Why Antibiotics Can Lead to a C. Diff Infection

By Madora Pennington, PNN Columnist

Got antibiotics? Then you may be on your way to a dangerous and potentially deadly infection. When antibiotics alter the balance of intestinal flora, a bacteria that causes diarrhea and inflammation of the colon -- clostridioides difficile -- can take over and result in a C. diff infection.

That is what happened to Kristy Collins. It took two rounds of antibiotics to clear up her severe ear and sinus infection. A few days later, a lunchtime salad left Kristy with a strangely upset stomach. She thought it was nothing more than a bit of food poisoning, but soon she was having malodorous belches and the foulest smelling diarrhea. She also became severely dehydrated.

At first, her doctor suspected a stomach virus. But when her stomach troubles didn’t relent, a stool test revealed that Kristy had C. diff.  Luckily, she was diagnosed and treated within a few days.

Because she has Ehlers-Danlos Syndrome (EDS), an inherited chronic illness, Kristy is a seasoned patient with a medical team in place. But having EDS also makes her more like to get C. diff. Thus far, she has had 19 surgeries for EDS-related problems. Most surgical procedures require a round of antibiotics to prevent infection and more if an infection occurs after surgery.

After her bout with C. diff, Kristy needed another surgery. She and her doctors were very concerned about a possible C. diff recurrence, as about 1 in 5 patients will get another infection. Kristy’s doctors tested her after surgery to ensure it had not returned.

Kristy worries whenever she needs antibiotics and questions her doctors if they are truly necessary. She already follows a very healthy diet, which helps manage her chronic illness and suspects this may be part of why she has not had a C. diff recurrence. She also follows her doctors’ advice.

“It was the first time doctors told me to take probiotics,” Kristy says, which she did while taking antibiotics. Probiotics are living microorganisms that enhance intestinal health. They are found in fermented food like yogurt and sauerkraut or made into supplements.

Antibiotics tend to alter that flora in the colon, creating an environment where C diff can flourish. Many people have immune systems that can handle a C. diff infection without symptoms, but others get very ill with watery diarrhea that may contain blood or mucus, or cause nausea, vomiting, loss of appetite, abdominal pain, and bloating. At its worst, C. diff can cause a loss of blood circulation, sepsis, perforated bowel, or swelling so severe it shuts down the colon.

It is not just antibiotics that can cause a C. diff infection. Other possibilities are chemotherapy treatment, proton pump inhibitor medications (usually used to treat acid reflux), kidney or liver disease, malnutrition, or simply being an older person. C. diff infects approximately half a million Americans annually, according to the CDC. 

C. diff can also be fatal. In the U.S., nearly 30,000 people die every year from a C. diff infection. Diagnosis is usually made by testing a stool sample. It is treated with antibiotics, monoclonal antibodies, or, in severe cases, surgery.

How to Prevent C. Diff

Good hygiene practices can help prevent its spread. For C. diff, hand washing with soap and water is more effective than using alcohol-based hand sanitizers. It is also essential to limit the use of antibiotics to situations when they are truly necessary, to avoid disrupting the balance of bacteria in the colon. Many doctors recommend repopulating the beneficial bacteria with probiotic supplementation during or after antibiotic treatment.

Recovering from a C. diff infection can be mysterious as well as complicated. Many patients are not advised on how or what to eat or drink. Food can seem like the enemy, and meals can feel traumatizing.

To address this unmet need, the Peggy Lillis Foundation, a non-profit advocacy organization created in honor of a beloved kindergarten teacher whose life was taken suddenly by C. diff, recently published a nutrition and lifestyle guide.

 “This guide begins to address the dearth of information by combining medical expertise, dietary guidance, and first-hand knowledge from C. diff survivors,” says Executive Director Christian John Lillis.

The guide is sponsored by probiotic manufacturer Bio-K Plus and put together by the PLF’s Scientific Advisory Council. It covers tips on managing the acute phase of a C. diff infection, preventing a recurrence, improving gut health, dealing with the emotional implications of C. diff, and recipes. It is available to download free by clicking here.

Madora Pennington is the author of the blog LessFlexible.com about her life with Ehlers-Danlos Syndrome. She graduated from UC Berkeley with minors in Journalism and Disability Studies. 

Lyme Disease Cases Soar in U.S.

By Pat Anson, PNN Editor

Diagnoses of Lyme disease in the United States have soared over the past 15 years, primarily in rural areas in the Northeast, according to a new analysis of private insurance claims by FAIR Health, a nonprofit that tracks healthcare costs and insurance trends.   

Lyme disease is a bacterial illness spread by ticks. Left untreated, it can lead to chronic fatigue, muscle and joint pain, cognitive issues and other long-term symptoms that are often misdiagnosed as fibromyalgia, neuropathy or autoimmune disorders.

In its analysis of over 36 billion insurance claims from 2007 to 2021, FAIR Health said that claims with a Lyme disease diagnosis rose 357 percent in rural areas and 65 percent in urban areas. The highest rates of Lyme disease were in New Jersey, Vermont, Maine, Rhode Island and Connecticut.

“Lyme disease remains a growing public health concern. FAIR Health will continue to use its repository of claims data to provide actionable and relevant insights to healthcare stakeholders seeking to better understand the ongoing rise of Lyme disease cases,” FAIR Health President Robin Gelburd said in a press release.

The FAIR Health study found that malaise, fatigue and soft-tissue-related symptoms were significantly more common in Lyme patients than in the overall patient population.

Other early symptoms of Lyme disease include fever, chills, headache, and swollen lymph nodes. A delayed rash often appears at the site of the tick bite. The rash grows in size and sometimes resembles a bulls-eye.

Although Lyme disease is treatable with antibiotics, some patients develop long-term symptoms known as Lyme disease syndrome or chronic Lyme disease.

About 30,000 Lyme cases are reported annually by state health departments. The CDC estimates the actual number of cases is probably much higher and that about 300,000 Americans may become infected every year.

Most reported cases of Lyme disease occur in the Northeast, mid-Atlantic and upper Midwest, especially during the summer months when more people spend time outdoors. Recent studies show Lyme is spreading to neighboring states and is no longer just a seasonal disease, possibly due to the effects of climate change.

Gut Bacteria Identified as Cause of IBS

By Pat Anson, PNN Editor

Canadian researchers have identified one of the primary causes of Irritable Bowel Syndrome (IBS), a frustrating intestinal condition that causes abdominal pain, cramps, bloating, gas and diarrhea.

The culprit appears to be Klebsiella aerogenes, a strain of bacteria that causes white blood cells to produce excess amounts of histamine, a chemical that triggers a painful immune system response. Gut bacteria have long been suspected as a likely cause of IBS, but this is the first time a specific bacterial strain has been identified.  

Researchers at McMaster University and Queen’s University studied stool samples from both Canadian and American IBS patients, and found Klebsiella aerogenes in about 25 percent of them.

“We followed up these patients for several months and found high levels of stool histamine at the time when the patients reported severe pain, and low stool histamine when they were pain-free,” said senior author Premysl Bercik, MD, a gastroenterologist and professor at McMaster’s Michael G. DeGroote School of Medicine.

Further tests on laboratory mice that were colonized with gut microbes from IBS patients showed that several types of bacteria produced histamine, but Klebsiella aerogenes was a “super-producer.” The chemical is produced when histidine, an essential amino acid in animal and plant protein, is converted into histamine, triggering pain and inflammation.

“Now that we know how the histamine is produced in the gut, we can identify and develop therapies that target the histamine producing bacteria,” said first author Giada de Palma, an assistant professor of medicine at McMaster.

Researchers found that when mice colonized with histamine producing bacteria were fed a diet low in carbohydrates, histamine production dramatically decreased. That would explain the benefits of diets low in carbohydrates and high in dietary fiber, which are often recommended to IBS patients. Allergy medications that block histamine production may also be useful in treating IBS.

“Many but not all IBS patients will benefit from therapies targeting this histamine driven pathway,” said co-first author David Reed, assistant professor of medicine at Queen’s University.

The McMaster-Queens study was funded by the Canadian Institutes of Health Research and published in the journal Science Translational Medicine.

How Emojis Could Enhance Pain Care

By Pat Anson, PNN Editor

Because pain is subjective and varies from patient to patient, there has long been a debate in the medical community about the best way to measure it.

The two most widely used methods, the numeric 0 to 10 pain scale and the Wong-Baker scale, both rely on patients to self-report their pain levels by assigning a number or a face to it. Someone in severe pain, for example, might rate it an “8” or point to an unhappy, grimacing face to help their doctor understand how much pain they are in.

Not exactly cutting-edge science, is it?

In an effort to find a more useful way to measure pain in the digital age, researchers at Massachusetts General Hospital (MGH) asked 109 patients to rate their pain on a numerical scale and by using an electronic device to select one of six emoji faces modeled after the Wong-Baker scale. The patients suffered from abdominal, chest, back or extremity pain, and were admitted for emergency care or surgery at MGH.

JAMA IMAGE

The study findings, published in JAMA, showed no discernible difference between the numerical and emoji scales – suggesting that digital emojis can be useful in collecting patient health data, particularly for young children and individuals with different cultural, language and cognitive abilities.

"By demonstrating concordance between emoji and the numerical pain rating scale, we've validated the use of emoji as an accurate, open-source and economical alternative to popular visual analog pain scales such as Wong-Baker," first author Shuhan He, MD, an MGH emergency department attending physician, said in a press release.

"Because emoji are open source and digital, they could encourage collection of data on a patient's condition over days, weeks, or months—information that could then be integrated into electronic health records and documented on patients' charts."

Rather than just an online fad, Dr. He and his colleagues say colorful emoji symbols could be a practical and imaginative way to break down communication barriers in the hospital setting.

"If a clinician doesn't understand the patient due to a language barrier or disability, it's tantamount to no treatment at all," said senior author Jarone Lee, MD, vice chief of Critical Care and Trauma Emergency Surgery at MGH. "Among populations that could benefit are patients in the intensive care unit who may have difficultly speaking, such as those on mechanical ventilators who need an alternative way to characterize their pain to caregivers."

Digital emojis originated in Japan over a decade ago. Of the 3,500 emoji symbols approved for use by the Unicode Consortium -- a nonprofit that maintains uniform text standards for computers — only 50 are relevant to medicine.

The first medical emojis, introduced in 2015, were the syringe and the pill. Emojis have since been added to represent disability, a stethoscope, bone, teeth, heart and lungs. Dr. He is working with professional medical societies to develop more emojis – including ones to represent pain -- with the goal of getting them approved by the Unicode Consortium.

He believes medical emojis could become mainstream tools for enhancing diagnosis and treatment. In emergency room cases where timing is critical, emojis could lead to a point-and-tap form of communication that bridges language gaps and speeds clinical decisions.

"As physicians, our job is to know how patients feel," Dr. He said, "and the use of emoji allows us to make that process more equitable and thus improve healthcare delivery for all patients in a very meaningful way."

What’s Missing in ‘Elvis’ Movie: The King’s Chronic Illness

By Pat Anson, PNN Editor

There’s a scene towards the end of the new “Elvis” movie when you know the end is coming soon. Presley, as depicted by actor Austin Butler, collapses in a hallway minutes before being scheduled to take the stage at the International Hotel in Las Vegas.

Instead of rushing an unconscious Elvis to a hospital, manager Tom Parker --- played by a surprisingly villainous Tom Hanks -- declares that the show must go on and summons “Dr. Nick” to make it right. After a quick injection of stimulant drugs, Elvis recovers just enough to sing, dance and entertain an adoring crowd in a packed showroom.   

That one scene sums up how the real Elvis Presley spent his final years before dying of an apparent heart attack in 1977 at the young age of 42. Popping pills. Slurring his words. Deeply depressed. And driven to continue performing by “Colonel” Parker and others.

“They really tried to push Elvis beyond his capacity in the last few years of his life. He was disabled,” says Dr. Forest Tennant, a retired physician and pain management expert who is one of the last people alive to be intimately familiar with Elvis’ drug use and medical problems.

In 1981, Tennant was hired by an attorney for Dr. George Nichopoulos (Dr. Nick), who faced criminal charges in Presley’s death. Tennant reviewed the autopsy report, medical records and a confidential 161-page private investigation, and testified as a defense witness for Nichopoulos, who would be acquitted of charges of overprescribing drugs.

After the trial, Tennant remained curious about Elvis’ medical problems and continued his research while treating people with intractable pain. The knowledge and experience Tennant gained in the last 50 years led to his recent book, appropriately titled “The Strange Medical Saga of Elvis Presley.”  

Elvis did indeed suffer from heart problems aggravated by an excessive use of drugs, but Tennant believes the ultimate cause of his death was a connective tissue disorder called Ehlers-Danlos syndrome (EDS), a major cause of intractable pain and other chronic health problems.

A diagnostic screening tool for EDS didn’t exist when Elvis was alive and few physicians were even aware of the condition. But Tennant thinks Presley had all the symptoms of EDS, including an unusual degree of flexibility and double jointness that allowed him to swing his hips and gyrate wildly. Those sexy dance moves helped make Elvis famous, but they also foretold what lay in store for him.

“EDS is a genetic connective tissue collagen disorder, and what that means is that you are genetically predetermined to have your collagen in certain tissues either disappear or deteriorate or become defective, and to put it bluntly, you can have a rectal problem and an eye problem at the same time due to the same cause because your collagen is deteriorating in these tissues,” Tennant told my colleague Donna Gregory Burch in a 2021 interview. “If you get a severe case like Elvis Presley, your life is going to be very miserable, and you're going to die young unless you get vigorous treatments.”      

The day before he died, a dentist gave Presley codeine for an aching tooth, not realizing how sick he was or that codeine could cause his heart to stop. Elvis collapsed in the bathroom 24 hours later. His sudden death led to rumors that he died from an overdose or even a horrible case of constipation. The truth is more complex.

“Nothing happened to Elvis Presley that we don't have a good logical, scientific explanation for now. But certainly back in those days we didn't,” Tennant explained. “Elvis Presley had multiple diseases. He was terribly ill, and he died accidentally in some ways with a dentist giving him codeine for his bad tooth, and his bad teeth were also part of the same disease that gave him a bad colon and a bad eye and a bad liver. They were all connected.

“He had all these metabolic defects due to his genetics, and so the codeine built up in his system. He had this terrible heart, so he died suddenly, within seconds, as he was trying to sit on the commode.”

Fortunately, the “Elvis” movie spares us any final scenes like that – ending instead with actual clips from one of Presley’s last concerts. They show a tired and very sick man, aged beyond his years and sweating profusely. But he still sang like “The King.”

All proceeds from sales of “The Strange Medical Saga of Elvis Presley” go the Tennant Foundation, which gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.

‘My Pain Was No Big Deal’: Obese Patients Often Stigmatized by Doctors

By Lauren Sausser, Kaiser Health News

When Melissa Boughton complained to her OB-GYN about dull pelvic pain, the doctor responded by asking about her diet and exercise habits.

The question seemed irrelevant, considering the type of pain she was having, Boughton thought at the time. But it wasn’t unusual coming from this doctor. “Every time I was in there, she’d talk about diet and exercise,” said Boughton, who is 34 and lives in Durham, North Carolina.

On this occasion, three years ago, the OB-GYN told Boughton that losing weight would likely resolve the pelvic pain. The physician brought up diet and exercise at least twice more during the appointment. The doctor said she’d order an ultrasound to put Boughton’s mind at ease.

The ultrasound revealed the source of her pain: a 7-centimeter tumor filled with fluid on Boughton’s left ovary.

“I hate that doctor for the way she treated me — like my pain was no big deal,” Boughton said. “She seemed to make a decision about me based off of a very cursory look.”

Research has long shown that doctors are less likely to respect patients who are overweight or obese, even as nearly three-quarters of adults in the U.S. now fall into one of those categories. Obesity, which characterizes patients whose body mass index is 30 or higher, is pervasive in the South and Midwest, according to the Centers for Disease Control and Prevention. The state with the highest rate is Mississippi, where 4 in 10 adults qualify as obese.

Obesity is a common, treatable condition linked to a long list of health risks, including Type 2 diabetes, heart disease, and some cancers. Despite obesity’s prevalence, it carries a unique stigma.

‘Almost Like Malpractice’

Doctors often approach the practice of medicine with an anti-fat bias and struggle to communicate with patients whose weight exceeds what’s considered the normal range. Some obesity experts blame a lack of focus on the subject in medical schools. Others blame a lack of empathy.

To counter that, the Association of American Medical Colleges plans to roll out in June new diversity, equity, and inclusion standards aimed at teaching doctors, among other things, about respectful treatment of people diagnosed as overweight or obese.

That’s not happening for many patients, said Dr. Scott Butsch, director of obesity medicine at the Cleveland Clinic’s Bariatric and Metabolic Institute. “This is almost like malpractice. You have these physicians or clinicians — whoever they are — relating everything to the patient’s obesity without investigation,” Butsch said. “The stereotypes and misperceptions around this disease just bleed into clinical practice.”

The problem, Butsch argued, is that too little attention is paid to obesity in medical school. When he trained and taught at Harvard Medical School for several years, Butsch said, students received no more than nine hours of obesity education spread over three days in four years.

In 2013, the American Medical Association voted to recognize obesity as a disease. But, Butsch said, doctors often approach it with a one-size-fits-all approach. “Eat less, move more” doesn’t work for everyone, he said.

Parents and medical providers need to take special care when talking to children who have been diagnosed with obesity about their weight, psychologists have warned. The way parents and providers talk to kids about their weight can have lifelong consequences and in some cases trigger unhealthy eating habits. For children who are obese, obesity experts agree, weight loss isn’t always the goal.

“There are many different forms of obesity, but we’re treating them like we’re giving the same chemotherapy to all kinds of cancer,” Butsch said.

Doctors Poorly Trained About Weight

All but four of the country’s 128 M.D.-granting medical schools reported covering content related to obesity and bariatric medicine in the 2020-21 academic year, according to curriculum data provided to KHN by the Association of American Medical Colleges, which does not represent osteopathic schools.

Even so, research suggests that many physicians haven’t been sufficiently trained to address weight issues with patients and that obesity education in medical schools across the world is “grossly neglected.” A survey completed by leaders at 40 U.S. medical schools found that only 10% felt their students were “very prepared” to manage patients with obesity.

Meanwhile, “half of the medical schools surveyed reported that expanding obesity education was a low priority or not a priority,” wrote the authors of a 2020 journal article that describes the survey’s results.

Butsch wants Congress to pass a resolution insisting that medical schools incorporate substantive training on nutrition, diet, and obesity. He acknowledged, though, that the medical school curriculum is already packed with subject matter deemed necessary to cover.

Dr. David Cole, president of the Medical University of South Carolina, said plenty of topics should be covered more comprehensively in medical school but aren’t. “There’s this massive tome — it’s about this big,” Cole said, raising his hand about a foot off the top of a conference table in Charleston. “The topic is: Things I never learned in medical school.”

The bigger issue, he said, is that medicine has historically been taught to emphasize memorization and has failed to emphasize culturally competent care. “That was valid 100 years ago, if you were supposed to be the fount of all knowledge,” Cole said. “That’s just not valid anymore.”

The Association of American Medical Colleges is trying to tackle the problem in two ways.

First, it developed a professional readiness exam for aspiring medical school students, called PREview, designed to assess an applicant’s cultural competence, social skills, and listening skills, as well as their ability to think through situations they may encounter in medical school and clinical settings.

“We call them softer skills, but they’re really the harder ones to learn,” said Lisa Howley, an educational psychologist and senior director of strategic initiatives at the association. More than a dozen medical schools now recommend or require that applicants submit their PREview test scores with their Medical College Admission Test scores.

Second, the medical college association will roll out new competency standards for existing medical students, residents, and doctors related to diversity, equity, and inclusion in June. Those standards will address racism, implicit bias, and gender equality and will aim to teach doctors how to talk with people who are overweight.

“The bias toward those individuals is way too high,” Howley said. “We have a lot more work to do in this space.”

After the source of Melissa Boughton’s pelvic pain was discovered, the OB-GYN who had recommended diet and exercise to ease her symptoms told Boughton the tumor was no big deal. “She acted like it was the most normal thing in the world,” Boughton said.

Boughton sought a second opinion from a doctor who marketed her practice as a “Healthy at Every Size” office. That doctor referred Boughton to a surgical oncologist, who removed the tumor, her left ovary, and part of a fallopian tube. The tumor was large, but it wasn’t cancerous. And although the surgery to remove it was considered successful, Boughton has since had trouble conceiving and is undergoing fertility treatment as she tries to have a baby.

“It’s an emotional roller coaster,” she said. “I feel very young at 34 to be going through this.”

Boughton — who describes herself as someone who doesn’t “fit into the BMI box” — said the experience taught her to choose her doctors differently.

“You can ask me if I diet and exercise like once,” she said. Any more than that, and she starts shopping for a different doctor.

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

Anti-Inflammatory Drugs May Contribute to Chronic Pain

By Pat Anson, PNN Editor

Anti-inflammatory drugs that are widely used to treat short-term acute pain disrupt the body’s natural healing process and increase the chances of developing chronic pain, according to a provocative new study by an international team of researchers.

If true, it means that ibuprofen, naproxen, diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) used by millions of people every day for the temporary relief of acute pain may contribute to long-term pain that is even harder to treat.    

“For many decades it’s been standard medical practice to treat pain with anti-inflammatory drugs. But we found that this short-term fix could lead to longer-term problems,” said co-author Jeffrey Mogil, PhD, Professor of Pain Studies and the Canada Research Chair in the Genetics of Pain at McGill University in Montreal.

In a series of studies, Mogil and his colleagues first analyzed genes and immune cells in the blood of 98 patients with acute lower back pain (LBP), noting which patients became free of pain and which ones developed chronic pain after three months.  

In patients who became pain free, there was an early inflammatory response to acute pain that activated neutrophils -- a type of white blood cell that helps the body fight infection.

In patients with chronic pain, there was no inflammatory immune response. This suggests that neutrophils play an active role in resolving pain and protecting patients from transitioning to chronic pain.

“Neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage. Inflammation occurs for a reason, and it looks like it’s dangerous to interfere with it,” said Mogil.

The study findings, published in Science Translational Medicine, were replicated in a cohort of patients with temporomandibular disorder (TMD), a painful inflammation of the jaw.

Researchers also tested their theory on laboratory animals, giving mice with acute pain the anti-inflammatory steroid dexamethasone or the NSAID diclofenac. While the drugs were initially effective, researchers found that blocking neutrophils in mice ultimately prolonged their pain up to ten times the normal duration. Three other analgesics without anti-inflammatory properties (gabapentin, morphine and lidocaine) produced short-term pain relief without affecting the overall duration of pain in mice.

These findings were also supported by a separate analysis of health records for 500,000 people in the United Kingdom with acute LBP. Those that took NSAIDs were nearly twice as likely to still have pain 2 to 6 years later than those who did not take NSAIDs. Patients who took acetaminophen (paracetamol) or antidepressants – neither of which are anti-inflammatory --  were not at higher risk of transitioning to chronic LBP.

“Our findings suggest it may be time to reconsider the way we treat acute pain. Luckily pain can be killed in other ways that don’t involve interfering with inflammation,” said co-author Massimo Allegri, MD, Head of Pain Service at Policlinico of Monza Hospital in Italy and Ensemble Hospitalier de la Cote in Switzerland.

Researchers say their findings should be followed up with larger clinical trials directly comparing the long-term effects of anti-inflammatory drugs to other pain relievers that don’t disrupt inflammation.

“Together, our results suggest that active immune processes confer adaptation at the acute pain stage, and impairment of such inflammatory responses in subjects with acute LBP (or TMD) increases the risk of developing chronic pain. These adaptive inflammatory responses are intrinsically transcriptionally driven, probably modified by both genetics and environmental factors, and can be inhibited by steroids and NSAIDs,” researchers said.

“Our conclusions may have a substantial impact on medical treatment of the most common presenting complaints to health care professionals. Specifically, our data suggest that the long-term effects of anti-inflammatory drugs should be further investigated in the treatment of acute LBP and likely other pain conditions.”

NSAIDs are widely used to treat everything from fever and headache to low back pain and arthritis. They are in so many different pain relieving products, including over-the-counter cold and flu medications, that many consumers may not be aware how often they use NSAIDs. At high doses, studies have found that NSAIDs increase the risk of a heart attack or stroke.

The current draft revision of the CDC opioid guideline recommends that NSAIDs should be used for low back pain, painful musculoskeletal injuries, dental pain, postoperative pain, kidney stones and acute pain caused by episodic migraine.

Acetaminophen also has its risks. Long-term use has been associated with liver, kidney, heart and blood pressure problems. Acetaminophen overdoses are involved in about 500 deaths and over 50,000 emergency room visits in the U.S. annually.

High-Frequency Spinal Cord Stimulators Provide More Pain Relief

By Pat Anson, PNN Editor

Spinal cord stimulators are often considered the treatment of last resort for patients with intractable or severe chronic pain. The surgically implanted devices emit low levels of electricity that reduce pain signals, but have high failure rates and often have to be removed because they’re ineffective, cause infections or need new batteries.

Two new studies suggest there are ways to improve the success rate of spinal cord stimulators (SCS) through improved patient selection and the use of high-frequency devices.

Low-frequency SCS (50 Hz) was first approved by the Food and Drug Administration for intractable back and leg pain in 1989. Six years later, the FDA approved high-frequency devices (10,000 Hz), that deliver pulses of electrical stimulation that are shorter in duration, lower in amplitude and do not cause paresthesia, an irritating sensation of tingling or prickling.

In a retrospective study of 237 patients who received stimulators between 2004 and 2020, researchers at the University of California San Diego School of Medicine reported that high-frequency devices were more effective at reducing pain and opioid use than low-frequency ones.

The study findings, published in the journal Bioelectronic Medicine, also show that male patients benefit more than women from high-frequency neuromodulation.

"Our work was sparked by a growing literature that demonstrate sex specific immune pathways differentially contribute to chronic pain processes," said senior author Imanuel Lerman, MD, an associate professor of anesthesiology at UC San Diego Health. "The observed parameter-specific (high versus low frequency) sex-based differences in spinal cord stimulation efficacy and opiate use are definitely intriguing.”

It’s not clear why men benefit more than women, but researchers believe it may be due to the male hormone testosterone having a modulating effect on pain signals. The sex differences may also be due to males and females processing chronic pain differently.

"Clearly more work needs to be done to carefully characterize sex specific pain regulatory pathways that may prove responsive to specific types of neuromodulation and or pharmaceutical therapies," said Lerman.

Improved Patient Selection  

Although most patients are required to undergo psychological testing and a trial treatment before getting a SCS, failure rates for the devices remain high at around 25 to 30 percent. With about 50,000 stimulators implanted in the U.S. every year, that means thousands of patients are getting poor results.

To improve patient outcomes, researchers at Florida Atlantic University developed machine-learning algorithms to help predict which patients may benefit from SCS. Working with a cohort of 151 SCS patients, they evaluated 31 features or characteristics in each patient.  

Researchers found two distinct clusters of patients which differ significantly in age, duration of chronic pain, preoperative pain levels and pain catastrophizing scores. They used computers to fine-tune the results, identifying the 10 most influential features that contribute the most to a successful SCS implant.

Results of the study, published in the journal Neurosurgery, demonstrate for the first time the ability of machine-learning algorithms to predict long-term patient response to SCS placement. The next step is to validate the data in future patients to ensure that the algorithm is useful in real-world situations, not just computer models.

"Our study resulted in the development of a model to predict which patients would benefit from spinal cord stimulation," said lead author Julie Pilitsis, MD, dean and vice president of medical affairs at Florida Atlantic University's Schmidt College of Medicine.  "After we validate this work, our hope is that this machine-learning model can inform a clinical decision support tool to help physicians better choose which patients may be most appropriate."

SCS is no longer limited to patients with intractable back and neck pain. Last year the FDA expanded the use of SCS to include lower limb pain from diabetic neuropathy.  Stimulators are also being used on patients with Complex Regional Pain Syndrome (CRPS).

A decision to get a SCS shouldn’t be taken lightly. A 2018 study by a team of investigative journalists found that stimulators have some of the worst safety records of medical devices tracked by the FDA. A 2020 FDA review of adverse events involving SCS found that nearly a third were reports of unsatisfactory pain relief. The review also identified nearly 500 deaths linked to the devices, along with nearly 78,000 injuries and 30,000 device malfunctions.

Steroids Raise Risk of Hospitalization for Sickle Cell Patients

By Pat Anson, PNN Editor

People with sickle cell disease who are prescribed a corticosteroid – an anti-inflammatory medicine often used to treat pain – are significantly more likely to be hospitalized with a severe pain episode, according to a new study.

Sickle cell disease (SCD) is a genetic disorder that causes red blood cells to form in a crescent or sickle shape, which creates painful blockages in blood vessels known as vaso-occlusive episodes (VOE), which can lead to infections, strokes and organ failure. About 100,000 Americans live with SCD, primarily people of African or Hispanic descent.

“Individuals living with SCD often suffer crippling episodes of pain, which can greatly impair their quality of life,” said Ondine Walter, MD, of Toulouse University Hospital in France, lead author of the study published in the journal Blood.

Walter and her colleagues looked at medical data for over 5,100 patients with SCD in the French National Health Insurance Database between 2010 and 2018. Patients had to have at least one hospitalization for VOE to be included, and their corticosteroid exposure was identified using outpatient prescribing records.

Researchers found that patients exposed to a corticosteroid in the month prior to a pain flare were nearly four times more likely to be hospitalized for VOE than those who did not get a steroid. The median time between filling a prescription for a corticosteroid and hospitalization was just five days.

Nearly half the patients (46%) were prescribed a corticosteroid during the study period, an indication of just how common steroid treatment is for SCD. Walter said the results demonstrate the need for better education of clinicians and patients about the potential risks of corticosteroids, especially when there isn’t a clear reason to use them.

“Based on our data, corticosteroids are commonly prescribed for conditions unrelated to their underlying SCD. Vaso-occlusive events and related hospitalization appear to follow corticosteroid prescription fairly quickly. This evidence suggests corticosteroids may be contributing to the events and should be avoided as much as possible in these patients,” Walter said. “Corticosteroids are mostly easy to avoid, and in circumstances when they are necessary, it’s important to start them in collaboration with an SCD expert and to take all appropriate precautionary measures to administer them safely.”

The American Society of Hematology’s Clinical Practice Guideline recommends against using corticosteroids for acute pain in SCD patients.

The French research team also found that SCD patients taking the drug hydroxyurea had about half the risk of being hospitalized for VOE than those not taking it, which may indicate the drug has a protective effect. Hydroxyurea is often prescribed to SCD patients to reduce the number of pain flares and the need for blood transfusions. Men benefited from hydroxyurea more than women and children.

It’s not uncommon for someone with SCD to visit an emergency room a few times each year due to acute pain or complications such as anemia. Many are disappointed by the experience. A 2021 survey of SCD patients in the U.S. found that nearly two-thirds felt ER staff were rude, ignorant or misinformed about sickle cell disease, didn’t take their pain seriously or believed they were drug seekers.

Long Covid Research Could Lead to New Treatments for Chronic Pain

By Pat Anson, PNN Editor

About a third of people infected with Covid-19 develop long-term symptoms, such as headaches, persistent muscle pain, joint pain, stomach pain, chest pain and respiratory discomfort. Three years into the pandemic, scientists are finally beginning to understand what causes long covid and how to possibly treat it.

In studies on hamsters infected with Covid-19, researchers at the Icahn School of Medicine found that the virus left behind a gene expression signature in the animals’ dorsal root ganglia – a cluster of nerves in the spinal cord that transmit pain signals from the body to the brain. The signature matched gene expression patterns seen in other forms of chronic pain.

“A significant number of people suffering from long COVID experience sensory abnormalities, including various forms of pain,” said Randal (Alex) Serafini, an MD/PhD candidate. “We used RNA sequencing to get a snapshot of the biochemical changes SARS-CoV-2 triggers in a pain-transmitting structure called dorsal root ganglia.”

Serafini presented his findings at the annual meeting of the American Society for Pharmacology and Experimental Therapeutics in Philadelphia. 

The symptoms experienced by hamsters infected with Covid-19 closely mirrored those of people. Researchers say the hamsters showed a slight hypersensitivity to touch early after the infection, which became more severe over time.

They performed similar experiments with the Influenza A virus to determine if other RNA viruses promote a similar response. Influenza A caused an early hypersensitivity that was more severe, but began to fade after a few days. Four weeks after recovering from the flu, the hamsters had no signs of long-term hypersensitivity.

In contrast, hamsters infected with SARS-CoV-2-showed more hypersensitivity, reflecting symptoms of chronic pain. The pain sensitivity remained even after the hamsters recovered from the initial Covid-19 infection. Further research found that SARS-CoV-2 downregulates the activity of several previously identified pain regulators and a protein called interleukin enhancer binding factor 3 (ILF3) — a potent cancer regulator.

Based on these findings, the researchers hypothesized that mimicking the acute effects of ILF3 could serve as a new pain treatment strategy. To test this theory, they gave laboratory mice suffering from inflammation a clinically tested anti-cancer drug that inhibits ILF3 activity. The drug was very effective at treating their pain.

“Our findings could potentially lead to new therapies for patients suffering from acute and long COVID, as well as other pain conditions,” said Serafini. “We think therapeutic candidates derived from our gene expression data, such as ILF3 inhibitors, could potentially target pain mechanisms that are specific to COVID patients, both acutely and chronically.

“Interestingly, we saw a few cancer-associated proteins come up as predicted pain targets, which is exciting because many drugs have already been developed to act against some of these proteins and have been clinically tested. If we can repurpose these drugs, it could drastically cut down therapeutic development timeline.”

Serafini and his colleagues are now working to identify other compounds that could be repurposed to treat pain, while also keeping an eye out for new compounds that might inhibit ILF3 activity.

“Our study also shows that SARS-CoV-2 causes long-term effects on the body in drastically new ways, further underscoring why people should try to avoid being infected,” he said.

Another study has suggested that long covid appears to be the result of an overactive immune system. Australian researchers identified biomarkers of a sustained inflammatory response in the blood samples of long covid patients – suggesting their immune systems were activated by the virus, but then failed to turn off.

Other studies have found similarities between long covid and autoimmune conditions such as lupus and myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS).  

In addition to widespread body pain, long covid symptoms include fatigue, cognitive impairment and difficulty sleeping.    

Better Pain Treatment Needed for People with Severe Mental Illness

By Pat Anson, PNN Editor

There is an urgent need to improve the way pain is diagnosed and treated in people with severe mental illness, according to a new review by UK researchers.

Depression and pain commonly co-exist, with pain prevalence in people with depression estimated at 65 percent. Pain is also experienced by 29% of people with bipolar disorder, about double that of healthy people.

But while the association between pain and mental illness is well-established, researchers say pain is not routinely assessed and managed in people with SMI, due in part to discrimination by healthcare providers. Mental health problems carry a fair amount of stigma – just like pain itself -- which impedes treatment.

“Healthcare professionals underestimate pain in the presence of perceived ‘psychosocial’ problems, making discounting of pain in people with SMI particularly likely. Indeed, there is evidence that they experience diagnostic overshadowing for physical healthcare,” lead author Whitney Scott, PhD, Kings College London, reported in PAIN, the official journal of the International Association for the Study of Pain (IASP).

“In addition to limiting treatment access, pain-related invalidation, stigma, and discrimination exacerbate distress. Investigation is needed to understand the impact of intersecting experiences of stigma and discrimination in people with SMI and pain, and how to address these.”

Scott and her colleagues say there is limited knowledge about the effectiveness of pain treatments in people with SMI because they are often excluded from clinical trials due to their perceived “complex mental health needs.”

Even when pain is diagnosed, providers may be reluctant to prescribe analgesics to people with SMI because it may interact with mental health drugs they are already taking.

“Pharmacological management of pain in SMI is complicated by the potential for harmful side effects and interactions with psychotropic medications and the underlying mental health condition,” said Scott. “Antidepressants, including serotonin-noradrenaline reuptake inhibitors, are effective for pain management in the absence of depression and of course may improve co-morbid depression; however, unopposed anti-depressants may destabilise mood in bipolar disorder. Collaborative pharmacological and psychological care for comorbid pain and major depression is promising, but scarce.”

Little is also known about the effectiveness of non-pharmacological pain treatments, such as exercise and physical therapy, because people with SMI often experience isolation, fatigue and mood disorders, making them harder to motivate.  

To overcome these barriers, Scott and her co-authors say pain and mental healthcare need to be more fully integrated, with caregivers, mental health professionals, pain specialists and policymakers working together to enable more personalized care and understanding of the needs of people with SMI.

$23 Billion Raised for Rare Disease Drug Development

By Roger Chriss, PNN Columnist

Monday, February 28 is Rare Disease Day, a global effort to recognize and raise awareness of rare diseases. The annual event has been held every year since 2008, but has taken on a new tenor amid Covid-19. Long Covid has become one of the biggest threats the coronavirus poses. But like rare diseases, long Covid is not often discussed in public health messaging about the pandemic.

The National Organization of Rare Disorders officially recognizes over 7,000 rare diseases. But the actual number is much higher. Each year some 250 new rare diseases are identified, and existing rare diseases like Charcot-Marie-Tooth disease and Ehlers-Danlos syndromes have new types and subtypes identified.

Rare diseases are often only familiar to the people who live with them and the specialists who treat them. For the goal of treatment to be met, rare diseases must be named and characterized. In Europe, a disease is classified as rare if it affects fewer than 1 in 2,000 people, while in the U.S. rare diseases are recognized as conditions that affect fewer than 200,000 people nationally.

They may be rare, but their impact is substantial. A recent study in the Orphanet Journal of Rare Diseases estimates that rare diseases affect 25 to 30 million people in the U.S. and more than 300 million people worldwide. Patients and their families have to endure a lengthy “diagnostic odyssey,” often at high financial and emotional cost.

The graphic below helps demonstrate the many barriers that a rare disease patient may encounter in getting a proper diagnosis, such as lack of knowledge about a disease, an overlap of symptoms, lack of diagnostic tests, and inaccurate test results.

According to the U.S. Government Accountability Office, the total cost of rare diseases in 2019 reached $966 billion, counting both direct medical costs and other indirect expenses such as loss of income. But research funding for rare disease has long been limited, in part because of the difficulty in diagnosing them.

Fortunately, that may be changing. A new report by the non-profit Global Genes estimates that nearly $23 billion was raised in 2021 from public and private sources to fund rare disease drug development. That’s a 28 percent increase over the money raised in 2020.

“Rare diseases continue to have a strong allure to investors, as evidenced by the significant capital raised in 2021 to advance companies and pipelines focused on rare conditions,” said Craig Martin, CEO of Global Genes. “We hope and expect that the sector will continue to be strengthened by the vast array of opportunities to advance promising biotechnologies, under expedited review, that can address the tremendous burdens and underlying causes of thousands of rare, genetic conditions currently without approved treatments.”

The past year saw many positive steps toward improving the diagnosis and treatment of rare diseases. Congress is considering the Speeding Therapy Access Today (STAT) Act of 2021,  which requires policy reforms at the FDA to speed up the development of treatments for rare diseases.

Although the STAT Act has yet to pass, the FDA has already taken action to address two rare diseases. The agency recently approved Pyrukynd (mitapivat) tablets to treat hemolytic anemia in adults with pyruvate kinase deficiency and Vyvgart (efgartigimod) for the treatment of generalized myasthenia gravis.

The past year also saw efforts to improve research and data collection for rare diseases. AllStripes added 100 rare disease research programs to its efforts, and RARE-X launched its initial set of data collection programs. And Rare Diseases International started its Collaborative Global Network for Rare Diseases to create a “a person-centered network of care and expertise” for people living with rare diseases.

But more work needs to be done. The EveryLife Foundation for Rare Diseases notes that 93% of rare diseases have no FDA-approved treatment. In some cases, the pathophysiology is not well understood and animal models do not even exist. In other cases, although the disease is known and treatments do exist, there are too few clinicians and too little financial support for patients.

For people with rare diseases, every day is “rare disease day.” Hopefully efforts to recognize and increase awareness of rare diseases will promote more progress in their diagnosis and treatment.

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. 

Study Finds Low Risk of Muscle Pain From Statins

By Pat Anson, PNN Editor

Have you experienced muscle pain, memory loss or other side effects from statins? If so, you’re not alone. A many as one in two patients stop taking the cholesterol-lowering drugs because they don’t like the side-effects.

But the authors of a large new study say statin intolerance is over-estimated and over-diagnosed, resulting in too many patients raising their risk of heart disease because they refuse to take the drugs.

An international team of researchers conducted a meta-analysis of 176 clinical studies involving over 4 million statin users and found that only about 9 percent have statin intolerance. Their findings are published in the journal European Heart Journal.

“I believe the size of our study, which is the largest in the world to investigate this question, means we are able to finally and effectively answer the question about the true prevalence of statin intolerance,” said lead author Maciej Banach, MD, a cardiologist and professor at Medical University of Lodz and the University of Zielona Góra in Poland.

“Patients need to know that statins may prolong their life, and in cases where side effects appear, we have enough knowledge to manage these effectively. The most important message to patients as a result of this study is that they should keep on taking statins according to the prescribed dose, and discuss any side effects with their doctor, rather than discontinuing the medication.”

The research team found that patients who are older, female, obese, diabetic, or suffering from an under-active thyroid or chronic liver or kidney failure were more likely to be statin intolerant.

Patients taking drugs used to control an irregular heartbeat or calcium channel blockers for chest pain and high blood pressure were also more likely to have side effects, as did those with high alcohol consumption.

“It is critically important to know about these risk factors so that we can predict effectively that a particular patient is at higher risk of statin intolerance. Then we can consider upfront other ways to treat them in order to reduce the risk and improve adherence to treatment. This could include lower statin doses, combination therapy and use of innovative new drugs,” said Banach. 

“Most cases of statin intolerance observed in clinical practice are associated with effects caused by patients’ misconceptions about the side effects of statins or may be due to other reasons. Therefore, we should carefully evaluate symptoms, assessing in detail patients’ medical histories, when the symptoms appeared, specific details of pain, other medications the patients are taking, and other conditions and risk factors. Then we will see that statins can be used safely in most patients.”

Previous research on side effects from statins have had mixed results. A 2017 study found that only about 2 percent of patients on Lipitor (atorvastatin) had muscle pain. That finding is in marked contrast to a Cleveland Clinic study, which found that 42% of patients taking Lipitor reported muscle pain and weakness.

In 2014, the Food and Drug Administration required warning labels on statins, cautioning that statins can cause a muscle injury called myopathy, which is characterized by muscle pain or weakness. In rare instances, the FDA says statins can also cause liver injury, diabetes and memory loss.

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

By Pat Anson, PNN Editor

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

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

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

Top 10 Countries on Quality of Death Index

SOURCE: LIEN FOUNDATION

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

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

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

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

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

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

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

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

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

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

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

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

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

Microplastic Particles Linked to IBD

By Pat Anson, PNN Editor

Microplastics — tiny bits of plastic so small they are invisible to the naked eye --- can be found in our food, water and even the air we breathe. But research is only beginning on the prevalence and health effects of plastic particles in humans.

A 2020 study found that babies fed formula from plastic bottles swallowed millions of microplastic particles every day. And a recent review that looked at the impact of microplastics on human cells found evidence of cell death, immune response and damage to cell walls.

“We are exposed to these particles every day: we’re eating them, we’re inhaling them. And we don’t really know how they react with our bodies once they are in,” lead author Evangelos Danopoulos, a postgraduate student at Hull York Medical School in the UK told The Guardian.

For the first time, Chinese researchers have now found evidence that people with inflammatory bowel disease (IBD) have more microplastics in their feces, suggesting that plastic particles in the digestive tract could play a role in the development of Crohn’s disease and ulcerative colitis.

Researchers obtained fecal samples from 52 people with IBD and 50 healthy people from different geographic regions of China. They found that feces from the IBD patients had significantly more microplastics than the control group – an average of 41.8 particles per gram in the IBD group vs. 28 particles in healthy people. People with more severe IBD symptoms had higher levels of microplastics. Their particles also tended to be smaller.

ENVIRONMENTAL SCIENCE AND TECHNOLOGY

Researchers surveyed both groups and found that people who consumed more bottled water and takeaway food, and were often exposed to dust had more microplastics (MPs) in their feces. The two most common types of plastic found were polyethylene terephthalate (PET; used in bottles and food containers) and polyamide (PA; found in food packaging and textiles).

Still unclear is whether exposure to microplastics causes or contributes to IBD, or whether people with IBD simply accumulate more microplastics in their digestive tracts because of their disease.

“We conclude that the plastic packaging of drinking water and food and dust exposure are important sources of human exposure to MPs. Furthermore, the positive correlation between fecal MPs and IBD status suggests that MP exposure may be related to the disease process or that IBD exacerbates the retention of MPs,” researchers reported in the journal Environmental Science & Technology.

The prevalence of IBD is rising around the world. A 2015 CDC study estimated that about 3.1 million adults in the U.S. were diagnosed with IBD, nearly double the 1.8 million Americans who reported having IBD in 1999. The researchers found an association between IBD and people with lower income and education levels, but did not look into the role of microplastics.