MedicalResearch.com Interview with: Gregory N. Kawchuk Ph.D. Department of Physical Therapy Faculty of Rehabilitation Medicine University of Alberta Edmonton, Alberta, Canada Medical Research: What is the background for this study? What are the main findings? Response: Jerome Fryer, one of our co-authors, had a new idea for why joints crack. So before delving into this, we went to...
MedicalResearch.com Interview with:
Gustavo C Machado, PhD student
The George Institute for Global Health, Sydney Medical School
University of Sydney Sydney Australia
(Editor’s note: Paracetamol isalso known as acetaminophen)
MedicalResearch: What is the background for this study? What are the main findings?
Response: Back pain and osteoarthritis are the two major musculoskeletal conditions affecting people worldwide, and paracetamol is the most used over the counter medicine to treat these conditions. Recent debates on the efficacy and safety of paracetamol prompted us to conduct a systematic review of literature on the efficacy of this medication. In our study we included all available clinical trials that compared paracetamol to placebo, and our conclusions are based on data from more than 5,300 patients with low back pain and hip or knee osteoarthritis. We found that paracetamol is ineffective for low back pain and provides small and not clinically important benefits to patients with osteoarthritis.
MedicalResearch.com Interview with:
Adam Culvenor Ι B.Physio(Hons), PhD
Division of Physiotherapy
School of Health & Rehabilitation Sciences
The University of Queensland
Medical Research: What is the background for this study?
Dr. Culvenor: Knee injury, such as anterior cruciate ligament (ACL) rupture, is a well-recognised risk factor for the accelerated development of knee osteoarthritis (OA). Previous studies report high rates of knee osteoarthritis with radiographs (x-rays) more than 5-10 years following ACL injury and reconstruction (ACLR). However, once OA becomes well-established and visible on radiographs, management options are limited. Potential therapies may be better placed to target the early stages of disease when management strategies, such as optimising knee load, may be more efficacious. Magnetic resonance imaging (MRI) enables the assessment of early osteoarthritis features affecting any joint tissue. Yet, MRI has not previously been used to assess early knee OA within the first year following ACLR.
Medical Research: What are the main findings?
Dr. Culvenor: Of the 111 patients who were one year following an anterior cruciate ligament rupture, the prevalence of early knee OA assessed with MRI was much higher than previously recognised. Medial and lateral tibiofemoral osteoarthritis was observed in 6% and 11%, respectively, while 17% had patellofemoral OA. These patterns of early OA are similar to previous radiographic findings; the patellofemoral joint is at particular risk of OA. Specifically, the femoral trochlea was the region most affected by bone marrow lesions, cartilage lesions and osteophytes. The prevalence of structural pathology was much higher than the uninjured control group of similar age and activity level, highlighting the impact of knee trauma (injury and/or surgery).
MedicalResearch.com Interview with:
Dr Naila Rabbani
Reader of Experimental Systems Biology
Protein Damage and Systems Biology Research Group, Division of Metabolic & Vascular Health, Warwick Medical School, University of Warwick,
Clinical Sciences Research Laboratories, University Hospital U.K.
Medical Research: What is the background for this study? What are the main findings?
Dr Rabbani: We performed a study to investigate biochemical markers indicative of early-stage decline in joint health and development of early-stage osteoarthritis OA), rheumatoid arthritis (RA) and other inflammatory joint disease. The main finding was that by combining measures of three substances in blood - citrullinated protein (CPs), antibodies to CPs and hydroxyproline we could detect and discriminate between early-stage osteoarthritis and rheumatoid arthritis.
MedicalResearch.com Interview with:
Professor Anne Barton FRCP PhD and
Dr John Bowes PhD
Centre for Musculoskeletal Research and
Centre for Genetics and Genomics,
The University of Manchester, Manchester UK
Medical Research: What is the background for this study?
Response: Psoriatic arthritis (PsA) is an inflammatory condition causing pain and stiffness in joints and tendons. Approximately one third of patients with psoriasis will go on to develop PsA resulting in a reduction in their quality of life caused by increasing disability and additional health complications. A key area of research within the Arthritis Research UK Centre for Genetics and Genomics in the Centre for Musculoskeletal Research is the identification of risk factors for the development of Psoriatic arthritis; this will allow us to understand the underlying cause of disease and ultimately help identify psoriasis patients at high risk of PsA, allowing early treatment to be introduced to reduce the impact of PsA.
Our study focuses on the identification of genetic risk factors for Psoriatic arthritis; we compared the frequency of genetic variants, referred to as single nucleotide polymorphisms (SNPs), between large numbers of DNA samples from patients with PsA and healthy control samples. When the frequency of the SNP is significantly different between cases and controls, the SNP is said to be associated with risk of developing Psoriatic arthritis and this association is interpreted as being important in the disease process.
Medical Research: What are the main findings?
Response: When we analysed the data from the study we found a new association to SNPs on chromosome 5, and when we investigated these SNPs for association with skin-only psoriasis, we did not find any evidence for association. In addition, we also found SNPs that were specifically associated with Psoriatic arthritis at a gene on chromosome 1. This gene is known to be associated with psoriasis, but our results show that there are different SNPs associated with PsA and psoriasis at this gene. Hence, our results identify new SNPs that are specifically associated with PsA.
In addition, identifying which cells are the key drivers of inflammation in Psoriatic arthritis will help us to focus on how the genetic changes act in those cells to cause disease. Our results show that many of the PsA associated SNPs occur in regions of the genome that are important in the function of CD8+ cells, an important cell type in the immune system.
MedicalResearch.com Interview with:
A/Prof Rana Hinman PhD
Australian Research Council Future Fellow
Centre for Health Exercise & Sports Medicine
Department of Physiotherapy School of Health Sciences
The University of Melbourne, Carlton, Victoria, Australia
Medical Research: What is the background for this study?
Response: It has been well established that hip and knee osteoarthritis (OA) is a major causes of musculoskeletal disease burden worldwide. There is currently no cure and joint replacement is typically reserved for advanced disease. Non-operative management strategies are the mainstay of osteoarthritis treatment. Clinical guidelines recommend the use of aerobic and/or resistance exercises, hydrotherapy and weight loss for those who are overweight for people with hip or knee osteoarthritis. Little is known about how often these treatments are used, and whether treatment use differs for those with hip osteoarthritis compared to those with knee osteoarthritis.
Medical Research: What are the main findings?
Response: The use of non-drug non-operative interventions was generally low amongst the entire cohort of people with hip or knee osteoarthritis. Although half reported making efforts to lose weight, very few were undertaking muscle strengthening, hydrotherapy or aerobic exercises, all of which are strategies most strongly endorsed by international guidelines. 12% of the cohort had never used any of the interventions listed in our survey.
Interestingly, use of five treatments was significantly higher among people with knee osteoarthritis than those with hip osteoarthritis, suggesting people with knee osteoarthritis may be more likely to try non-drug non-operative treatments than those with hip osteoarthritis, however there is no clear explanation for this.
Medical Research Interview
Dr Gomez-Puerta MD, PhD, MPH
Division of Rheumatology, Immunology, and Allergy; Brigham and Women's Hospital, Harvard Medical School, Boston, MA
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Gomez-Puerta: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology which can cause multiorgan system damage and which disproportionately affects women and non- Caucasian minorities. Up to 60% of SLE patients develop renal disease, lupus nephritis (LN), and of these, approximately one fifth progress to end-stage renal disease (ESRD). The risk of cardiovascular (CV) events and mortality is higher in patients with ESRD and in particular in patients suffering SLE. However, information about CV outcomes and mortality is limited in patients with LN associated ESRD.
We observed important variation in cardiovascular outcomes and mortality by race and ethnicity among lupus nephritis related ESRD patients. After adjusting for multiple demographic and clinical factors and accounting for the competing risk of kidney transplantation and loss to follow-up, our results illustrate for the first time that Asian (vs. White) and Hispanic (vs. non-Hispanic) lupus nephritis related ESRD patients have lower mortality risks.
MedicalResearch.com Interview with:
Dr Geeske Peeters
Postdoctoral Research Fellow
School of Public Health
The University of Queensland Australia
Medical Research: What is the background for this study? What are the main findings?
Dr. Peeters:
The hypothesis we set out to investigate was that statin use is associated with reduced joint pain/stiffness and consequently improved physical functioning and quality of life. This hypothesis was based on findings from previous studies suggesting that statin use may prevent the development of radiographic osteoarthritis. However, in contrast with this hypothesis, results from this large study did not demonstrate an association between statin use and reduced onset of joint pain or stiffness. Moreover, statin use did seem to be associated with an increased risk of functional limitations and poorer self-reported health, especially in the middle-aged women.
MedicalResearch.com Interview with:
Sandra Goldsmith, MA, MS, RD
Director of Public and Patient Education at Hospital for Special Surgery
New York City.
Medical Research: What is the background for this study? What are the main findings?
Response: Almost 50 million adults in the United States suffer from some form of musculoskeletal disorder, which can affect their mobility and quality of life. Osteoarthritis (OA) is the leading cause of disability in the U.S. and affects more than 70 percent of adults between the ages of 55 and 78. Research has shown that there is a connection between being physically active and maintaining joint health, pain relief and improved quality of life. This study attempts to support the efficacy of Hospital for Special Surgery’s hospital-based exercise programs in increasing physical activity and improving quality of life through pain relief and improved stiffness, fatigue and balance in the older adult community.
This study found that after taking the exercise classes, fewer participants reported experiencing a high level of muscle/joint pain from their condition (56 percent before the program started vs. 47 percent after completing the program). The study also reported improved quality of life, as evidenced by statistically significant reductions in how much their pain interfered with their general activities, ability to walk, mood, sleep and enjoyment of life. In addition, 83 percent of participants indicated a reduction in stiffness; 82 percent said they felt their balance improved; and 67 percent said they experienced less fatigue as a result of taking part in the program. Health outcomes were also related to the type of exercise class participants chose, with the greatest reduction in muscle/joint pain reported by those who took t’ai chi.
MedicalResearch.com Interview with:
Dr. Grace Hsiao-Wei Lo
Baylor College of Medicine
Assistant Professor, Section of Immunology, Allergy and Rheumatology, Department of Medicine, Baylor College of Medicine
Faculty, Immunology, Allergy, and Rheumatology Section,
Michael E. DeBakey VA Medical Center
Medical Research:What is the background for this study? What are the main findings?
Dr. Hsiao-Wei Lo: Controversy exists regarding whether running is harmful versus beneficial to the knee. There is concern that chronic repetitive loading of the knee could physically damage structures within the knee. Alternatively, runners have a lower body mass index, which we know is protective of knee osteoarthritis. Limitations of prior studies evaluating the relationship between running and osteoarthritis include that they have been small studies and they have focused on those participating in a high level or an elite level of running which may not be very generalizable. Addressing the question of whether running is associated with osteoarthritis is of particular relevance given that recent CDC guidelines recommend that all adults participate in regular physical activity, as there is definitive evidence that increased physical activity is associated with reduced cardiovascular events and mortality.
To address this question, we used data from a multicenter observational study, the Osteoarthritis Initiative (OAI). Of 2,683 participants, 56 percent were female, the mean age was 64.5 and the mean BMI was 28.6. Twenty-nine percent of the participants reported that they ran at some time in their lives.
Patients had knee X-rays, were given symptom assessments, and were asked to complete the Lifetime Physical Activity Questionnaire (LPAQ), identifying the top three most frequently performed physical activities (≥ 10 times in life) they performed at different age ranges throughout their life. Age ranges included 12-18, 19-34, 35-49, and 50 years or older.
Knee X-rays were taken and then scored for evidence of radiographic OA using the Kellgren-Lawrence (KL) grade scale. Participants with KL grades of two or higher were considered as having radiographic OA (ROA). The researchers also measured if participants had frequent knee pain. Researchers considered a participant to have symptomatic OA (SOA) if they had at least one knee with both ROA and frequent knee pain. Anyone with a total knee replacement was classified as having frequent knee pain, ROA and SOA.
After collecting all the data, the researchers reported that runners, regardless of the age when they ran, had a lower prevalence of knee pain, ROA and SOA than non-runners. For people who had run at any time in their lives, 22.8 percent had SOA compared to 29.8 percent of non-runners. People with the lowest BMI scores were the most likely to report being habitual runners. Regular running, even at a non-elite level, not only does not increase the risk of developing knee osteoarthritis but may protect against it, the researchers concluded.
MedicalResearch.com Interview with:
Diederik De Cock
PhD student - CareRA project
Department Rheumatology
Medical Research: What is the background for this study? What are the main findings?
Response: Rheumatoid Arthritis (RA) is a chronic systemic auto immune disease characterized by pain and swelling in the joints, mostly in arms and legs. Around 1% of the world population is affected by this hazardous disease. Left untreated this can lead in the short term to loss of quality of life and in the long term to major bone damage and immobility. Rheumatoid Arthritis can not be cured, but the disease can be suppressed.
International guidelines recommend to treat a patient with Rheumatoid Arthritis early, intensive and to target low disease activity, but leave much freedom in choice of medication and strategy. Our CareRA ( Care in early RA) research group, under the leadership of Prof Dr Verschueren and Prof Dr Westhovens tried to untangle long standing questions regarding the management of Rheumatoid Arthritis.
In this RCT, we want to question the benefit of a combination of disease modifying anti rheumatic drugs compared to monotherapy and the benefit of a high starting dose of glucocorticoids versus moderate dose. We choose glucocorticoid therapy over biological therapy because of its widespread use in RA and cost-effectiveness compared to the expensive biological therapy.
Therefore, 290 patients with the presence of poor prognostic markers (disease activity, erosions and serum markers RF/ACPA) were randomzied into 1 of 3 medication schemes:
1. Cobra Classic: methotrexate + sulphasalazine + 60mg glucocorticoid starting dose
2. Cobra Slim: methotrexate + 30mg glucocorticoid starting dose
3. Cobra Avant-Garde: methotrexate + leflunomide + 30 mg glucocorticoid starting dose
The glucocorticoid doses were tapered every week. After 6 or 7 weeks, they were on maintenance dosage and discontinued after 28 weeks.
All patients are followed in a tight control schedule ( a close follow-up scheme), aiming for low disease acitvity.
After 16 weeks, 7 out of 10 patients were in remission, a state where the disease is clinically suppressed. No differences in efficacy outcomes were observed between the three groups. However, the safety profile of the Cobra Slim group is much more favourable because only half of the number of adverse events were observed in this group compared to Classic and Avant-Garde.
MedicalResearch.com Interview with:
Professor Flavia Cicuttin
School of Public Health and Preventive Medicine
Monash University and Alfred Hospital
Melbourne, Australia
Medical Research: What is the background for this study? What are the main findings?
Prof. Cicuttin: Previous research found that low birth weight and preterm birth have been linked to hypertension, cardiovascular disease, insulin resistance and reduced bone mass in adulthood. Given these adverse outcomes related to birth weight and preterm birth we set out to investigate if low birth weight and preterm birth also played a role in increase risk of joint replacement surgery as adults.
We found that low birth weight and preterm birth were associated with a 2-fold increased risk of hip but not knee replacement surgery.
MedicalResearch.com Interview
Professor Paul Emery
Arthritis Research UK Professor of Rheumatology
Director - Leeds Musculoskeletal Biomedical Research Unit, LTHT Director – Leeds Institute of Rheumatic and Musculoskeletal Medicine University of Leeds
Medical Research: What is the background for this study? What are the main findings?
Professor Emery: Joint damage and functional disability are common in people who suffer from rheumatoid arthritis (RA), even in those with early disease. We know that early aggressive treatment with biologics, such as the anti-TNF agent etanercept, results in rapid remission in many patients with moderate-to-severe rheumatoid arthritis, which can help reduce the risk of joint destruction and disability long term. However, we don’t yet know whether remission achieved with biologic therapy can be maintained after doses are reduced or therapy is withdrawn.
The PRIZE trial, a “state-of-the-art” biologic treatment trial conducted in adults with early untreated rheumatoid arthritis, was designed to fill this knowledge gap. The trial included three phases:
MedicalResearch.com: Interview Invitation
Dr. Bente Glintborg:
Copenhagen Centre for Arthritis Research
Centre for Rheumatology and Spine Diseases
Copenhagen University Hospital Glostrup
Copenhagen, Denmark
Medical Research: What are the main findings of the study?
Dr. Glintborg: Current smoking had a negative impact among patients with psoriatic arthritis treated with TNFi. This was especially observed among male patients and among patients treated with infliximab and etanercept. Current smokers had a shorter treatment duration (=poorer treatment adherence rate) compared to non-smokers. And current smokers had poorer treatment response (measured as ACR20, ACR50 and ACR70 responses and EULAR good response) compared to non smokers. Especially among male smokers the EULAR good response and ACR20 response rates were nearly half of the rates among male non-smokers. The response rates among women did not seem to be affcted by smoking status. Current smokers had poorer self reported outcome measures (HAQ and VAS global and VAS fatigue) when they started treatment with TNFi.
MedicalResearch.com Interview with:
Dr. Bing Lu, M.D., Dr.P.H.
Division of Rheumatology
Immunology & Allergy
Brigham & Women's Hospital and Harvard Medical School
Boston, MA 02115
Medical Research: What are the main findings of the study?
Dr. Lu: In two large cohorts of women, we observed that being obese increased the risk of rheumatoid arthritis in women by 40–70% depending on age and serologic status. The highest risk for rheumatoid arthritis was among women who were overweight or obese at age 18 years, emphasizing the public health importance of combating the obesity epidemic at all ages. Our study implicates being overweight or obese throughout adult life as a risk factor in the development of seropositive and seronegative RA for women diagnosed with rheumatoid arthritis at age 55 years or younger. The attenuated association between BMI and rheumatoid arthritis diagnosed at older ages may reflect differences in the pathophysiology of RA diagnosed at earlier ages compared with that diagnosed at older ages, or may be a result of the limitations of BMI as a measure of total fat mass as women age.
MedicalResearch.com Interview with:
Yang Hu
From the Division of Rheumatology, Immunology, and Allergy
Brigham and Women's Hospital and Harvard Medical School
Boston, MA
MedicalResearch.com: What are the main findings of the study?
Answer: We find regular (≥ 1 serving/day) consumption of sugar-sweetened soda, but not diet soda, is associated with increased risk of seropositive rheumatoid arthritis in women, independent of other dietary and lifestyle factor.
MedicalResearch.com Interview with:
Ling Zhao Ph. D.
Associate Professor
College of Acupuncture-Tuina,
Shanghai University of Traditional Chinese Medicine,
China
Medical Research: What are the main findings of the study?
Dr. Zhao: In our study, we found that a 6-week course of moxibustion treatment (i.e., a modality of traditional acupuncture using burning moxa to warm and stimulate the acupoint) significantly reduced pain and improved function in patients with knee osteoarthritis compared to a credible placebo control. Our findings suggest that this ancient modality might be a useful adjunctive treatment for knee osteoarthritis. We also found that our sham device is credible for a double-blind randomized clinical trial assessing this traditional treatment modality.
MedicalResearch.com Interview with:
Daniel L. Riddle, PT, Ph.D., F.A.P.T.A.
Otto D. Payton Professor
Assistant department chair
Department of Physical Therapy
Virginia Commonwealth University
MedicalResearch: What are the main findings of the study?
Dr. Riddle: We used a classification system developed by researchers in Spain in the late 1990s and found that classifications of appropriate, inappropriate and inclusive ratings for persons undergoing knee replacement surgery were 44.0%, 21.7%, and 34.3%, respectively. We studied 175 persons who underwent unilateral total knee replacement in the Osteoarthritis Initiative study, an NIH and privately funded multi-year cohort study of persons with are at high risk for knee osteoarthritis. These findings need to be considered cautiously because the classification system was developed more than 15 years ago and was designed to place greatest priority on persons with end stage knee osteoarthritis and severe pain and functional loss.
MedicalResearch.com Interview with
Bethanie Wilkinson, Ph.D.
Pfizer
445 Eastern Point Rd.
Groton, CT 06340
MedicalResearch: What are the main findings of the study?
Dr. Wilkinson: ORAL Start showed that XELJANZ (tofacitinib citrate) 5 and 10 mg twice daily (BID), taken by itself without methotrexate (MX), inhibited the progression of structural damage and reduced the signs and symptoms of rheumatoid arthritis (RA), and was statistically significantly superior to methotrexate on these measures at Month 6 (primary endpoint) and at all measured time points up to 24 months in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate. XELJANZ is not indicated in patients who had not previously received methotrexate.
MedicalResearch.com: Interview with:
Dr. Patrick Le Goux
Rheumatologist Hôpitaux universitaires Paris Ouest France
French Tennis Federation medical staff
MedicalResearch: What are the main findings of the study?
Dr. Le Goux: The therapeutic effect of platelet-rich plasma (PRP) of two ultrasound guided PRP injections at 4 weeks interval compared to two saline injections (as placebo or treatment of reference) is similar on a visual analogic scale for epicondylitis of recent evolution (3 months duration maximum) in a prospective randomized double blind study with 12 months follow up. We have no intrinsic or inherent benefit of the PRP injections.
MedicalResearch.com Interview
Professor Kim Bennell
ARC Future Fellow
Department of Physiotherapy
University of Melbourne
Parkville, Vic 3010 Australia
MedicalResearch: What are the main findings of the study?
Professor Bennell: In 102 people with painful hip osteoarthritis, we compared a 'real' physical therapy program involving exercise, manual therapy techniques,education and provision of a cane if appropriate to a sham physical therapy treatment that was made to look as though it was real but instead involved turned off ultrasound and gentle application of a hand crème to the hip region. Participants in both groups went to see a physical therapist on 10 occasions over 12 weeks and performed home exercises if in the 'real' physical therapy group or lightly applied the cream at home if in the sham group. Participants were followed for 9 months in total. We found that while both groups showed improvements in pain and physical function, the improvements were similar between the two groups. That is, the real physical therapy program did not show greater benefits over a sham treatment.
MedicalResearch.com Interview with:
Maria E.C. Sandberg, MSc PhD
Institutet för Miljömedicin / Institute of Environmental Medicine
Karolinska Institutet
Stockholm, Sweden
MedicalResearch: What are the main findings of the study?
Dr. Sandberg: Overweight at diagnosis significantly decreases the chance of achieving good disease control during the early phase of rheumatoid arthritis (RA).
MedicalResearch.com Interview with:
Zhang, Xuan MD
Professor of Medicine
Dept. of Rheumatology
Peking Union Medical College Hospital
Beijing,China,100730 and
Dr. Peter E. Lipsky, MD
Formerly National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institutes of Health, Bethesda, MD,
MedicalResearch.com: What are the main findings of the study?
Prof. Zhang & Lipsky--The results of this study indicate that TwHF is effective for the treatment of active rhematoid arthritis (RA). Importantly, these are the first data indicating that TwHF is effective in DMARD-naïve patients with active rheumatoid arthritis. At week 24, TwHF monotherapy resulted in significant improvement of disease activity, including pain assessment, the patient’s and physician’s global assessment, tender joint counts, swollen joint counts, ESR, CRP, and HAQ and SF-36 scores. MTX monotherapy and TwHF monotherapy had similar efficacy as shown by ACR20, ACR50 and ACR70 response criteria, EULAR and cDAI good response criteria, as well as DAS28 remission criteria and low disease activity(LDA) rate. The efficacy of TwHF was not inferior to that of MTX, and MTX +TwHF combination therapy was more effective than monotherapy in treating active rhematoid arthritis. A safety evaluation of the study demonstrated that the frequency of total adverse events and severe adverse events of TwHF monotherapy was not significantly higher than that of MTX monotherapy, except for a slightly increased frequency of irregular menstruation.