Krill Oil for Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Knee osteoarthritis is disabling, with few effective treatments. Preliminary evidence suggested that krill oil supplementation improved knee pain, but effects on knee osteoarthritis remain unclear. Objective: To evaluate efficacy of krill oil supplementation, compared with placebo, on knee pain in people with knee osteoarthritis who have significant knee pain and effusion-synovitis. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled clinical trial in 5 Australian cities. Participants with clinical knee osteoarthritis, significant knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from December 2016 to June 2019; final follow-up occurred on February 7, 2020. Interventions: Participants were randomized to 2 g/d of krill oil (n = 130) or matching placebo (n = 132) for 24 weeks. Main Outcomes and Measures: The primary outcome was change in knee pain as assessed by visual analog scale (range, 0-100; 0 indicating least pain; minimum clinically important improvement = 15) over 24 weeks. Results: Of 262 participants randomized (mean age, 61.6 [SD, 9.6] years; 53% women), 222 (85%) completed the trial. Krill oil did not improve knee pain compared with placebo (mean change in VAS score, -19.9 [krill oil] vs -20.2 [placebo]; between-group mean difference, -0.3; 95% CI, -6.9 to 6.4) over 24 weeks. One or more adverse events was reported by 51% in the krill oil group (67/130) and by 54% in the placebo group (71/132). The most common adverse events were musculoskeletal and connective tissue disorders, which occurred 32 times in the krill oil group and 42 times in the placebo group, including knee pain (n = 10 with krill oil; n = 9 with placebo), lower extremity pain (n = 1 with krill oil; n = 5 with placebo), and hip pain (n = 3 with krill oil; n = 2 with placebo). Conclusions and Relevance: Among people with knee osteoarthritis who have significant knee pain and effusion-synovitis on magnetic resonance imaging, 2 g/d of daily krill oil supplementation did not improve knee pain over 24 weeks compared with placebo. These findings do not support krill oil for treating knee pain in this population. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000726459; Universal Trial Number: U1111-1181-7087.

Population-wide long-term study of incidence, renal failure, and mortality rates for lupus nephritis.

OBJECTIVE: Given limited regional data, we investigate the state-wide epidemiology, renal and patient outcomes for lupus nephritis (LN) in Western Australia (WA). METHODS: Patients hospitalized with incident SLE (≥2 diagnostic codes in the state-wide WA Health Hospital Morbidity Data Collection) in the period 1985-2015 were included (n = 1480). LN was defined by the presence of glomerulonephritis and/or raised serum creatinine. Trends over three study decades for annual incidence rate (AIR)/100.000 population, mortality (MR), and end-stage renal disease (ESRD) rates/100 person years were analyzed by least square regression and compared with a matched control group (n = 12 840). RESULTS: Clinical evidence of LN developed in 366 SLE patients (25.9%) after a median disease duration of 10 months (IQR 0-101) with renal biopsy performed in 308 (84.2%). The AIR for LN (0.63/100.000) did not change significantly over time (R2 = .11, p = .85), while point prevalence reached 11.9/100.000 in 2015. ESRD developed in 14.1% (n = 54) of LN patients vs. 0.2% in non-LN SLE patients and 0.05% in controls (all p ≤ 0.01). ESRD rates increased over time in LN patients (0.4 to 0.7, R2 = .52, p = .26). The odds ratio for death was 8.81 (CI 3.78-22.9) for LN and 6.62 (CI 2.76-17.9) for non-LN SLE patients compared to controls and MR for LN patients increased over time (1.3 to 2.2, R2 = .84, p = .26). CONCLUSIONS: The incidence rate of LN in WA remained unchanged over 30 years. A lack of improvement in renal failure and mortality rates illustrates the pressing need for better long-term treatment options and/or strategies in LN.

The longitudinal study of muscle changes with ultrasound: differential changes in idiopathic inflammatory myopathy subgroups.

OBJECTIVES: We investigated shear wave elastography (SWE), B mode US and power Doppler (PDUS) as imaging biomarkers for longitudinal follow-up in idiopathic inflammatory myopathy (IIM), with a particular focus on immune-mediated necrotizing myopathy (IMNM) and DM. METHODS: Participants had serial SWE, PDUS on the deltoid (D) and vastus lateralis (VL) muscles on four occasions at intervals of 3-6 months. Clinical assessments included manual muscle testing, and patient- and physician-reported outcome scales. RESULTS: Thirty-three participants were included: IMNM = 17, DM = 12, overlap myositis = 3, PM = 1. Twenty were in a prevalent clinic group, and 13 were recently treated cases in an incident group. Differential changes in SWS and US domains occurred with time in both the prevalent and incident groups. In the VL-prevalent subgroup, echogenicity increased over time (P = 0.040), while in the incident cases there was a trend for reduction to normal over time (P = 0.097) with treatment. Muscle bulk reduced in the D-prevalent subgroup over time (P = 0.096), suggesting atrophy. SWS also reduced in the VL-incident subgroup over time (P = 0.096), suggesting a trend towards improvement in muscle stiffness with treatment. CONCLUSION: SWE and US appear promising as imaging biomarkers for patient follow-up in IIM and indicate changes over time, especially with echogenicity, muscle bulk and SWS in the VL. Due to the limitations of the participant numbers, additional studies with a larger cohort are needed to help evaluate these US domains further and outline specific characteristics within the IIM subgroups.

Mortality Trends Among Patients with Rheumatoid Arthritis in Western Australia.

INTRODUCTION: With scarce comparative data on mortality in Australian patients with rheumatoid arthritis (RA), we investigated temporal changes in standardized mortality rates for patients with RA using longitudinal linked population-wide health data in Western Australia (WA) over the period 1980 to 2015. METHODS: The study included 17,125 patients with a first-time hospital contact for RA (ICD-10-AM M05.00-M06.99 and ICD-9-AM 714.00-714.99) in the study period. Standardized mortality rate ratios (SMRRs) for the RA cohort versus the WA general population was estimated using direct age standardization. We analyzed temporal trends over with dates and causes provided by the WA Death Registry. RESULTS: During 356,069 patient-years of follow-up, a total of 8955 (52%) deaths occurred in the RA cohort. The SMRR was 2.24 (95% CI 2.15-2.34) in males and 3.09 (95% CI 3.00-3.19) in females over the study period. SMRR decreased since 2000 to 1.59 (95% CI 1.39-1.81) for the period 2011-2015. Median survival was 26.80 years (95% CI 26.30-27.30), where age and comorbidity independently increased the risk of death. The leading causes of deaths were cardiovascular diseases (26.60%), cancer (16.80%), rheumatic diseases (5.80%), chronic pulmonary disease 491 (5.50%), dementia (3.00%), and diabetes 235 (2.6%). CONCLUSIONS: The mortality rate in patients with RA in WA has decreased but remains 1.59-times higher than in community counterparts, suggesting that there is room for further improvement. Comorbidity is the main modifiable risk factor to further reduce mortality in patients with RA.

Imaging of giant cell arteritis - recent advances.

Imaging is increasingly being used to guide clinical decision-making in patients with giant cell arteritis (GCA). While ultrasound has been rapidly adopted in fast-track clinics worldwide as an alternative to temporal artery biopsy for the diagnosis of cranial disease, whole-body PET/CT is emerging as a potential gold standard test for establishing large vessel involvement. However, many unanswered questions remain about the optimal approach to imaging in GCA. For example, it is uncertain how best to monitor disease activity, given there is frequent discordance between imaging findings and conventional disease activity measures, and imaging changes typically fail to resolve completely with treatment. This chapter addresses the current body of evidence for the use of imaging modalities in GCA across the spectrum of diagnosis, monitoring disease activity, and long-term surveillance for structural changes of aortic dilatation and aneurysm formation and provides suggestions for future research directions.

The relationship between clinical phenotype and kallikrein-kinin bioregulation in different forms of arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of life, and imaging characteristics (e.g. ultrasonography) of different arthritides. METHODS: Patients with osteoarthritis (OA, n = 29), gout (n = 10) and RA (n = 8) were recruited and screened for clinical symptoms, quality of life, and ultrasonographical assessment of arthritis. Blood neutrophils were assessed for the expression of bradykinin receptors (B1R and B2R), kininogens and kallikreins by immunocytochemistry with visualization by bright field microscopy. Levels of plasma biomarkers were measured by ELISA and cytometric bead array. RESULTS: Quality of life (SF-36 domains and summary scores; including pain; and, HAQ) was similar across OA, gout and RA patients; with the exception of worse physical functioning scores between OA and gout patients. Synovial hypertrophy (on ultrasound) differed between groups (p = 0.001), and the dichotomised Power Doppler (PD) score of greater than or equal to 2 (PD-GE2) was marginally significant (p = 0.09). Plasma IL-8 were highest in patients with gout followed by RA and OA (both, P < 0.05). Patients with RA had higher plasma levels of sTNFR1, IL-1ß, IL-12p70, TNF and IL-6, compared to OA and gout patients (all, P < 0.05). Patients with OA had higher expression of K1B and KLK1 on blood neutrophils followed by RA and gout patients (both, P < 0.05). Bodily pain correlated with B1R expression on blood neutrophils (r = 0.334, p = 0.05), and inversely with plasma levels of CRP (r = -0.55), sTNFR1 (r = -0.352) and IL-6 (r = -0.422), all P < 0.05. Expression of B1R on blood neutrophils also correlated with Knee PD (r = 0.403) and PD-GE2 (r = 0.480), both P < 0.05. CONCLUSIONS: Pain levels and quality of life were similar between patients with OA, RA and gout with knee arthritis. Plasma inflammatory biomarkers and B1R expression on blood neutrophils correlated with pain. Targeting B1R to modulate the kinin-kallikrein system may pose as a new therapeutic target in the treatment of arthritis.

Trends in Hospitalization for Tuberculosis and Other Opportunistic Infections in Australian Patients with Inflammatory Joint Diseases.

OBJECTIVE: As immune-modulating therapy has become the standard of care for idiopathic inflammatory joint diseases (IJD), we investigated whether this has changed the rates for hospitalization with opportunistic infections (OI). METHODS: Administrative longitudinal state-wide health data identified patients hospitalized at least twice with diagnostic codes for rheumatoid arthritis (RA, n = 7730), psoriatic arthritis (PsA, n = 529) or axial spondylarthritis (AS, n = 1126) in Western Australia in the period 1985-2015. Overall incidence rates/1000 person-years (IR with 95% CI) for microbiologically confirmed OI (mycobacterial, fungal, and viral infections) during 180,963 person-years were analyzed across 10-year periods with IR trend rates analyzed by least square regression (R2) for all IJD categories. RESULTS: A total of 2584 OI occurred with higher IR rates observed in RA (15.34, CI 14.71-15.99) than PsA (8.73, CI 7.14-10.56) and AS (10.88, CI 9.63-12.24) patients (p < 0.001). IR rates were highest for Candidiasis across all three IJD categories (IR 10.0 vs. 6.32 vs. 6.88, respectively), while Varicella-zoster (VZV) was most frequent non-candida OI (IR 2.83.0 vs. 1.50 vs. 1.49, respectively) followed by mycobacterial (IR 1.14 vs. 0.08 vs. 0.24, respectively) and other mycotic infections (IR 0.60 vs. 0.58 vs. 0.86, respectively). Over time, the IR for tuberculosis and pneumocystosis decreased and remained stable for VZV infections in RA patients, but IR for all other OI increased across all disease categories. OI admission associated with 6.5% (CI 5.6-7.5) in-hospital mortality. CONCLUSIONS: Despite decreasing admission rates for tuberculosis and pneumocystosis in RA patients, an overall increase in mycotic and viral infection rates over time was seen across all three IJD. Together with a significant case fatality rate, this indicates continued efforts are needed to improve OI prevention in the management of IJD patients.

Reliability and Diagnostic Accuracy of Radiography for the Diagnosis of Calcium Pyrophosphate Deposition: Performance of the Novel Definitions Developed by an International Multidisciplinary Working Group.

OBJECTIVE: To assess the reliability and diagnostic accuracy of new radiographic imaging definitions developed by an international multidisciplinary working group for identification of calcium pyrophosphate deposition (CPPD). METHODS: Patients with knee osteoarthritis scheduled for knee replacement were enrolled. Two radiologists and 2 rheumatologists twice assessed radiographic images for presence or absence of CPPD in menisci, hyaline cartilage, tendons, joint capsule, or synovial membrane, using the new definitions. In case of disagreement, a consensus decision was made and considered for the assessment of diagnostic performance. Histologic examination of postsurgical specimens under compensated polarized light microscopy was the reference standard. Prevalence-adjusted bias-adjusted kappa values were used to assess reliability, and diagnostic performance statistics were calculated. RESULTS: Sixty-seven patients were enrolled for the reliability study. The interobserver reliability was substantial in most of the assessed structures when considering all 4 readers (κ range 0.59-0.90), substantial to almost perfect among radiologists (κ range 0.70-0.91), and moderate to almost perfect among rheumatologists (κ range 0.46-0.88). The intraobserver reliability was substantial to almost perfect for all the observers (κ range 0.70-1). Fifty-one patients were included in the accuracy study. Radiography demonstrated an overall specificity of 92% for CPPD, but sensitivity remained low for all sites and for the overall diagnosis (54%). CONCLUSION: The new radiographic definitions of CPPD are highly specific against the gold standard of histologic diagnosis. When the described radiographic findings are present, these definitions allow for a definitive diagnosis of CPPD, rather than other calcium-containing crystal depositions; however, a negative radiographic finding does not exclude the diagnosis.

Development and validation of an OMERACT ultrasound scoring system for the extent of calcium pyrophosphate crystal deposition at the joint level and patient level.

BACKGROUND: The Calcium Pyrophosphate Deposition (CPPD) subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound working group was established to validate ultrasound as an outcome measure instrument for CPPD, and in 2017 has developed and validated standardised definitions for elementary lesions for the detection of calcium pyrophosphate crystals in joints. The aim of this study was to develop and evaluate the reliability of a consensus-based ultrasound scoring system for CPPD extent, representing the next phase in the OMERACT methodology. METHODS: In this study the novel scoring system for CPPD was developed through a stepwise process, following an established OMERACT ultrasound methodology. Following a previous systematic review to gather available evidence on existing scoring systems for CPPD, the novel scoring system was developed through a Delphi survey based on the expert opinion of the members of the OMERACT Ultrasound working group-CPPD subgroup. The reliability of the scoring system was then tested on a web-based and patient-based exercise. Intra-reader and inter-reader reliability of the new scoring system was assessed using weighted Light's κ coefficients. FINDINGS: The four-grade semiquantitative scoring system consisted of: grade 0 (no findings consistent with CPPD), grade 1 (≤3 single spots or 1 small deposit), grade 2 (>3 single spots or >1 small deposit or ≥1 larger deposit occupying ≤50% of the structure under examination in the reference image-ie, the scanning view with the highest grade of depositions), and grade 3 (deposits that occupy more than 50% of the structure under examination in the reference image). The score should be applied to the knee (menisci and hyaline cartilage) and the triangular fibrocartilage complex of the wrist. The intra-reader and inter-reader reliabilities on static images were almost perfect (κ 0·90 [95% CI 0·79-1·00] and κ 0·84 [0·79-0·88]), and on the eight patients recruited (four [50%] female and four [50%] male) were substantial (κ 0·72 [95% CI 0·47 to 0·96] and 0·66 [0·61 to 0·71]). INTERPRETATION: This OMERACT ultrasound scoring system for CPPD was reliable on both static images and patients. The scoring system might be a valuable tool for ensuring valid and comparable results in clinical trials and could help monitor the extent of crystal deposition in patients with CPPD in clinical practice. FUNDING: The Italian Ministry of Health - Ricerca Corrente.

Mortality Rates in Patients With Ankylosing Spondylitis With and Without Extraarticular Manifestations and Comorbidities: A Retrospective Cohort Study.

OBJECTIVE: To examine mortality rates in hospitalized patients with ankylosing spondylitis (AS) and the association of extraarticular manifestations (EAMs) and comorbidities with mortality rates. METHODS: This study was a retrospective, population-based cohort study using linked administrative data from patients with AS who were hospitalized (n = 1791) and patients in a matched comparison group (n = 8955). Mortality data for patients were obtained from the Western Australia Death Register. The presence of EAMs and comorbidities was identified from hospital records. Mortality rates were compared between the 2 groups using Cox proportional hazard models overall and stratified by a history of EAMs, comorbidities, and smoking status. RESULTS: Crude mortality rates were significantly higher among patients with AS than among patients in the comparison group (hazard ratio [HR] 1.85, 95% CI 1.62-2.12), with excess mortality in the AS group associated with cardiovascular disease (CVD; HR 5.32, 95% CI 3.84-7.35), cancer (HR 1.68, 95% CI 1.27-2.23), external causes (HR 3.92, 95% CI 2.28-6.77), and infectious diseases (HR 25.92, 95% CI 7.50-89.56). When patients were stratified by history of EAMs, CVD, and smoking, the risk of mortality was elevated in patients both with and without each risk factor. Among patients with AS, histories of CVD (HR 6.33, 95% CI 4.79-8.38), diabetes (HR 2.81, 95% CI 1.99-3.95), smoking (HR 1.49, 95% CI 1.18-1.89), and EAMs (HR 1.62, 95% CI 1.24-2.11) were associated with an increased risk of mortality. CONCLUSION: The presence of comorbidities, EAMs, and smoking contributes to an increased risk of all-cause mortality among patients with AS who are hospitalized compared to patients in the comparison group. These results support the need to prevent or reduce the occurrence of comorbidities and smoking in patients with AS.

Mortality and cause of death in patients with ANCA-associated vasculitis and polyarteritis nodosa in Australia-a population-based study.

OBJECTIVES: We compared survival and causes of death in Western Australian (WA) ANCA-associated vasculitis (AAV) and PAN patients with controls and the WA population. METHODS: In this data linkage study, we identified patients with incident AAV/PAN and age, sex and temporally matched controls 1980-2014 from the WA Rheumatic Disease Epidemiological Registry. Survival analyses and time-varying analyses were performed. RESULTS: Six hundred and fourteen patients with incident AAV/PAN were compared with 6672 controls; 229 AAV/PAN patients died over 5277 person-years of follow-up and 1009 controls died over 73835 person-years. Survival was reduced in patients with AAV/PAN compared with matched controls [hazard ratio (HR) 3.5 (95% CI: 3.1, 4.1)], and matched WA population rates [standardized mortality ratio 3.3 (95% CI: 2.9, 3.8)]. Greatest excess mortality in AAV/PAN patients was observed in the first year after diagnosis and remained higher than controls throughout follow-up. Greater excess mortality was observed in patients >60 years at diagnosis. In cause-specific analyses, mortality HR for vasculitis, infection and non-infective respiratory disease were greatest early after diagnosis and remained persistently elevated. The HRs for malignancy and cerebrovascular disease related deaths increased during follow-up, and were constant for ischaemic heart disease related deaths. CONCLUSION: Mortality was increased in AAV/PAN patients compared with controls, with patients older at diagnosis at greater risk. These findings provide mortality risk for AAV/PAN in an Australian population, highlighting key contributors to mortality at different time periods over follow-up and potential areas of focus for reducing mortality.

Assessment of liver fibrosis markers in people with rheumatoid arthritis on methotrexate.

BACKGROUND: Up to 3% of methotrexate (MTX)-treated rheumatoid arthritis (RA) patients might develop liver fibrosis or cirrhosis, requiring effective screening algorithms. AIMS: To assess the utility of non-invasive liver fibrosis assessment in RA patients on MTX. METHODS: Fifty-six patients were recruited from rheumatology outpatient clinics in a public tertiary centre from July 2017 to October 2018. Clinical data was collected. Screening for hepatic fibrosis was performed using transient elastography (TE), aminoaspartate transaminase to platelet ratio index (APRI), Hepascore and Fibrosis-4 index (FIB-4). Those with suspected significant liver fibrosis based on these screening tests were assessed by a hepatologist. RESULTS: Twenty-seven patients were suspected to have liver fibrosis on screening, including 10/56 (18%) by TE, 20/56 (36%) by Hepascore, 2/56 by APRI (4%) and 1/56 by FIB-4 (2%). Of these 27 patients, 11 were reviewed by a hepatologist and one diagnosed with significant liver fibrosis. TE, but not APRI, Hepascore or FIB-4, was found to have 100% sensitivity and 84% specificity (P = 0.029) for hepatologist-diagnosed liver fibrosis. CONCLUSION: Liver fibrosis develops in a minority of MTX-treated RA patients. The present study suggests that TE is a more sensitive screening test than APRI, FIB-4 or Hepascore in the identification of people with RA at risk of hepatic fibrosis.

Conventional ultrasound and elastography as imaging outcome tools in autoimmune myositis: A systematic review by the OMERACT ultrasound group.

AIMS: To analyze whether there is sufficient data from published literature to demonstrate that ultrasound, including elastography, present good metric properties (truth, discrimination and feasibility) in autoimmune myositis (AIM). METHODS: A population, intervention, comparator and outcome-structured (PICO) search was performed in Medline, Cochrane Library and Embase database from 01/01/1973 to 08/05/2019. The inclusion criteria required original research involving adult humans, reported in English, assessing ultrasound and elastography in patients with an AIM. Conference abstracts and computer-assisted diagnostics that focused on technique and not ultrasound domains were excluded. RESULTS: Approximately 2670 articles were identified. Forty-one full-text articles were included in the final analysis. There were 551 AIM patients studied. Eighteen studies (43.9%) had a control group, of which 15 (63.3%) were healthy controls. The age of participants (including controls) varied from 18 to 86 years, and most were females (59%). Diagnosis of AIM was largely biopsy-proven, although some were derived through clinical presentation, positive clinical imaging (ultrasound or otherwise) and/or electromyography and steroid responsiveness. The features examined with ultrasound in the 41 included articles consisted of: muscle echogenicity, bulk, atrophy, architecture, power Doppler, perfusion characteristics, shear wave modulus, shear wave velocity, elasticity index and fasciculations. Twelve studies (29.2%) used quantitative methods to assess these characteristics, whilst others used semi-quantitative, dichotomous/binary and descriptive scoring systems. Criterion validity was met in 14 studies (12/14, 85.7%) and construct validity in 22 studies (22/25, 88.0%). Most published articles reported Level 3b to Level 5 evidence with varying degrees of bias. There was only one longitudinal study examining discrimination. Reliability and feasibility were under-reported. CONCLUSION: This is the first systematic review studying the utility of ultrasound, including elastography, in AIM. There is some evidence for criterion and construct validity, suggesting that ultrasound may be a promising outcome measurement instrument in AIM. Agreement on the standardization of acquisition, and the definitions of target domains, is required. Additionally, further validation studies are required to determine discrimination, reliability and feasibility.

The Risk and Consequences of Vertebral Fracture in Patients with Ankylosing Spondylitis: A Population-based Data Linkage Study.

OBJECTIVE: To compare the long-term prevalence, incidence, and outcomes of vertebral fracture (VF) between ankylosing spondylitis (AS) patients and matched controls, including the role of extraarticular manifestations (EAM) and osteoporosis. METHODS: This was a statewide observational study using linked health data for 2321 patients with AS and 22,976 controls presenting to hospital from 1980 to 2015. Data were analyzed using incidence rates (per 1000 person-yrs) and ratios (IRR), multivariable Cox proportional hazards regression, and Kaplan-Meier survival curves. RESULTS: Over a median 13.92 (interquartile range 7.58-21.67) years of follow-up, patients with AS had a greater VF prevalence and greater incidence of developing a new VF compared to controls (9.3% vs 2.5%, 6.8% vs 1.9%, respectively, all P < 0.001). Patients with AS had an increased risk of developing a VF after adjustments for age, sex, and osteoporosis (HR 2.55, 95% CI 2.11-3.09) compared to controls; this risk remained throughout the study period. Patients with AS were 5 years younger at time of first VF (P = 0.008) and had a greater likelihood of a recurrent VF (IRR 4.64; 95% CI 4.54-4.75) compared to respective controls. Mortality overall was comparable between patients with AS and controls after adjustment for age, sex, osteoporosis, and VF status (HR 0.90; 95% CI 0.80-1.01). CONCLUSION: The significantly increased risk of VF in patients with AS has not altered following the introduction of tumor necrosis factor inhibitor treatment. Although patients with AS experience a first VF at a younger age than controls, this does not lead to an increased risk of death.

Imaging as a potential outcome measure in gout studies: A systematic literature review.

OBJECTIVE: Despite major progress in the imaging of gout, it is unclear which domains these techniques can evaluate and whether imaging modalities have the potential to provide valid outcome measures. The aim of this study was to assess the use of imaging instruments in gout according to the Outcomes in Rheumatology Clinical Trials (OMERACT) filter to inform the development of imaging as an outcome measure. METHODS: A systematic literature search of imaging modalities for gout was undertaken. Articles were assessed by two reviewers to identify imaging domains and summarize information according to the OMERACT filter. RESULTS: The search identified 78 articles (one abstract). Modalities included were conventional radiography (CR) (16 articles), ultrasound (US) (29), conventional computed tomography (CT) (11), dual energy computed tomography (DECT) (20), and magnetic resonance imaging (MRI) (16). Three domains were identified as follows: urate deposition, joint damage, and inflammation. Although sufficient data were available to assess feasibility, validity, and reliability, comprehensive assessment of discrimination was not possible due to the paucity of prospective imaging studies. CR is widely accessible, inexpensive with a validated damage scoring system. US and MRI offer radiation-free methods of evaluating urate deposition, damage and inflammation, but may be limited by accessibility. DECT provides excellent definition of urate deposition and bone damage, but has restricted availability and requires radiation. CONCLUSIONS: Imaging methods can detect urate deposition, damage, and inflammation in gout. More than one modality may be required depending on the domains and therapeutic agent of interest. No single imaging method currently fulfils all aspects of the OMERACT filter for any domain.

Systematic review of MRI, ultrasound, and scintigraphy as outcome measures for structural pathology in interventional therapeutic studies of knee arthritis: focus on responsiveness.

OBJECTIVE: validated imaging outcome tools to assess response to therapies in a single joint are required. Our aim was to review the published literature to ascertain the responsiveness of novel imaging techniques as outcome measures in interventional therapeutic studies of knee arthritis. METHODS: an Ovid Medline search was performed for original articles in English that used imaging techniques to assess response at the knee joint to therapy in osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. Changes in response to therapy were assessed with regard to both internal and external responsiveness. RESULTS: in the studies that presented appropriate statistical data to allow responsiveness to be assessed, MRI was generally found to be internally responsive to pathologies imaged, and externally responsive, referenced against both other imaging modalities and biochemical biomarkers of arthritis. Ultrasonography was found to demonstrate internal responsiveness with regard to synovial thickness, effusion size, and popliteal cyst size. External responsiveness was demonstrated against several referenced health status measures. Scintigraphy was found to be externally responsive in the majority of studies, with internal responsiveness demonstrated in 1 study. CONCLUSION: while the imaging techniques appear to be responsive from the data we present, further inspection reveals that interpreting the responsiveness of imaging techniques was difficult, largely because of a lack of standardization of image acquisition, definitions of pathology, and scoring systems. Refined pathological definitions and scoring systems are required to enable the development of valid and responsive tools for interventional clinical trials.