Researchers identify genetic variants associated with psoriatic arthritis

PsA is a common form of inflammatory form of arthritis causing pain and stiffness in joints and tendons that can lead to joint damage. Nearly all patients with PsA also have skin psoriasis and, in many cases, the skin disease is present before the arthritis develops. However, only one third of patients with psoriasis will go on to develop PsA.

The researchers, who are part of a European consortium, say that their work, which took three years to complete and is published in Nature Communications, is a breakthrough because genetic changes have been identified that increase the risk of PsA but not psoriasis.

Until recently opinion was divided as to whether psoriatic arthritis was a disease in its own right, or psoriasis combined with rheumatoid arthritis.

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The findings could, in future, lead to the identification of people with psoriasis who are at risk of developing psoriatic arthritis.

Dr John Bowes, who led the analysis of the work, said: “Our study is beginning to reveal key insights into the genetics of PsA that explain fundamental differences between psoriasis and PsA. Our findings also highlight that CD8+ cells are likely to be the key drivers of inflammation in PsA. This will help us to focus on how the genetic changes act in those immune cells to cause disease.”

The gene identified by the research team lies on chromosome 5 and is not the first PsA-specific gene to be identified. Patients who carry the HLA-B27 gene are also more likely to develop PsA.

Professor Anne Barton, a rheumatologist and senior author on the study explained: “By identifying genes that predispose people to PsA but not psoriasis, we hope in the future to be able to test patients with psoriasis to find those at high risk of developing PsA. Excitingly, it raises the possibility of introducing treatments to prevent the development of PsA in those individuals in the future.”

Dr Stephen Simpson, director of research at Arthritis Research UK added:” This is a significant finding. Not only does it help establish PsA as a condition in its own right, but it could have major implications in the way that patients with this condition are treated and lead to the development of drugs specifically developed for PsA, which are greatly needed.”

Source:

University of Manchester

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Study focuses on two natural approaches to preventing breast cancer

Preventing cancer requires intimate knowledge of how cancer starts, what causes it to grow and flourish, and how to stop it in its tracks. Sometimes this comes in the form of a vaccine (the HPV vaccine for cervical and head and neck cancers), a screening (a colonoscopy for colorectal cancer) or a blood test (the PSA level test for prostate cancer).

Carol Fabian, M.D., co-leader of The University of Kansas Cancer Center Cancer Prevention Program and the Morris Family Endowed Chair in Cancer Prevention, is leading a study for women with a higher risk of breast cancer that focuses on two natural approaches to preventing breast cancer: weight loss and omega-3 fatty acids EPA and DHA.

“Women in this study have a family history of breast cancer or a previous biopsy showing precancerous breast disease,” said Dr. Fabian. “Prior to entering the study, they have their breast tissue tested and are found to have too many cells in the breast ducts, called hyperplasia. Their blood and breast tissues are also tested for other risk factors for breast cancer.”

All the women in the trial are placed on a calorie-restricted diet, along with support from a nutritionist and online weight loss and exercise tracking tools. Their goal is to lose 10 percent of their body weight in the first six months and maintain it in the second six months. In addition, half of the participants are given a high-dose omega-3 supplement while the other half are given a placebo. Their blood and breast tissue is tested again at six and 12 months. Periodically, the women’s biomarker levels will be tested.

Research has already shown a link between obesity and breast cancer risk. Abnormal fat cells increase the amount of hormones as well as inflammation in the body. The majority of breast cancers are fueled by hormones such as estrogen, and it is likely that some breast cancers are stimulated by inflammation as well.

Previous studies by Dr. Fabian and her team showed that if an overweight or obese person loses at least 10 percent of their body weight, there’s a reduction in hormone production and fewer inflammatory biomarkers. “The challenge is keeping those extra pounds off,” she said, as anyone who has lost any amount of weight knows.

As a result, Dr. Fabian is seeing if higher doses of the omega-3 fatty acids EPA and DHA would help with weight loss maintenance as well as favorably reduce risk biomarkers for breast cancer. Omega-3 fatty acids have multiple important body functions, such as cell signaling, proper immune system function and improving cognitive function. Higher dose EPA and DHA (fish oil supplements) are already used for prevention of cardiovascular diseases and to help with inflammatory disorders such as rheumatoid arthritis and irritable bowel disorder. The omega-3 fatty acids are primarily found in fatty cold water fish such as salmon and leafy green vegetables, which typically aren’t eaten in abundance.

A schema of Dr. Fabian’s omega-3 and weight loss trial and when the presence of breast cancer biomarkers is measured.

Dr. Fabian first got the idea to study omega-3 fatty acids and how they might affect cancer after hearing about a “miracle” food for dogs with mammary cancer or lymphoma.

“Six years ago I heard about this Topeka, Kan., company named Hill’s Pet Nutrition, which was founded by veterinarians and manufactured a special diet dog formulation. It didn’t cure cancer, but it helped dogs with these cancers of an advanced stage live for a long time,” said Dr. Fabian. “So I asked what was in it, and they said it was a really high dose of omega-3.”

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The specific omega-3 fatty acids that are most beneficial to humans are DHA and EPA, which are mostly found in fatty, cold water fish. The average person only ingests about 100 milligrams of EPA and DHA a day when they should be getting about 30 times that amount.

Dr. Fabian has already done a study looking at how omega-3 fatty acids work in pre- and postmenopausal women with an increased risk for breast cancer. The amount of a specific inflammatory biomarker, MCP1, was decreased in the women taking an omega-3 supplement. Previous research has also shown that omega-3 in particular seems to affect similar reward brain pathways as weight loss does.

Does this mean taking an omega-3 supplement can help people who have already lost weight keep it off by keeping those brain pathways active?

“Omega-3 seems to affect the same pathways in the brain as losing weight,” explained Dr. Fabian. “If we could help people who have lost weight from gaining it back, that would be a big help in reducing their cancer risk. We want to see if omega-3 can improve the biomarker risk factor along with the weight loss and if it will make the maintenance phase easier.”

Several scientists are working with Dr. Fabian on this project, including Bruce Kimler, PhD, in Radiation Biology, and Steve Hursting, PhD, MPH, a basic scientist working on obesity from the University of North Carolina at Chapel Hill. Susan Carlson, PhD, is measuring fatty acid levels, Christie Befort, PhD, and Debra Sullivan, PhD, are in charge of the weight loss aspects and Jennifer Klemp, PhD, is examining quality of life. Two unique features of this grant are to determine whether EPA and DHA change bacteria in the colon associated with inflammation and whether these omega -3 fatty acids change reward center responses to food.

“Certain types of bacteria increase inflammation in the colon, which increases the risk for colon cancer and likely other diseases too,” said Dr. Fabian. “We’re seeing if anything changes with the omega-3, and I’m convinced it will.” Shadid Umar, PhD, KU Cancer Center member and associate professor in molecular and integrative physiology, is determining whether EPA and DHA have a favorable effect on gut bacteria.

Women are also undergoing a functional brain MRI after six months of weight loss with or without the EPA and DHA. Cary Savage, PhD, director of the Center for Health Behavior Neuroscience at the University of Kansas Medical Center, Laura Martin, PhD, associate director of functional MRI and William Brooks, PhD, director of the Hoglund Brain Imaging Center, are looking at the brain’s response to food after weight loss via MRIs.

“Mice studies done by Dr. Hursting have shown that some of these important cancer-causing pathways are stimulated in obese mice,” said Dr. Fabian. “When you lose weight, these pathways partially, but not fully, normalize. We hope that omega-3 may help with this process.”

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University of Kansas Cancer Center

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Can-Fite BioPharma completes patient enrollment in CF101 Phase II/III psoriasis trial

Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, announced today that all patients enrolled in its Phase II/III psoriasis trial for the Company’s drug candidate CF101 have completed the study’s 32 week treatment protocol. The trial has been completed and the final data is ready for analysis. The Company plans to publish top line results by the end of March 2015. Interim results from this Phase II/III trial and final results from the prior Phase II trial for CF101 in psoriasis were both positive.

“Following a thorough analysis of the data over the coming weeks, we look forward to announcing top line results on the efficacy and safety of CF101 in the treatment of moderate-to-severe plaque psoriasis. If these results are in line with the previously published favorable interim data, then we believe CF101 could offer a much-needed treatment alternative to patients living with psoriasis,” stated Can-Fite CEO Dr. Pnina Fishman.

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The psoriasis therapeutic market is dominated by biological drugs that are primarily administered via intravenous injection (IV) and have potential side effects. According to Global Data, the psoriasis treatment market was worth $3.6 billion in 2010 and is forecast to grow to $6.7 billion by 2018.

This Phase II/III double-blind, placebo-controlled study is designed to test the efficacy of CF101 in patients with moderate-to-severe plaque psoriasis. Can-Fite enrolled 326 patients through 17 clinical centers in the U.S., Europe, and Israel. The first study cohort was comprised of three arms with patients receiving: 1 mg of CF101; 2 mg of CF101; and placebo. All patients receiving placebo were switched to either 1 mg or 2 mg of CF101 after 12 weeks. The primary efficacy endpoints are a statistically significant improvement in standard measures used by dermatologists to assess psoriasis including the Psoriasis Area Sensitivity Index (PASI) score and the secondary end points among others are the Physicians’ Global Assessment (PGA) score as well as various safety parameters.

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Can-Fite BioPharma Ltd.

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Seeing the knee in a new light: Fluorescent probe tracks osteoarthritis development

A fluorescent probe may make it easier to diagnose and monitor osteoarthritis, a painful joint disease affecting nearly 27 million Americans. The disease is often detected late in development after painful symptoms occur. Earlier diagnosis might lead to better management and patient outcomes. A new study reports that a fluorescent probe tracked the development of osteoarthritis in male mice, brightening as the disease progressed. The findings are published in the February issue of Arthritis & Rheumatology.

In this case, the “probe” was a harmless fluorescent molecule that detected the activity leading to cartilage loss in the joint, the key characteristic of osteoarthritis. This lab and mouse study, led by researchers from Tufts University School of Medicine (TUSM) and the Sackler School of Graduate Biomedical Sciences at Tufts, is the first to demonstrate that near-infrared fluorescence — a specific type of light invisible to the human eye but possible to see with optical imaging — can be used to detect osteoarthritis changes over time. The new approach might also help analyze the effectiveness of osteoarthritis drugs, leading to improved treatments.

“Patients are frequently in pain by the time osteoarthritis is diagnosed. The imaging tests most frequently used, X-rays, don’t indicate the level of pain or allow us to directly see the amount of cartilage loss, which is a challenge for physicians and patients,” said co-first author Averi A. Leahy, B.A., an M.D./Ph.D. student in the medical scientist training program at TUSM and the Sackler School.

“The fluorescent probe made it easy to see the activities that lead to cartilage breakdown in the initial and moderate stages of osteoarthritis, which is needed for early detection and adequate monitoring of the disease. To measure the probe’s signal, we used an optical imaging system, to non-invasively look inside the knee,” said co-first author Shadi A. Esfahani, M.D., M.P.H., post-doctoral fellow in the division of nuclear medicine and molecular imaging at Massachusetts General Hospital, and in the department of radiology at Harvard Medical School.

The right knees of 54 mice were affected by injury-induced osteoarthritis and served as the experimental group (the mice received pain medication). The healthy, left knees of the mice served as the control group.

Over a two-month period, the researchers took images of each knee every two weeks to determine if the fluorescent probe emitted a signal. Strikingly, the signal became brighter in the injured right knee, at every examined time point, through the early to moderate stages of osteoarthritis. The probe emitted a lower signal in the healthy left knee, and did not increase significantly over time.

The corresponding and senior author is Li Zeng, Ph.D., associate professor in the department of integrative physiology and pathobiology at TUSM, and member of the cellular, molecular and developmental biology program faculty at the Sackler School. Averi Leahy is one of her students. The work was done in collaboration with Umar Mahmood, M.D., Ph.D., director of the Center for Translational Nuclear Medicine and Molecular Imaging, co-director of Nuclear Medicine and Molecular Imaging, both at Massachusetts General Hospital; and associate professor in the department of radiology at Harvard Medical School.

Zeng reports that the next step is to monitor the fluorescent probe over a longer period of time to determine whether the same results are produced during the late stages of osteoarthritis. She also hopes to use the probe to help develop treatments for animals, as some dogs are prone to osteoarthritis.

Osteoarthritis, the most common type of arthritis, causes pain, swelling, and reduced motion by breaking down cartilage that covers the ends of bones. The disease often results from an injury or long term wear and tear to the hip, hands, or knees. Reducing the burden of osteoarthritis has been a top priority for US public health officials. The National Public Health Agenda for Osteoarthritis, created by the Arthritis Foundation and the Centers for Disease Control and Prevention, calls for more research into osteoarthritis to better understand effective strategies for intervention.

The Zeng laboratory at Tufts studies the mechanisms of tissue formation and degradation to develop effective strategies to treat arthritis. Her team uses tissue engineering techniques to examine approaches that can be used to generate stronger, more stable cartilage tissue that is resistant to inflammation commonly caused by osteoarthritis.

Previous research had identified that an increase in enzymes called matrix metalloproteinases (MMP) contributes to the cartilage degradation that occurs with osteoarthritis. The fluorescent probe was introduced into the knee joint and measured MMP activity.

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The above story is based on materials provided by Tufts University. Note: Materials may be edited for content and length.

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Shared symptoms of Chikungunya virus, rheumatoid arthritis may cloud diagnosis

A mosquito-borne virus that has spread to the Caribbean and Central and South America and has caused isolated infections in Florida often causes joint pain and swelling similar to that seen in patients with rheumatoid arthritis.

Researchers at Washington University School of Medicine in St. Louis also found that blood tests of patients with the Chikungunya virus and those with rheumatoid arthritis can produce similar results. This may lead some patients with the virus to be misdiagnosed.

The findings, reported in the January issue of Arthritis and Rheumatology, underscore the need for doctors to obtain detailed travel and medical histories from patients being evaluated for rheumatoid arthritis. Such details could help distinguish between the two conditions.

“For now, good travel histories of patients are among the best diagnostic tools for physicians,” said senior author Wayne Yokoyama, MD, the Sam and Audrey Loew Levin Professor of Medicine. “Recent travel to the Caribbean, Central and South America, Africa, India or other areas where the virus is prevalent should raise suspicions of Chikungunya infection. In addition, the disease typically starts with high fever and abrupt onset of severe pain in the joints, which are not usually seen with rheumatoid arthritis.”

The global spread of the Chickungunya virus suggests that the disease is likely to be a diagnostic challenge in the years ahead. Physicians treat rheumatoid arthritis with drugs that suppress the immune system, but it’s not yet known whether that approach will help or harm patients with Chikungunya virus.

The virus is spread by infected mosquitoes and first was identified 60 years ago in eastern Africa. Since then, it has spread to many parts of the world.

In 2014, more than 2,000 people in the United States developed the infection after traveling abroad, mostly to the Caribbean. That same year, the Centers for Disease Control and Prevention reported 11 cases of Chikungunya infection among people living in Florida who had not traveled outside the United States, suggesting that mosquitoes in that state were spreading the virus.

In most patients, the infection causes a fever, rash and severe joint pain in the hands, feet, knees, neck and elbows. The fever and rash typically subside in seven to 10 days, but symptoms of arthritis may persist for 12-15 months in up to 60 percent of patients. Some patients’ symptoms persist for up to three years.

For the study, lead author Jonathan Miner, MD, PhD, a rheumatology fellow, studied 10 St. Louis-area residents who traveled in June 2014 to Haiti, where they were infected with Chikungunya virus. The patients were evaluated seven to 10 weeks after the onset of symptoms. During that time, eight patients developed persistent arthritis, several with joint pain so severe they had difficulty walking.

“All eight patients with Chikungunya-related arthritis met the American College of Rheumatology’s criteria for a diagnosis of rheumatoid arthritis,” Miner said. “Their recent travel to Haiti led us to suspect they had Chikungunya virus infections.”

As a comparison, the study also included healthy subjects and patients newly diagnosed with rheumatoid arthritis who had not yet received treatment.

Laboratory tests that measured levels of specialized immune cells in the blood showed additional similarities between Chikungunya virus infection and rheumatoid arthritis, including elevated levels of specialized T cells, which suggest, despite the persistence of symptoms, that the immune system has recognized and is fighting the virus. These studies were performed on state-of-the-art instruments in the university’s newly established Center for Human Immunology and Immunotherapy Programs.

To positively identify Chikungunya virus, the researchers performed highly specialized tests of the immune system, with results that showed antibodies against the Chikungunya virus in patients’ blood. Such testing is only available at the CDC and in research laboratories.

According to Yokoyama, a Howard Hughes Medical Institute investigator, the similarities between Chikungunya virus infection and rheumatoid arthritis suggest that learning more about the virus may help scientists better understand rheumatoid arthritis, which affects about one in every 100 people worldwide.

Said co-author Deborah Lenschow, MD, PhD, associate professor of medicine and of pathology and immunology: “We’re anticipating that Chikungunya virus will spread broadly in the United States, so it’s important to develop better tools for diagnosis, prevention and treatment.”

The researchers also have established a Chikungunya registry at chikv.dom.wustl.edu to build a database of cases for studying the virus in more detail.

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Researchers develop optimised PSA screening programme for prostate cancer

As an indicator of prostate cancer, the PSA test is regarded in urology as highly controversial since it is not always unequivocal. A team of researchers from the Comprehensive Cancer Center at the MedUni Vienna and Vienna General Hospital has now developed a programme that compensates the shortfalls of PSA screening with methods from personalised medicine. As a result, prostate cancer screening is able to reach a new level of quality.

According to Statistik Austria, around 4,700 men develop prostate cancer (adenocarcinoma) every year in Austria. Around 1,146 of these men die during the same period. The PSA (prostate-specific antigen) is the most important marker used for diagnosing prostate cancer. In the professional field, however, it is viewed as being too inaccurate and therefore serves merely as an indicator. A team of scientists led by Shahrokh Shariat, Head of the University Department of Urology at the MedUni Vienna and the Vienna General Hospital and member of the Comprehensive Cancer Center (CCC) Vienna, has now developed a programme that optimises the testing procedure. As a result, prostate cancer screening is markedly improved.

PSA: still the best bio-marker in oncology

Says Shariat: “Although the PSA is not an ideal marker, it is still the best diagnostic bio-marker across the whole of oncology. At a younger age, i.e. around 40 – 45 years, it is very useful in terms of predicting the risk of prostate cancer. The data also confirms this. Since the PSA screening test was introduced, deaths from prostate cancer have fallen by 40 per cent. So the question isn’t about whether PSA screening should be carried out or not. It’s more about doing it cleverly.”

Personalised medicine for the PSA test too

The weak point of the PSA test is that a raised PSA level does not always indicate an increased risk of prostate cancer, or even the presence of a cancer at all. Consequently, if the PSA level was raised, the previous approach has been to instigate aggressive therapy, which was often associated with major risks such as incontinence or erectile dysfunction. To counteract these side effects of “overtherapy”, Shariat and his team have developed a programme that harnesses the methods of personalised medicine.

If the patient is still young and the PSA level is only slightly raised, he is actively monitored with regular follow-ups. This avoids unnecessary procedures and also ensures that any malignant development of the tumour does not go undetected. If the value is so raised that a biopsy needs to be considered, the test is repeated within twelve weeks at the most and further bio-markers and mathematical calculation models are factored into the decision-making process.

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Says Shariat: “In addition to the PSA test, we use the new molecular methods in imaging and pathology to create a comprehensive biological profile of the cells. This enables us to make a precise risk assessment in the MDT, localise the tumour accurately and determine its molecular structure. We also use special calculation models in formulating a prognosis.”

With this method, doctors can better estimate whether treatment is needed and would be useful, and how likely it is that the patient will respond to surgical or drug-based therapy. As a result, patients are spared unnecessary treatments and possibly also side effects.

If the MDT still recommends surgery as the therapy of choice, Shariat strongly advises having the surgery carried out in a specialist hospital that carries out this type of surgery often, since this is where the expertise of the clinicians, the familiarity with the condition that is required and the relevant diagnostic procedures can be found. Says Shariat: “These hospitals also have the latest specialist equipment. The MedUni Vienna and the Vienna General Hospital, for example, have the latest Da Vinci robots, which make the procedure more precise and more tolerable for the patient, who is of course at the centre of everything.”

CCC on Cancer Day at Vienna’s City Hall

For patients who would like to learn more about this or other oncology-related matters, Cancer Day is again being held at Vienna’s City Hall on Tuesday, 10 February 2015. The Comprehensive Cancer Center Vienna will be there with its Cancer School CCC Vienna, its educational organisation for patients, and will be on hand to answer questions. At the Cancer School CCC Vienna, CCC experts offer brief lectures under the motto “Cancer knowledge for all” about the condition, its causes and development, diagnostic procedures and treatment options. The next block of lectures will begin at the end of April / start of May 2015.

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Do Patients and Family Stall End-of Life-Care Talks?

Action Points

  • Hospital-based clinicians in Canada cite patients and family members as the greatest barriers to goals of care and end-of-life decision making in seriously ill patients.
  • Hospital-based clinicians rate their own communication skills and system factors as relatively less significant barriers to goals of care and end-of-life decision making.

Patients and their family members were cited as the biggest barriers to end-of-life decision making, according to a survey of hospital-based physicians and nurses.

Staff at 13 teaching hospitals in Canada rated 21 barriers to goals of care discussions on a 7-point scale (7=extremely important). They named family member and patient reluctance to accept a poor prognosis as major barriers (mean scores of 5.8 and 5.6, respectively), as well as family member and patient difficulty understanding the limitations and complications of treatments (mean score of 5.8 for both), reported John You, MD, of McMaster University, Ontario, and colleagues.

However, the surveyed clinicians rated their own communication skills and system factors as far less significant obstacles to facilitating end-of-life discussions, the authors wrote in JAMA Internal Medicine.

Other leading barriers cited by the doctors and nurses were family member disagreements about the goals of care and patient difficulty understanding the limitations and complications of life-sustaining therapies.

“Desire to maintain hope” and “Desire to avoid being sued” were rated as the least important obstacles to end-of-life discussions and decisions.

In an accompanying editorial, cardiologist and ethics consultant James N. Kirkpatrick, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, said that the survey results might be interpreted by some as clinicians blaming the patient.

But he pointed out that “despite barriers, the authors found that clinicians were willing to engage in goals of care communication and decision making … Importantly, both nurses and physicians indicated that all types of healthcare professionals, not just physicians, have legitimate roles to play in goals of care discussions.”

In an interview with MedPage Today, Kirkpatrick said medical professionals who routinely treat critically ill patients would benefit from goal of care discussion training, but many are not getting it.

“We tend to get frustrated when we think that family members and patients don’t understand the prognosis or that they can’t come to grips with it,” Kirkpatrick said. “But we also often don’t understand or appreciate how difficult it is to do this.”

Kirkpatrick noted that end-of-life discussions have become more important as high-tech interventions that prolong life have proliferated in hospitals.

In a 2013 survey of hospitalized, critically ill, elderly patients and their family members, the Canadian Researchers at the End of Life Network (CARENET) reported that patients and family members often expressed preferences for limiting end-of-life medical treatments, but physicians’ orders for life-sustaining treatments such as cardiopulmonary resuscitation were frequently inconsistent with these wishes.

The researchers concluded that communication with healthcare professionals and documentation of these preferences remains inadequate.

In the current study, You’s group surveyed 525 nurses, 484 resident physicians, and 260 staff physicians. Questionnaires were completed from September 2012 to March of 2013. The overall response rate was 77.7%.

All three groups cited family member-related and patient-related factors as the most important barriers to goals of care discussions.

On the 7-point scale, disagreement among family members about goals of care and patient incapacity to make goal of care decisions received mean scores of 5.8 and 5.6, respectively.

Language barriers, cultural differences, lack of substitute decision maker, and uncertainty about who the substitute decision maker would be all scored around 5.

Lack of time, disagreement among the health team about goals of care, lack of a written advance directive, and lack of training in end-of-life discussions all had mean scores between 4 and 5.

‘Desire to avoid being sued’ was considered the least important barrier (mean score of 3.5).

When asked to rate their own willingness to engage in discussions and decision making on end-of-life care, staff physicians and residents were more willing than nurses and more willing than residents, the authors reported. Nurses said they felt neither supported nor unsupported in their work environment to engage in communication and decision making about goals of care.

“Our findings underscore and support recent calls for more and better training for all clinicians in having end-of-life discussions,” the researchers wrote. “Communication skills training and tools that enhance clinicians’ ability to build rapport, listen with empathy, and discuss prognosis — along with its inherent uncertainty — could help clinicians to better support patients and families through decisions about goals of care.”

Kirkpatrick noted that this training may be particularly useful for nurses who often have the most contact with patients and family members.

Just 9.6% of nurses in the study reported having formal training in goals of care discussions compared with 35% of resident physicians and 28.5% of staff physicians.

The researchers concluded that in addition to better training, promising interventions include conversation guides for end-of-life discussions, decision aids to support advance care planning, and greater involvement of the healthcare team.

“Given the diversity of barriers to goals of care discussions, any single intervention is unlikely to succeed on its own,” You and colleagues wrote. “Multifaceted interventions directed at patients and their families, clinicians, and the healthcare system will likely be necessary to achieve this important goal.”

The study had some limitations. The findings may not apply to institutions outside of Canada, to nonteaching hospitals, or to outpatient settings. Also, the authors asked respondents to rate the importance of barriers on the basis of their recall of past experience.

“It is possible that participants were disproportionately influenced by infrequent but memorable interactions with patients and families when rating the importance of barriers,” they explained.

This study was funded by the Canadian Institutes for Health Research, Hamilton Health Sciences, and the Heart and Stroke Foundation, Ontario, Canada.

You and co-authors disclosed no relevant relationships with industry.

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No Relief for Painful Knees

Action Points

  • Note that this large, cross-sectional study of European patients with knee osteoarthritis found that a significant percentage reported inadequate pain relief.
  • Be aware that opioid use was associated with a greater likelihood of inadequate pain relief.

Inadequate pain relief (IPR) is widespread among patients with knee osteoarthritis (OA), especially women, those with depression or diabetes, and those who have had the disease for a long time, according to a new prospective, longitudinal cohort study.

In a large group of patients with knee OA, 54% met the definition of IPR, which was a score of >4 on the Brief Pain Inventory (BPI) scale, according to Philip G. Conaghan, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, England, and colleagues.

“The fact that 54% of patients in this real-world setting had persistent moderate to severe pain suggests that currently prescribed pain treatments for knee OA are not meeting the needs of the majority of patients,” they wrote in an article published in Rheumatology.

The prevalence of IPR could be as high as 70% if a pain score of =3 on the BPI (no worse than mild pain) was used as a treatment target, said the researchers.

The Survey of Osteoarthritis Real World Therapies (SORT) was carried out at 53 centers in six European countries. The analysis included 1,187 patients with knee OA who were prescribed topical or oral pain medication within the previous 2 weeks. They were recruited from November 2011 to January 2012.

The mean age of participants was 67.8 years and 68.1% were female. The most common comorbidity was hypertension, affecting 58.3% of patients. Just over half (52.2%) of the subjects had OA affecting both knees while almost a quarter had an affected left knee (24.1%) or right knee (23.8%).

Study participants assessed average OA pain using question 5 of the BPI, which rates pain on a scale of 0-10. A score of 0-4 is defined as mild pain; 5-6 as moderate pain; and 7-10 as severe pain.

Patients also assessed their pain, stiffness, and physical function in the knee using the Western Ontario and McMaster (WOMAC) osteoarthritis index. As well, they reported their quality of life and satisfaction with symptomatic treatment for knee OA.

The study found that the prevalence of IPR (54%) as determined by patient responses to the BPI average pain question was well correlated with the WOMAC pain subscale (P <0.001), “further demonstrating that the concept of IPR is not an artifact of how IPR is defined and assessed,” wrote the authors.

The IPR and non-IPR groups differed in many respects. IPR patients were more likely to be female (adjusted odds ratio [adjOR] 1.90, 95% confidence interval [CI] 1.46-2.48), and to have a longer disease duration, greater opioid use and co-morbid hypertension, depression, and diabetes.

“Clinicians should recognize this constellation of characteristics as constituting special risk,” said the authors.

As well, a significantly greater percentage of patients with IPR had OA affecting both knees (P<0.001) and partial or total disability (P=0.009) compared with the non-IPR group.

The most commonly prescribed analgesic was a nonsteroidal anti-inflammatory drug (NSAID) (65.1%), followed by paracetamol (39.6%,) and opioid drugs (21.4%). IPR patients were more likely than non-IPR patients to be prescribed paracetamol or opioid-containing medications.

These findings, said the authors, indicate that “management of OA in primary care may not conform to the recommendations in clinical practice guidelines or to the intensity of patients’ pain.”

The study also showed that, overall, 51% of the IPR group reported their general health status to be fair or poor compared with 31% of the non-IPR cohort (P<0.001). At baseline, 48% of patients with IPR reported dissatisfaction with response to treatment and 38% reported dissatisfaction with tolerability of medication.

Since not all invited patients consented to participate in the study, selection bias is a possible limitation. And as the analysis is cross-sectional, the causal link between IPR and functional status can’t be fully characterized.

Paul M. Peloso was a full-time employee of Merck at the time this study was designed and conducted; Ceri J. Phillips has received honoraria from Merck.

Christopher M. Black is an employee of Merck; Francois Rannou has received honoraria from MSD for the SORT study.

Srinivasan Rajagopalan has worked as a consultant on this project and others at MSD.

Stephanie D. Taylor, Sharlette V. Everett, and Panagiotis Mavros are employees of MSD and is a shareholder of Merck & Co., Inc.

Mart AFJ van de Laar has provided consultancy services to Pfizer, Novartis, and MSD and has received research grants from AbbVie, Pfizer, MSD, BMS, and Roche.

The other authors have declared no conflicts of interest.


  • Reviewed by
    F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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