Management of giant-cell arteritis in Switzerland: an online national survey.

AIMS OF THE STUDY: To assess current practices in diagnosing, treating, and following-up giant-cell arteritis by specialists in Switzerland and to identify the main barriers to using diagnostic tools. METHODS: We performed a national survey of specialists potentially caring for patients with giant-cell arteritis. The survey was sent by email to all members of the Swiss Societies of Rheumatology and for Allergy and Immunology. A reminder was sent to nonresponders after 4 and 12 weeks. Its questions covered the following dimensions: respondents' main characteristics, diagnosis, treatment, and imaging's role during follow-up. The main study results were summarized using descriptive statistics. RESULTS: Ninety-one specialists, primarily aged 46-65 years (n = 53/89; 59%), working in academic or nonacademic hospitals or private practice, and treating a median of 7.5 (interquartile range [IQR]: 3-12) patients with giant-cell arteritis per year participated in this survey. Ultrasound of temporal arteries/large vessels (n = 75/90; 83%) and positron-emission-tomography-computed tomography (n = 52/91; 57%) or magnetic resonance imaging (n = 46/90; 51%) of the aorta/extracranial arteries were the most common techniques used to diagnose giant-cell arteritis with cranial or large vessel involvement, respectively. Most participants reported a short time to obtain imaging tests or arterial biopsy. The glucocorticoid tapering scheme, glucocorticoid-sparing agent, and glucocorticoid-sparing treatment duration varied among the participants. Most physicians did not follow a predefined repeat imaging scheme for follow-up and mainly relied on structural changes (vascular thickening, stenosis, or dilatation) to drive treatment choice. CONCLUSIONS: This survey indicates that imaging and temporal biopsy are rapidly accessible for diagnosing giant-cell arteritis in Switzerland but highlights heterogeneous practice in many disease management areas.

High-Resolution 3D versus Standard-Resolution 2D T2-Weighted Turbo Spin Echo MRI for the Assessment of Lumbar Nerve Root Compromise.

Radiculopathy can be caused by nerve root irritation and nerve root compression at the level of the lateral recess or at the level of the intervertebral foramen. T2-weighted (T2w) MRI is considered essential to evaluate the nerve root and its course, starting at the lateral recess through the intervertebral foramen to the extraforaminal space. With the introduction of novel MRI acceleration techniques such as compressed SENSE, standard-resolution 2D T2w turbo spin echo (TSE) sequences with a slice-thickness of 3-4 mm can be replaced with high-resolution isotropic 3D T2w TSE sequences with sub-millimeter resolution without prolonging scan time. With high-resolution 3D MRI, the course of the nerve root can be visualized more precisely due to a detailed depiction of the anatomical situation and less partial volume effects, potentially allowing for a better detection of nerve root compromise. In this intra-individual comparison study, 55 patients with symptomatic unilateral singular nerve root radiculopathy underwent MRI with both 2D standard- and 3D high-resolution T2w TSE MRI sequences. Two readers graded the degree of lumbar lateral recess stenosis and lumbar foraminal stenosis twice on both image sets using previously validated grading systems in an effort to quantify the inter-readout and inter-sequence agreement of scores. Inter-readout agreement was high for both grading systems and for 2D and 3D imaging (Kappa = 0.823-0.945). Inter-sequence agreement was moderate for both lumbar lateral recess stenosis (Kappa = 0.55-0.577) and lumbar foraminal stenosis (Kappa = 0.543-0.572). The percentage of high degree stenosis with nerve root deformity increased from 16.4%/9.8% to 41.8-43.6%/34.1% from 2D to 3D images for lateral recess stenosis/foraminal stenosis, respectively. Therefore, we show that while inter-readout agreement of grading systems is high for both standard- and high-resolution imaging, the latter outperforms standard-resolution imaging for the visualization of lumbar nerve root compromise.

Current practice of transitional care for adolescents and young adults in Swiss paediatric and adult rheumatology centres.

BACKGROUND: About half of all children with rheumatic diseases need continuous medical care during adolescence and adulthood. A good transition into adult rheumatology is essential. Guidelines for a structured transition process have therefore been recommended by the European League Against Rheumatism (EULAR) and the Paediatric Rheumatology European Society (PReS). However, implementation of these guidelines requires resources often not available in a busy clinical practice. AIMS: To assess the current practice of transitional care in Switzerland in relation to EULAR/PReS recommendations and to describe gaps and challenges in following the recommendations. METHODS: All paediatric Swiss rheumatology centres and their collaborating adult centres offering a transition service to adult care were invited to participate in this survey. The responsible paediatric and adult rheumatologist of each centre was interviewed separately using a structured manual addressing the EULAR/PReS transitional care recommendations. RESULTS: All 10 paediatric and 9 out of 10 adult rheumatologists agreed to participate. Centres varied in the number of patients in transition, from n = 0 to n = 111. The following EULAR/PReS recommendations were implemented and applied in most centres: continuity in the healthcare team, consultations focused on adolescents and young adults, joint consultations between the paediatric and adult rheumatologist, and access to the EULAR website. Only rarely did a centre have a written transition policy or evaluate their transitional care programme. The vast majority of the interviewees had no specific training in adolescent health. Most centres rated their transitional care performance as very good. CONCLUSION: Transition in Switzerland is not uniform and consequently the implementation of the EULAR/PReS recommendations is variable in Swiss rheumatology centres. Skills of healthcare professionals, continuity between clinical settings, size of the centres, and hospital focus on the needs of adolescents and young adults may represent key predictors of successful transitional care for patients with chronic rheumatic diseases. Future studies should examine these variables.

Influence of weekday of admission and level of distress on length of hospital stay in patients with low back pain: a retrospective cohort study.

BACKGROUND: Low back pain (LBP) is often a complex problem requiring interdisciplinary management to address patients' multidimensional needs. Providing inpatient care for patients with LBP in primary care hospitals is a challenge. In this setting, interdisciplinary LBP management is often unavailable during weekends. Delays in therapeutic procedures may result in a prolonged length of hospital stay (LoS). The impact of delays on LoS might be strongest in patients reporting high levels of psychological distress. Therefore, this study investigates the influence of weekday of admission and distress on LoS of inpatients with LBP. METHODS: This retrospective cohort study was conducted between 1 February 2019 and 31 January 2020. In part 1, a negative binomial model was fitted to LoS with weekday of admission as a predictor. In part 2, the same model included weekday of admission, distress level, and their interaction as covariates. Planned contrast was used in part 1 to estimate the difference in log-expected LoS between group 1 (admissions Friday/Saturday) and the reference group (admissions Sunday-Thursday). In part 2, the same contrast was used to estimate the corresponding difference in (per-unit) distress trends. RESULTS: We identified 173 patients with LBP. The mean LoS was 7.8 days (SD = 5.59). Patients admitted on Friday (mean LoS = 10.3) and Saturday (LoS = 10.6) had longer stays, but not those admitted on Sunday (LoS = 7.1). Analysis of the weekday effect and planned contrast showed that admission on Friday or Saturday was associated with a significant increase in LoS (log ratio = 0.42, 95% CI = 0.21 to 0.63). A total of 101 patients (58%) returned questionnaires, and complete data on distress were available from 86 patients (49%). According to the negative binomial model for LoS and the planned contrast, the distress effect on LoS was significantly influenced (difference in slopes = 0.816, 95% CI = 0.03 to 1.60) by dichotomic weekdays of admission (Friday/Saturday vs. Sunday-Thursday). CONCLUSIONS: Delays in interdisciplinary LBP management over the weekend may prolong LoS. This may particularly affect patients reporting high levels of distress. Our study provides a platform to further explore whether interdisciplinary LBP management addressing patients' multidimensional needs reduces LoS in primary care hospitals.

Circulating collagen neo-epitopes and their role in the prediction of fibrosis in patients with systemic sclerosis: a multicentre cohort study.

BACKGROUND: Extracellular matrix remodelling is a hallmark of systemic sclerosis. We evaluated extracellular matrix neo-epitopes as potential serum biomarkers for progression of fibrosis in systemic sclerosis. METHODS: We included patients meeting the 2013 American College of Rheumatology and European League Against Rheumatism criteria and healthy controls from a derivation and validation cohort. The primary outcome was progression of fibrosis at follow-up, defined as decline in percentage of predicted forced vital capacity of 10% or more in patients with interstitial lung disease or increase in modified Rodnan skin score of 25% or more and more than 5 points at a 1-year follow-up visit. Longitudinal assessment and biobanking followed European Scleroderma Trials and Research standards. Extracellular matrix-degradation (BGM, C3M, C4M, and C6M) and extracellular matrix-formation neo-epitopes (PRO-C1, PRO-C3, PRO-C4, PRO-C5, and PRO-C6) were measured in serum using validated ELISAs. FINDINGS: Between Aug 18, 2011, and Jan 19, 2015, 149 patients with systemic sclerosis (27 [18%] progressors and 122 [82%] non-progressors) and 29 healthy controls were included in the derivation cohort. Concentrations of type III and IV collagen neo-epitopes were higher in patients with systemic sclerosis compared with healthy controls and were significantly associated with systemic sclerosis in univariable logistic regression. Concentrations of degradation neo-epitopes of type III and IV collagens and their turnover ratios distinguished between progressors and non-progressors (C3M area under the curve 0·77 [95% CI 0·67-0·86], p<0·0001; PRO-C3:C3M 0·70 [0·59-0·80], p=0·0013; C4M 0·73 [0·63-0·82], p<0·0001; PRO-C4:C4M 0·75 [0·64-0·86], p<0·0001). 384 patients with systemic sclerosis (73 [19%] progressors) and 60 healthy controls were included in the multicentre validation cohort between April 17, 2003, and Jan 24, 2017. Analysis of the validation cohort confirmed that neo-epitopes of type III and IV collagens are changed in progressors. In a pooled analysis of both cohorts, the serum concentrations of formation neo-epitopes PRO-C3 and PRO-C4 and the turnover ratio of type IV collagen (PRO-C4:C4M) were higher in skin progressors. The turnover ratio of type IV collagen and PRO-C3 significantly predicted skin progression in a multivariable model adjusted for modified Rodnan skin score, sex, and age. INTERPRETATION: These data suggest that neo-epitopes of type III and IV collagens are promising biomarkers for the assessment and prediction of extracellular matrix remodelling in systemic sclerosis. They could be used in clinical practice to risk stratify patients at risk of progression of fibrosis. FUNDING: None.

RheumaTool, a novel clinical decision support system for the diagnosis of rheumatic diseases, and its first validation in a retrospective chart analysis.

AIMS: RheumaTool is a clinical decision support system designed to support the diagnostic process in rheumatology by presenting a differential diagnosis list after the input of clinical information. The objective of this study was to evaluate the performance of RheumaTool in detecting the correct diagnosis in referrals to a rheumatology clinic. METHODS: In this retrospective chart analysis, data were gathered from patients with musculoskeletal complaints and an uncertain diagnosis who were referred to a Swiss tertiary rheumatology outpatient clinic. Data were entered into RheumaTool in a standardised fashion, while the principal diagnoses in the medical reports were blinded. RheumaTool’s output was compared to the correct diagnoses, established either by widely accepted diagnostic criteria or through the expert consensus of independent rheumatologists. Diagnostic precision, the primary endpoint, was defined as the proportion of correctly diagnosed cases among all cases. RESULTS: One hundred and sixty cases with 46 different diseases were included in this analysis. RheumaTool correctly diagnosed 40% (95% confidence interval 32.4–48.1) of all cases. In 63.8% (95% confidence interval 55.7–71.1), the correct diagnosis was present in a differential diagnosis list consisting of a median of two diagnoses. CONCLUSION: In this first validation, RheumaTool provides a useful list of differential diagnoses. However, there is not sufficient diagnostic reliability for unfiltered data entry, especially in patients with multiple concomitant musculoskeletal disorders. This must be taken into account when using RheumaTool.

[CME Answers: Crowned Dens Syndrome - the Chameleon of Neck Pain]. / CME-Antworten: Crowned- Dens-Syndrom ­ das Chamäleon der Nackenschmerzen.

CME Answers: Crowned Dens Syndrome - the Chameleon of Neck Pain Abstract. Crowned Dens Syndrome (CDS) is a rare, under-diagnosed differential diagnosis of acute neck pain. Diagnosis is a challenge in clinical practice due to the similarity of symptoms to other diseases. Knowing this differential diagnosis of acute neck pain, unnecessary examinations and expensive therapy attempts can be avoided with a targeted approach. With this article we would like to sensitize colleagues accordingly.

[CME: Crowned-Dens-Syndrome - the Chameleon of Neck Pain]. / CME: Crowned-Dens-Syndrom ­ das Chamäleon der Nackenschmerzen.

CME: Crowned-Dens-Syndrome - the Chameleon of Neck Pain Abstract. Crowned Dens Syndrome (CDS) is a rare, under-diagnosed differential diagnosis of acute neck pain. Diagnosis is a challenge in clinical practice due to the similarity of symptoms to other diseases. Knowing this differential diagnosis of acute neck pain, unnecessary examinations and expensive therapy attempts can be avoided with a targeted approach. With this article we would like to sensitize colleagues accordingly.

Response to Tumor Necrosis Factor Inhibition in Male and Female Patients with Ankylosing Spondylitis: Data from a Swiss Cohort.

OBJECTIVE: To investigate sex differences in connection with the effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with ankylosing spondylitis (AS). METHODS: A total of 440 patients with AS (294 men; 146 women) initiating a first TNFi in the prospective Swiss Clinical Quality Management Cohort were included. We evaluated the proportion of patients achieving the 20% and 40% improvement in the Assessment of Spondyloarthritis international Society criteria (ASAS20 and ASAS40) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) improvement and status scores at 1 year. Patients having discontinued TNFi were considered nonresponders. Logistic regression analyses were performed to adjust for important predictors of response. RESULTS: Compared to men, female patients had lower mean C-reactive protein levels, better spinal mobility, and more peripheral disease at the start. There was no sex disparity with regard to the ASDAS, the Bath Ankylosing Spondylitis Disease Activity and Functional indices, and the quality of life. At 1 year, 52% of women and 63% of men achieved an ASAS20 response (OR 0.63, 95% CI 0.37-1.07, p = 0.09). An inactive disease status (ASDAS < 1.3) was reached by 18% of women and 26% of men (OR 0.65, 95% CI 0.32-1.27, p = 0.22). These sex differences in response to TNFi were more pronounced in adjusted analyses (OR 0.34, 95% CI 0.16-0.71, p = 0.005 for ASAS20 and OR 0.10, 95% CI 0.03-0.31, p < 0.001 for ASDAS < 1.3) and confirmed for all the other outcomes assessed. CONCLUSION: In AS, fewer women respond to TNFi and women show a reduced response in comparison to men.

TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort.

OBJECTIVES: To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). METHODS: Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. RESULTS: A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97). CONCLUSION: TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity.

Nodular Regenerative Hyperplasia of the Liver: A Rare Vascular Complication in Systemic Sclerosis.

OBJECTIVE: To investigate nodular regenerative hyperplasia (NRH) as a vascular complication of systemic sclerosis (SSc) with microvasculopathy as a common denominator. METHODS: Cases of SSc-NRH were identified by systematic literature review and by screening the Zurich cohort. NRH had to be diagnosed by liver biopsy. RESULTS: Literature review retrieved 22 cases. In our cohort, 1.4% of patients with SSc were diagnosed with NRH. Most had vasculopathy, were positive for anticentromere antibodies, had elevated alkaline phosphatase and gamma-glutamyl transferase levels, normal liver morphology on ultrasound yet increased stiffness on ultrasound elastography, and had portal hypertension. CONCLUSION: NRH might represent a rare yet potentially life-threatening vascular complication in SSc.

Impact of obesity on the response to tumor necrosis factor inhibitors in axial spondyloarthritis.

BACKGROUND: Few studies have investigated the impact of obesity on the response to tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). The aim of our study was to investigate the impact of different body mass index (BMI) categories on TNFi response in a large cohort of patients with axSpA. METHODS: Patients with axSpA within the Swiss Clinical Quality Management (SCQM) program were included in the current study if they fulfilled the Assessment in Spondyloarthritis International Society (ASAS) criteria for axSpA, started a first TNFi after recruitment, and had available BMI data as well as a baseline and follow-up visit at 1 year (±6 months). Patients were categorized according to BMI: normal (BMI 18.5 to <25), overweight (BMI 25-30), and obese (BMI >30). We evaluated the proportion of patients achieving the 40% improvement in ASAS criteria (ASAS40), as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) improvement and status scores at 1 year. Patients having discontinued the TNFi were considered nonresponders. We controlled for age, sex, HLA-B27, axSpA type, BASDAI, BASMI, elevated C-reactive protein (CRP), current smoking, enthesitis, physical exercise, and co-medication with disease-modifying antirheumatic drugs, as well as with nonsteroidal anti-inflammatory drugs in multiple adjusted logistic regression analyses. RESULTS: A total of 624 axSpA patients starting a first TNFi were considered in the current study (332 patients of normal weight, 204 patients with overweight, and 88 obese patients). Obese individuals were older, had higher BASDAI levels, and had a more important impairment of physical function in comparison to patients of normal weight, while ASDAS and CRP levels were comparable between the three BMI groups. An ASAS40 response was reached by 44%, 34%, and 29% of patients of normal weight, overweight, and obesity, respectively (overall p = 0.02). Significantly lower odds ratios (ORs) for achieving ASAS40 response were found in adjusted analyses in obese patients versus patients with normal BMI (OR 0.27, 95% confidence interval (CI) 0.09-0.70). The respective adjusted ASAS40 OR in overweight versus normal weight patients was 0.62 (95% CI 0.24-1.14). Comparable results were found for the other outcomes assessed. CONCLUSIONS: Obesity is associated with significantly lower response rates to TNFi in patients with axSpA.

Magnetic Resonance Imaging Findings in the Knee Before and After Long-Distance Running-Documentation of Irreversible Structural Damage? A Systematic Review.

BACKGROUND: Various studies have investigated structural knee changes after running, with conflicting results. PURPOSE: To perform a systematic review of acute changes in knee structures as detected by magnetic resonance imaging (MRI) after running and assess the reversibility of these changes. STUDY DESIGN: Systematic review. METHODS: A systematic literature search in Medline, Cochrane, Embase, and Scopus was performed. Articles that fulfilled predefined inclusion criteria were included and systematically reviewed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. RESULTS: A total of 19 studies were included in this review. All studies performed standard knee MRI; 6 studies additionally performed T1ρ and T2 mapping. Sixteen studies assessed cartilage or meniscal morphological changes. Ten found no significant morphological changes after running. Six studies showed significant changes at the first follow-up. Six performed a second follow-up. Five showed no change compared with baseline and the first follow-up, and 1 showed a significant recovery compared with the first follow-up and no significant difference compared with baseline. Five of the 6 studies performing T1ρ and T2 mapping found significant changes in T2 and T1ρ values at the first follow-up. Three performed a second follow-up. Two found a significant recovery of T2 but no recovery of T1ρ. One study did not find a significant change compared with baseline. Ten studies assessed the patellar tendon, ligaments, synovial fluid, or subchondral bone. Changes at the first follow-up were not significant. A second follow-up was performed in 5 studies. All studies discovered recovery from the first follow-up. CONCLUSION: These data suggest that healthy athletes who have no risk factors for degenerative joint disease may present fleeting quantitative alterations after running. No irreversible, qualitative harmful effects seemed to occur, with the exception of persistent T1ρ elevation representing a proteoglycan depletion. Whether T1ρ changes need more than 3 months to recover or represent permanent structural damage remains to be investigated.

Computer-based diagnostic expert systems in rheumatology: where do we stand in 2014?

Background. The early detection of rheumatic diseases and the treatment to target have become of utmost importance to control the disease and improve its prognosis. However, establishing a diagnosis in early stages is challenging as many diseases initially present with similar symptoms and signs. Expert systems are computer programs designed to support the human decision making and have been developed in almost every field of medicine. Methods. This review focuses on the developments in the field of rheumatology to give a comprehensive insight. Medline, Embase, and Cochrane Library were searched. Results. Reports of 25 expert systems with different design and field of application were found. The performance of 19 of the identified expert systems was evaluated. The proportion of correctly diagnosed cases was between 43.1 and 99.9%. Sensitivity and specificity ranged from 62 to 100 and 88 to 98%, respectively. Conclusions. Promising diagnostic expert systems with moderate to excellent performance were identified. The validation process was in general underappreciated. None of the systems, however, seemed to have succeeded in daily practice. This review identifies optimal characteristics to increase the survival rate of expert systems and may serve as valuable information for future developments in the field.

Cross-cultural adaptation of the German version of the spinal stenosis measure.

PURPOSE: To validate the German version of the spinal stenosis measure (SSM), a disease-specific questionnaire assessing symptom severity, physical function, and satisfaction with treatment in patients with lumbar spinal stenosis. METHODS: After translation, cross-cultural adaptation, and pilot testing, we assessed internal consistency, test-retest reliability, construct validity, and responsiveness of the SSM subscales. Data from a large Swiss multi-center prospective cohort study were used. Reference scales for the assessment of construct validity and responsiveness were the numeric rating scale, pain thermometer, and the Roland Morris Disability Questionnaire. RESULTS: One hundred and eight consecutive patients were included in this validation study, recruited from five different centers. Cronbach's alpha was above 0.8 for all three subscales of the SSM. The objectivity of the SSM was assessed using a partial credit approach. The model showed a good global fit to the data. Of the 108 patients 78 participated in the test-retest procedure. The ICC values were above 0.8 for all three subscales of the SSM. Correlations with reference scales were above 0.7 for the symptom and function subscales. For satisfaction subscale, it was 0.66 or above. Clinically meaningful changes of the reference scales over time were associated with significantly more improvement in all three SSM subscales (p < 0.001). Conclusion: The proposed version of the SSM showed very good measurement properties and can be considered validated for use in the German language.

Relevant baseline characteristics for describing patients with knee osteoarthritis: results from a Delphi survey.

BACKGROUND: Inclusion/exclusion criteria and baseline characteristics are essential for assessing the applicability of trial results to a given patient and the comparability of study populations for meta-analyses. This Delphi survey aimed to generate a set of baseline characteristics for describing patients with knee osteoarthritis enrolled in clinical studies. METHODS: Survey participants comprised clinical experts (n = 23; mean age 54 y; from 4 continents) that had authored at least two randomized trials on knee osteoarthritis. First, given a prepared list of baseline patient characteristics, the experts were asked to add characteristics they considered important for assessing comparability of patient populations in different trials that evaluated the efficacy of non-surgical interventions for treating knee osteoarthritis. Next, they were asked to rate the importance of each characteristic, on a scale of 0 (not important) to 10 (highly important), according to three outcome categories: pain, function, and structure. RESULTS: Participants identified 121 baseline characteristics. A rating ≥7 points was assigned to 39 characteristics (e.g., age, depression, global knee pain, daily dose of pain killers, Kellgren-Lawrence grading); of these, 20 were related to pain, 15 to function, and 23 to structural outcomes. Global knee pain was the only baseline characteristic that fulfilled among experts the predefined consensus criteria. CONCLUSIONS: Experts identified a large number of characteristics for describing patients with knee osteoarthritis. Disagreement and uncertainty prevailed over the relevance of these characteristics. Our findings justified further efforts to define appropriate, broadly acceptable sets of baseline characteristics for describing patients with knee osteoarthritis.

Assessment of cartilage changes over time in knee osteoarthritis disease-modifying osteoarthritis drug trials using semiquantitative and quantitative methods: pros and cons.

OBJECTIVE: To evaluate the impact of 2 magnetic resonance imaging (MRI) sequences on cartilage defect assessment in knee osteoarthritis (OA) patients and the sensitivity to change over time comparing cartilage defect (semiquantitative) with cartilage volume loss (quantitative) methods. METHODS: Gradient-echo (GRE) and intermediate-weighted fast spin-echo (IW-FSE) sequences were compared. Knee OA MRIs were from two 2-year studies (cohort 1, n = 55; cohort 2, n = 143). For both cohorts, a GRE sequence was used and patients in cohort 1 underwent an additional IW-FSE sequence. Cohort 2 included patients from a previous trial. Cartilage defects and cartilage volume were evaluated. RESULTS: The cartilage defect assessment provided consistently significantly higher scores in IW-FSE than in GRE sequences at baseline and 2 years. However, there was no difference in the change at 2 years between the sequences. The standardized response mean (SRM) for change did not show a difference between the 2 sequences, but was consistently higher (2-2.5-fold) for the quantitative method. The cartilage defect score change between the 2 treatment groups revealed a trend toward significance only in the medial tibial plateau, whereas the change in cartilage volume loss demonstrated a significant difference in the global knee, global femur, lateral femur, and lateral compartment. The SRMs for the treatment groups combined were markedly higher for cartilage volume loss than for the defect scoring by 4.3- to 6.0-fold. CONCLUSION: The direct comparison between GRE and IW-FSE sequences did not suggest superior sensitivity to cartilage defect change over time of one sequence over the other. Interestingly, the quantitative cartilage volume assessment was more sensitive than the semiquantitative scoring in the detection of treatment effect on OA cartilage changes.

Total Knee Replacement as a Knee Osteoarthritis Outcome: Predictors Derived from a 4-Year Long-Term Observation following a Randomized Clinical Trial Using Chondroitin Sulfate.

OBJECTIVE: To predict, using clinical and qMRI data, the incidence of total knee replacement (TKR) during the long-term follow-up of knee osteoarthritis (OA) patients who formerly received chondroitin sulfate (CS) or placebo treatment. DESIGN: A post hoc intention-to-treat analysis to evaluate the incidence of TKR was done on knee OA patients who had participated in a 12-month trial evaluating the impact of CS (800 mg/d) versus placebo for 6 months, followed by a 6-month open-phase in which all patients received CS. Additionally, the clinical and qMRI predictors of TKR were determined. RESULTS: Thirteen TKRs were performed in the population after a 4-year follow-up. More TKRs were performed in the placebo group than in the CS group (69% vs. 31%, P = 0.150, logistic regression). The statistically significant predictors of TKRs were, at baseline, higher WOMAC pain and function scores, presence of bone marrow lesions (BMLs), and higher C-reactive protein levels. Loss of medial cartilage volume and increase in WOMAC pain and function at one-year were also predictors of TKR. Multivariate analyses revealed that baseline presence of BML and higher WOMAC pain score were independent predictors. Time to occurrence of the TKR also favored the CS group versus placebo (log-rank, P = 0.094). CONCLUSION: Symptoms such as knee pain and function, presence of BML, and cartilage volume loss predict the long-term occurrence of a "hard" outcome such as TKR.