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).

A review of the sapporo and revised Sapporo criteria for the classification of antiphospholipid syndrome. Where do the revised sapporo criteria add value?

OBJECTIVE: The preliminary classification criteria for antiphospholipid syndrome (APS), or the Sapporo criteria, are widely used for the inclusion of patients with APS into clinical studies. Revised Sapporo criteria have been proposed as an improved criteria set. Whether these criteria sets fulfill the current standards of measurement science are unknown. The purpose of this study was (1) to evaluate the developmental methodology and measurement properties of the Sapporo and the revised Sapporo criteria for use in clinical trials; and (2) to evaluate if the revised Sapporo criteria provide added value over the Sapporo criteria. METHODS: A computer search for articles describing use of the Sapporo and the revised Sapporo criteria was performed. Item generation, item reduction, sensibility, validity, and reliability of the criteria were evaluated. RESULTS: The Sapporo criteria set has incremental face and content validity over its predecessors. However, through separation of anti-ss2-glycoprotein I antibodies as a sub-item, the specification of a wider time interval between serologic testing, the specification of a time interval between serology and clinical manifestations, and specification of definitions for clinical manifestations and laboratory titer thresholds, the revised Sapporo criteria set has incremental face and content validity over the Sapporo criteria. The complexity of the criteria, diagnostic tests, and immunologic tests limits their feasibility. The reliability of each criterion is unknown. The discriminative capacity of the Sapporo criteria is good, with sensitivity, specificity, and positive and negative predictive values of 0.71, 0.98, 0.95, and 0.88, respectively, compared to patients with systemic lupus erythematosus. The discriminative capacity of the revised Sapporo criteria is unknown. CONCLUSION: The revised Sapporo criteria set has incremental face and content validity compared its predecessors. Reliability testing of each criterion is needed before these criteria can be confidently used in multicenter APS trials. Discriminatory testing of the revised Sapporo criteria is required.

Tolerability of different dosing regimens of bisphosphonates for the treatment of osteoporosis and malignant bone disease.

Bisphosphonates are the primary pharmacological agents used for the management of osteoporosis and hypercalcaemia of malignant bone disease. The efficacy of these agents in these two conditions has been demonstrated in many well designed trials published over the past 2 decades. The variety of bisphosphonates currently available to us provides a wide range of tolerability and dosing profiles thus necessitating a thorough comparison of the most recent oral and intravenous bisphosphonates to differentiate the clinical context in which they should be used. Despite the fact that bisphosphonates are generally well accepted, their tolerability is dependent on complications which encompass gastrointestinal (GI) and renal toxicity. Other adverse events include osteonecrosis of the jaw, arthralgias, flu-like symptoms and uveitis. Studies have shown that various dosing regimens are able to modulate these rates of toxicity. To maximise tolerability, the direction of future therapy will likely fall into a pattern of decreasing the frequency of administration of bisphosphonates, whether it is oral or intravenous formulations, thus improving patient adherence. To review the literature on different dosing regimens of various bisphosphonates and their associated tolerability, we searched MEDLINE for articles from 1975 to 2006. Oral bisphosphonates, in particular alendronate and risedronate, have been systematically evaluated with regards to GI toxicity. Overall tolerability with these oral formulations has found GI toxicity to be the primary adverse event of interest. Both alendronate and risedronate have been found to have similar rates of GI toxicity when compared with placebo. Mounting evidence has developed validating the use of intravenous ibandronate and zoledronic acid for the purpose of treating hypercalcaemia secondary to malignancy. Unique to all other bisphosphonates, ibandronate also has an oral form which has a similar GI-toxicity profile to placebo. In addition, no significant differences in renal toxicity have been observed between those receiving intravenous ibandronate compared with placebo. Because of its potency and mode of administration, zoledronic acid has been widely accepted for the treatment of hypercalcaemia secondary to malignancy. However, a decrease in renal function, albeit rare, remains a significant complication of zoledronic acid; therefore, regular renal monitoring is recommended.