General Anesthesia as Safe as Spinal Injections for Hip Fracture Surgery

By Pat Anson, PNN Editor

General anesthesia is just as safe as spinal anesthesia for patients undergoing hip fracture surgery, according to a large new study that dispels a common belief that patients who receive spinal injections have better outcomes.

Researchers from the Perelman School of Medicine at the University of Pennsylvania enrolled 1,600 mostly elderly patients having hip fracture surgery at 46 U.S. and Canadian hospitals, and randomly assigned them to receive either spinal or general anesthesia.

They found that rates of survival, delirium and functional recovery post-surgery were similar for patients, regardless of the type of anesthesia they received. The findings are published in The New England Journal of Medicine.

“Our study argues that, in many cases, either form of anesthesia appears to be safe," said lead investigator Mark D. Neuman, MD, an associate professor of Anesthesiology and Critical Care at Perelman. "This is important because it suggests that choices can be guided by patient preference rather than anticipated differences in outcomes in many cases."

During general anesthesia, inhaled and intravenous medications are used to make patients unconscious, which often requires a breathing tube during surgery. For spinal anesthesia, medications are used to numb the lower part of the body through an injection into the spinal column. Patients anesthetized this way are typically able to breathe on their own during surgery and rarely require a breathing tube.

About 250,000 people have hip fracture surgery annually in the United States. In the past, most would receive general anesthesia, but in recent years the use of spinal anesthesia for hip fracture surgeries has increased significantly, due in part to the belief by some anesthesiologists that it was safer for frail, older patients.  

To get a better idea of possible outcomes associated with both forms form of anesthesia, researchers looked at post-surgical death rates, whether patients regained the ability to walk, and if they experienced any cognitive decline.

Statistically, there was hardly any difference in outcomes between the two groups. Sixty days after surgery, 18.5% of patients assigned to spinal anesthesia had either died or were unable to walk; versus 18 percent of patients who received general anesthesia. About 21 percent of patients assigned to spinal anesthesia experienced delirium, versus 20 percent of those given general anesthesia.

"What our study offers is reassurance that general anesthesia can represent a safe option for hip fracture surgery for many patients," said Neuman. "This is information that patients, families, and clinicians can use together to make the right choice for each patient's personalized care."

Neuman and his research team say previous comparisons of general and spinal anesthesia came from studies that didn’t randomly assign patients, which creates self-selection bias. Some patients may have chosen spinal anesthesia with the goal of avoiding complications, while others opted for general anesthesia to avoid a spinal injection or because they feared inadequate sedation during surgery.

The most common types of medications used during spinal injections are anesthetics, opioids or corticosteroids. A recent study of patients with hip osteoarthritis warned of serious long-term complications for those given steroid injections. Patients who received steroids were 8.5 times more likely to develop rapidly destructive hip disease, a condition that causes the loss of blood flow and death of bone tissue in the hip.

Cannabis Oil Effective for UK Chronic Pain Patients

By Pat Anson, PNN Editor

Medical cannabis has been legal in the United Kingdom since 2018, but we’re only now getting the first evidence on the effectiveness of cannabis oil for UK chronic pain patients.

One hundred ten patients enrolled in the UK Medical Cannabis Registry reported significant improvements in their pain, discomfort and sleep quality after one, three and six months of treatment with cannabis oil. There was also statistically significant improvement in their health-related quality of life.

Due to strict rules, it is difficult to get a prescription for medical cannabis from the UK’s National Health Service. Patients can only be prescribed cannabis when conventional therapy has not provided adequate relief for conditions such as pain, anxiety and multiple sclerosis.

Most of the patients (65%) in the study had never used cannabis before. Their most common primary diagnosis was chronic non-cancer pain (48%), followed by neuropathic pain (24%) and fibromyalgia (16%).

“With the increasing number of prescriptions for medical cannabis in the UK, capturing patient outcomes and real-world evidence is essential for wider understanding and appropriate access for eligible patients,” Dr. Simon Erridge, head of research at Sapphire Medical Clinics, said in a statement.

“This research is the first of its kind in Europe and we continue to review condition and product-specific outcomes via the UK Medical Cannabis Registry. Though this is still observational data it will inform critical future research including randomised controlled trials.”

Sapphire Medical Clinics created the registry and surveyed patients to help fill some of the gaps in knowledge about medical cannabis. The findings were recently published in the Journal of Clinical Pharmacology.

“Despite promising preclinical data, there is a paucity of high-quality evidence to support the use of CBMPs (cannabis-based medicinal products). The evidence base, while broad, is inconclusive, variable across chronic pain types, and thus insufficient to inform guidelines, funders, and licensing agencies,” researchers said.

The cannabis oil used in the study is made by Adven, a subsidiary of Curaleaf International, Europe’s largest independent cannabis company. The median CBD dose was 20 mg per day, while the median THC dose was 1 mg per day, giving the oil a CBD/THC ratio of 20 to 1. Adverse events such as nausea, dizziness and constipation were reported by nearly a third of patients, with most symptoms being mild or moderate.

Sapphire Medical Clinics is planning further studies of cannabis products as more participants enroll in its cannabis registry.

‘Mother of All Cannabinoids’

Another study conducted in the U.S. found that people who use cannabis products that are rich in cannabigerol (CBG) reported significant improvement in their pain, anxiety, depression and insomnia.

CBG is known as the “mother of all cannabinoids” because it rapidly converts into THC and CBD. Only trace amounts of CBG are found in most cannabis plants, but in recent years cultivated strains rich in CBG have been grown in the Pacific Northwest.

Researchers at Washington State University and the University of California Los Angeles surveyed 127 people who self-identified as consumers of CBG-dominant cannabis. Most reported their pain and other symptoms were “very much improved” or “much improved” by CBG.

About 75% said CBG-predominant cannabis was superior to conventional medications for chronic pain, depression, insomnia and anxiety. A little over half reported minor side effects such as dry mouth, sleepiness, increased appetite, and dry eyes. Most reported no withdrawal symptoms.

“This is the first patient survey of CBG-predominant cannabis use to date, and the first to document self-reported efficacy of CBG-predominant products, particularly for anxiety, chronic pain, depression, and insomnia. Most respondents reported greater efficacy of CBG-predominant cannabis over conventional pharmacotherapy, with a benign adverse event profile and negligible withdrawal symptoms,” researchers reported in the journal Cannabis and Cannabinoid Research. 

“This study demonstrates that CBG-predominant cannabis and related products are available and being used by cannabis consumers and demonstrates the urgent need for randomized controlled trials of CBG-predominant cannabis-based medicines to be studied rigorously to assess safety and efficacy.”

Preliminary research suggests CBG has antibacterial properties and might be useful in treating inflammatory bowel disease (IBD), glaucoma, Huntington’s disease and some forms of cancer.  

Do Infections or Vaccines Provide Better Covid Immunity?

By Arthur Allen, Kaiser Health News

Dr. Aaron Kheriaty, a University of California-Irvine psychiatry professor, felt he didn’t need to be vaccinated against covid because he’d fallen ill with the disease in July 2020.

So, in August, he sued to stop the university system’s vaccination mandate, saying “natural” immunity had given him and millions of others better protection than any vaccine could.

A judge on Sept. 28 dismissed Kheriaty’s request for an injunction against the university over its mandate, which took effect Sept. 3. While Kheriaty intends to pursue the case further, legal experts doubt that his and similar lawsuits filed around the country will ultimately succeed.

That said, evidence is growing that contracting SARS-CoV-2, the virus that causes covid-19, is generally as effective as vaccination at stimulating your immune system to prevent the disease. Yet federal officials have been reluctant to recognize any equivalency, citing the wide variation in covid patients’ immune response to infection.

Like many disputes during the covid pandemic, the uncertain value of a prior infection has prompted legal challenges, marketing offers and political grandstanding, even as scientists quietly work in the background to sort out the facts.

For decades, doctors have used blood tests to determine whether people are protected against infectious diseases. Pregnant mothers are tested for antibodies to rubella to help ensure their fetuses won’t be infected with the rubella virus, which causes devastating birth defects. Hospital workers are screened for measles and chickenpox antibodies to prevent the spread of those diseases. But immunity to covid seems trickier to discern than those diseases.

The Food and Drug Administration has authorized the use of covid antibody tests, which can cost about $70, to detect a past infection. Some tests can distinguish whether the antibodies came from an infection or a vaccine. But neither the FDA nor the Centers for Disease Control and Prevention recommend using the tests to assess whether you’re, in fact, immune to covid. For that, the tests are essentially useless because there’s no agreement on the amount or types of antibodies that would signal protection from the disease.

“We don’t yet have full understanding of what the presence of antibodies tells us about immunity,” said Kelly Wroblewski, director of infectious diseases at the Association of Public Health Laboratories.

‘Natural Immunity’

By the same token, experts disagree on how much protection an infection delivers.

In the absence of certainty and as vaccination mandates are levied across the country, lawsuits seek to press the issue. Individuals who claim that vaccination mandates violate their civil liberties argue that infection-acquired immunity protects them. In Los Angeles, six police officers have sued the city, claiming they have natural immunity.

In August, law professor Todd Zywicki alleged that George Mason University’s vaccine mandate violated his constitutional rights given he has natural immunity. He cited a number of antibody tests and an immunologist’s medical opinion that it was “medically unnecessary” for him to be vaccinated. Zywicki dropped the lawsuit after the university granted him a medical exemption, which it claims was unrelated to the suit.

Republican legislators have joined the crusade. The GOP Doctors Caucus, which consists of Republican physicians in Congress, has urged people leery of vaccination to instead seek an antibody test, contradicting CDC and FDA recommendations. In Kentucky, the state Senate passed a resolution granting equal immunity status to those who show proof of vaccination or a positive antibody test.

Hospitals were among the first institutions to impose vaccine mandates on their front-line workers because of the danger of them spreading the disease to vulnerable patients. Few have offered exemptions from vaccination to those previously infected. But there are exceptions.

Two Pennsylvania hospital systems allow clinical staff members to defer vaccination for a year after testing positive for covid. Another, in Michigan, allows employees to opt out of vaccination if they present evidence of previous infection and a positive antibody test in the previous three months. In these cases, the systems indicated they were keen to avoid staffing shortages that could result from the departure of vaccine-shunning nurses.

For Kheriaty, the question is simple. “The research on natural immunity is quite definitive now,” he told KHN. “It’s better than immunity conferred by vaccines.” But such categorical statements are clearly not shared by most in the scientific community.

Dr. Arthur Reingold, an epidemiologist at UC-Berkeley, and Shane Crotty, a virologist at the respected La Jolla Institute for Immunology in San Diego, gave expert witness testimony in Kheriaty’s lawsuit, saying the extent of immunity from reinfection, especially against newer variants of covid, is unknown. They noted that vaccination gives a huge immunity boost to people who’ve been ill previously.

Yet not all of those pushing for recognition of past infection are vaccine critics or torchbearers of the anti-vaccine movement.

Dr. Jeffrey Klausner, clinical professor of population and public health sciences at the University of Southern California, co-authored an analysis published last week that showed infection generally protects for 10 months or more. “From the public health perspective, denying jobs and access and travel to people who have recovered from infection doesn’t make sense,” he said.

In his testimony against Kheriaty’s case for “natural” immunity to covid, Crotty cited studies of the massive covid outbreak that swept through Manaus, Brazil, early this year that involved the gamma variant of the virus. One of the studies estimated, based on tests of blood donations, that three-quarters of the city’s population had already been infected before gamma’s arrival. That suggested that previous infection might not protect against new variants. But Klausner and others suspect the rate of prior infection presented in the study was a gross overestimate.

A large August study from Israel, which showed better protection from infection than from vaccination, may help turn the tide toward acceptance of prior infection, Klausner said. “Everyone is just waiting for Fauci to say, ‘Prior infection provides protection,’” he said.

When Dr. Anthony Fauci, the top federal expert on infectious diseases, was asked during a CNN interview last month whether infected people were as well protected as those who’ve been vaccinated, he hedged. “There could be an argument” that they are, he said. Fauci did not immediately respond to a KHN request for further comment.

CDC spokesperson Kristen Nordlund said in an email that “current evidence” shows wide variation in antibody responses after covid infection. “We hope to have some additional information on the protectiveness of vaccine immunity compared to natural immunity in the coming weeks.”

A “monumental effort” is underway to determine what level of antibodies is protective, said Dr. Robert Seder, chief of the cellular immunology section at the National Institute of Allergy and Infectious Diseases. Recent studies have taken a stab at a number.

Antibody tests will never provide a yes-or-no answer on covid protection, said Dr. George Siber, a vaccine industry consultant and co-author of one of the papers. “But there are people who are not going to be immunized. Trying to predict who is at low risk is a worthy undertaking.”

This story was produced by Kaiser Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation.

More Evidence That Rapid Opioid Tapering Is Harmful

By Roger Chriss, PNN Columnist

The overdose crisis has motivated a sea change in prescribing practices. Opioid tapering is seen as a part of this change. But the risks and harms of tapering often outweigh its potential benefits, especially when tapering is rapid.

The risks of rapid tapers are well known. The CDC warns providers to “avoid abrupt tapering or sudden discontinuation of opioids,” with a dose decrease of 10% per month a “reasonable starting point.”

But more rapid tapers are very common. A new study looked at retail pharmacy claims for over 810,000 patients taken off high-dose opioids in 2017 and 2018, finding that 72% were tapered more rapidly than recommended by clinical guidelines. Rapid tapering was significantly more common among Medicare patients than in commercially insured ones. Critically, the study also found that counties with high overdose rates had more rapid opioid discontinuation.

The U.S. military health system has also significantly reduced opioid prescriptions. Among active-duty members, a recent study found a 69% decline in prescriptions filled for opioids at daily doses of 50 morphine milligram equivalents (MME) or more.

The Departments of Defense and Veterans Affairs adopted guidelines in 2017 that urge military doctors to taper or discontinue opioids for patients on high doses. But a recent Washington Post investigation found that the VA’s Opioid Safety Initiative was associated with a 75% increase in suicides among veterans living in rural areas and a 30% increase in suicides for veterans in urban areas.

Further, a recent JAMA investigation found that in a study of over 113,000 patients on stable, high-dose opioid therapy, tapering was “significantly associated with increased risk of overdose and mental health crisis.”

“This study highlights important potential harms that are associated with prescription opioid tapering in people with chronic pain,” Beth Darnall, PhD, director of the Stanford Pain Relief Innovations Lab at Stanford University, told Practical Pain Management. “While work remains to understand these associations in greater detail, these findings reveal that patients with chronic pain need better protections within the healthcare system.”

There is, in other words, a clear pattern of harm here. Rapid tapers are destabilizing individual patients and are associated with increased rates of overdose and suicide. The goal of tapering was to reduce opioid-related risks and harms, but the data to date suggests the opposite is happening.

In general, the overdose crisis is getting worse fast. The latest data from the CDC shows over 96,000 drug overdose deaths in the 12 months ending in February, 2021. Opioid tapering has coincided with the rise in drug overdose deaths, though how and to what extent this happens is an open question that urgently requires attention.

There are, of course, risks to prescription opioids and patients may benefit from consensual tapering as described in a federal guideline for dosage reduction. Some people may also do better with non-opioid approaches to pain management.

But the current tapering efforts seem geared toward satisfying a statistical need to reduce prescriptions at the expense of individual welfare. As more and more public health data shows increasing harms without attendant benefits, it’s time to reconsider tapering practices and slow down deprescribing.

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. 

Researchers Warn of Serious Risks in ‘Unproven’ Stem Cells

By Pat Anson, PNN Editor

A new study is warning patients and healthcare providers of possible bacterial contamination and other serious risks in “unproven” stem cell products being marketed as treatments for chronic pain, arthritis and other medical conditions.   

The study findings, published in JAMA Network Open, are the outcome of an investigation that began in 2018 after public health officials began receiving reports of bacterial infections in stem cell patients. At least 20 patients in eight states developed serious infections after receiving stem cells derived from umbilical cord blood.

All of the infections were traced back to a single stem cell manufacturing lab in California, where over half the samples tested by the CDC were found to be infected with E coli and other bacteria. The contaminated products were recalled and the lab was ordered to improve its infection control procedures, but researchers say the risk of another outbreak remains.

“The findings from this outbreak underscore that unapproved and unproven stem cell products can expose patients to serious risks without clear benefit, including the possibility of product contamination,” wrote lead author Kiran Perkins, MD, an epidemiologist at the CDC Division of Healthcare Quality Promotion. “Patients and health care practitioners who are considering the use of unapproved products marketed as stem cell treatment should be aware of their unproven benefits and potential risks, including serious infections.”

The only stem cell products that are currently approved by the Food and Drug Administration are derived from umbilical cord blood, which are used to treat sickle cell disease and some cancers.

Despite FDA threats to crackdown on unproven stem cell treatments, over a thousand clinics have opened around the country, promoting stem cell injections and infusions to treat a wide variety of diseases and injuries. Many use stem cell products derived from a patient’s own body tissue – such as fat or bone marrow -- which clinic operators don’t consider a “drug” that falls under FDA jurisdiction.

Researchers say the clinics are taking advantage of desperate patients who want quick solutions to complex medical problems.

“Hundreds of clinics across the US unlawfully advertise stem cell treatments to patients as a cure for a variety of conditions for which there are currently no effective medical treatments, including certain neurological disorders, autism, and aging. Although some patients may be willing to risk unproven stem cell treatment over surgery for conditions such as chronic pain and degenerative joint diseases, this investigation demonstrates the potential risk associated with the use of these products,” Perkins and her colleagues wrote.

“Manufacturers of unlicensed products, such as those associated with this outbreak, violate the law for profit at the expense of public health. Many create market confusion by erroneously describing their products as novel therapies that do not require FDA premarketing review or approval. That is not the case.”

Of course, just because a treatment is unapproved or unlicensed doesn’t mean it’s ineffective. There are numerous examples of stem cells being used successfully to treat serious neurological conditions such as arachnoiditis and paralysis. Professional athletes have also embraced stem cells and platelet injections as therapies for stubborn muscle and joint injuries, often traveling overseas for treatments they can’t get in the U.S.

The FDA has been slow to take action against stem cell clinics and manufacturers, 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. The grace period ended in May 2021, with no indication that many stem cell providers took the agency up on its offer.      

A recent report from the Pew Charitable Trust identified 360 patients who had adverse events involving stem cells over a 17-year period. While that pales in comparison to the number of Americans who die every year from medical errors -- over 250,000 --  Pew said it was time for “increased FDA enforcement action” against stem cell clinics.

Can Psychotherapy Treat Chronic Back Pain?

By Pat Anson, PNN Editor

Anyone who has lived with chronic back pain knows how difficult it is to treat. Pain medications provide only temporary relief, and surgeries and injections can be risky.

An extensive review of back pain treatments by The Lancet concluded that many were of “dubious benefit” and that most people with low back pain would respond to “simple physical and psychological therapies” that keep them active.

A small study recently published in JAMA Psychiatry lends some support to that belief, finding that two-thirds of chronic back pain patients who received a novel psychological treatment called Pain Reprocessing Therapy (PRT) were pain-free or nearly pain-free after four weeks. Most continued to experience relief for a year.

The researchers behind the study liken chronic pain to an alarm clock stuck in the “on” position long after the initial injury has healed.

“For a long time we have thought that chronic pain is due primarily to problems in the body, and most treatments to date have targeted that,” said lead author Yoni Ashar, PhD, a postdoctoral associate at Weill Cornell Medical College. “This treatment is based on the premise that the brain can generate pain in the absence of injury or after an injury has healed, and that people can unlearn that pain. Our study shows it works.”

PRT therapy was developed by Alan Gordon, a Los Angeles-based psychotherapist and author of a new book on healing chronic pain called “The Way Out.”

PRT is based on the premise that patients can reduce or even eliminate chronic pain by changing the way they think about it, using mindfulness and cognitive behavioral therapy. The goal is to eliminate fear and avoidance techniques that many patients have about their pain.

“The idea is that by thinking about the pain as safe rather than threatening, patients can alter the brain networks reinforcing the pain, and neutralize it,” Ashar explained.

For the randomized controlled trial, Ashar and his colleagues recruited 151 people who had low to moderate back pain for at least six months, with an intensity of at least four on a pain scale of zero to 10.

Those in the treatment group received 8 one-hour sessions of PRT, in which they were encouraged to reappraise the severity of their pain by engaging in movements they were afraid to do. This helped them overcome some of the negative emotions they had about pain. 

After four weeks, 66 percent of patients in the treatment group were pain-free or nearly pain-free, compared to 20% in a placebo group and 10% who received no treatment.

The findings were confirmed post-treatment by MRI brain scans, which showed that brain regions associated with pain processing – such as the anterior insula and anterior midcingulate — had quieted significantly in those who had PRT therapy. 

“The magnitude and durability of pain reductions we saw are very rarely observed in chronic pain treatment trials,” Ashar said.

The study focused only on PRT therapy for back pain, so future studies are needed to determine if PRT would produce similar results for other types of chronic pain. 

“This study suggests a fundamentally new way to think about both the causes of chronic back pain for many people and the tools that are available to treat that pain,” said co-author Sona Dimidjian, PhD, a professor of psychology and neuroscience at CU Boulder. “It provides a potentially powerful option for people who want to live free or nearly free of pain.”

Study Identifies Medications Most Involved in ER Visits

By Pat Anson, PNN Editor

Here’s a question for you: What type of medication is most likely to be involved in a visit to a hospital emergency room?

1. Opioid pain relievers

2. Blood thinners

3. Psychiatric drugs

4. Insulin

5. Antibiotics

Given the well-publicized risks of addiction and overdose associated with opioids, you might assume it was opioid pain relievers. You’d also be wrong, according to a large new study that looked at medications associated with emergency department (ED) visits in the U.S. from 2017 to 2019.

CDC researchers looked at a representative sample of nearly 97,000 cases of adverse events involving medication and found that warfarin (Coumadin) and other anti-coagulant blood thinners – typically prescribed to reduce the risk of heart attack and stroke -- were the leading cause of ED visits.

Among patients of all ages, insulin was the second leading cause of medication-related adverse events, followed by psychiatric drugs, antibiotics and the over-the-counter pain relievers ibuprofen and acetaminophen. The opioid oxycodone came in last on a Top 10 list of drugs involved in ED visits.

TOP 10 MEDICATIONS INVOLVED IN EMERGENCY DEPARTMENT VISITS

SOURCE: CDC

The study findings, published in JAMA, help dispel many of the myths associated with the risks of opioids — at least in comparison to other widely used medications.

There are many reasons for someone to have an adverse reaction to medication, ranging from allergies to dosage errors to taking drugs intended for someone else. About a third of the ED visits were so serious, the patient was admitted for hospitalization.

Compared to seniors age 65 and older, young adults were significantly more likely to abuse a medication or to use it for intentional self-harm. Seniors were far more likely to only take a drug for its intended therapeutics use.

SOURCE: jama

The age of a patient also plays a significant role in the type of drug they have an adverse reaction to. For example, the antibiotic amoxicillin was the leading cause of medication harm for patients under the age of 14; while the anti-anxiety drug alprazolam (Xanax) was the leading cause of adverse events for patients aged 15 to 44.  Insulin ranked first for patients aged 45-64; while warfarin was first for patients aged 65 and older.

Analgesics, sedatives and antidepressants were the drugs most likely to be abused. About 63% of adverse events involving prescription opioids were cases of “non-therapeutic” abuse, while 89% of cases involving benzodiazepines were classified as abuse. The vast majority of cases involving blood thinners, insulin or antibiotics were for their intended therapeutic use.    

The role of opioids in ED visits has been falling for over a decade. A 2017 study showed a significant decline in the number of patients admitted to U.S. hospitals for abusing opioid medication. Hospital admissions for overdoses from opioid medication started falling in 2010, the same year that opioid prescriptions peaked in the U.S.

Surprise Discovery Could Lead to Vaccine for Rheumatoid Arthritis

By Pat Anson, Editor

A surprise discovery at a university laboratory could lead to a vaccine that can prevent rheumatoid arthritis, a chronic and incurable disease in which the body’s own immune system attacks joint tissues.

Researchers at The University of Toledo years were studying a protein called 14-3-3 zeta and its role in immune system pathologies. Previous studies have suggested the protein could be a possible trigger for rheumatoid arthritis (RA) and other autoimmune conditions that cause pain, inflammation and bone erosion.

But researchers found just the opposite. The team discovered that 14-3-3 zeta proteins may actually help prevent arthritis. When they removed the proteins through gene-editing technology, it caused severe early onset arthritis in laboratory animals.

Realizing that the proteins may be beneficial, the team developed an experimental vaccine using purified 14-3-3 zeta protein grown in a bacterial cell. They found the vaccine promoted a strong, immediate and long-lasting response in rodents that protected them from RA.

"Much to our happy surprise, the rheumatoid arthritis totally disappeared in animals that received a vaccine," said Ritu Chakravarti, PhD, an assistant professor at UToledo College of Medicine and lead author of research published in the journal Proceedings of the National Academy of Sciences. "Sometimes there is no better way than serendipity. We happened to hit a wrong result, but it turned out to be the best result. Those kinds of scientific discoveries are very important in this field."

In addition to suppressing the immune system response, the vaccine also significantly improved collagen content and bone quality — findings that suggests there could be long-term benefits following immunization.

Currently, rheumatoid arthritis is treated with steroids or medications that suppress the immune system, such as biologics and biosimilar drugs. While those therapies can alleviate pain and reduce inflammation, they can also make patients more vulnerable to infection and, in the case of biologics, are expensive. Biologic drugs can cost $25,000 a year.

“We have not made any really big discoveries toward treating or preventing rheumatoid arthritis in many years,” Chakravarti said. “Our approach is completely different. This is a vaccine-based strategy based on a novel target that we hope can treat or prevent rheumatoid arthritis. The potential here is huge.”

RA affects about 1.5 million Americans and about one percent of the global population. Women experience RA at a rate three times greater than men, have more severe symptoms and increased disability.

“In spite of its high prevalence, there is no cure and we don’t entirely know what brings it on. This is true of nearly all autoimmune diseases, which makes treating or preventing them so difficult,” said Chakravarti. “If we can successfully get this vaccine into the clinic, it would be revolutionary.”

Chakravarti and her colleagues have filed for a patent on their discovery and are seeking pharmaceutical industry partners to fund more research and preclinical trials.

FDA Approves Another Expensive Migraine Drug

By Pat Anson, PNN Editor

The highly competitive and lucrative market for migraine drugs will grow more crowded this month when AbbVie introduces Qulipta (atogepant), an oral CGRP medication developed for the prevention of episodic migraines.

The Food and Drug Administration approved Qulipta after seeing the results of a Phase 3 clinical trial that found the drug was 50 to 100% effective in preventing migraines.

"During the trial while taking Qulipta, I had many fewer migraine days. For the first time ever, I don't have difficulty doing my daily activities and I don't have to worry as much that a migraine attack will cause me to miss important events with family and friends," said Kelsi Owens, a trial participant who has lived with migraine for nearly three decades.

Like other CGRP inhibitors, Qulipta blocks proteins called calcitonin gene-related peptides from binding to nerve receptors in the brain and causing migraine pain. Since 2018, the FDA has approved over half a dozen CGRP medications, most of which are injected monthly.

Qulipta is a pill meant to be taken daily that comes in three different doses. Like other CGRP inhibitors, Qulipta is expensive. The wholesale price for a patient without insurance is $991 for 30 pills, according to Abbvie. Insured patients or those enrolled in an AbbVie patient support program will pay less.     

"Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients," said study investigator Peter Goadsby, MD, a neurologist and professor at University of California, Los Angeles. “I'm particularly encouraged by the convenience of the oral daily use of Qulipta, its rapid onset of significant efficacy, and its safety and tolerability as well as its high patient response rates.”   

Qulipta is expected to compete directly with Nurtec, an oral CGRP inhibitor made by Biohaven Pharmaceuticals that is approved for both migraine prevention and treatment. A supply of eight Nurtec tablets costs about $941, depending on insurance coverage. Since it was introduced in 2020, Nurtec has generated about $200 million in revenue for Biohaven, with over 750,000 prescriptions filled.

AbbVie says Qulipta will be available in early October. Wall Street analysts project Qulipta sales will reach $1 billion by 2030.

Side effects from Qulipta include nausea, constipation, fatigue and loss of appetite. AbbVie is currently conducting a clinical trial to seek if Qulipta should also be approved for the prevention of chronic migraine – patients who have 15 or more headaches per month.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

What Pain Patients Should Know About the GABA Neurotransmitter

By Forest Tennant, PNN Columnist

“GABA” is short for the neurotransmitter, gamma aminobutyric acid. GABA is the natural (endogenous) biochemical substance in the brain, spinal cord, and all nerves that control electrical conduction.

Without proper GABA function, we experience pain. New research also shows that low levels of GABA make it harder to keep negative emotions such as fear, worry, anxiety and depression in check. 

All Intractable Pain Syndrome (IPS) patients have nerve damage somewhere in their brain, spinal cord, or nerves. Consequently, IPS patients will either need extra GABA or a GABA surrogate to force damaged nerve tissue to correctly function and relieve pain. 

GABA Surrogates

Without realizing it, you may already be taking a GABA surrogate. And you may have found that your pain gets worse without one. Here are the most effective prescription surrogates:

• Gabapentin (Neurontin)

• Carisoprodol (Soma)

• Diazepam (Valium)

• Alprazolam (Xanax)

• Lorazepam (Ativan)

There are also herbs and amino acids available without a prescription that can be used as GABA surrogates:

• Valerian root

• Ashwagandha

• Taurine

• Brahmi

• Bacopa

Glutamine: GABA’s Precursor

The term “precursor” refers to nutrients or raw material that help make a neurotransmitter. Glutamine is the precursor of GABA. A dose of 2000 mg or more of glutamine a day when taken on an empty stomach with vitamin B6 (2mg or more), will increase your natural level of GABA and probably reduce your pain levels. 

Pure GABA is available as a tablet, capsule or in sublingual (under-the tongue) form in most health food stores or online. Unfortunately, when swallowed in tablet or capsule form, GABA may be digested just like food or fail to cross the blood-brain barrier, and be rendered ineffective.

But sublingual GABA is well absorbed by the body and should be given a thorough trial by every person with IPS. You can take 100 to 300mg sublingual GABA to treat pain flares, or 100 to 200mg of GABA simultaneously with an opioid medication or GABA surrogate for added pain relief.

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

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

Why Pain Is Not ‘All in Your Head’

By Gabriella Kelly-Davies, PNN Columnist

Anyone who lives with chronic pain knows it can affect their emotions. Every morning when I wake with a migraine, I feel a sense of doom. My heart races and I panic about how I will cope with everything that lies ahead of me that day — the meetings, deadlines and responsibilities, not to mention family and social commitments that often end up taking a back seat as I scramble to find ways of simplifying my day.

After decades of living with chronic migraine, I now know these emotions intensify my experience of pain. Having said this, I know it is not “all in my head” as some might claim, but part of a complex interaction between my emotions and the way my central nervous system incorrectly processes pain signals.

Exciting new Australian research using sophisticated brain imaging is shedding new light on what happens at an emotional level for people living with chronic pain.

Chemical “messengers” known as neurotransmitters facilitate communication between brain cells. Some neurotransmitters are inhibitory, helping to dial down our emotions, while others are excitatory and increase the intensity of emotions. A molecule known as γ-aminobutyric acid or GABA is the main inhibitory neurotransmitter.

Neuroscientist and psychologist Sylvia Gustin, PhD, discovered that GABA levels are lower in people with chronic pain and this affects their ability to regulate their emotions. The link between lower levels of GABA and chronic pain had been shown in animal studies, but Gustin’s research, recently published in the European Journal of Pain, is the first time it has been demonstrated in humans.

“A decrease in GABA means our brain cells can no longer communicate with each other properly,” explained Gustin, an associate professor at the University of Sydney’s School of Psychology. “When there’s a decrease in GABA, it makes it harder to keep emotions such as fear, worry, anxiety and depression in check.”

Gustin’s research shows there’s a physical change in the central nervous system that helps explain the roller coaster of emotions people living with pain often experience.

“If you live with chronic pain, it’s important to remember it’s not you -- there’s something physically happening to your brain. We don’t yet know why this happens, but we’re working on finding solutions on how to change it,” Gustin told me.

Her research confirms that chronic pain, which affects one in five people worldwide, is more than just an uncomfortable sensation. “It can affect our feelings, beliefs and the way we are,” she says. “Almost half the people living with chronic pain also experience major anxiety and depression disorders.”

GABA is not the only neurotransmitter that behaves differently in people living with chronic pain. In an earlier study, Gustin and her colleagues found levels of the main excitatory neurotransmitter in the central nervous system – glutamate -- are also lower in people with chronic pain. Lower glutamate levels are linked to increased feelings of fear, worry and negative thinking. They disrupt how brain cells talk to each other, affecting the ability to feel positive emotions such as happiness, motivation and confidence.

“My research results are reassuring for people living with pain because they show that physical changes in the brain are contributing to anxiety and depression and it’s not a person’s fault they struggle with these emotions,” Gustin said.

Her research team recently developed and tested an online recovery program that teaches people skills to help modify negative emotions such as fear, worry, anxiety and depression. The program helps to address the neurotransmitter disruption in chronic pain.

“Online programs offer hope to people living with disabilities or those in rural and remote communities who often struggle to access pain management services,” she said. “Online programs are also ideal during COVID-19 lockdowns.

“We know that chronic pain is always present, and we can’t get rid of it. But we can change the way we experience it by learning new skills. Like all skills, it takes practice to master it, but we hope it will offer another tool for people to change the way they experience pain.”

Gustin says preliminary results of this research, which will be published in a few months, are encouraging. Several organizations, including Australia’s National Health and Medical Research Council and Medical Research Future Fund, the International Association for the Study of Pain (IASP) and the U.S. Department of Defense, are helping to fund her work. To learn more about this research, click here.

Gabriella Kelly-Davies lives with chronic migraine.  She is the author of “Breaking Through the Pain Barrier,” a biography of trailblazing Australian pain specialist Dr. Michael Cousins. Gabriella is President of Life Stories Australia Association and founder of Share your life story.

Holistic Therapy Won’t Cure You, But It Can Help

By Mia Maysack, PNN Columnist 

To mark the end of Pain Awareness Month,  I'd like to share a few holistic therapies that have proven helpful on my journey. 

I’m not suggesting they are magic remedies or that they're the right choices for everyone. Many of us who live with chronic or intractable pain have our minds closed off to new things. And after all we've been through, who could blame us?   

There is an endless amount of misinformation and misinterpretation regarding holistic and preventative medicine, and no shortage of judgement. I'll be honest by confessing that I have also been a skeptic to some extent about holistic therapy, but it has ultimately helped me more than two decades of “mainstream" traditional medicine.  

I'd like to think I have established credibility as it pertains to my own personal experiences, just as I honor anyone else's. Here is what I have learned about holistic therapy:   

Having an open mind and willingness to expand consciousness about the limitations that pain imposes on our lives -- and taking leadership in our own journey – means coping, managing, adapting, transcending and evolving as best we can.  

These therapies don't really work until WE WORK ‘EM and add them to a tool box full of different things to pull from.  Allow yourself the curiosity of what could be possible if you were to try something new. If there are still doubts or if you tried and failed with them in the past, then ask yourself: When’s the last time anything went perfectly right the first time?   

We cannot know unless we try. To have found anything that's assisted, helped or if you're lucky enough to have something that actually works would not be possible without an attempt to try it in the first place.  

The great thing I have found about these holistic therapies is that they have positive side effects, are healthy and habit forming.  

Soaking in Warm Water:  I use generous amounts of Epsom salt (magnesium sulfate) in a bathtub. It creates a soothing buoyancy that makes the body seem weightless.  

Massage Therapy:  Manipulation of soft tissues of the body, consisting primarily of manual techniques, such as applying fixed or movable pressure, holding, and moving muscles and body tissues. 

Mindfulness:  A mental state achieved by focusing one's awareness on the present moment, while calmly acknowledging and accepting one's feelings, thoughts, and bodily sensations. 

Energy Healing:  Also known as Reiki or Qigong, energy healing offers the potential for a positive shift in physiological state and present moment awareness that may alter the perspectives that sustain the burden of symptoms. 

Yoga:  A mind and body practice. Various styles of yoga combine physical postures, breathing techniques, and meditation or relaxation to promote mental and physical well-being. There are several types and many different disciplines. 

None of these are meant to replace any existing care plan, but rather contribute to a well-rounded approach to our whole being and health. Imagine committing the same amount of energy spent fighting against these concepts into exploring ways to incorporate them into your life. You just might find that they help.          

Mia Maysack lives with traumatic brain injury, migraine disease, cluster headache and fibromyalgia. Mia is the founder of Keepin’ Our Heads Up, a Facebook advocacy and support group, and Peace & Love, a wellness and life coaching practice for the chronically ill. 

Mia was recently chosen as a recipient of the 2021 iPain Community Impact Award for her advocacy work.

DEA Warns of Sharp Increase in Counterfeit Prescription Pills

By Pat Anson, PNN Editor

The U.S. Drug Enforcement Administration has issued a public safety alert warning of a sharp increase in the black market of fake painkillers and other counterfeit medications containing illicit fentanyl and methamphetamine. The alert, the DEA’s first in six years, coincides with the launch of a public awareness campaign to educate the public about the dangers of counterfeit pills.

“The United States is facing an unprecedented crisis of overdose deaths fueled by illegally manufactured fentanyl and methamphetamine,” DEA Administrator Anne Milgram said in a statement. “Counterfeit pills that contain these dangerous and extremely addictive drugs are more lethal and more accessible than ever before. In fact, DEA lab analyses reveal that two out of every five fake pills with fentanyl contain a potentially lethal dose.

It takes only two milligrams of fentanyl – an amount small enough to fit on the tip of a pencil – to constitute a lethal dose. The DEA says it has seized over 9.5 million fake pills so far this year, which is more than the last two years combined.

A recent raid on a home in Perris, California resulted in the seizure of 46 pounds of carafentanil,  – a chemical cousin of fentanyl – which is potentially enough to kill more than 50 million people, according to the Riverside County District Attorney.

Carfentanil is a synthethic opioid 100 times more potent than fentanyl and 10,000 times more potent than morphine.

FAKE OXYCODONE PILLS

The DEA says most of the counterfeit pills manufactured or smuggled into the U.S are produced by Mexican drug cartels, using illicit chemicals that originate in China.

One of the most commonly produced fake pills are tablets made to look like 30mg oxycodone pills. Known on the street as “Mexican Oxy” or “M30s,” the tablets are virtually indistinguishable from legitimate oxycodone pills used for pain relief.   

Law enforcement agencies are also finding counterfeit anti-anxiety medications made to look like Xanax and fake pills that look like the stimulant Adderall, which are made with methamphetamine.  

‘One Pill Can Kill’

The goal of the DEA’s “One Pill Can Kill” campaign is to make the public more aware of the proliferation of counterfeit medications — now found in every state — and to warn drug users not trust any pill that doesn’t come from a pharmacist.  

“Counterfeit pills have become a real and viable threat to the American People,” said Daniel Comeaux, Special Agent in Charge of the DEA’s Houston Division.  “We caution every person to never consume any pill that is not sourced from a licensed pharmacy. These illicit counterfeit pills often contain fentanyl, where just a miniscule amount can result in death.”

Ironically, the DEA itself has played a significant role in the profusion of fake pills and its PR campaign is little more than a fig leaf covering years of disastrous policies.

Counterfeit medication made with illicit fentanyl first began appearing in quantity in the U.S. in 2016, around the same time federal and state regulators began recommending more cautious opioid prescribing for pain.

Faced with pressure from Congress to combat the so-called opioid epidemic by cracking down on painkillers, the DEA began cutting the legal supply of opioids in 2017. It has reduced opioid production quotas for five consecutive years, cutting the legal supply of hydrocodone and oxycodone in half.

The agency also began arresting and prosecuting doctors and pharmacists thought to be prescribing or dispensing opioids excessively, and revoked the DEA registrations of hundreds of physicians. As a result, opioid prescribing fell to 20-year lows, but the crackdown has had a negligible impact on drug overdoses, which rose to record levels.

With opioid medication harder to obtain, illegal online pharmacies began to proliferate and legitimate patients turned to street drugs for relief. A recent PNN survey of pain patients found that nearly 10% have obtained prescription opioids from family, friends or the black market.

In a 2020 report, the DEA said drug cartels were actively targeting pain sufferers as potential customers for counterfeit medication.  The report said nearly two-thirds (64%) of people who misuse painkillers “identified relieving pain as the main purpose” of their drug use.

Researchers Urge Caution on Using Steroid Injections for Pain

By Pat Anson, PNN Editor

Doctors and patients should be more cautious about using corticosteroid injections for pain relief, according to new studies that warn of rare, but serious long-term complications for patients who receive epidurals during childbirth or high doses and multiple injections in their hips.

Researchers at Kaiser Moanalua Medical Center in Hawaii looked at health data for nearly 700 patients with hip osteoarthritis and found that those who received steroid injections were 8.5 times more likely to develop rapidly destructive hip disease (RDHD), a condition that causes the loss of blood flow and death of bone tissue in the hip.

Higher rates of RDHD were especially apparent in patients receiving multiple and/or high-dose injections of the steroid triamcinolone. The risk of RDHD following a single, low-dose injection was about two percent, but rose to five percent following multiple low-dose injections or a single high-dose injection, and up to 10 percent following multiple high-dose injections.

“While the risk of RDHD following a single low-dose (40 mg or less) triamcinolone injection is low, the risk is higher following high-dose (80 mg or more) injection and multiple injections. These findings provide information that can be used to counsel patients about the risks associated with this common procedure. In addition, caution should be taken with intra-articular hip injections utilizing 80 mg of corticosteroid and multiple injections,” wrote lead author Kanu Okike, MD, of Hawaii Permanente Medical Group in Honolulu.

As they became more aware of a possible link with RDHD, orthopedic surgeons at the hospital started ordering fewer hip corticosteroid injections. In subsequent years, the number of RDHD cases decreased. The hospital also added a discussion of post-injection RDHD to the informed consent process for patients and stopped performing high-dose corticosteroid injections.

The study, recently published in The Journal of Bone & Joint Surgery, is believed to be the largest to date of patients with post-injection RDHD.

Epidural Injections

Two new studies have also found that women receiving epidural injections for pain relief during labor are at high risk of long-term headaches and chronic back pain if the needle accidentally punctures the dural lining of the spinal cord. Dural punctures or “wet taps” cause the leak of spinal fluid, which can result in serious neurological complications.  

“I’ve likely performed more than 10,000 epidurals in my lifetime, and I still have wet taps from time to time,” Pamela Flood, MD, a professor of anesthesiology at Stanford University School of Medicine, told Anesthesiology News. “But no matter how many we’ve seen, we still feel terrible about each one. We’re trying to relieve people’s pain and give them a wonderful childbirth experience, and the last thing we want to do is cause them complications.”

A study published in the journal Anaesthesia found that over half of women (58%) with an accidental dural puncture were still experiencing headaches 18 months after the epidural, and nearly half (48%) suffered from chronic low back pain. A recent study in the British Journal of Anaesthesia had similar findings.    

Dural punctures during epidurals are relatively uncommon. Women are usually warned there is a risk of short-term headaches, but not about long-term health problems.

“While this information has been creeping into our consciousness in the form of retrospective trials, only this year has it been confirmed with two large prospective trials,” Flood said. “Unfortunately, clinicians have been slow to hear this, perhaps because we don’t want to admit that the short-term concern that we have been discussing for years carries long-term consequences in a significant percentage of women.”

The two most common types of medications used during epidural injections are anesthetics (lidocaine or bupivacaine) or corticosteroids (betamethasone, dexamethasone, hydrocortisone, methyl-prednisolone, triamcinolone). 

In addition to treating labor pain, epidural steroid injections are widely used for back pain. About 9 million epidural steroid injections are performed annually in the U.S., even though they are not FDA-approved. The FDA has warned that injection of steroids into the epidural space can result in rare but serious neurological problems, including loss of vision, stroke and paralysis. Some patients have also developed arachnoiditis, a chronic and painful inflammation of the spinal cord, after getting steroid injections for back pain.

Epidemiological Sleuthing During the Pandemic

By Roger Chriss, PNN Columnist

How do we figure out what is really going on with Covid-19? Amid the ongoing surge of Covid cases from the delta variant of SARS-CoV-2, this is very important.

As hospitals are overwhelmed with patients, beds are unavailable, supplies of monoclonal antibody drugs are limited, and frontline healthcare workers are strained. Understanding what is really happening becomes vital to an effective response.

One of the tools most widely used to track the severity of the pandemic is the number of patients that are hospitalized. According to the CDC, we’re currently seeing an average of 9,636 new admissions every day, which is about 14% less than a week ago.   

New Hospital Admissions for Covid-19

But how reliable are these numbers? And just how sick are the patients?

A recent preprint study of VA patients before the delta surge suggested that almost half of hospitalized Covid-19 cases had mild or asymptomatic symptoms. This finding prompted The Atlantic to conclude that the significance of the hospitalization gauge “can easily be misinterpreted.”

As often happens with public health data in the US, information is missing. SFGate recently investigated Covid-19 hospitalizations in the Bay Area and found that simply tracking patient numbers was unreliable. Three major hospital systems -- San Francisco General, Kaiser Permanente and Sutter Health -- could not say if mild and asymptomatic cases made up a large proportion of their Covid patients.

In other words, in many cases hospitals simply don’t have the data needed to assess the severity of outbreaks. We need better ways to validate hospitalization counts and assess local conditions in near real time.  

Fortunately, we have them. Broadly speaking, these include community surveillance, hospital monitoring and indirect signals. Each of these comprises multiple sources of information, and when combined, the result is a deep assessment of Covid conditions.

Carnegie Mellon University’s COVIDCast gives early indicators, including doctor’s visits and symptoms in communities across the nation. This can be paired with public behaviors like masking and distancing, visits to bars or restaurants, local vaccination rates, and searches on Google for Covid symptoms. All of this helps build a risk profile for a community that can be confirmatory for hospitalization data.

Similarly, wastewater epidemiology provides a close look at something all communities produce. For instance, the Sewershed Surveillance Project in Missouri has tracked virus levels in effluent for a year, with spikes often warning of possible outbreaks in cities and counties throughout the state. Wastewater epidemiology is already used in Europe and many parts of the US to help track drug use and disease activity.  

Next comes personnel. Hospital staff is in constant flux, and job postings provide valuable clues about what hospitals are expecting or confronting. For instance, travel nurses move around the US in response to calls for supplementary staff, so job boards like TravelNurse Source offer valuable insight for assessing a hospital’s needs.

The same for respiratory therapists, imaging technicians, and other frontline healthcare workers. Hospitals know their everyday needs, which can be readily found in reports from the American Hospital Association’s Data & Insights database. These reports include the number of staffed beds, admissions, and outpatient visits for most hospitals in the US. If we know what hospitals typically have and see, that allows us to check if they are experiencing a Covid surge.

Further, we have drug and equipment orders. Hospitals have to track all orders for financial and regulatory reasons. So new orders for fentanyl to sedate patients who need intubation, requests for ECMO respiratory machines, or just reordering PPE equipment and other supplies are all readily monitored via federal and state databases.

There are also indirect signals. Hospitals redirecting patients to other facilities, requesting ambulance or helicopter transport, arranging for at-home care for patients they might otherwise admit, or activating emergency plans are all publicly visible, as are signals such as requests for mobile morgues or National Guard assistance.

The above information can be combined to create a reasonably accurate profile of a hospital’s situation. Better, however, is to use such information proactively in order to avoid the severe surges seen in the South over the summer or in Idaho and Montana at present.

Early attempts to use wastewater epidemiology proactively have met with some success. When a wastewater sample from a dorm at the University of Arizona came back positive last year, the school quickly tested all 311 people who live and work there and found two asymptomatic students who tested positive.

All of the above is not limited to the pandemic. The same approach could be used for other infectious diseases, drug overdoses and other areas of public health. If the data streams and information analysis are combined and coordinated, the results could be that much better and more useful.

We cannot and should not rely on a single number, not with so many other tools available to be used. Hopefully we’ll see these tools put to use fast.

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.