Assessing the Reliability of a Semiautomated Segmentation Algorithm for Quantifying Erosions in the Metacarpophalangeal Joints of Patients with Rheumatoid Arthritis.

OBJECTIVE: Assess the reliability of early erosions in rheumatoid arthritis (EERA) software for quantifying erosive damage to the metacarpophalangeal joints of patients with rheumatoid arthritis (RA). METHODS: One hundred magnetic resonance image sets from 68 patients with early referral RA were evaluated. Reliability was assessed using 95% limits of agreement and intraclass correlation coefficient (ICC) with 95% CI. RESULTS: Limits of agreement linearly depended on erosion volume: 0.44× between readers and 0.19× within readers. Interrater ICC was 0.976 (95% CI 0.965-0.984) and intrarater ICC was 0.996 (95% CI 0.994-0.997). CONCLUSION: EERA is highly reproducible for quantifying erosions in patients with early RA.

A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled trial.

BACKGROUND: Permanent joint damage is a major consequence of rheumatoid arthritis (RA), the most common and destructive form of inflammatory arthritis. In aggressive disease, joint damage can occur within 6 months from symptom onset. Early, intensive treatment with conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) can delay the onset and progression of joint damage. The primary objective of the study is to investigate the value of magnetic resonance imaging (MRI) or radiography (X-ray) over standard of care as tools to guide DMARD treatment decision-making by rheumatologists for the care of RA. METHODS: A double-blind, randomized controlled trial has been designed. Rheumatoid and undifferentiated inflammatory arthritis patients will undergo an MRI and X-ray assessment every 6 months. Baseline adaptive randomization will be used to allocate participants to MRI, X-ray, or sham-intervention groups on a background of standard of care. Prognostic markers, treating physician, and baseline DMARD therapy will be used as intervention allocation parameters. The outcome measures in rheumatology RA MRI score and the van der Heijde-modified Sharp score will be used to evaluate the MRI and X-ray images, respectively. Radiologists will score anonymized images for all patients regardless of intervention allocation. Disease progression will be determined based on the study-specific, inter-rater smallest detectable difference. Allocation-dependent, intervention-concealed reports of positive or negative disease progression will be reported to the treating rheumatologist. Negative reports will be delivered for the sham-intervention group. Study-based radiology clinical reports will be provided to the treating rheumatologists for extra-study X-ray requisitions to limit patient radiation exposure as part of diagnostic imaging standard of care. DMARD treatment dose escalation and therapy changes will be measured to evaluate the primary objective. A sample size of 186 (62 per group) patients will be required to determine a 36% difference in pharmacological treatment escalation between the three groups with intermediate dispersion of data with 90% power at a 5% level of significance. DISCUSSION: This study will determine if monitoring RA and undifferentiated inflammatory arthritis patients using MRI and X-ray every 6 months over 2 years provides incremental evidence over standard of care to influence pharmacotherapeutic decision-making and ultimately hinder disease progression. TRIAL REGISTRATION: This trial has been registered at ClinicalTrials.gov: NCT00808496 (registered on 12 December 2008).

Marathon-related cardiac arrest.

OBJECTIVE: To investigate the incidence and assess the outcomes of cardiac arrest occurring in the context of participation in marathon or half-marathon races. DESIGN: Incidence study. SETTING: Data came from long-distance race records in the United States from January 1, 2001, to May 31, 2010. PARTICIPANTS: All participants were registered entrants in the long-distance races. Participation statistics (sex, participant identity numbers, and race distance) were publicly accessible from Running USA. ASSESSMENT OF RISK FACTORS: Data on possible risk factors for cases were obtained retrospectively through computer searches (age, sex, location of cardiac arrest, publicly released cause of death). Three attempts were made to obtain information from survivors or from the next-of-kin of deceased cases. This information included demographic characteristics, exercise and running history, and personal and family medical history. MAIN OUTCOME MEASURES: The main outcome measures were the incidence and characteristics of cases of cardiac arrest that occurred during the race, at the finish-line, or ≤ 1 hour after completion of a marathon or half marathon. Cardiac arrests were defined by a medical professional as an unconscious state and an absence of spontaneous respirations and pulse. Successful resuscitation and discharge from hospital defined a survivor, whereas a nonsurvivor was a person who was not successfully resuscitated in the field or who died before hospital discharge. Cases of cardiac arrest had to be independently identified in 3 separate sources of data or confirmed with official race medical staff. Further information, including details of the cardiac arrest, was obtained from medical records and autopsies and the survivors or next of kin. MAIN RESULTS: Among 10.9 million registered race participants there were 40 cardiac arrests in marathons and 19 in half marathons (overall incidence, 0.54 per 100,000; 95% confidence interval [CI], 0.41-0.70). The mean age of runners with cardiac arrest was 42 (SD 13) years and 86% were men. The incidence per 100,000 was higher in marathons (1.01; 95% CI, 0.72-1.38) than in half marathons (0.27; 95% CI, 0.17-0.43; and among men (0.90; 95% CI, 0.67-1.18) than among women (0.16; 95% CI, 0.07-0.31). More runners died than survived the cardiac arrest (42 [71%] vs 17[29%]); the incidence of sudden death was 0.39 per 100,000 participants (95% CI, 0.28-0.52). The mean age of the nonsurvivors was younger than that of the survivors (39 vs 49 years; P = 0.002). Complete clinical information on cause of death was available for 23 runners. The most common confirmed or possible cause of death was hypertrophic cardiomyopathy (15 cases, of whom 9 had an additional clinical factor). Among the 8 survivors with complete information, ischemic heart disease was the cause of cardiac arrest in 5. The survivors were older than nonsurvivors (53 vs 40 years), had completed more long-distance races, and were more likely to have known cardiac risk factors. The strongest predictors of survival were initiation of cardiopulmonary resuscitation by bystanders (P = 0.01) and an underlying diagnosis other than hypertrophic cardiomyopathy (P = 0.01) CONCLUSIONS:: The incidence of cardiac arrest and sudden death per 100,000 runner hours was 0.2 and 0.14. Risk factors for cardiac arrest were full marathon and male sex. Younger age and no previous knowledge of cardiovascular risk were associated with sudden death.

Corticosteroid and other injections in the management of tendinopathies: a review.

OBJECTIVE: To determine the efficacy and risk of adverse effects of peritendinous corticosteroid and other injections in the management of tendinopathy. DATA SOURCES: In March 2010, using terms describing common tendinopathies and injections, including steroids, local anesthetics, sclerosing solutions, aprotinin, platelet-rich plasma, botulinum toxins, and glycosaminoglycans, 8 databases were searched without language, publication, or date restrictions. Reference lists were scanned for additional articles. STUDY SELECTION: Criteria for inclusion were randomized controlled trials that compared ≥1 peritendinous injection with placebo or other nonsurgical intervention. Study methods were independently assessed by 2 reviewers (reliability, κ = 0.85) on a modified PEDro scale, and scores were required to be ≥50% for inclusion. Studies with a high proportion of patients with adhesive capsulitis, full-thickness rotator cuff tears, or rheumatologic disease were excluded. Of 2954 studies screened, 174 full-text articles were evaluated for inclusion by 1 investigator and confirmed by a second. Of 64 studies that were initially included, the 41 that scored >50% on the PEDro scale were retained. DATA EXTRACTION: Information about injection type and comparison treatments, site of the tendinopathy, duration of follow-up (short term, <12 weeks; long term, ≥52 weeks), outcomes (pain, function, and patient-rated overall improvement), and frequency of adverse events was extracted. Study results were pooled when the data were sufficiently homogeneous. MAIN RESULTS: Clinically diagnosed lateral epicondylalgia: In 3 trials that compared corticosteroid injections with no intervention, corticosteroid injections were effective in the short term in pain reduction [standard mean difference (SMD), 1.44; 95% confidence interval (CI), 1.17-1.71], in improving function (SMD, 1.50; 95% CI, 1.22-1.77), and in overall improvement [relative risk (RR), 3.47; 95% CI, 2.11-5.69]. In the intermediate and long term, corticosteroid injections were less effective than no intervention. In comparison with placebo injection (4 studies), there was limited evidence for the effectiveness of corticosteroid injection in relieving pain. In comparison with physiotherapy (4 studies), corticosteroid injection was more effective in the short term for improving function (SMD, 1.29; 95% CI, 1.03-1.55) and in overall improvement (RR, 2.37; 95% CI, 1.75-3.21), and there was strong evidence among heterogeneous studies for reducing pain. Intermediate and long-term results were worse in pain and function for the corticosteroid injection intervention. Corticosteroid injections were more effective than orthotic devices for the wrist or elbow for overall improvement in the short term but not in the long term (2 studies). Effectiveness did not differ in comparisons of high- versus low-corticosteroid dosage, and between triamcinolone and hydrocortisone. Pain and function improved more with corticosteroid than with platelet-rich plasma injection in the short term but were worse in the long term. Rotator cuff tendinopathy: In the short term, corticosteroid injection improved pain (SMD, 0.68; 95% CI, 0.35-1.01) and function (SMD, 0.62; 95% CI, 0.29-0.95) more than placebo (3 studies). In comparisons with nonsteroidal anti-inflammatory drugs (NSAIDs) and with NSAIDs plus placebo injection, no differences in pain or function were found (3 studies) or when NSAIDs were administered in addition to corticosteroid and placebo injections (4 studies). Corticosteroid injection and physiotherapy did not differ in effectiveness (2 studies), although 1 study found short-term greater overall improvement and function after corticosteroid injection. Adverse effects were reported in 82% of corticosteroid injection trials. In comparison with placebo injections, corticosteroid injections were associated with an increased risk of atrophy for Achilles and patellar tendons but not elbow tendons. In trials of injections of sclerosant, platelet-rich plasma, proteinase, glycosaminoglycan polysulfate, sodium hyaluronate, prolotherapy, and botulinum toxin compared with placebo injection or other therapies, only sodium hyaluronate compared with placebo showed consistently better results in the short and long term in overall improvement and pain reduction of lateral epicondylalgia (1 study). Adverse effects were reported for all these injections except sclerosant and platelet-rich plasma. CONCLUSIONS: Corticosteroid injection is beneficial in the short term for the treatment of tendinopathies but may be worse than other treatments in the intermediate and long terms. No clear evidence of benefit of other injections was shown, except for sodium hyaluronate in the short and long term.

Supervised exercise versus usual care for patellofemoral pain syndrome.

OBJECTIVE: To compare the effectiveness of supervised exercise therapy with usual care on self-reported recovery, pain, and function in persons with patellofemoral pain syndrome. DESIGN: Randomized, controlled, unblinded, multicenter trial of 3 month's duration. Sample size was calculated with 80% power to show a minimum clinically important difference of 22% in recovery after 1 year, at P or=18y). SETTING: Sport and general medicine practices in the Netherlands. PARTICIPANTS: Inclusion criteria were: age, 14 to 40 years; presence of symptoms for between 2 months and 2 years; >or=3 of: pain when ascending or descending stairs, squatting, running, cycling, or sitting with flexed knees; grinding of the patella; and a positive clinical patellar test. Exclusion criteria were knee osteoarthritis, patellar tendinopathy, or other pathological conditions of the knee, previous knee injuries or surgery or treatment with supervised exercise. Patients were recruited by general practitioners or sport physicians (n randomized = 131; mean age, 24y; 70% 18y or older; 64% women; bilateral knee symptoms, 60%; participation in sport, 76%). INTERVENTION: The standardized 25-minute exercise protocol was tailored to individual achievement and supervised by a physical therapist. It comprised warm-up, followed by static and dynamic exercises for the quadriceps, adductor, and gluteal muscles, and included balance and thigh-muscle flexibility components. The load was increased progressively by increasing repetitions or intensity of the exercises. Patients attended 9 sessions, and were asked to practice the exercises daily for 3 months. The intervention and control patients received a pamphlet from their physicians about patellofemoral pain syndrome, advice to refrain from sports activities that provoked pain, and instructions for daily isometric quadriceps contractions. Analgesics were recommended for severe pain. Additional interventions, other than referrals to a physical therapist, were permitted. MAIN OUTCOME MEASURES: Patients reported the primary outcomes at 3 and 12 months on questionnaires. End points included perceived recovery since baseline (7-point scale from "completely recovered" to "worse than ever"), functional disability measured on the Kujala Patellofemoral Scale (0 = complete disability to 100 = fully functional) and pain severity at rest and on activity (0 = no pain to 10 = unbearable pain). Recovery was defined as "fully recovered" or "strongly recovered". Approximately 90% of patients were followed for 12 months. MAIN RESULTS: After 3 months, in intention-to-treat analysis, the groups did not differ in proportions recovered; however, when the category "slightly recovered" was included, a greater proportion of the exercise group had improved (81% vs 53%; adjusted odds ratio, 4.07; 95% confidence interval [CI], 1.86 to 8.90). After 12 months, recovery did not differ for the intervention and control groups. Pain scores decreased progressively for both groups, but more for the exercise group than the control group (adjusted difference [AD] at 3 mo for pain at rest, -1.07; 95% CI, -1.92 to -0.22 and at 12 mo, -1.29; 95% CI, -2.16 to -0.42; and at 3 mo for pain on activity, -1.00; 95% CI, -1.91 to -0.08 and at 12 mo, -1.19; 95% CI, -2.22 to -0.16). Function scores also improved for both groups. At 3 months the increase in function score was greater for the exercise group (AD, 4.92; 95% CI, 0.14 to 9.72) but by 12 months the difference was no longer significant. CONCLUSIONS: Supervised exercise therapy improved patients' pain at rest and during activity, and self-reported function improved faster than with no supervised intervention. The patients' perception of recovery from patellofemoral pain syndrome was not greater among the supervised exercise group.

The relationship between exercise and osteoarthritis in the elderly.

OBJECTIVES: To review within a prescribed evidence-based framework (1) the relationship between intermittent or lifelong physical activity and the subsequent onset or progression of osteoarthritis (OA) in later life and (2) the effect of structured exercise routines on the management of OA in the elderly. DATA SOURCES: A systematic literature search of MEDLINE (1950 to April Week 2, 2008) and EMBASE (1980 to 2008 Week 16) was carried out using the Ovid interface. Relevant mapped terms addressing the identified objectives were combined and exploded according to a defined protocol. STUDY SELECTION: Studies that met relevancy criteria and were of high methodologic quality (prospective cohort studies for the risk factor component and systematic reviews and randomized controlled trials for the therapy component) were extracted and then hand searched for any additional studies. Final inclusion was based on agreement between two independent assessors, according to prescribed criteria. Any studies that were not in the English language, did not address the questions of interest in humans, or did not include a population that had at least a mean age of 55 years at the time of study termination, were excluded. Only land-based regimens were included in the therapy component of the review. DATA EXTRACTION: Pertinent information on subjects, risks, and outcomes (when assessing physical activity as a risk factor for OA in the elderly) and subjects, interventions, and outcomes (when evaluating the application of exercise in the management of OA in older persons) was extracted from the selected studies. DATA SYNTHESIS: Ten studies met entry criteria for examining the relationship between physical activity and the development or progression of OA. Likely because of study variations and differences in the nature, duration and intensities of exercise regimens, no clearcut consensus was apparent on whether or not physical activity was a risk factor for OA. Six scientific reviews and ten single blinded randomized controlled trials were included when evaluating the effect of exercise on OA management. Regardless of wide variability in the included studies, a majority demonstrated that structured exercise programs were effective in the management of older subjects with OA. CONCLUSIONS: : Nuances of study design, differences in age and type of target populations, variability in the intensity, duration, and nature of physical activity in the respective studies, and lack of standardization in the way radiographic data are interpreted are among the factors that prevent consensus regarding the effect of physical activity on later development of OA. Similarly, there is considerable heterogeneity in the studies that assessed exercise in the treatment of OA. Nonetheless, there is substantive evidence in support of the benefits of one or another strength training or aerobic exercise regimen in the management of OA in middle-aged and elderly subjects.

Is regular exercise a friend or foe of the aging immune system? A systematic review.

OBJECTIVE: The purpose of the current review is to synthesize the available evidence from prospective clinical trials that are relevant to the clinical question: "What, if any, are the effects of regular aerobic and/or resistance exercise on the immune system in healthy older adults?" DATA SOURCES: Electronic databases were searched, using terms pertaining to immunology, exercise, and aging. Using the Ovid interface, the following databases were explored: Allied and Complimentary Medicine (AMED) (1985 to 2008), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 2008), all EBM Reviews (Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED), EMBASE (1980 to 2008), and MEDLINE (1950 to 2008). The MEDLINE database was searched a second time through the PubMed interface. STUDY SELECTION: Prospective controlled clinical trials were selected for review if they investigated the effects of an exercise intervention (minimum 4 weeks in duration) on an immune outcome measure in an older but otherwise healthy population. A total of 19 articles representing 17 trials were identified. DATA EXTRACTION: Quality assessment of the relevant articles was performed using the Jadad et al criteria. Data extraction was performed using a standardized instrument. Data regarding the participants, interventions, and laboratory and clinical immunologic outcomes were synthesized. DATA SYNTHESIS: Available data provide no clear evidence of acute or chronic effects of exercise on lymphocyte or natural killer (NK) cell numbers or phenotype (ie, surface markers)/activity, with 2 exceptions: (1) strength or endurance exercise may cause an acute transient elevation in circulating CD8+ T cells, and (2) regular aerobic exercise appears to enhance immunologic memory in the context of vaccination. The effects of strength training on NK cell activity are unclear. Furthermore, regular aerobic exercise appears to be associated with a reduction in chronic inflammation. Finally, no prospective controlled trials have clearly documented clinical immunologic benefits of regular exercise, which may well relate to underpowering of these studies. CONCLUSIONS: Overall, in healthy older adults, regular, particularly aerobic, exercise appears to be a friend of the immune system, helping to offset diminished adaptive responses and chronic inflammation. The possibility exists that particularly strenuous exercise may cause acute immunologic changes, such as diminished NK cell activity, which could predispose to infection in certain individuals. However, given the possible benefits of regular exercise on the immune system and the many definite benefits on other systems, the evidence presented here should not dissuade practitioners from suggesting regular exercise to otherwise healthy older adults.