. The online survey was conducted five weeks after the start of a nationwide lockdown in which at-risk patients were told to “shield” at home, avoid all social contact, and postpone or cancel non-urgent healthcare appointments.  

"When lockdown happened, we were worried that this may become a much greater problem - particularly for those with bone, joint and muscle pain,” said co-author Toby Smith, PhD, a professor at UEA's School of Health Sciences. “We wanted to know how the new restrictions might affect pain, and better understand who is most at risk of experiencing flare-ups, or reduced well-being due to social isolation and loneliness.

"Our results show that the coronavirus pandemic is a major challenge to people's health and well-being, both to young and older people.”

Over half the patients (53%) reported that their musculoskeletal symptoms had worsened since the start of lockdown. About a third said they had seen a general practitioner or hospital rheumatologist because their pain, stiffness and overall health had significantly worsened. Those who reported greater social isolation and loneliness were less likely to access healthcare.

The vast majority of respondents, over 88 percent, reported little difficulty getting medication during the lockdown, but nearly half (44%) needed the assistance of others to do it.

"Should further isolation measures need to be enforced as we have seen in some part of the UK as the pandemic continues, particular efforts should be made to protect and support the socially isolated as a vulnerable group,” said co-author Alex MacGregor, PhD, a professor at UEA's Norwich Medical School. "Healthcare providers should reach out to individual patients who do not come forward for advice, and who might be silently struggling with their disease.”

Due to a recent surge in coronavirus infections, British Prime Minister Boris Johnson recently tightened nationwide restrictions, ordering bars and restaurants to close by 10pm. More people are also being required to wear masks. Asked about reports the government was planning a “total social lockdown” in northern England and London, Johnson’s health minister told the BBC she wouldn’t rule it out.

The UK survey findings, published in the journal Rheumatology: Advances in Practice, are similar to those found in a PNN survey of over 2,200 patients in April. About 70% said they were worried about going to a hospital or doctor’s office and had postponed or cancelled a medical appointment. A little over half said social isolation made them feel lonely.

Turmeric Moderately Effective in Treating Osteoarthritis Pain

By Pat Anson, PNN Editor

A yellow spice used in food and traditional Chinese medicine – turmeric – is effective in treating osteoarthritis knee pain, according to small placebo-controlled study published in the Annals of Internal Medicine.

Researchers from the University of Tasmania, Australia randomly assigned 70 participants with knee osteoarthritis to receive either 2 capsules per day of turmeric or a placebo. Changes in pain and swelling in the knees were assessed by questionnaire and MRIs.

After 12 weeks, researchers found that patients taking daily turmeric supplements reported moderate improvement in pain compared to the placebo group. They also consumed fewer pain medications. There was no difference in the cartilage or structural changes in the knees between the two groups.

Due to the modest effect of turmeric on knee pain, small sample size and short duration of the study, researchers suggest that multi-center clinical trials with more patients are needed to assess the clinical significance of their findings.

prachi-palwe-YUIMwavk7AQ-unsplash.jpg

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. Knee OA is quite common and affects over 250 million people worldwide. Women are more likely than men to have knee OA and to have more severe pain. Studies have also found that women with knee OA are at greater risk of early death from cardiovascular disease.

No disease-modifying drugs are currently available to treat osteoarthritis. Common pain relievers, such as acetaminophen (paracetamol) and non-steroidal anti-inflammatory drugs (NSAIDs) have only mild to moderate effects on OA pain and can have side events.

Turmeric is a medicinal herb that is used in Indian, Southeast Asian and Middle Eastern foods as a spice. Curcumin is the main active ingredient in turmeric. It has potent anti-inflammatory effects and is a strong antioxidant.

In a PNN guest column, Judie Plumley reported that curcumin supplements helped ease the chronic back pain that left her bedridden. “I am amazed with the results!  My pain is now bearable. I can do about twice as much as I could before, and I am spending much less time in bed,” wrote Plumley.

Turmeric and curcumin are often touted as treatments for everything from diabetes and depression to cancer and high cholesterol. However, research results on their effectiveness have been mixed.

Lupus and Arthritis Patients at No Greater Risk from COVID-19

By Pat Anson, PNN Editor

Patients with lupus and other forms of arthritis are not at increased risk of being hospitalized with COVID-19 due to medications that weaken their immune systems, according to researchers at NYU’s Grossman School of Medicine.

Lupus, spondyloarthritis, psoriatic and rheumatoid arthritis are autoimmune conditions in which the body’s immune system attacks joints, skin, kidneys and other tissues, causing pain and inflammation. The arthritic conditions are often treated with steroids, biologics and other immune suppressing medications, which has raised concern that the drugs could also make patients more susceptible to risks from coronavirus infection.

But in two studies recently published in the journal Arthritis and Rheumatology, researchers found that most patients with arthritis had the same risk of hospitalization as the general population.

“People with lupus or inflammatory arthritis have the same risk factors for getting seriously ill from COVID-19 as people without these disorders,” said co-author Ruth Fernandez-Ruiz, MD, a postdoctoral fellow in rheumatology in the Department of Medicine at NYU Langone.

The first study involved 226 adult patients in New York City who were being treated for mild to severe forms of lupus between April 13 and June 1, when the coronavirus pandemic peaked in the New York City region. Forty-one of the lupus patients were also diagnosed with COVID-19. Of those, 24 were hospitalized and four died. Another 42 patients had COVID-19-like symptoms but were not formally tested.

The second study involved 103 women being treated for inflammatory arthritis between March 3 and May 4 in New York City. All tested positive for COVID-19 or had symptoms highly suggesting they were infected. Twenty-seven of them were hospitalized and four died.

Researchers say the lupus patients taking immune-suppressing medications such as mycophenolate mofetil (Cellcept) and azathioprine (Imuran), had no greater risk of hospitalization than patients not using the drugs. Similarly, hospitalization rates for people with inflammatory arthritis and COVID-19 were no greater than for all New Yorkers.

“Patients receiving therapy for lupus and inflammatory arthritis should not automatically stop taking their medications for fear that they would be worse off if they also caught the coronavirus,” said co-author Rebecca Haberman, MD, a clinical instructor in rheumatology in the Department of Medicine at NYU Langone.

Haberman and her colleagues say arthritis patients taking biologic drugs such as adalimumab (Humira) and etanercept (Enbrel), or the antiviral drug hydroxychloroquine, were also at no greater or lesser risk of hospitalization than those not taking the drugs.

However, arthritis patients taking glucocorticoids, a type of steroid, even in mild doses, were up to 10 times more likely to be hospitalized than patients not using steroids. The researchers caution that although statistically significant, the study’s small size may overestimate the actual risk from steroids.

“Our findings represent the largest of its kind for American patients with lupus or arthritis and COVID-19, and should reassure most patients, especially those on immunosuppressant therapy, that they are at no greater risk of having to be admitted to hospital from COVID-19 than other lupus or arthritis patients,” said Fernandez-Ruiz.

Risk factors that can double the risk of hospitalization from COVID-19 are having multiple health conditions, such as obesity, hypertension and diabetes.

Hospitals Hit Hard by Loss of Joint Replacement Surgeries

By Bernard J. Wolfson, Kaiser Health News

Dr. Ira Weintraub, a recently retired orthopedic surgeon who now works at a medical billing consultancy, saw a hip replacement bill for over $400,000 earlier this year.

“The patient stayed in the hospital 17 days, which is only 17 times normal. The bill got paid,” mused Weintraub, chief medical officer of Portland, Oregon-based WellRithms, which helps self-funded employers and workers’ compensation insurers make sense of large, complex medical bills and ensure they pay the fair amount.

Charges like that go a long way toward explaining why hospitals are eager to restore joint replacements to pre-COVID levels as quickly as possible — an eagerness tempered only by safety concerns amid a resurgence of the coronavirus in some regions of the country. Revenue losses at hospitals and outpatient surgery centers may have exceeded $5 billion from canceled knee and hip replacements alone during a roughly two-month hiatus on elective procedures earlier this year.

The cost of joint replacement surgery varies widely — though, on average, it is in the tens, not hundreds, of thousands of dollars. Still, given the high and rapidly growing volume, it’s easy to see why joint replacement operations have become a vital chunk of revenue at most U.S. hospitals.

The rate of knee and hip replacements more than doubled from 2000 to 2015, according to inpatient discharge data from the Agency for Healthcare Research and Quality. And that growth is likely to continue: Knee replacements are expected to triple between now and 2040, with hip replacements not far behind, according to projections published last year in the Journal of Rheumatology.

Joint procedures are usually not emergencies, and they were among the first to be scrubbed or delayed when hospitals froze elective surgeries in March — and again in July in some areas plagued by renewed COVID outbreaks. Loss of the revenue has hit hospitals hard, and regaining it will be crucial to their financial convalescence.

“Without orthopedic volumes returning to something near their pre-pandemic levels, it will make it difficult for health systems to get back to anywhere near break-even from a bottom-line perspective,” said Stephen Thome, a principal in health care consulting at Grant Thornton, an advisory, audit and tax firm.

Billions in Revenue Lost

It’s impossible to know exactly how much knee and hip replacements are worth to hospitals, because no definitive data on total volume or price exists.

But using published estimates of volume, extrapolating average commercial payments from published Medicare rates based on a study, and making an educated guess of patient coinsurance, Thome helped KHN arrive at an annual market value for American hospitals and surgery centers of between $15.5 billion and $21.5 billion for knee replacements alone.

That suggests a revenue loss of $1.3 billion to $1.8 billion per month for the period the surgeries were shut down. These figures include ambulatory surgery centers not owned by hospitals, which also suspended most operations in late March, all of April and into May.

If you add hip replacements, which account for about half the volume of knees and are paid at similar rates, the total annual value rises to a range of $23 billion to $32 billion, with monthly revenue losses from $1.9 billion to $2.7 billion.

The American Hospital Association projects total revenue lost at U.S. hospitals will reach $323 billion by year’s end, not counting additional losses from surgeries canceled during the current coronavirus spike. That amount is partially offset by $69 billion in federal relief dollars hospitals have received so far, according to the association. The California Hospital Association puts the net revenue loss for hospitals in that state at about $10.5 billion, said spokesperson Jan Emerson-Shea.

Hospitals resumed joint replacement surgeries in early to mid-May, with the timing and ramp-up speed varying by region and hospital. Some hospitals restored volume quickly; others took a more cautious route and continue to lose revenue. Still others have had to shut down again.

At the NYU Langone Orthopedic Hospital in New York City, “people are starting to come in and you see the operating rooms full again,” said Dr. Claudette Lajam, chief orthopedic safety officer.

At St. Jude Medical Center in Fullerton, California, where the coronavirus is raging, inpatient joint replacements resumed in the second or third week of May — cautiously at first, but volume is “very close to pre-pandemic levels at this point,” said Dr. Kevin Khajavi, chairman of the hospital’s orthopedic surgery department. However, “we are constantly monitoring the situation to determine if we have to scale back once again,” he said.

In large swaths of Texas, elective surgeries were once again suspended in July because of the COVID-19 resurgence. The same is true at many hospitals in Florida, Alabama, South Carolina and Nevada.

The Mayo Clinic in Phoenix suspended nonemergency joint replacement surgeries in early July. It resumed outpatient replacement procedures the week of July 27, but still has not resumed nonemergency inpatient procedures, said Dr. Mark Spangehl, an orthopedic surgeon there. In terms of medical urgency, joint replacements are “at the bottom of the totem pole,” Spangehl said.

In terms of cash flow, however, joint replacements are decidedly not at the bottom of the totem pole. They have become a cash cow as the number of patients undergoing them has skyrocketed in recent decades.

‘Industrial-Scale’ Surgeries

The volume is being driven by an aging population, an epidemic of obesity and a significant rise in the number of younger people replacing joints worn out by years of sports and exercise.

It’s also being driven by the cash. Once only done in hospitals, the operations are now increasingly performed at ambulatory surgery centers — especially on younger, healthier patients who don’t require hospitalization.

The surgery centers are often physician-owned, but private equity groups such as Bain Capital and KKR & Co. have taken an interest in them, drawn by their high growth potential, robust financial returns and ability to offer competitive prices.

“Generally the savings should be very good — but I do see a lot of outlier surgery centers where they are charging exorbitant amounts of money — $100,000 wouldn’t be too much,” said WellRithm’s Weintraub, who co-owned such a surgery center in Portland.

After canceling his hip replacement surgery in March because of COVID-19, Matthew Davis overcame his concerns and rescheduled in June because the procedure was performed at an outpatient surgery center, which meant no overnight hospital stay. (Matthew Davis)

Fear of catching the coronavirus in a hospital is reinforcing the outpatient trend. Matthew Davis, a 58-year-old resident of Washington, D.C., was scheduled for a hip replacement on March 30 but got cold feet because of COVID-19, and canceled just before all elective surgeries were halted. When it came time to reschedule in June, he overcame his reservations in large part because the surgeon planned to perform the procedure at a free-standing surgery center.

“That was key to me — avoiding an overnight hospital stay to minimize my exposure,” Davis said. “These joint replacements are almost industrial-scale. They are cranking out joint replacements 9 to 5. I went in at 6:30 a.m. and I was walking out the door at 11:30.”

Joint Replacement Often Unnecessary

Acutely aware of the financial benefits, hospitals and surgery clinics have been marketing joint replacements for years, competing for coveted rankings and running ads that show healthy aging people, all smiles, engaged in vigorous activity.

However, a 2014 study concluded that one-third of knee replacements were not warranted, mainly because the symptoms of the patients were not severe enough to justify the procedures.

“The whole marketing of health care is so manipulative to the consuming public,” said Lisa McGiffert, a longtime consumer advocate and co-founder of the Patient Safety Action Network. “People might be encouraged to get a knee replacement, when in reality something less invasive could have improved their condition.”

McGiffert recounted a conversation with an orthopedic surgeon in Washington state who told her about a patient who requested a knee replacement, even though he had not tried any lower-impact treatments to fix the problem.

“I asked the surgeon, ‘You didn’t do it, did you?’ And he said, ‘Of course I did. He would just have gone to somebody else.’”

Kaiser Health News, a nonprofit health newsroom whose stories appear in news outlets nationwide, is an editorially independent part of the Kaiser Family Foundation.

Stem Cell Osteoarthritis Studies Advance

By Pat Anson, PNN Editor

A Canadian doctor is recruiting patients for a "first of its kind" stem cell research project for osteoarthritis. The Phase II study could further advance the use of regenerative medicine in treating osteoarthritis, a joint disease for which treatment options are currently limited to pain medication, steroid injections or joint replacement surgery.

"This is a potential game changer in the management of osteoarthritis," says lead investigator Dr. Grant Pagdin.  "Evidence is building that regenerative procedures using the combination of biologic materials we are investigating here have the potential to reduce joint pain and improve function.” 

Pagdin is recruiting 255 Canadians with osteoarthritis from 19 to 79 years of age. The purpose of the study is to demonstrate the effectiveness of combining platelet-rich plasma (PRP) derived from a patient’s own blood with stem cells derived from their body fat (adipose tissue) or bone marrow.  

Participants will be randomly assigned to one of three groups that will receive injections of PRP and adipose stem cells, PRP and bone marrow stem cells, or PRP with both types of stem cells. Three injections of the biologic material will be made into an arthritic joint. Participants will then be followed for up to 24 months to see which treatment worked better

Meanwhile, a California stem cell company has announced that enrollment has officially ended for a similar study of stem cells. Thirty-eight patients with knee osteoarthritis have been recruited by Personalized Stem Cells (PSC) for a Phase I trial to have adipose stem cells injected into one knee. The study was originally set to have up to 125 patients, but was scaled back due to COVID-19 concerns.

"While stem cells have previously been used successfully in the treatment of osteoarthritis, our goal is to produce high quality data and ultimately receive FDA approval so that arthritic patients have access to PSC's quality tested stem cell treatments," Dr. Robert Harman, PSC’s CEO, said in a statement.

PSC hopes to submit results from the study to the FDA by the end of 2020, after which a Phase II blinded, placebo-controlled study will be launched.

In addition to the osteoarthritis knee study, PSC recently received FDA approval to launch a small clinical trial for the treatment of COVID-19 patients with stem cells. The company also plans to pursue FDA approval of stem cells for the treatment of back pain and traumatic brain injuries, as well as arthritis affecting other joints.

A small Phase II clinical trial recently found a single injection of adipose stem cells can significantly reduce osteoarthritis knee pain for up to a year with no serious side effects, according to findings published in the American Journal of Sports Medicine.

More than 27 million Americans live with osteoarthritis, a progressive condition caused by the breakdown of joint cartilage. Osteoarthritis causes pain, physical disability, lower quality of life, and is associated with early death and cardiovascular problems.

Newly Discovered Blood Cells Predict Rheumatoid Arthritis Flareups

By Pat Anson, PNN Editor

A simple blood test could give an early warning to rheumatoid arthritis sufferers that their symptoms are about to get worse, according to a new study published in the New England Journal of Medicine.   

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. The symptoms come in waves, with periods of remission interspersed with painful flareups.

Researchers at Rockefeller University have identified a new type of cell – called "PRIME cells" – that dramatically increase in the blood of RA patients a week before a disease flareup.

“If we can reliably identify these new cells in patients, we may be able to tell them ‘You’re about to have a flare,’ so they can prepare themselves,” says lead author Robert Darnell, MD, a neuroscientist at Rockefeller’s Howard Hughes Medical Institute. “This would make flares less disruptive and easier to manage.”

Over a four-year period, researchers analyzed hundreds of blood samples from four RA patients, who collected the blood at home using finger pricks and sent them to Darnell’s lab. Each participant also kept a record of their symptoms to identify when flares occurred.

National Institutes of Allergy and Infectious Diseases

National Institutes of Allergy and Infectious Diseases

Darnell and his colleagues looked for molecular changes in the blood prior to the onset of symptoms, and saw an increase in immune cells two weeks prior to a flare. That was not surprising, because the cells are known to attack the joints of RA patients.

But in samples collected one week before a flare, researchers saw an increase in cells that didn't match the genetic signature of any known type of blood or immune cell. The RNA signature of the cells resembled that of bone, cartilage or muscle cells – which are not typically found in blood.

“We were so surprised to see that the genes expressed right before a flare are normally active in the bone, muscle, and extracellular matrix -- strange pathways to find in blood cells,” said coauthor Dana Orange, MD, a rheumatologist at Rockefeller. “That really piqued our interest.”

Darnell's team named their discovery PRIME cells because they are "pre-inflammation mesenchymal" cells -- a type of stem cell that can develop into bone or cartilage. Notably, while PRIME cells accumulated in the blood before flares, they disappeared during them.

Researchers say PRIME cells have RNA profiles that are strikingly similar to synovial fibroblasts, which are found in the tissue lining of joints and are known to play a role in causing RA symptoms. In experiments on laboratory mice, fibroblasts that were removed from inflamed joints and transplanted into healthy mice caused them to become arthritic too.

Researchers are now recruiting RA patients for a larger study to confirm whether PRIME cells can predict a flare. If the cells do act as a precursor, it could lead to the development of drugs that target PRIME cells and stop flares before symptoms worsen.

“For doctors and patients, intervention before a flare up is always better than just treating symptoms,” says Darnell. “If these cells are the antecedents to joint sickness, they become a potential target for new drugs.”