Sita M. A. Bierma-Zeinstra

OARSI guidelines for the non-surgical management of knee osteoarthritis

OBJECTIVE To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, and allied healthcare professionals worldwide. METHOD Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1-10 risk and benefit scores. RESULTS Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation). CONCLUSION These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.

Platelet-rich plasma injection for chronic Achilles tendinopathy: A randomized controlled trial

CONTEXT Tendon disorders comprise 30% to 50% of all activity-related injuries; chronic degenerative tendon disorders (tendinopathy) occur frequently and are difficult to treat. Tendon regeneration might be improved by injecting platelet-rich plasma (PRP), an increasingly used treatment for releasing growth factors into the degenerative tendon. OBJECTIVE To examine whether a PRP injection would improve outcome in chronic midportion Achilles tendinopathy. DESIGN, SETTING, AND PATIENTS A stratified, block-randomized, double-blind, placebo-controlled trial at a single center (The Hague Medical Center, Leidschendam, The Netherlands) of 54 randomized patients aged 18 to 70 years with chronic tendinopathy 2 to 7 cm above the Achilles tendon insertion. The trial was conducted between August 28, 2008, and January 29, 2009, with follow-up until July 16, 2009. INTERVENTION Eccentric exercises (usual care) with either a PRP injection (PRP group) or saline injection (placebo group). Randomization was stratified by activity level. MAIN OUTCOME MEASURES The validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire, which evaluated pain score and activity level, was completed at baseline and 6, 12, and 24 weeks. The VISA-A score ranged from 0 to 100, with higher scores corresponding with less pain and increased activity. Treatment group effects were evaluated using general linear models on the basis of intention-to-treat. RESULTS After randomization into the PRP group (n = 27) or placebo group (n = 27), there was complete follow-up of all patients. The mean VISA-A score improved significantly after 24 weeks in the PRP group by 21.7 points (95% confidence interval [CI], 13.0-30.5) and in the placebo group by 20.5 points (95% CI, 11.6-29.4). The increase was not significantly different between both groups (adjusted between-group difference from baseline to 24 weeks, -0.9; 95% CI, -12.4 to 10.6). This CI did not include the predefined relevant difference of 12 points in favor of PRP treatment. CONCLUSION Among patients with chronic Achilles tendinopathy who were treated with eccentric exercises, a PRP injection compared with a saline injection did not result in greater improvement in pain and activity. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00761423.

Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis

Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2–24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis.

What Is the Clinical Course of Acute Ankle Sprains? A Systematic Literature Review

BACKGROUND Ankle sprains are one of the most common musculoskeletal injuries. In order to evaluate the effectiveness of therapeutic interventions and to guide management decisions, it is important to have clear insight of the course of recovery after an acute lateral ankle injury and to evaluate potential factors for nonrecovery and re-sprains. METHODS A database search was conducted in MEDLINE, CINAHL, PEDro, EMBASE, and the Cochrane Controlled trial register. Included were observational studies and controlled trials with adult subjects who suffered from an acute lateral ankle sprain that was conventionally treated. One of the following outcomes had to be described: pain, re-sprains, instability, or recovery. Two reviewers independently assessed the methodological quality of each included study. One reviewer extracted relevant data. RESULTS In total, 31 studies were included, from which 24 studies were of high quality. There was a rapid decrease in pain reporting within the first 2 weeks. Five percent to 33% of patients still experienced pain after 1 year, while 36% to 85% reported full recovery within a period of 3 years. The risk of re-sprains ranged from 3% to 34% of the patients, and re-sprain was registered in periods ranging from 2 weeks to 96 months postinjury. There was a wide variation in subjective instability, ranging from 0% to 33% in the high-quality studies and from 7% to 53% in the low-quality studies. One study described prognostic factors and indicated that training more than 3 times a week is a prognostic factor for residual symptoms. CONCLUSIONS After 1 year of follow-up, a high percentage of patients still experienced pain and subjective instability, while within a period of 3 years, as much as 34% of the patients reported at least 1 re-sprain. From 36% up to 85% of the patients reported full recovery within a period of 3 years.

The association between lumbar disc degeneration and low back pain: the influence of age, gender, and individual radiographic features.

Study Design. Cross-sectional open population based study (nested in a prospective cohort study). Objective. To explore the association of the different individual radiographic features, including osteophytes and disc space narrowing, with self-reported low back pain (LBP). Different definitions of lumbar disc degeneration with self-reported LBP and disability were considered in a large open population sample. Furthermore, in order to disentangle the discrepancies in reported strength of the associations, we characterized the frequency of the different individual radiographic features of lumbar disc degeneration and definitions of lumbar disc degeneration, as well as their association with LBP status, by age, gender, and vertebral level. Summary of Background Data. Currently within the literature, there have been no studies that have explored different definitions of lumbar disc degeneration and their association with LBP within one study sample. Methods. The intervertebral disc spaces (L1/2 to L5–S1) were evaluated for the presence and severity of anterior osteophytes and disc space narrowing using a semiquantitative score (grade 0–3). Logistic regression was used to determine the association between these individual radiographic features of lumbar disc degeneration and different definitions of lumbar disc degeneration for LBP. Results. Lumbar radiographs were scored for 1204 men, and 1615 women. Osteophytes were the most frequent radiographic feature observed, with men having the greatest frequency. Disc space narrowing was more frequent in women than men. Both radiographic features increased in frequency with age. Disc space narrowing appeared more strongly associated with LBP than osteophytes, especially in men (odds ratio [OR] = 1.9; 95% confidence interval [CI]: 1.4–2.8). Disc space narrowing at 2 or more levels appeared more strongly associated with LBP than disc space narrowing at only 1 level (OR = 2.4; 95% CI: 1.6–3.4). After excluding level L5–S1, the strength of almost all associations increased. Conclusion. We are the first to report different possible lumbar disc degeneration definitions and their associations with LBP. Disc space narrowing at 2 or more levels appeared more strongly associated with LBP than other radiographic features, especially after excluding level L5–S1.

One-Year Follow-up of Platelet-Rich Plasma Treatment in Chronic Achilles Tendinopathy A Double-Blind Randomized Placebo-Controlled Trial

Background Achilles tendinopathy is a common disease among both athletes and in the general population in which the use of platelet-rich plasma has recently been increasing. Good evidence for the use of this autologous product in tendinopathy is limited, and data on longer-term results are lacking. Purpose To study the effects of a platelet-rich plasma injection in patients with chronic midportion Achilles tendinopathy at 1-year follow-up. Study Design Randomized controlled trial; Level of evidence, 1. Methods Fifty-four patients, aged 18 to 70 years, with chronic tendinopathy 2 to 7 cm proximal to the Achilles tendon insertion were randomized to receive either a blinded injection containing platelet-rich plasma or saline (placebo group) in addition to an eccentric training program. The main outcome was the validated Victorian Institute of Sports Assessment–Achilles score. Patient satisfaction was recorded and ultrasound examination performed at baseline and follow-up. Results The mean Victorian Institute of Sports Assessment–Achilles score improved in both the platelet-rich plasma group and the placebo group after 1 year. There was no significant difference in increase between both groups (adjusted between-group difference, 5.5; 95% confidence interval, –4.9 to 15.8, P = .292). In both groups, 59% of the patients were satisfied with the received treatment. Ultrasonographic tendon structure improved significantly in both groups but was not significantly different between groups (adjusted between-group difference, 1.2%; 95% confidence interval, –4.1 to 6.6, P = .647). Conclusion This randomized controlled trial showed no clinical and ultrasonographic superiority of platelet-rich plasma injection over a placebo injection in chronic Achilles tendinopathy at 1 year combined with an eccentric training program.

Psychological factors affecting the outcome of total hip and knee arthroplasty: a systematic review.

OBJECTIVES Recently, numerous studies have reported that psychological factors can influence the outcome of total knee arthroplasty (TKA) and total hip arthroplasty (THA). However, a systematic overview is missing. The objective of this study was to examine which psychological factors influence the outcome of TKA and THA and to what extent. METHODS Data were obtained from the MEDLINE and EMBASE databases from inception to January 2011. Search terms included TKA and THA, outcome measures, and psychological aspects. Two reviewers independently selected the studies. Studies with a prospective before-after design with a minimum follow-up time of 6 weeks were included. One reviewer extracted the results and 2 reviewers independently conducted quality assessment. We distinguished between follow-up shorter and equal or longer than 1 year. RESULTS Thirty-five of 1837 studies met the inclusion criteria and were included in this systematic review. In follow-ups shorter than 1 year, and for knee patients only, strong evidence was found that patients with pain catastrophizing reported more pain postoperatively. Furthermore, strong evidence was found that preoperative depression had no influence on postoperative functioning. In long-term follow-up, 1 year after TKA, strong evidence was found that lower preoperative mental health (measures with the SF-12 or SF-36) was associated with lower scores on function and pain. For THA, only limited, conflicting, or no evidence was found. CONCLUSIONS Low preoperative mental health and pain catastrophizing have an influence on outcome after TKA. With regard to the influence of other psychological factors and for hip patients, only limited, conflicting, or no evidence was found.

Cam impingement causes osteoarthritis of the hip: a nationwide prospective cohort study (CHECK)

Objective To determine the association between cam impingement, which is hip incongruity by a non-spherical femoral head and development of osteoarthritis. Methods A nationwide prospective cohort study of 1002 early symptomatic osteoarthritis patients (CHECK), of which standardised anteroposterior pelvic radiographs were obtained at baseline and at 2 and 5 years follow-up. Asphericity of the femoral head was measured by the α angle. Clinically, decreased internal hip rotation (≤20°) is suggestive of cam impingement. The strength of association between those parameters at baseline and development of incident osteoarthritis (K&L grade  2) or end-stage osteoarthritis (K&L grades 3, 4, or total hip replacement) within 5 years was expressed in OR using generalised estimating equations. Results At baseline, 76% of the included hips had no radiographic signs of osteoarthritis and 24% doubtful osteoarthritis. Within 5 years, 2.76% developed end-stage osteoarthritis. A moderate (α angle >60°) and severe (α angle >83°) cam-type deformity resulted in adjusted OR of 3.67 (95% CI 1.68 to 8.01) and 9.66 (95% CI 4.72 to 19.78), respectively, for end-stage osteoarthritis. The combination of severe cam-type deformity and decreased internal rotation at baseline resulted in an even more pronounced adjusted OR, and in a positive predictive value of 52.6% for end-stage osteoarthritis. For incident osteoarthritis, only a moderate cam-type deformity was predictive OR=2.42 (95% CI 1.15 to 5.06). Conclusions Individuals with both severe cam-type deformity and reduced internal rotation are strongly predisposed to fast progression to end-stage osteoarthritis. As cam impingement might be a modifiable risk factor, early recognition of this condition is important.

Mind the MIC: large variation among populations and methods

OBJECTIVE There is no consensus on the best method to determine the minimal important change (MIC) of patient-reported outcomes. Recent publications recommend the use of multiple methods. Our aim was to assess whether different methods lead to consistent values for the MIC. STUDY DESIGN AND SETTING We used two commonly used anchor-based methods and three commonly used distribution-based methods to determine the MIC of the subscales: pain and physical functioning of the Western Ontario and McMaster University Osteoarthritis Index questionnaire in five different studies involving patients with hip or knee complaints. We repeated the anchor-based methods using relative change scores, to adjust for baseline scores. RESULTS We found large variation in MIC values by the same method across studies and across different methods within studies. We consider it unlikely that this variation can be explained by differences between disease groups, disease severity, or lengths of follow-up. The variation persisted when using relative change scores. It was not possible to conclude whether this variation is because of true differences in MIC values between populations or to conceptual and methodological problems of the MIC methods. CONCLUSION To better disentangle these two possible explanations, the MIC methodology should be improved and standardized. In the meantime, caution is needed when interpreting and using published MIC values.

Phenotypic spectrum of the SMAD3-related aneurysms–osteoarthritis syndrome

Background Aneurysms–osteoarthritis syndrome (AOS) is a new autosomal dominant syndromic form of thoracic aortic aneurysms and dissections characterised by the presence of arterial aneurysms and tortuosity, mild craniofacial, skeletal and cutaneous anomalies, and early-onset osteoarthritis. AOS is caused by mutations in the SMAD3 gene. Methods A cohort of 393 patients with aneurysms without mutation in FBN1, TGFBR1 and TGFBR2 was screened for mutations in SMAD3. The patients originated from The Netherlands, Belgium, Switzerland and USA. The clinical phenotype in a total of 45 patients from eight different AOS families with eight different SMAD3 mutations is described. In all patients with a SMAD3 mutation, clinical records were reviewed and extensive genetic, cardiovascular and orthopaedic examinations were performed. Results Five novel SMAD3 mutations (one nonsense, two missense and two frame-shift mutations) were identified in five new AOS families. A follow-up description of the three families with a SMAD3 mutation previously described by the authors was included. In the majority of patients, early-onset joint abnormalities, including osteoarthritis and osteochondritis dissecans, were the initial symptom for which medical advice was sought. Cardiovascular abnormalities were present in almost 90% of patients, and involved mainly aortic aneurysms and dissections. Aneurysms and tortuosity were found in the aorta and other arteries throughout the body, including intracranial arteries. Of the patients who first presented with joint abnormalities, 20% died suddenly from aortic dissection. The presence of mild craniofacial abnormalities including hypertelorism and abnormal uvula may aid the recognition of this syndrome. Conclusion The authors provide further insight into the phenotype of AOS with SMAD3 mutations, and present recommendations for a clinical work-up.