Definition of rheumatoid arthritis flare based on SDAI and CDAI.

OBJECTIVE: To develop and validate definitions for disease flares in rheumatoid arthritis (RA) based on the quantitative Simplified and Clinical Disease Activity Indices (SDAI, CDAI). METHODS: We analysed RA treatment courses from the Norwegian disease-modifying antirheumatic drug registry (NOR-DMARD) and the Vienna RA cohort. In a receiver operating curve analysis, we determined flare definitions for absolute changes in SDAI and CDAI based on a semiquantitative patient anchor. NOR-DMARD was sampled into an 80%-training cohort for cut point derivation and a 20%-test cohort for internal validation. The definitions were then externally validated in the independent Vienna RA cohort and tested regarding their performance on longitudinal, content, face, and construct validity. RESULTS: We analysed 4256 treatment courses from NOR-DMARD and 2557 from the Vienna RA cohort. The preliminary definitions for absolute changes in SDAI and CDAI for flare are an increase of 4.7 and 4.5, respectively. The definitions performed well in the test and external validation cohorts, and showed clinical face and construct validity, as flares significantly impact both functional ( ∆ Health Assessment Questionnaire flare vs no-flare +0.43; p<0.001) and structural ( ∆ modified Sharp Score 43% higher after flare; p<0.001) disease outcomes, and reflect consistent worsening across all disease core sets, both patient reported and objective. CONCLUSION: We here provide novel definitions for flare in RA based on SDAI and CDAI, validated in two large independent real-world cohorts. In times of highly effective medications for RA, and consideration of their tapering, these definitions will be useful for guiding decision making in clinical practice and designing clinical trials.

Cut-Offs for Disease Activity States in Axial Spondyloarthritis With Ankylosing Spondylitis Disease Activity Score (ASDAS) Based on C-Reactive Protein and ASDAS Based on Erythrocyte Sedimentation Rate: Are They Interchangeable?

OBJECTIVE: Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) is recommended over ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1, and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs. METHODS: We used data from patients with axSpA from 9 European registries initiating a tumor necrosis factor inhibitor. ASDAS-ESR cut-offs were estimated using the Youden index. The level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other. RESULTS: In 3664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9, and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data. CONCLUSION: We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.

Uptake and effectiveness of newer biologic and targeted synthetic disease-modifying antirheumatic drugs in psoriatic arthritis: results from five Nordic biologics registries.

BACKGROUND: We aimed to describe the uptake of newer biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in psoriatic arthritis (PsA) in the Nordic countries and to compare their retention and effectiveness. METHODS: Patients with PsA starting a b/tsDMARD in 2012-2020 in five Nordic rheumatology registers were included. Uptake and patient characteristics were described, with comorbidities identified from linkages to national patient registries. One-year retention and 6-month effectiveness (proportions achieving low disease activity (LDA) on the Disease Activity Index for PSoriatic Arthritis based on 28-joint evaluation) for the newer b/tsDMARDs (abatacept/apremilast/ixekizumab/secukinumab/tofacitinib/ustekinumab) were compared with adalimumab through adjusted regression models stratified by treatment course (first, second/third, and fourth or more). RESULTS: In total, 5659 treatment courses with adalimumab (56% biologic-naïve) and 4767 courses with a newer b/tsDMARD (21% biologic-naïve) were included. The uptake of newer b/tsDMARDs increased from 2014 and plateaued in 2018. Patient characteristics appeared similar across treatments at treatment start. Adalimumab was more often used as the first course and newer b/tsDMARDs more often in biologic-experienced patients. Used as a second/third b/tsDMARD, the retention rate and the proportion achieving LDA were significantly better for adalimumab (rate 65%, proportion 59%) compared with abatacept (45%, 37%), apremilast (43%, 35%), ixekizumab (LDA only, 40%) and ustekinumab (LDA only, 40%), but not significantly different from other b/tsDMARDs. CONCLUSION: Uptake of newer b/tsDMARDs occurred mainly in biologic-experienced patients. Regardless of mode of action, only a minority of patients starting a second or later b/tsDMARD course remained on drug and achieved LDA. Superior outcomes for adalimumab indicate that the positioning of newer b/tsDMARDs in the PsA treatment algorithm remains to be established.

Persisting mortality gap in systemic lupus erythematosus; a population-based study on juvenile- and adult-onset SLE in Norway 1999-2022.

OBJECTIVE: To estimate mortality and survival rates of systemic lupus erythematosus (SLE) in a contemporary, population-based setting and assess potential influences by time, sex, ethnicity, classification criteria and age at diagnosis. METHODS: We assessed mortality and survival in the Nor-SLE cohort, which includes all chart-review confirmed SLE cases resident in Southeast Norway (population 2.9 million) 1999-2017. Study end was at death, emigration, or 1 October 2022. We defined juvenile SLE by age <16 years at diagnosis. For standardized mortality rate (SMR) estimates, we applied 15 population controls per case, all matched for age, sex, residency, and ethnicity. We analyzed survival by Kaplan-Meier and risk factors by cox regression. RESULTS: The Nor-SLE cohort included 1558 SLE cases, of whom 749 were incident and met the 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology (2019-EA) classification criteria. SMR was increased to 1.8 (95% CI 1.6-2.2) in incident adult-onset SLE but did not differ between females and males. Survival rates at 5-, 10-, 15 and 20-years were lower in incident adult-onset SLE than in matched controls. In multivariable analysis, lupus nephritis associated with decreased survival, while sex did not. Separate, long-term mortality analyses in the total Nor-SLE cohort showed that SMR peaked at 7.2 (95% CI 3.3-14) in juvenile-onset SLE (n = 93) and fell gradually by increasing age at SLE diagnosis. CONCLUSION: This study shows persistence of a mortality gap between adult-onset SLE and controls at population level and provides indications of worryingly high mortality in juvenile-onset SLE.

Is the risk of infection higher during treatment with secukinumab than with TNF inhibitors? An observational study from the Nordic countries.

OBJECTIVES: The positioning of secukinumab in the treatment of axial SpA (axSpA) and PsA is debated, partly due to a limited understanding of the comparative safety of the available treatments. We aimed to assess the risk of the key safety outcome infections during treatment with secukinumab and TNF inhibitors (TNFi). METHODS: Patients with SpA and PsA starting secukinumab or TNFi year 2015 through 2018 were identified in four Nordic rheumatology registers. The first hospitalized infection during the first year of treatment was identified through linkage to national registers. Incidence rates (IRs) with 95% CIs per 100 patient-years were calculated. Adjusted hazard ratios were estimated through Cox regression, with secukinumab as the reference. Several sensitivity analyses were performed to investigate confounding by indication. RESULTS: Among 7708 patients with SpA and 5760 patients with PsA, we identified 16 229 treatment courses of TNFi (53% bionaïve) and 1948 with secukinumab (11% bionaïve). For secukinumab, the first-year risk of hospitalized infection was 3.5% (IR 5.0; 3.9-6.3), compared with 1.7% (IR 2.3; 1.7-3.0) during 3201 courses with adalimumab, with the IRs for other TNFi lying in between these values. The adjusted HR for adalimumab, compared with secukinumab, was 0.58 (0.39-0.85). In sensitivity analyses, the difference from secukinumab was somewhat attenuated and in some analyses no longer statistically significant. CONCLUSION: When used according to clinical practice in the Nordic countries, the observed first-year absolute risk of hospitalized infection was doubled for secukinumab compared with adalimumab. This excess risk seemed largely explained by confounding by indication.

Serious infections in patients with rheumatoid arthritis and psoriatic arthritis treated with tumour necrosis factor inhibitors: data from register linkage of the NOR-DMARD study.

OBJECTIVES: To estimate the incidence of serious infections (SIs) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with tumour necrosis factor inhibitor (TNFi), and compare risk of SIs between patients with RA and PsA. METHODS: We included patients with RA and PsA from the NORwegian-Disease Modifying Anti-Rheumatic Drug registry starting TNFi treatment. Crude incidence rates (IRs) and IR ratio for SIs were calculated. The risk of SIs in patients with RA and PsA was compared using adjusted Cox-regression models. RESULTS: A total of 3169 TNFi treatment courses (RA/PsA: 1778/1391) were identified in 2359 patients. Patients with RA were significantly older with more extensive use of co-medication. The crude IRs for SIs were 4.17 (95% CI 3.52 to 4.95) in patients with RA and 2.16 (95% CI 1.66 to 2.81) in patients with PsA. Compared with the patients with RA, patients with PsA had a lower risk of SIs (HR 0.59, 95% CI 0.41 to 0.85, p=0.004) in complete set analysis. The reduced risk in PsA versus RA remained significant after multiple adjustments and consistent across strata based on age, gender and disease status. CONCLUSIONS: Compared with patients with RA, the risk of SIs was significantly lower in patients with PsA during TNFi exposure.

Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries.

OBJECTIVES: To compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator. METHODS: Observational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008-2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort. RESULTS: 24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted. CONCLUSION: The rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs.

The changing states of fibromyalgia in patients with axial spondyloarthritis: results from the British Society of Rheumatology Biologics Register for Ankylosing Spondylitis.

OBJECTIVES: To identify factors associated with FM development and recovery in patients with axial SpA (axSpA). METHODS: The British Society of Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) recruited patients with axSpA from 83 centres in a prospective study. FM was diagnosed using the self-reported Fibromyalgia Survey Diagnostic Criteria from 2015. Measures of axSpA disease activity and clinical findings were recorded at regular intervals. We identified predictors for FM development and recovery between yearly visits using uni- and multivariable logistic regression models. RESULTS: A total of 801 participants, 247 (30.8%) female, had two or more visits and were eligible for inclusion. A total of 686 participants did not have FM at baseline, of whom 45 had developed FM at follow-up, while 115 participants had FM at baseline, of whom 77 had recovered at follow-up. A high baseline BASDAI score [odds ratio (OR) 1.27 (95% CI 1.08, 1.49)] and Widespread Pain Index (WPI) [OR 1.14 (95% CI 1.02, 1.28)] were significantly associated with FM development in the final multivariable model. A low baseline BASFI score [OR 0.68 (95% CI 0.53, 0.86)] and WPI [OR 0.84 (95% CI 0.720, 0.97)] and starting a TNF inhibitor [OR 3.86 (95% CI 1.54, 9.71)] were significantly associated with FM recovery. CONCLUSION: High levels of disease activity and the presence of widespread pain is associated with the development of FM in patients with axSpA, while low levels of the same variables and starting a TNF inhibitor are associated with recovery from FM. The presence of comorbid FM should be considered in patients with persistent high axSpA disease activity and widespread pain.

Inflammatory hallmarks of lesser prominence in psoriatic arthritis patients starting biologics: a Nordic population-based cohort study.

OBJECTIVES: To assess secular trends in baseline characteristics of PsA patients initiating their first or subsequent biologic DMARD (bDMARD) therapy and to explore prescription patterns and treatment rates of bDMARDs from 2006 to 2017 in the Nordic countries. METHODS: PsA patients registered in the Nordic rheumatology registries initiating any treatment with bDMARDs were identified. The bDMARDs were grouped as original TNF inhibitor [TNFi; adalimumab (ADA), etanercept (ETN) and infliximab (IFX)]; certolizumab pegol (CZP) and golimumab (GOL); biosimilars and ustekinumab, based on the date of release. Baseline characteristics were compared for the five countries, supplemented by secular trends with R2 calculations and point prevalence of bDMARD treatment. RESULTS: A total of 18 089 patients were identified (Denmark, 4361; Iceland, 449; Norway, 1948; Finland, 1069; Sweden, 10 262). A total of 54% of the patients were female, 34.3% of patients initiated an original TNFi, 8% CZP and GOL, 7.5% biosimilars and 0.3% ustekinumab as a first-line bDMARD. Subsequent bDMARDs were 25.2% original TNFi, 9% CZP and GOL, 12% biosimilars and 2.1% ustekinumab. From 2015 through 2017 there was a rapid uptake of biosimilars. The total of first-line bDMARD initiators with lower disease activity increased from 2006 to 2017, where an R2 close to 1 showed a strong association. CONCLUSION: Across the Nordic countries, the number of prescribed bDMARDs increased from 2006 to 2017, indicating a previously unmet need for bDMARDs in the PsA population. In recent years, PsA patients have initiated bDMARDs with lower disease activity compared with previous years, suggesting that bDMARDs are initiated in patients with a less active inflammatory phenotype.

Trends in all-cause and cardiovascular mortality in patients with incident rheumatoid arthritis: a 20-year follow-up matched case-cohort study.

OBJECTIVES: To examine all-cause and cardiovascular disease (CVD) mortality in consecutive cohorts of patients with incident RA, compared with population comparators. METHODS: The Oslo RA register inclusion criteria were diagnosis of RA (1987 ACR criteria) and residency in Oslo. Patients with disease onset 1994-2008 and 10 matched comparators for each case were linked to the Norwegian Cause of Death Registry. Hazard ratios for all-cause and CVD mortality were calculated for 5, 10, 15 and 20 years of observation using stratified cox-regression models. Mortality trends were estimated by multivariate cox-regression. RESULTS: 443, 479 and 469 cases with disease incidence in the periods 94-98, 99-03 and 04-08 were matched to 4430, 4790 and 4690 comparators, respectively. For cases diagnosed between 1994 and 2003, the all-cause mortality of cases diverged significantly from comparators after 10 years of disease duration [hazard ratio (95% CI) 94-98 cohort 1.42 (1.15-1.75): 99-03 cohort 1.37 (1.08-1.73)]. CVD related mortality was significantly increased after 5 years for the 94-98 cohort [hazard ratio (95% CI) 1.86 (1.16-2.98) and after 10 years for the 99-03 cohort 1.80 (1.20-2.70)]. Increased mortality was not observed in the 04-08 cohort where cases had significantly lower 10-year all-cause and CVD mortality compared with earlier cohorts. CONCLUSION: All-cause and CVD mortality were significantly increased in RA patients diagnosed from 1994 to 2003, compared with matched comparators, but not in patients diagnosed after 2004. This may indicate that modern treatment strategies have a positive impact on mortality in patients with RA.

Swollen, but not tender joints, are independently associated with ultrasound synovitis: results from a longitudinal observational study of patients with established rheumatoid arthritis.

OBJECTIVES: Joint swelling and tenderness are considered a proxy for inflammation in patients with rheumatoid arthritis (RA). With ultrasound-detected inflammation as reference, our objectives were to explore on patient and joint level the associations between ultrasound synovitis and joint swelling, tenderness and patient-reported joint pain (PRJP). METHODS: 209 patients with established RA were examined six times during 12 months with assessment of 32 joints in upper/lower extremities for joint swelling/tenderness and Grey scale (GS)/power Doppler (PD) synovitis. PRJP was assessed on a manikin. Correlations between different sum scores were at each examination calculated using Spearman's rho (r), agreement at joint level was examined by Cohen's kappa and logistic regression models were used to explore the associations between joint assessment and GS/PD scores. RESULTS: At patient level, swollen joints were strongly correlated with GS/PD sum scores (r=0.64-0.88), while tender joints were primarily associated with PRJP (r=0.54-0.68). At joint level, GS/PD pathology had higher agreement with swelling (kappa 0.54-0.57) than tenderness (kappa 0.20-0.21) or PRJP (0.23-0.25). Higher percentages of joints were swollen according to increasing GS/PD scores, independently of joint tenderness. However, joints being tender, but not swollen, were not associated with GS/PD scores. Receiver operating curves showed swollen but not tender joints to be associated with GS/PD scores. CONCLUSIONS: Swollen joints were strongly associated with ultrasound detected synovitis at both patient and joint level, while this association was not found for tender joints. These results may question if tender joints reflect ongoing inflammation in established RA.

Carbon nitrides: synthesis and characterization of a new class of functional materials.

Carbon nitride compounds with high N : C ratios and graphitic to polymeric structures are being investigated as potential next-generation materials for incorporation in devices for energy conversion and storage as well as for optoelectronic and catalysis applications. The materials are built from C- and N-containing heterocycles with heptazine or triazine rings linked via sp2-bonded N atoms (N(C)3 units) or -NH- groups. The electronic, chemical and optical functionalities are determined by the nature of the local to extended structures as well as the chemical composition of the materials. Because of their typically amorphous to nanocrystalline nature and variable composition, significant challenges remain to fully assess and calibrate the structure-functionality relationships among carbon nitride materials. It is also important to devise a useful and consistent approach to naming the different classes of carbon nitride compounds that accurately describes their chemical and structural characteristics related to their functional performance. Here we evaluate the current state of understanding to highlight key issues in these areas and point out new directions in their development as advanced technological materials.

Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015.

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.

CRP and ASDAS are associated with future elevated arterial stiffness, a risk marker of cardiovascular disease, in patients with ankylosing spondylitis: results after 5-year follow-up.

OBJECTIVE: To identify factors associated with elevated arterial stiffness in a 5-year follow-up of patients with ankylosing spondylitis (AS). METHODS: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath AS disease activity index (BASDAI) and AS disease activity score (ASDAS) were recorded in 2003, and arterial stiffness (Augmentation Index (AIx) and pulse wave velocity (PWV)) in 2008/2009. Patients were grouped into quartiles according to baseline CRP, ESR and BASDAI and four ASDAS groups. Trend analyses were performed using ANCOVA (AIx/PWV as dependent variable) with separate models for CRP, ESR, BASDAI and ASDAS (age and gender adjusted). Independent predictors of future AIx and PWV levels were identified in multivariate linear regression models. RESULTS: In total, 85 patients participated. Increasing baseline values of CRP, ESR and ASDAS were associated with elevated AIx on follow-up (p(trend) 0.01, 0.05 and 0.04, respectively). Similar non-significant patterns were seen for PWV. In the multivariate analyses, baseline CRP and ASDAS were independently associated with future elevated AIx (p=0.03 and0.02, respectively). In the multivariate PWV model, results for CRP and ASDAS were non-significant. CONCLUSIONS: Baseline CRP and ASDAS were associated with future elevated arterial stiffness measured as AIx, supporting that disease activity is related to future risk of cardiovascular disease in patients with AS.

Relationship between types of radiographic damage and disability in patients with rheumatoid arthritis in the EURIDISS cohort: a longitudinal study.

OBJECTIVE: The aim of this study was to assess if any of the different types of radiographic damage [true joint space narrowing (JSN), (sub)luxation and erosions] are preferentially related to disability in patients with RA. METHODS: Longitudinal data from 167 RA patients from the European Research on Incapacitating Diseases and Social Support study over 10 years were analysed to investigate the relationship between the three types of radiographic damage and disability [grip strength, HAQ and the dexterity scale in the Arthritis Impact Measurement Scales (AIMS)]. A longitudinal analysis including separate models per type of damage and joint group and combined models including all information was conducted. RESULTS: All types of damage were inversely related to grip strength in the analysis of separate models, but only true JSN independently remained statistically significant in the combined analysis [ß = -0.087 (95% CI -0.151, -0.022)]. Neither JSN, (sub)luxation nor erosions were associated with HAQ score, while erosions were associated with AIMS dexterity only in the analysis of separate models. After stratifying for hand joint group, erosions at MCP joints [ß = -0.288 (95% CI -0.556, -0.019)] and true JSN at the wrist [ß = -0.132 (95% CI -0.234, -0.030)] were significantly related to grip strength. Erosions at the PIP [ß = 0.017 (95% CI 0.005, 0.028)] and MCP joints [ß = 0.114 (95% CI 0.010, 0.217)] was the only type of damage associated with HAQ and AIMS dexterity, respectively. CONCLUSION: All types of radiographically visible joint damage interfere with important aspects of physical functions. True JSN is most closely related to hand function.

Insights into cancer surveillance in Central and Eastern Europe, Israel and Turkey.

The current cancer landscape within transitional economies in central and Eastern Europe and the Mediterranean area is not particularly optimistic. Current perceptions are often based on extrapolations from other countries and regions; and hence the authors collaborated with the South Eastern Europe Oncology Group (SEEROG) to collect information on cancer registration in Central and Eastern Europe, Israel and Turkey. Healthcare authorities and specialist oncology centres in 21 countries in the region were contacted for information on cancer registries in their countries. Based on this information, the authors believe that the recording and reporting of data on cancer in the region is at an acceptable level. The authors discuss and compare institution- and population-based registries, and present opinions on elements of an 'ideal registry' based on the survey replies and comparisons with other registries. A comparison with the sources used for GLOBOCAN 2008 illustrates the need for consistent data to be communicated, published and utilised throughout the region and the oncology community. The authors conclude by considering the potential value of collaboration between health authorities across the region, as well as between the clinical and epidemiological communities, to ensure that cancer data are consistently collected, verified and made public.

Non-steroidal anti-inflammatory drugs and risk of pulmonary embolism in patients with inflammatory joint disease-results from the nationwide Norwegian Cardio-rheuma registry.

AIMS: Patients with inflammatory joint diseases (IJD), including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) have increased rates of pulmonary embolism (PE). Non-steroidal anti-inflammatory drugs (NSAIDs) use is associated with PE in the general population. Our aim was to evaluate the association between NSAIDs use and PE in IJD patients. METHODS AND RESULTS: Using individual-level registry data from the whole Norwegian population, including data from the Norwegian Patient Registry and the Norwegian Prescription Database, we: (1) evaluated PE risk in IJD compared to non-IJD individuals, (2) applied the self-controlled case series method to evaluate if PE risks were associated with use of traditional NSAIDs (tNSAIDs) and selective cox-2 inhibitors (coxibs). After a one-year wash-out period, we followed 4 660 475 adults, including 74 001 with IJD (RA: 39 050, PsA: 20 803, and axSpA: 18 591) for a median of 9.0 years. Crude PE incidence rates per 1000 patient years were 2.02 in IJD and 1.01 in non-IJD individuals. Age and sex adjusted hazard ratios for PE events were 1.57 for IJD patients compared to non-IJD. Incidence rate ratios (IRR) [95% confidence interval (CI)] for PE during tNSAIDs use were 0.78 (0.64-0.94, P = 0.010) in IJD and 1.68 (1.61-1.76, P < 0.001) in non-IJD. IRR (95% CI) for PE during coxibs use was 1.75 (1.10-2.79, P = 0.018) in IJD and 2.80 (2.47-3.18, P < 0.001) for non-IJD. CONCLUSION: Pulmonary embolism rates appeared to be higher in IJD than among non-IJD subjects in our study. Traditional NSAIDs may protect against PE in IJD patients, while coxibs may associated with increased PE risk.

Participatory Development of a Virtual Reality Exercise Program for People with Chronic Pain.

Background: By describing how a participatory process led to changes in the design of a study of a virtual reality (VR)-guided exercise and mindfulness intervention tailored to people with chronic musculoskeletal pain, this article makes the case for including end user at an early stage when planning research within this field. Methods: A multidisciplinary panel including end-user representatives, researcher, clinicians, and VR developers participated in a 1-day workshop to design a randomized study and a VR-guided intervention. Results: Through the participatory process, changes were made to the original study design with respect to experimental design, duration, content of VR interventions and mode of delivery. Conclusion: This case exemplifies the importance of including end-user participants in the early phases of planning VR interventions for people with chronic pain.