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.

Left Main Stem Compression by Intrapericardial Paraganglioma Associated With Succinate Dehydrogenase Mutation.

Paragangliomas are rare extra-adrenal tumors originating from chromaffin cells. We discovered a large intrapericardial mass confirmed to be a primary cardiac paraganglioma encasing the left main stem coronary artery in a 38-year-old woman who presented with dyspnea and subscapular pain. Genetic predisposition related to succinate dehydrogenase A mutation was identified.

[Trends in the frequency of cancer in France]. / Évolution de la fréquence des cancers en France.

We present and discuss recent data on the frequency of cancer in France. In the male population, the incidence of cancer has been stable since 2010 and mortality is decreasing; changes in the incidence of all cancers are dominated by changes in the incidence of prostate cancer, which is highly dependent on the extent of screening. In the female population, cancer incidence is rising and mortality is falling; the increase in the incidence of all cancers is partly due to the rise in the incidence of lung cancer, a consequence of women taking up smoking in the early 1970s.

Jaw claudication and jaw stiffness in giant cell arteritis: secondary analysis of a qualitative research dataset.

Objective: Jaw symptoms can be a vital clue to the diagnosis of GCA. Guidelines recommend more intensive treatment if jaw claudication is present. We sought to explore how patients with GCA described their jaw symptoms. Methods: We carried out a secondary, qualitative analysis of interview data from 36 participants from the UK (n = 25) and Australia (n = 11), originally collected in order to develop a patient-reported outcome measure for GCA. In all cases, GCA had been confirmed by biopsy/imaging. Interview transcripts were organized within QSR NVivo 12 software and analysed using template analysis. Themes were refined through discussion among the research team, including a patient partner. Results: Twenty of 36 participants reported jaw symptoms associated with GCA. The median age of these 20 participants was 76.5 years; 60% were female. Five themes were identified: physical sensations; impact on function; impact on diet; symptom response with CSs; and attribution to other causes. Physical sensations included ache, cramp, stiffness and 'lockjaw'. Functional impacts included difficulty in eating/chewing, cleaning teeth, speaking or opening the mouth. Dietary impacts included switching to softer food. Response to CSs was not always immediate. Jaw symptoms were initially mis-attributed by some participants to arthritis, age or viral illnesses; or by health-care professionals to a dental cavity, ear infection or teeth-grinding. Conclusion: Jaw symptoms in GCA are diverse and can lead to diagnostic confusion with primary temporomandibular joint disorder, potentially contributing to delay in GCA diagnosis. Further research is needed to determine the relationship of jaw stiffness to jaw claudication.

Trajectories of self-reported pain-related health outcomes and longitudinal effects on medication use in rheumatoid arthritis: a prospective cohort analysis using the Australian Rheumatology Association Database (ARAD).

OBJECTIVE: To determine distinct trajectories of self-reported pain-related health status in rheumatoid arthritis (RA), their relationship with sociodemographic factors and medication use. METHODS: 988 Australian Rheumatology Association Database participants with RA (71% female, mean age 54 years, mean disease duration 2.3 years) were included. Distinct multi-trajectories over 15-year follow-up for five different self-reported pain-related health outcome measures (Health Assessment Questionnaire Disability Index, visual analogue scores for pain, arthritis, global health and the Assessment of Quality of Life utility index) were identified using latent variable discrete mixture modelling. Random effects models were used to determine associations with medication use and biologic therapy modification during follow-up. RESULTS: Four, approximately equally sized, pain/health status groups were identified, ranging from 'better' to 'poorer', within which changes over time were relatively small. Important determinants of those with poorer pain/health status included female gender, obesity, smoking, socioeconomic indicators and comorbidities. While biologic therapy use was similar between groups during follow-up, biologic therapy modifications (plinear<0.001) and greater tendency of non-tumour necrosis factor inhibitor use (plinear<0.001) were observed in those with poorer pain/health status. Similarly, greater use of opioids, prednisolone and non-steroidal anti-inflammatory drugs was seen in those with poorer pain/health status. CONCLUSION: In the absence of disease activity information, distinct trajectories of varying pain/health status were seen from the outset and throughout the disease course in this RA cohort. More biologic therapy modifications and greater use in anti-inflammatories, opioids and prednisolone were seen in those with poorer pain/health status, reflecting undesirable lived experience of persistent pain in 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.

Incidence of biopsy-proven giant cell arteritis (GCA) in South Australia 2014-2020.

Objective: To determine the incidence of biopsy proven giant cell arteritis (GCA) in South Australia. Methods: Patients with biopsy-proven GCA were identified from pathology reports of temporal artery biopsies at state-based pathology laboratories, from 1 January 2014 to 31 December 2020. Incidence rates for biopsy-proven GCA were calculated using Australian Bureau of Statistics data for South Australian population sizes by age, sex, and calendar year. Seasonality was analyzed by cosinor analysis. Results: There were 181 cases of biopsy-proven GCA. The median age at diagnosis of GCA was 76 years (IQR 70, 81), 64% were female. The estimated population incidence for people over 50 was 5.4 (95% CI 4.7, 6.1) per 100,000-person years. The female: male incidence ratio was 1.6 (95% CI 1.2, 2.2). There was no ordinal trend in GCA incidence rates by calendar year (p = 0.29). The incidence was, on average, highest in winter, but not significantly (p = 0.35). A cosinor analysis indicated no seasonal effect (p = 0.52). Conclusion: The incidence of biopsy-proven GCA remains low in Australia. A higher incidence was noted compared to an earlier study. However, differences in ascertainment and methods of GCA diagnosis may have accounted for the change.

Clinical phenotype and complications of large vessel giant cell arteritis: A systematic review and meta-analysis.

BACKGROUND: Giant Cell Arteritis (GCA) is a heterogenous systemic granulomatous vasculitis involving the aorta and any of its major tributaries. Despite increased awareness of large vessel (LV) involvement, studies reporting incidence, clinical characteristics and complications of large-vessel GCA (LV-GCA) show conflicting results due to inconsistent disease definitions, differences in study methodologies and the broad spectrum of clinical presentations. The aim of this systematic literature review was to better define LV-GCA based on the available literature and identify distinguishing characteristics that may differentiate LV-GCA patients from those with limited cranial disease. METHODS: Published studies indexed in MEDLINE and EMBASE were searched from database inception to 7th May 2021. Studies were included if they presented cohort or cross-sectional data on a minimum of 25 patients with LV-GCA. Control groups were included if data was available on patients with limited cranial GCA (C-GCA). Data was quantitatively synthesised with application of a random effects meta-regression model, using Stata. RESULTS: The search yielded 3488 studies, of which 46 were included. Diagnostic criteria for LV-GCA differed between papers, but was typically dependent on imaging or histopathology. Patients with LV-GCA were generally younger at diagnosis compared to C-GCA patients (mean age difference -4.53 years), had longer delay to diagnosis (mean difference 3.03 months) and lower rates of positive temporal artery biopsy (OR: 0.52 [95% CI: 0.3, 0.91]). Fewer LV-GCA patients presented with cranial manifestations and only 53% met the 1990 ACR Classification Criteria for GCA. Vasculitis was detected most commonly in the thoracic aorta, followed by the subclavian, brachiocephalic trunk and axillary arteries. The mean cumulative prednisolone dose at 12-months was 6056.5mg for LV-GCA patients, relapse rates were similar between LV- and C-GCA patients, and 12% of deaths in LV-GCA patients could be directly attributed to an LV complication. CONCLUSION: Patients with LV-GCA have distinct disease features when compared to C-GCA, and this has implications on diagnosis, treatment strategies and surveillance of long-term sequalae.

Mortality estimates and excess mortality in rheumatoid arthritis.

OBJECTIVES: To determine long-term (20 year) survival in RA patients enrolled in the Australian Rheumatology Association Database (ARAD). METHODS: ARAD patients with RA and data linkage consent who were diagnosed from 1995 onwards were included. Death data were obtained through linkage to the Australian National Death Index. Results were compared with age-, gender- and calendar year-matched Australian population mortality rates. Analysis included both the standardized mortality ratio (SMR) and relative survival models. Restricted mean survival time (RMST) at 20 years was calculated as a measure of life lost. Cause-specific SMRs (CS-SMRs) were estimated for International Classification of Diseases, Tenth Revision cause of death classifications. RESULTS: A total of 1895 RA patients were included; 74% were female, baseline median age 50 years (interquartile range 41-58), with 204 deaths. There was no increase in mortality over the first 10 years of follow up, but at 20 years the SMR was 1.49 (95% CI 1.30, 1.71) and the relative survival was 94% (95% CI 91, 97). The difference between observed (18.41 years) and expected (18.68 years) RMST was 4 months. Respiratory conditions were an important underlying cause of death in RA, primarily attributable to pneumonia [CS-SMR 5.2 (95% CI 2.3, 10.3)] and interstitial lung disease [CS-SMR 7.6 (95% CI 3.0, 14.7)], however, coronary heart disease [CS-SMR 0.82 (95% CI 0.42, 1.4)] and neoplasms [CS-SMR 1.2 (95% CI 0.89, 1.5)] were not. CONCLUSION: Mortality risk in this RA cohort accrues over time and is moderately increased at 20 years of follow-up. Respiratory diseases may have supplanted cardiovascular diseases as a major contributor to this mortality gap.

Bone Marrow Lesions and Magnetic Resonance Imaging-Detected Structural Abnormalities in Patients With Midfoot Pain and Osteoarthritis: A Cross-Sectional Study.

OBJECTIVE: To compare magnetic resonance imaging (MRI)-detected structural abnormalities in patients with symptomatic midfoot osteoarthritis (OA), patients with persistent midfoot pain, and asymptomatic controls, and to explore the association between MRI features, pain, and foot-related disability. METHODS: One hundred seven adults consisting of 50 patients with symptomatic and radiographically confirmed midfoot OA, 22 adults with persistent midfoot pain but absence of radiographic OA, and 35 asymptomatic adults underwent 3T MRI of the midfoot and clinical assessment. MRIs were read for the presence and severity of abnormalities (bone marrow lesions [BMLs], subchondral cysts, osteophytes, joint space narrowing [JSN], effusion-synovitis, tenosynovitis, and enthesopathy) using the Foot Osteoarthritis MRI Score. Pain and foot-related disability were assessed with the Manchester Foot Pain and Disability Index. RESULTS: The severity sum score of BMLs in the midfoot was greater in patients with midfoot pain and no signs of OA on radiography compared to controls (P = 0.007), with a pattern of involvement in the cuneiform-metatarsal joints similar to that in patients with midfoot OA. In univariable models, BMLs (ρ = 0.307), JSN (ρ = 0.423), and subchondral cysts (ρ = 0.302) were positively associated with pain (P < 0.01). In multivariable models, MRI abnormalities were not associated with pain and disability when adjusted for covariates. CONCLUSION: In individuals with persistent midfoot pain but no signs of OA on radiography, MRI findings suggested an underrecognized prevalence of OA, particularly in the second and third cuneiform-metatarsal joints, where BML patterns were consistent with previously recognized sites of elevated mechanical loading. Joint abnormalities were not strongly associated with pain or foot-related disability.

Association between popliteal artery wall thickness and structural progression in patients with symptomatic knee osteoarthritis.

OBJECTIVE: There is increasing evidence for the involvement of vascular disease in the pathogenesis of knee OA. Popliteal artery wall thickness can be used as a surrogate marker of atherosclerosis. We examined the association between popliteal artery wall thickness and knee cartilage volume in individuals with symptomatic knee OA. METHODS: This prospective cohort study analysed 176 participants from a randomized placebo-controlled trial examining the effect of atorvastatin on structural progression in knee OA. The participants underwent MRI of the study knee at baseline and 2-year follow-up. Popliteal artery wall thickness and tibial cartilage volume were measured from MRI using validated methods. The top quartile of the rate of tibial cartilage volume loss was defined as rapid progression. RESULTS: At baseline, every 10% increase in popliteal artery wall thickness was associated with 120.8 mm3 (95% CI 5.4, 236.2, P = 0.04) lower of medial tibial cartilage volume and 151.9 mm3 (95% CI 12.1, 291.7, P = 0.03) lower of lateral tibial cartilage volume. Longitudinally, for every 10% increase in popliteal artery wall thickness, the annual rate of medial tibial cartilage volume loss was increased by 1.14% (95% CI 0.09%, 2.20%, P = 0.03), and there was a 2.28-fold (95% CI 1.07, 4.83, P = 0.03) risk of rapid progression of medial tibial cartilage loss, adjusted for age, sex, BMI, tibial bone area, smoking, vigorous physical activity, and intervention group allocation. CONCLUSION: The findings support a role for vascular pathology in the progression of knee OA. Targeting atherosclerosis has the potential to improve outcomes in knee OA.

Giant cell arteritis: A population-based retrospective cohort study exploring incidence and clinical presentation in Canterbury, Aotearoa New Zealand.

Background/aim: To determine the epidemiology and clinical features of giant cell arteritis (GCA) in Canterbury, Aotearoa New Zealand, with a particular focus on extra-cranial large vessel disease. Methods: Patients with GCA were identified from radiology and pathology reports, outpatient letters and inpatient hospital admissions in the Canterbury New Zealand from 1 June 2011 to 31 May 2016. Data was collected retrospectively based on review of electronic medical records. Results: There were 142 cases of GCA identified. 65.5% of cases were female with a mean age of 74.2 years. The estimated population incidence for biopsy-proven GCA was 10.5 per 100,000 people over the age of 50 and incidence peaked between 80 and 84 years of age. 10/142 (7%) people were diagnosed with large vessel GCA, often presenting with non-specific symptoms and evidence of vascular insufficiency including limb claudication, vascular bruits, blood pressure and pulse discrepancy, or cerebrovascular accident. Those with limited cranial GCA were more likely to present with the cardinal clinical features of headache and jaw claudication. Patients across the two groups were treated similarly, but those with large vessel disease had greater long-term steroid burden. Rates of aortic complication were low across both groups, although available follow-up data was limited. Conclusion: This study is the first of its kind to describe the clinical characteristics of large vessel GCA in a New Zealand cohort. Despite small case numbers, two distinct subsets of disease were recognized, differentiating patients with cranial and large vessel disease. Our results suggest that utilization of an alternative diagnostic and therapeutic approach may be needed to manage patients with large vessel disease.

Diagnosis of giant cell arteritis by temporal artery biopsy is associated with biopsy length.

Aims: Temporal artery biopsy (TAB) is a widely used method for establishing a diagnosis of Giant Cell Arteritis (GCA). The optimal TAB length for accurate histological GCA diagnosis has been suggested as 15 mm post-fixation (15-20 mm pre-fixation). The aim of this study was to determine the relationship between a histological GCA diagnosis and optimal TAB length in the South Australian (SA) population. Materials and methods: Pre-fixation TAB length (mm) was reported in 825/859 of all samples submitted to SA Pathology between 2014 and 2020 from people aged 50 and over. When more than one biopsy was taken, the longest length was recorded. Analyses of both TAB length and TAB positive proportions were performed by multivariable linear and logistic regression analysis, including covariates sex, age, and calendar year. Results: The median age of participants was 72 (IQR 65, 79) years, 549 (66%) were female. The TAB positive proportion was 172/825 (21%) with a median biopsy length of 14 mm (IQR 9, 18). Biopsy length (mm) was shorter in females (p = 0.001), increased with age (p = 0.006), and a small positive linear trend with calendar year was observed (p = 0.015). The TAB positive proportion was related to older age (slope/decade: 6, 95% CI 3.6, 8.3, p < 0.001) and to TAB length (slope/mm 0.6, 95% CI 0.2, 0.9, p = 0.002), but not sex or calendar year. Comparison of models with TAB length cut-points at 5, 10, 15, 20 mm in terms of diagnostic yield, receiver operating characteristics and Akaike Information Criteria confirmed ≥ 15 mm as an appropriate, recommended TAB length. However, only 383 (46%) of the biopsies in our study met this criteria. The diagnostic yield at this cut-point was estimated as 25% which equates to an expected additional 30 histologically diagnosed GCA patients. Conclusion: This study confirms that TAB biopsy length is a determinant of a histological diagnosis of temporal arteritis, and confirms that a TAB length ≥ 15 mm is optimal. Approximately half the biopsies in this study were shorter than this optimal length, which has likely led to under-diagnosis of biopsy-proven GCA in SA. Further work is needed to ensure appropriate TAB biopsy length.

Attitudes of Australians with inflammatory arthritis to biologic therapy and biosimilars.

Objectives: To investigate the knowledge and beliefs of Australian patients with inflammatory arthritis regarding biologic/targeted synthetic DMARDs (b/tsDMARDs) and biosimilars and their sources of information. Methods: Participants enrolled in the Australian Rheumatology Association Database (ARAD) with RA, PsA and axial SpA were sent an online survey. They were asked about information sources for b/tsDMARDs and how positive or negative this information was. The Beliefs about Medicine Questionnaire (BMQ) was used to measure beliefs about b/tsDMARDs with scores ranging from 1 (strongly disagree) to 5 (strongly agree). Participants were asked about their knowledge of biosimilars and willingness to switch to biosimilar. Results: There was a response rate of 66% (994/1498; 67% female, median age 62 years). Participants currently taking b/tsDMARDs (n = 794) had a high b/tsDMARD-specific BMQ 'necessity' score {median 4.2 [interquartile range (IQR) 3.6-4.8]}, with a lower specific 'concerns' score [median 2.4 (IQR 2.0- 3.0)]. Participants consulted multiple information sources [median 3 (IQR 2-5)]. Positive sources were rheumatologists and educational websites and negative were chat rooms and social media. Only 18% were familiar with biosimilars, with half knowing of availability in Australia. Following a short paragraph describing biosimilars, 75% (744) of participants indicated they would consider switching if recommended by their rheumatologist, with nearly half identifying safety and efficacy of biosimilars as an important concern. Conclusion: Australian patients have positive attitudes towards b/tsDMARDs overall, although little knowledge of biosimilars specifically. They have a high degree of trust in their rheumatologist regarding treatment decisions, even if they are unfamiliar with the medication recommended.

Krill oil improved osteoarthritic knee pain in adults with mild to moderate knee osteoarthritis: a 6-month multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Osteoarthritis (OA) is a major cause of chronic pain and disability worldwide. Treatment generally focuses on symptom relief through nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics, which may incur side effects. Krill oil, rich in anti-inflammatory long-chain (LC) omega-3 ( ω-3) PUFAs and astaxanthin, may be a safe and effective alternative treatment. OBJECTIVES: This study sought to investigate the effects of a commercially available krill oil supplement on knee pain in adults with mild to moderate knee OA. Secondary outcomes were knee stiffness; physical function; NSAID use; Omega-3 Index; and lipid, inflammatory, and safety markers. METHODS: Healthy adults (n = 235, 40-65 y old, BMI >18.5 to <35 kg/m2), clinically diagnosed with mild to moderate knee OA, regular knee pain, and consuming <0.5 g/d LC ω-3 PUFAs, participated in a 6-mo double-blind, randomized, placebo-controlled, multicenter trial. Participants consumed either 4 g krill oil/d (0.60 g EPA/d, 0.28 g DHA/d, 0.45 g astaxanthin/d) or placebo (mixed vegetable oil). Knee outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) numeric scale (normalized to scores of 0-100). Outcomes were assessed at baseline, 3 mo, and 6 mo. RESULTS: Omega-3 Index increased with the krill oil supplement compared with placebo (from 6.0% to 8.9% compared with from 5.5% to 5.4%, P < 0.001). Knee pain score improved in both groups with greater improvements for krill oil than for placebo (difference in adjusted mean change between groups at 6 mo: -5.18; 95% CI: -10.0, -0.32; P = 0.04). Knee stiffness and physical function also had greater improvements with krill oil than with placebo (difference in adjusted mean change between groups at 6 mo: -6.45; 95% CI: -12.1, -0.9 and -4.67; 95% CI: -9.26, -0.05, respectively; P < 0.05). NSAID use, serum lipids, and inflammatory and safety markers did not differ between groups. CONCLUSIONS: Krill oil was safe to consume and resulted in modest improvements in knee pain, stiffness, and physical function in adults with mild to moderate knee OA.This trial was registered at clinicaltrials.gov as NCT03483090.

Patient Perspectives of Disease Activity, Medications and Substance Use in People with Fibromyalgia.

Objective: To explore patient perspectives on disease activity and experiences, as well as medication use of a group of fibromyalgia patients attending a single-centre rheumatology public hospital outpatient setting. Methods: Patients seen in fibromyalgia clinic within a rheumatology unit from July 2016 to December 2019 were posted a voluntary survey with questionnaires pertaining to patient-reported measures of disease impact (FIQR), fatigue (MFI-20) and psychological distress (K10). A free-text section allowed description of disease impact. Patients were also asked to record medication use and comorbidities, which were then compared to the electronic medical records (EMR) of the overall clinic cohort. Results: Forty-five patients responded to the survey (43/45, 95.6% female; mean age 56.5 years). Respondents had generally severe fibromyalgia (mean FIQR 67.1/100, range 23.7-92.8), moderate psychological distress (mean K10 27.5/50, range 14-45) and high fatigue (mean MFI 74.9/100, range 40-96). Free-text responses generated themes of pervasive disease impact and the necessity of adjusting life around unpredictable symptoms. Almost half reported opioid (21/45, 46.7%) and gabapentinoid (19/45, 42.2%) use. 16/41 (39%) use cannabinoids for their fibromyalgia symptoms. Comparing medication use with survey non-respondents (n=85), there was generally similar representation except for significantly greater NSAID use among survey respondents (33/45, 73.3% vs 22/85, 25.9%, p<0.001). Conclusion: For patients living with fibromyalgia in this study, there were high levels of disease activity, psychological distress and fatigue. Patients described the need to accept disease-imposed limitations and life adjustments. Almost half reported opioid use, despite evidence suggesting poor efficacy and possible harm.

Factors influencing clinician prescribing of disease-modifying anti-rheumatic drugs for inflammatory arthritis: A systematic review and thematic synthesis of qualitative studies.

Understanding factors that influence prescribing of disease-modifying anti-rheumatic drugs (DMARDs) will inform strategies to optimise care of people with inflammatory arthritis. We performed a systematic review and thematic synthesis of qualitative studies to explore these factors. Inclusion criteria were: use of qualitative or mixed methods; rheumatologist, nurse or pharmacist perspectives; prescription of any DMARD (conventional [cs], targeted synthetic [ts], biologic [b], biosimilars) and/or glucocorticoids; in any healthcare setting in any country. MEDLINE, Embase and EBSCOhost CINAHL Plus were searched from inception to 15 June 2021. Pairs of review authors independently identified studies for inclusion, assessed methodological quality using the Critical Appraisal Skills Programme checklist, and extracted and thematically synthesised data. Confidence in synthesis themes was evaluated using the GRADE Confidence in Evidence from Reviews of Qualitative research (CERQual) approach. We included 15 studies involving 716 clinicians (683 rheumatologists, 27 nurses, 6 pharmacists) across 10 countries, all focusing on management of patients with rheumatoid arthritis (RA). Six themes were identified: Rheumatologist prescribing is influenced by patients' characteristics, preferences, symptoms and negative responses to medication; Rheumatologist knowledge, experience, habits and subjective judgements are strong drivers of prescribing behaviour; High demands on consultation time impede shared decision-making; Costs and complexity of medication funding arrangements limit prescribing options; Clinicians recognise the importance of providing patient education about medication options; and Clinicians value colleagues' opinions and support to inform prescribing decisions. The majority of themes were graded as moderate confidence (n  =  4), reflecting they are likely to reasonably represent the factors influencing prescribing of DMARDs to people with RA. Quality improvement strategies that address these factors are likely to support best practice pharmacologic management of RA and may be potentially applicable to other types of inflammatory arthritis. High demand on consultation time and complexity of medication funding arrangements are system factors that may or may not be amenable to change. Easily accessible living national guidelines which include lay summaries and treatment algorithms to support prescribing decisions may address some of the themes.

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.