Experts Say Weather’s Not to Blame for Your Pain

By Pat Anson, Editor

The age old debate over weather’s impact on pain is heating up again with new research indicating that cold, rainy weather has no impact on symptoms associated with back pain or osteoarthritis.

Researchers at The George Institute for Global Health in Australia say damp weather makes people more aware of their pain, but the symptoms disappear as soon as the sun comes out – suggesting there’s a psychological cause.

“Human beings are very susceptible so it’s easy to see why we might only take note of pain on the days when it’s cold and rainy outside, but discount the days when they have symptoms but the weather is mild and sunny,” said Professor Chris Maher, director of the George Institute’s Musculoskeletal Division.  

“The belief that pain and inclement weather are linked dates back to Roman times. But our research suggests this belief may be based on the fact that people recall events that confirm their pre-existing views.”

Maher and his colleagues conducted two studies involving nearly 1,000 Australians with back pain and 345 people with osteoarthritis.

Using weather data from the Australian Bureau of Meteorology, researchers compared the weather at the time patients first noticed pain with weather conditions one week and one month before the onset of pain as a control measure. 

Results showed no association between back pain and temperature, humidity, air pressure, wind direction or precipitation. Warmer temperatures did slightly increase the chances of lower back pain, but the amount of the increase was not clinically important. 

A previous study on back pain and weather at The George Institute had similar findings, but received widespread criticism from the public.

“People were adamant that adverse weather conditions worsened their symptoms so we decided to go ahead with a new study based on data from new patients with both lower back pain and osteoarthritis. The results though were almost exactly the same – there is absolutely no link between pain and the weather in these conditions,” said Maher.

The back pain study was published in the journal Pain Medicine. The study on osteoarthritis was published in Osteoarthritis and Cartilage.

“People who suffer from either of these conditions should not focus on the weather as it does not have an important influence on your symptoms and it is outside your control,” said Associate Professor Manuela Ferreira.

The Greek philosopher Hippocrates in 400 B.C was one of the first to note that changes in the weather can affect pain levels. Although a large body of folklore has reinforced the belief that there is a link between weather and pain, the science behind it is mixed.

PNN readers say there’s little doubt in their minds that there’s a connection.

“I totally agree that rainy weather does affect pain. I have osteoarthritis and fibromyalgia, and pain is most severe when there is a change happening in the weather especially rain,” wrote Dee.

“It's been well established that the source of weather-related pain is a direct result from the variance in barometric pressure,” said Judith Bohr. “Changes in the intensity of that pressure is felt more acutely in the parts of the body where there are injuries, degenerative changes, surgeries, wherever there is an increased sensitivity because of inflammation.”

Others say they can predict the weather based on their pain levels.

“So many sunny days and I've said it’s going to rain. People thought I was crazy for a while, but now they know,” said Ashley. “My kids are always asking if it’s going to rain.”

A study currently underway in England suggests there is a connection between weather and pain. Over 9,000 people are participating in The University of Manchester’s Cloudy with a Chance of Pain project, using a special app on their smartphones to record their daily pain levels. The app also captures hourly weather conditions.

Preliminary results show that as the number of sunny days increase, the amount of time participants spend in severe pain decreases. When the weather turns rainy and cloudy, however, the amount of time people spent in severe pain increases.

Can Gum Disease Cause Rheumatoid Arthritis?

By Pat Anson, Editor

Scientists have long suspected that pathogens and bacterial infections may play a role in the development of autoimmune diseases such as rheumatoid arthritis (RA). Now there is evidence that a bacterium associated with chronic gum infections may trigger an inflammatory response characteristic of RA, a discovery that could lead to new ways to treat and prevent the disease.

"This research may be the closest we've come to uncovering the root cause of RA," said Maximilian Konig, MD, a former Johns Hopkins University School of Medicine fellow now at Massachusetts General Hospital.

Rheumatoid arthritis is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. About 1.5 million Americans and one percent of adults worldwide suffer from RA. There is no cure for the disease and treatments only focus on slowing its progression.

In a study of nearly 200 RA patients, Konig and his colleagues found that nearly half had antibodies against Aggregatibacter actinomycetemcomitans in their blood.  

The level of infection with the bacteria was similar in patients with periodontal (gum) disease, but quite different in healthy patients, only 11 percent of whom tested positive for A. actinomycetemcomitans.

An infection with A. actinomycetemcomitans appears to induce the production of citrullinated proteins, which are suspected of activating the immune system and driving the cascade of events leading to RA.

"This is like putting together the last few pieces of a complicated jigsaw puzzle that has been worked on for many years," says Felipe Andrade, MD, a senior study investigator and associate professor of Medicine at the Johns Hopkins University School of Medicine.

Andrade cautions that over half of the study participants with RA had no evidence of an infection with A. actinomycetemcomitans, which may indicate that other bacteria in the gut, lung or elsewhere could be involved. He says more research is needed to determine if there is a cause and effect relationship between bacteria and RA.

"If we know more about the evolution of both combined, perhaps we could prevent rather than just intervene," he said.

The Johns Hopkins study is published in the journal Science Translational Medicine.

Scientists have observed an association between periodontal disease and RA since the early 1900s, and have suspected that both diseases may be triggered by a common factor. In the last decade, studies have focused on a bacterium known as Porphyromonas gingivalis, which is found in patients with gum disease. However, research has so far failed to corroborate such a link.

Researchers in the current study found inflammation in the joints of RA patients that was similar to the inflamed gums of patients with periodontal disease, an inflammatory process known as hyper-citrullination.

Citrullination occurs naturally in everyone as a way to regulate the function of proteins. But in people with RA, the process becomes hyperactive, resulting in the abnormal accumulation of citrullinated proteins. This drives the production of antibodies against proteins that create inflammation and attack a person's own tissues, the hallmark of RA.

Can Running Help Prevent Osteoarthritis?

By Pat Anson, Editor

People suffering from aching muscles and joint pain are often told that exercise is the best remedy. It sounds counter-intuitive, but now there’s evidence that running can actually reduce joint inflammation – at least in the knees.

"It flies in the face of intuition," says Matt Seeley, an associate professor of exercise science at Brigham Young University. "This idea that long-distance running is bad for your knees might be a myth."

Seeley and his colleagues conducted a small study of six healthy men and women who ran on treadmills for 30 minutes. Blood samples and synovial fluid from their knee joints were collected both before and after they ran.

The researchers found that two inflammatory markers in the synovial fluid -- cytokines named GM-CSF and IL-15 -- decreased in concentration in the runners after a treadmill session.  Cytokines are small proteins released by cells that play an important role in pain and inflammation.

"What we now know is that for young, healthy individuals, exercise creates an anti-inflammatory environment that may be beneficial in terms of long-term joint health," said Robert Hyldahl, a BYU assistant professor of exercise science.

image courtesy of Nate Edwards/BYU

The findings, published in the European Journal of Applied Physiology, indicate that running may be chondroprotective, which means exercise may help delay the onset of joint diseases such as osteoarthritis (OA), a disorder that leads to thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

“This is the first study to evaluate a wide panel of inflammatory mediators in the knee joints of healthy subjects following running. Our results suggest that running decreases intra-articular inflammation and brings to light a novel potential mechanism for the chondroprotective nature of exercise in non-pathologic knees,” the BYU researchers said.

The researchers now plan to study subjects with previous knee injuries, by conducting similar tests on people who have suffered ACL injuries.

"This study does not indicate that distance runners are any more likely to get osteoarthritis than any other person," Seeley said. "Instead, this study suggests exercise can be a type of medicine."

‘Spicy’ Injection Could Take Sting Out of Foot Pain

By Pat Anson, Editor

The U.S. Food and Drug Administration has given "fast track" designation to an injectable pain reliever containing a synthetic form of capsaicin, the active ingredient that makes chili peppers spicy.

The move speeds the development of CNTX-4975 as a treatment for Morton’s neuroma, a painful nerve disorder of the foot. If clinical trials are successful and CNTX-4975 gains full FDA approval, it would be the first use of capsaicin in an injectable analgesic. Capsaicin is already used in skin patches and topical ointments for temporary pain relief.

“We feel the Fast Track designation is recognition that we are pursuing an unmet need for a serious condition with a novel therapy. CNTX-4975 has the potential to help patients avoid surgery, meaning they can avoid the potential complications and recovery associated with surgery, while still achieving the pain relief they are seeking,” said Jim Campbell, MD., founder and President of Centrexion Therapeutics, which is developing the drug.

“We also believe the FDA is trying to encourage development of novel therapies, like CNTX-4975. As a non-opioid, we believe CNTX-4975 could have a major impact in the treatment of chronic pain.”

Centrexion is also studying CNTX-4975 as a possible treatment for osteoarthritis in both humans and dogs.

Morton’s neuroma involves a thickening of the tissue around a nerve leading to the toes, which causes sharp, burning pain in the foot, especially when walking.

The current standard of treatment is steroid injections or surgery to remove the nerve. The surgery often results in permanent numbness in the toes and a potentially long recovery period. 

There are currently no FDA-approved treatments for Morton's neuroma. The agency’s Fast Track process is designed to speed the review of drugs to fill an unmet medical need.

“CNTX-4975 has the potential to provide a high degree and long duration of pain relief without having to undergo surgery. Additionally, CNTX-4975 is highly selective for the capsaicin receptor, which allows it to selectively inactive the local pain fibers while leaving the rest of the nerve fiber functioning, meaning the patient won’t experience numbness in the area of the injection,” said Campbell in an email to PNN.

CNTX-4975 has a short half-life and is cleared from the body within 24 hours, but Campbell says a single injection provides pain relief that lasts for months.

A recent Phase 2b study of CNTX-4975 showed a statistically significant decrease in pain from Morton’s neuroma over a 12-week period. Centrexion plans to begin a Phase 3 trial in 2017.

The company is expecting results later this year on a Phase 2b trial of CNTX-4975 as a treatment for knee osteoarthritis in humans, as well as a study on pet dogs with canine osteoarthritis.

A recent study found that a skin patch containing capsaicin works better than Lyrica (pregabalin) in treating patients with neuropathic pain. Over half the patients using Qutenza had pain relief after about a week, compared to 36 days for those taking pregabalin.  

Study Shows Potential for Early Diagnosis of Arthritis

By Pat Anson, Editor

A new study by British researchers has demonstrated the potential for an experimental blood test that can diagnose arthritis in its earliest stages. Such a test could lead to earlier treatment of osteoarthritis (OA) and rheumatoid arthritis (RA), years before joint damage and physical symptoms begin.

Researchers at Warwick Medical School recruited 225 people with early or advanced OA, RA or another inflammatory joint disease, along with a control group of healthy volunteers with no joint problems.  Their blood and fluid from affected knee joints were then analyzed with mass spectrometry.

The test found patterns in blood plasma amino acids that were damaged by oxygen, nitrogen and sugar molecules. The damage was highest in the blood samples of patients with OA or RA, and markedly lower in the blood of healthy volunteers -- giving researchers identifiable biomarkers that could be used for an early diagnosis.

“This is a big step forward for early-stage detection of arthritis that will help start treatment early and prevent painful and debilitating disease,” said Naila Rabbani, PhD, of Warwick Medical School. “Damage to proteins in the arthritic joint have been known for many years but this is the first time it has been exploited for early-stage diagnosis.

“For the first time we measured small fragments from damaged proteins that leak from the joint into blood. The combination of changes in oxidised, nitrated and sugar-modified amino acids in blood enabled early stage detection and classification of arthritis – osteoarthritis, rheumatoid arthritis or other self-resolving inflammatory joint disease."

Dr. Naila Rabbani of Warwick Medical School

Rabbani says the blood test could be available to patients within two years. Her study is published online in Arthritis Research and Therapy.

Osteoarthritis is a progressive joint disorder caused by painful inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine. The World Health Organization estimates that about 10% of men and 18% of women over age 60 have osteoarthritis. There currently is no diagnostic blood test for osteoarthritis.

Rheumatoid arthritis is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing swelling, inflammation and bone erosion. About 1.5 million Americans and 1% of adults worldwide suffer from RA.

A blood test for RA is already on the market in the United States, Canada, Europe, Japan and Australia. The JOINTstat test looks for a protein that is usually found at high levels in the joints of people with RA.

No Increase in Physical Activity after Hip Replacement

By Pat Anson, Editor

A new study by British researchers has come to the surprising conclusion that physical activity such as walking and climbing stairs does not increase after hip replacement surgery.

Total hip replacement is one of the most common elective procedures. The surgery is usually performed on the elderly to relieve pain from osteoarthritis, which causes a loss of cartilage and joint function.

But in the first systematic review to examine the differences in physical activity both before and after hip replacement, researchers were left questioning the purpose of the surgery.

"The most common reason for a hip replacement is to reduce pain on movement. We expected that the amount of physical activity post-surgery would therefore increase. What we found surprised us," said lead researcher Tom Withers, from the University of East Anglia’s School of Health Sciences.

Withers and his colleagues looked at the physical activity of over 1,000 patients who had hip replacements, analyzing how far and how fast they walked, as well as cycling and climbing stairs.

"We found that there was no clear evidence of a change in physical activity following surgery,” said Withers. "The benefits of regular physical activity following a hip replacement are well known, so this research is important for healthcare professionals because it suggests that patients need to be encouraged to be more physically active."

The research findings are being published in the journal Clinical Rehabilitation.

"The lack of significant difference in physical activity after patients undergo such a common procedure suggests there is a need for further research, including further investigation into how other personal characteristics or pre-existing conditions might also influence the results,” says Toby Smith, a lecturer in physiotherapy in UEA's School of Health Sciences.

"Healthcare professionals and researchers need to better understand this lack of change and how patient's perceptions of physical activity might be modified to increase their engagement in physical activity post-operatively."

Recent studies in the United States have questioned whether many joint replacement surgeries are appropriate. A five year study of 175 knee replacement patients by the National Institutes of Health found that over a third of the surgeries were inappropriate. Many patients had pain and other symptoms that were too mild to justify having their knees replaced.  

About 30 million Americans have osteoarthritis, including a growing number of younger patients, aged 40 to 65. Doctors are often reluctant to perform hip replacement surgery on patients under age 50 because prosthetic joints typically last for less than 20 years. A second surgery to remove a worn prosthetic can destroy bone and put patients at risk for infection and other complications.

Nanoparticles May Help Repair Injured Joints

By Pat Anson, Editor

Injecting an injured joint with nanoparticles – tiny, ultrafine particles so small they are invisible to the naked eye – controls inflammation and may help prevent the development of osteoarthritis, according to a new study.

Researchers at the Washington University School of Medicine in St. Louis found that injecting nanoparticles into the injured joints of laboratory mice reduces inflammation and the destruction of cartilage.

The nanoparticles used are more than 10 times smaller than a red blood cell, which helps them penetrate deeply into tissues.  The nanoparticles carry a peptide derived from a natural protein called melittin that has been modified to enable it to bind to a molecule and interfere with inflammation.

“The nanoparticles are injected directly into the joint, and due to their size, they easily penetrate into the cartilage to enter the injured cells,” said Samuel Wickline, MD, a professor of Biomedical Sciences at Washington University.

“Previously, we’ve delivered nanoparticles through the bloodstream and shown that they inhibit inflammation in a model of rheumatoid arthritis. In this study, they were injected locally into the joint and given a chance to penetrate into the injured cartilage.”

The nanoparticles were injected into the mice soon after an injury to prevent the inflammation and cartilage breakdown that can lead to osteoarthritis.

INFLAMMATORY PROTEIN (GREEN) IN CARTILAGE CELLS. IMAGE COURTESY of UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE

Whether such a strategy will work in humans years after an injury -- when osteoarthritis is established and there is severe cartilage loss -- still needs to be studied. But the findings suggest that the nanoparticles, if given soon after joint injuries occur, could help maintain cartilage and prevent the progression to osteoarthritis.

“I see a lot of patients with osteoarthritis, and there’s really no treatment,” said senior author Christine Pham, MD, an associate professor of medicine. “We try to treat their symptoms, but even when we inject steroids into an arthritic joint, the drug only remains for up to a few hours, and then it’s cleared. These nanoparticles remain in the joint longer and help prevent cartilage degeneration.”

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA, and those numbers are expected to grow as the population ages. Frequently, an osteoarthritis patient has suffered an earlier injury — a torn meniscus or ACL injury in the knee. The body naturally responds to joint injuries with inflammation.

“The inflammatory molecule that we’re targeting not only causes problems after an injury, but it’s also responsible for a great deal of inflammation in advanced cases of osteoarthritis,” said Linda Sandell, PhD, a professor of Orthopaedic Surgery and director of Washington University’s Center for Musculoskeletal Research.

“So we think these nanoparticles may be helpful in patients who already have arthritis, and we’re working to develop experiments to test that idea.”

The study findings are published in the Proceedings of the National Academy of Sciences. The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Heart, Lung, and Blood Institute; and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

Amgen Biologic Drug Approved by FDA

By Pat Anson, Editor

A new biologic drug may soon be available for rheumatoid arthritis patients and others who suffer from autoimmune diseases – if they can afford it and if the drug clears a patent challenge.

The Food and Drug Administration has approved Amgen’s Amjevita as a biosimilar to Humira for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis and severe plaque psoriasis. 

“Approval of Amjevita is an exciting accomplishment as it marks a new chapter in Amgen’s story of being a leader in biotechnology. In addition, Amjevita holds the potential to offer patients with chronic inflammatory diseases an additional treatment option,” said Sean Harper, M.D., executive vice president of Research and Development at Amgen.

Amjevita is Amgen’s first approved biosimilar and the fourth to receive regulatory approval in the U.S.

“The biosimilar pathway is still a new frontier and one that we expect will enhance access to treatment for patients with serious medical conditions,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

A biosimilar is nearly identical to an already-approved biological drug and there is no clinically meaningful difference in terms of their safety, purity and potency. Unlike generic drugs, however, biosimilars are not considered interchangeable with their branded counterparts – and are not given the generic label.

Zarxio was the first biosimilar product approved by the FDA as a version of Neupogen. The second was Inflectra, a biosimilar to Remicade. Last month the FDA approved Erelzi as a biosimilar to Enbrel.

Biologic products are generally derived from a living organism and can come from many sources, including humans and animals. They help inhibit the joint damage caused by rheumatoid arthritis, a chronic disease in which the body’s own immune system attacks joint tissues, causing pain, inflammation and bone erosion.

Injectable biologic drugs often work well in controlling RA and other autoimmune diseases, but can lose their effectiveness over time. They are also notoriously expensive, with some of the newer drugs costing $20,000 annually. A study last year found that Medicare patients paid an average of $835 in out-of-pocket costs every month to obtain them.

Last year Humira generated sales of more than $8 billion for drug maker AbbVie. In anticipation of Amjevita being approved by the FDA, AbbVie filed a lawsuit against Amgen last month, alleging that Amjevita infringes on 61 of its patents for Humira.

Because of that pending court case, a spokesperson for Amgen told PNN the company would be unable to provide a launch date for Amjevita or a projected price for the drug.

The most serious side effects of Amjevita are infections and malignancies. The drug will have a "Boxed Warning" to alert healthcare providers and patients about an increased risk of serious infections leading to hospitalization or death. The warning also notes that lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including Humira (adalimumab) products.

Stem Cell Therapy Could Avoid Joint Replacement

By Pat Anson, Editor

An experimental stem cell treatment that grows new cartilage could someday help millions of arthritis patients avoid joint replacement surgery.

Researchers at Washington University School of Medicine in St. Louis and Cytex Therapeutics in Durham, N.C. have developed a 3-D, biodegradable synthetic scaffold that is molded into the precise shape of a patient’s hip joint.

The scaffold, which is covered with cartilage made from the patient’s own stem cells, is designed to be implanted onto the surface of an arthritic hip.

Resurfacing the hip joint with this “living” tissue could ease arthritis pain, and may delay or even eliminate the need for hip replacement surgery, according to researchers.

Joint replacement surgery is usually performed on the elderly to relieve pain from osteoarthritis, a painful and disabling condition caused by a loss of cartilage and the degradation of joints. Over a million hip and knee joint replacement surgeries are performed annually – a number expected to surpass four million by 2030 due to the aging of the U.S. population. 

WASHINGTON UNIVERSITY IMAGE

“We’ve developed a way to resurface an arthritic joint using a patient’s own stem cells to grow new cartilage, combined with gene therapy to release anti-inflammatory molecules to keep arthritis at bay. Our hope is to prevent, or at least delay, a standard metal and plastic prosthetic joint replacement,” said Farshid Guilak, PhD, a professor of orthopedic surgery at Washington University.

After inserting a gene into the newly grown cartilage and activating it with a drug, researchers say the gene will release anti-inflammatory molecules to fight arthritis.

“When there is inflammation, we can give a patient a simple drug, which activates the gene we’ve implanted, to lower inflammation in the joint,” said Guilak. “We can stop giving the drug at any time, which turns off the gene.”

By adding gene therapy to the stem cell and scaffold technique, Guilak and his colleagues believe it will be possible to coax patients’ joints to fend off arthritis, preserve cartilage, and function better for a longer time.

The 3-D scaffold is built using a weaving pattern that gives the device the structure and properties of normal cartilage. It is made with hundreds of biodegradable fiber bundles that are woven together to create a high-performance fabric that functions like normal cartilage.

“The woven implants are strong enough to withstand loads up to 10 times a patient’s body weight, which is typically what our joints must bear when we exercise,” said Franklin Moutos, PhD, vice president of technology development at Cytex.

Scientists have tested the tissue engineering in cell culture, and some customized implants are being tested in laboratory animals. If all goes well, such devices could be ready for testing in humans in three to five years.

Currently, there are about 30 million Americans who have osteoarthritis. That number includes a growing number of younger patients — ages 40 to 65 — who have limited treatment options.  Doctors are often reluctant to perform hip replacement surgery on patients under age 50 because prosthetic joints typically last for less than 20 years. A second surgery to remove a worn prosthetic can destroy bone and put patients at risk for infection and other complications.

“We envision in the future that this population of younger patients may be ideal candidates for this type of biological joint replacement,” said Bradley Estes, PhD, vice president of research and development at Cytex.

The research findings, which are published in the Proceedings of the National Academy of Sciences, are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging, which are both part of the National Institutes of Health (NIH).

New Molecules May Combat Immune System Disease

By Pat Anson, Editor

A team of international researchers may have unlocked an ancient secret in the human immune system that could lead to new treatments for rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease (IBD).

"Innate immunity is so old it goes all the way down to frogs, fish and even insects," says Professor Matt Cooper of the University of Queensland’s Institute of Molecular Bioscience.

Cooper and colleagues at Kings College London and the U. S. National Institutes of Health say the human immune system is basically comprised of two parts: the adaptive immune system, which produces antibodies against infection, and a very ancient pathway, known as the innate immune system.

"It stops us getting infections, but it also drives a lot of inflammatory diseases,” explains Cooper.  "So, in one case it's keeping us alive by stopping the bugs getting us, but if it goes wrong, we start to get diseases like arthritis, multiple sclerosis and IBDs such as colitis.

"Researchers always thought key components of these pathways acted alone, but our teams have discovered they can communicate and work together."

IBD is a chronic and painful inflammation of the gastrointestinal tract. Inflammation affects the entire digestive tract in Crohn’s disease, but only the large intestine in ulcerative colitis.

The study findings, published in the journal Science, may have significant implications for treating millions of people who suffer from inflammatory diseases.

"Inflammation in diseases such as colitis occurs when the immune system is activated inappropriately, and causes symptoms including pain, diarrhea, fever and weight loss," said Cooper. "Current treatments are not always effective, possibly because they are only blocking one of the key pathways and inflammation still occurs through the other pathway."

Researchers have developed two small molecules that each block one pathway.

activated immune cells

"We have tested these molecules and the results show that they both reduce inflammation when administered separately," Cooper said. "This work is still in the early stages but we are hopeful our ongoing research will lead to more effective treatments for the millions of IBD sufferers.

"It may give other scientists opportunities to develop new drugs against these diseases."

A healthy immune system is activated when the body recognizes invading microbes and alerts immune cells, such as T cells. Disease begins when the immune response spirals out of control and begins attacking healthy tissue.  

Researchers at New York University’s Langone Medical Center are also working on a theory known as the "hygiene hypothesis" that may explain why there is an increase in inflammatory bowel disease worldwide. They believe intestinal parasites and bacteria that humans were long exposed to are beneficial and help balance the immune system.

Sanitary practices have sharply reduced these parasitic and bacterial infections in developed nations, which now have some of the highest rates of Crohn’s and colitis. Researchers believe the immune response to infections triggers the growth of Clostridia, a bacterium known to counter inflammation.

Rheumatoid Arthritis Drug Linked to Overdoses

Pat Anson, Editor

A drug that’s long been used to treat rheumatoid arthritis and other autoimmune diseases has been linked to dozens of deaths in the U.S. and Australia, mainly because patients have taken it daily rather than the recommended weekly dose, according to a new study published in the Medical Journal of Australia.

Methotrexate was originally developed and is still used for chemotherapy because of its ability to stop the growth and spread of tumors. Because it is also effective as an immune system inhibitor, low doses of methotrexate became a front line therapy for rheumatoid arthritis in the 1950’s. It is also used to treat psoriasis, lupus, sarcoidosis, and inflammatory bowel diseases such as Crohn’s.

Researchers say methotrexate is safe when taken once or twice a week, but the drug is so potent that accidental daily dosing can be lethal.

“The unusual dosing schedule of low dose methotrexate is associated with a risk that it will be prescribed, dispensed or administered daily instead of weekly,” said lead author Rose Cairns, PhD, of the NSW Poisons Information Centre in Australia.

“Used appropriately, methotrexate is considered safe and efficacious; accidental daily dosing, however, can potentially be lethal. Higher or more frequent doses can result in gastro-intestinal mucosal ulceration, hepatotoxicity, myelosuppression, sepsis and death.”

In a review of medication errors in Australia from 2004 to 2014, researchers linked methotrexate to 22 deaths, including seven cases in which erroneous daily dosing was documented. One patient took methotrexate for 10 consecutive days. Reasons for the errors included patient misunderstanding and incorrect packaging of the drug by pharmacists.

A similar study of medication errors in the U.S. over a 4 year period identified over 100 methotrexate dosing errors that resulted in 25 deaths. Over a third (37%) of the errors were attributed to the prescriber, 20% to the patient, 19% to pharmacists, and 18% to administration by a health care professional.

The researchers also found a “worrying increase” in the number of medication errors just in the past year.

“It is difficult to explain this increase, but the risk of methotrexate medication error may be increasing as the population ages. Older people may be at increased risk because of a range of problems that includes confusion, memory difficulties, and age-related decline in visual acuity,” said Cairns.

Cairns and her colleagues say more needs to be done by drug makers and health professionals to reduce the risk of methotrexate overdosing, such as clearer labeling, smaller sized packages, and distinctly colored tablets.

"Methotrexate use is likely to continue increasing as Australia's population ages, so that additional measures are needed to prevent these errors," the authors concluded.

Prince Treated for Opioid Overdose Days Before Death

By Pat Anson, Editor

Pop icon Prince suffered from chronic pain and was treated for an opioid overdose just days before his death, according to tabloid reports.

Prince’s body was found Thursday in an elevator at his compound in Minneapolis. A cause of death has not yet been determined.

According to TMZ, Prince was treated at a hospital in Moline, Illinois last Friday when his private jet made an unscheduled landing after a concert in Atlanta. Initial reports were that Prince was treated at the hospital for the flu, but TMZ reported he may have needed emergency treatment for an overdose.

“Multiple sources in Moline tell us, Prince was rushed to a hospital and doctors gave him a ‘save shot’ ... typically administered to counteract the effects of an opiate,” TMZ said.

A “save shot” most likely means an injection of naloxone, a life-saving drug that quickly reverses the effects of an opiate overdoses.

TMZ later updated the story to say that Prince was actually given the injection by paramedics at a local airport and then taken to the hospital.

“Our sources further say doctors advised Prince to stay in the hospital for 24 hours. His people demanded a private room, and when they were told that wasn't possible ... Prince and co. decided to bail. The singer was released 3 hours after arriving and flew home,” TMZ said.

An autopsy was performed on the body of 57-year old entertainer this morning, but preliminary findings and a toxicology analysis could take days or weeks.

"As part of a complete exam, relevant information regarding Mr. Nelson's medical and social history will be gathered," the coroner said in a statement, referring to Prince as Rogers Nelson, his birth name. TMZ said authorities were trying to obtain Prince’s hospital records in Moline.

"We have no reason to believe it was suicide," said Carver County Sheriff Jim Olson, who also refused to address reports that Prince had overdosed last week.

"I'm not able to confirm that at this time at all," Olson said. "There have been so many rumors out that I've read about. I don't know if I can dispel all the rumors that are out there."

Prince reportedly suffered from hip problems for over a decade and needed a double-hip replacement. But as a devout Jehovah’s Witness, he would not have a blood transfusion, which made surgery nearly impossible.

“Prince has suffered for years,” a source told The National Enquirer in January. “It’s harder for him to get around.”

The Enquirer said years of strutting and dancing onstage had taken a toll on Prince’s joints and he may have suffered from severe osteoarthritis. 

“If he ignores the doctor’s advice, his walking will become impaired,” said Dr. Stuart Fischer, who did not treat Prince. “He’ll need a cane or a wheelchair for the rest of his life.”

Prince appeared hobbled and used a cane during the 2013 Grammy Awards, but in the past he has also used canes as a fashion accessory.

Prince was seen leaving a Walgreens pharmacy the night before his death. It was his fourth visit to the pharmacy this week. An employee there said he looked frail, according to TMZ.

Another Reason for Arthritis Patients to Quit Smoking

By Pat Anson, Editor

Rheumatoid arthritis sufferers who quit smoking can significantly reduce their risk of an early death, according to a British study published in the journal Arthritis Care and Research.

University of Manchester researchers studied a database of over 5,600 rheumatoid arthritis (RA) patients that included hospital admissions and death certificates. They found that the risk of death was almost two times higher in RA patients who smoked compared to those who never smoked.

The good news for smokers is that if they quit, the risk of death fell for each year they didn’t smoke. Former smokers have a risk similar to that of RA patients who had never smoked.

"This research provides important evidence that the risk of early death starts to decline in patients who stop smoking, and continues year on year,” said Deborah Symmons, Professor of Rheumatology and Musculoskeletal Epidemiology at The University of Manchester.

“We hope that this research can be used by public health professionals and rheumatologists to help more people quit smoking and reduce premature deaths, particularly for newly diagnosed patients with rheumatoid arthritis."

RA is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing swelling, inflammation and bone erosion. Many health experts believe the inflammation triggered by RA in the joints may cause inflammation throughout the body, including the heart’s coronary arteries.

According to the Arthritis Foundation, more than 50 percent of premature deaths in people with rheumatoid arthritis result from cardiovascular disease. The heightened risk of heart disease applies to all forms of arthritis, including osteoarthritis, gout, lupus and psoriatic arthritis.

"Rheumatoid arthritis is a debilitating and painful condition affecting over 400,000 people in the UK, it can begin at any age and is unpredictable - one day you can feel fine and the next day be confined to bed, unable to get up to dress, even go to the toilet unaided,” said Stephen Simpson, Director of Research and Programmes for Arthritis Research UK.

"As a charity, we are committed to preventing, transforming and curing arthritis and musculoskeletal diseases, and this research shows that cutting out smoking is one intervention which can help this condition from developing."

There is already plenty of evidence to show an association between smoking and increased risk of death in the general population, but the habit is especially risky for chronic pain sufferers. Studies have found that smoking increases your chances of having several types of chronic pain conditions, such as degenerative disc disease.

A study of over 6,000 Kentucky women found that those who smoked had a greater chance of having fibromyalgia, sciatica, chronic neck pain, chronic back pain and joint pain than non-smokers. Women in the study who smoked daily more than doubled their odds of having chronic pain.

A large study in Norway found that smokers and former smokers were more sensitive to pain than non-smokers. Smokers had the lowest tolerance to pain, while men and women who had never smoked had the highest pain tolerance.

A recent study in Sweden published in JAMA Neurology found that smoking after a diagnosis of multiple sclerosis significantly accelerates progression of the disease.

Promising Results for New Rheumatoid Arthritis Drug

By Pat Anson, Editor

A new drug being developed by Eli Lilly significantly reduces pain, inflammation and other symptoms of rheumatoid arthritis, according to the findings of an international research team published in the New England Journal of Medicine. Nearly ten percent of the patients taking the drug Baricitinib went into full remission.

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. Most RA treatments focus on suppressing the immune system to reduce inflammation and slow progression of the disease.

Baricitinib inhibits two enzymes, called Janus kinase 1 and 2, which are activated in the inflammatory response to RA.

“This is the first drug to demonstrate meaningful clinical benefit in patients who’ve failed virtually every other commercial drug for rheumatoid arthritis,” said lead author Mark Genovese, MD, a professor of immunology and rheumatology at Stanford University School of Medicine.

Researchers at Stanford and Medical University of Vienna in Austria enrolled 527 RA patients from 24 countries in the Phase 3 clinical study. The patients had been living with the autoimmune disease for 14 years, on average, had moderate to severe symptoms, and had not responded well to previous treatments. Patients were divided into three groups, one with a daily dosage of 2 mg of Baricitinib, one with 4 mg, and a control group given placebos.

After 24 weeks, the patients who received Baricitinib had significant improvements in their symptoms, suffering less pain, joint swelling and other signs of disease activity. The group with the 4 mg dose showed even better results than those with the 2 mg dose, compared to the placebo group.

"With Baricitinib, we will have a drug that works even if the currently employed medications are not sufficiently effective,” said co-author Joseph Smolen, manager of the University Clinic for Internal Medicine III at Medical University of Vienna. “Almost 10 % of the patients went into full remission (a cure-like state) within six months, and almost half of the patients demonstrated significant improvement of in disease activity and physical functioning. All this may constitute a new basis for the treatment of rheumatoid arthritis that could become available in the near future."

Another advantage of Baricitinib is that it can be taken orally once a day and does not have to be administered intravenously or through injections, unlike other RA medications. Some patients in the study had side effects, such as mild upper respiratory infections and shingles.

About 1.5 million Americans and 1% of adults worldwide have rheumatoid arthritis. About three of every four people with the disease are women.

New injectable biologic drugs often work in controlling RA initially, but lose their effectiveness over time or have unacceptable side effects. They are also notoriously expensive, with some of the newer drugs costing $20,000 annually.

According to a recent study, RA patients enrolled in Medicare Part D plans paid an average out-of-pocket cost of $835 a month for a biologic in 2013. Costs varied widely depending on the drug – from $269 a month for the biologic infliximab to $2,993 a month for anakinra.

The Baricitinib trial was sponsored by Eli Lilly, which has filed for approval of the drug with the U.S. Food and Drug Administration. Three other Lilly-sponsored studies have shown  Baricitinib was effective in newly diagnosed patients, and in head-to-head competition with the RA medications adalimumab and methotrexate. Baricitinib is also being studied in trials for atopic dermatitis and systemic lupus erythematosus.

Vitamin D Ineffective for Knee Osteoarthritis

By Pat Anson, Editor

Recent studies have suggested that Vitamin D supplements may help reduce pain from fibromyalgia, arthritis and other chronic conditions.

But the “sunshine vitamin” did not relieve pain or stop cartilage loss in patients with knee osteoarthritis, according to new research published in JAMA.

Osteoarthritis is a joint disorder that leads to thinning of cartilage and progressive joint damage. Knee osteoarthritis (OA) is very common and affects over 250 million people worldwide. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

Over 400 people with knee OA and low serum levels of Vitamin D participated in the placebo controlled study in Australia and Tasmania. They were divided into two groups; with one receiving Vitamin D supplements and the other a placebo.

Over the course of the two-year study, knee pain, stiffness and physical function were measured with the WOMAC pain scale and MRI scans were used to monitor cartilage volume, defects and bone marrow lesions.  

While the supplements did increase Vitamin D blood levels, they did not reduce knee pain. MRI’s also showed no significant differences in cartilage between the two groups.

“Vitamin D supplementation, when compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or change in WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain among patients with knee osteoarthritis,” said lead author Changhai Ding, MD, of the University of Tasmania.

Vitamin D helps control levels of calcium and phosphate in the body and is essential for the formation of strong bones and teeth. Vitamin D also modulates cell growth, improves neuromuscular and immune function, and reduces inflammation

Vitamin D deficiency – a condition known as hypovitaminosis D -- is caused by poor nutritional intake of Vitamin D, inadequate sunlight or conditions that limit Vitamin D absorption. The most severe type of hypovitaminosis D causes general body pain, especially in the shoulder, rib cage, lumbar and pelvic regions.

Researchers at National Taiwan University Hospital recently found a “positive crude association” between fibromyalgia and hypovitaminosis D.  According to the Vitamin D Council, low levels of Vitamin D could be the result of fibromyalgia, rather than the cause of the disease.

Sources of Vitamin D include oily fish and eggs, but it can be difficult to get enough through diet alone. Ultraviolet rays in sunlight are the principal source of Vitamin D for most people.