Discovery of calcite as a new pro-inflammatory calcium-containing crystal in human osteoarthritic synovial fluid.

OBJECTIVE: We aimed to characterize calcium-containing crystals present in synovial fluid from patients with knee osteoarthritis (OA) using Raman spectroscopy, and specifically investigate the biological effects of calcite crystals. DESIGN: Thirty-two synovial fluid samples were collected pre-operatively from knee OA patients undergoing total joint arthroplasty. An integrated Raman polarized light microscope was used for identification of crystals in synovial fluid. Human peripheral blood mononuclear cells (PBMC's), human OA articular chondrocytes (HACs) and fibroblast-like synoviocytes (FLSs) were exposed to calcite crystals. Expression of relevant cytokines and inflammatory genes were measured using ELISA and real-time PCR. RESULTS: Various calcium-containing crystals were identified, including calcium pyrophosphate (37.5 %) and basic calcium phosphate (21.8 %), but they were never found simultaneously in the same OA synovial fluid sample. For the first time, we discovered the presence of calcite crystals in 93.8 % of the samples, while dolomite was detected in 25 % of the cases. Characterization of the cellular response to calcite crystal exposure revealed increased production of innate immune-derived cytokines by PBMC's, when co-stimulated with lipopolysaccharide (LPS). Additionally, calcite crystal stimulation of HACs and FLSs resulted in enhanced secretion of pro-inflammatory molecules and alterations in the expression of extracellular matrix remodeling enzymes. CONCLUSIONS: This study highlights the unique role of Raman spectroscopy in OA crystal research and identified calcite as a novel pro-inflammatory crystal type in OA synovial fluid. Understanding the role of specific crystal species in the OA joint may open new avenues for pharmacological interventions and personalized approaches to treating OA.

Physiological Effects of High-Flow Tracheal Oxygen in Tracheostomized Patients Weaning From Mechanical Ventilation.

BACKGROUND: High-flow tracheal oxygen (HFTO) is being used as supportive therapy during weaning in tracheostomized patients difficult to wean from invasive mechanical ventilation. There is, however, no clinical evidence for such a strategy. Therefore, we conducted a systematic review to summarize studies evaluating the physiologic effects of HFTO during tracheostomy-facilitated weaning and to identify potential areas for future research in this field. METHODS: Observational and interventional studies on critically ill subjects weaning from mechanical ventilation via tracheostomy published until December 22, 2022, were eligible. Studies on high-flow oxygen, only in children, non-human models or animals, on clinical outcome only, abstracts without full-text availability, case reports, and reviews were excluded. Main outcomes were end-expiratory lung volume (EELV) and tidal volume using electrical impedance tomography, respiratory effort assessed by esophageal manometry, work of breathing and neuroventilatory drive as assessed by electrical activity of the diaphragm (EAdi) signal, airway pressure (Paw), oxygenation (PaO2 /FIO2 or SpO2 /FIO2 ), breathing frequency, tidal volume, and PaCO2 . RESULTS: In total, 1,327 references were identified, of which 5 were included. In all studies, HFTO was administered with flow 50 L/min and compared to conventional O2 therapy in a crossover design. The total average duration of invasive ventilation at time of measurements ranged from 11-27 d. In two studies, PaO2 /FIO2 and mean Paw were higher with HFTO. EELV, tidal volumes, esophageal pressure swings, and EAdi were similar during high-flow tracheal oxygen and conventional O2 therapy. CONCLUSIONS: The main physiological effect of HFTO as compared to conventional O2 therapy in tracheostomized subjects weaning from mechanical ventilation was improved oxygenation that is probably flow-dependent. Respiratory effort, lung aeration, neuroventilatory drive, and ventilation were similar for HFTO and conventional O2 therapy. Future studies on HFTO should be performed early in the weaning process and should evaluate its effect on sputum clearance and patient-centered outcomes like dyspnea.

Diagnostic Accuracy of Raman Spectroscopy Integrated With Polarized Light Microscopy for Calcium Pyrophosphate-Associated Arthritis.

OBJECTIVE: We studied the performance of integrated Raman polarized light microscopy (iRPolM) for the identification of calcium pyrophosphate (CPP)-associated arthritis (CPPD). METHODS: This is a diagnostic accuracy study including 400 consecutive synovial fluid samples from a single hospital in the Netherlands. Accuracy measures were calculated against polarized light microscopy (PLM) and the 2023 American College of Rheumatology (ACR)/EULAR criteria set for CPPD. RESULTS: The interrater reliability between iRPolM and the 2023 ACR/EULAR criteria set for CPPD was strong (κ = 0.88). The diagnostic performance of iRPolM compared to the 2023 ACR/EULAR criteria set was sensitivity 86.0% (95% confidence interval [CI] 73.3-94.2), specificity 99.1% (95% CI 97.5-99.8), positive likelihood ratio 100.33 (95% CI 32.3-311.3), negative likelihood ratio 0.14 (95% CI 0.07-0.28), positive predictive value 93.5% (95% CI 82.2-97.8), negative predictive value 98.0% (95% CI 82.2-97.8), and accuracy 97.5% (95% CI 95.5-98.8). We allowed rheumatologists to rate the certainty of their microscopic identification of CPP and found a large correspondence between iRPolM and a certain identification (κ = 0.87), whereas only 10% of the uncertain CPP identifications could be confirmed with iRPolM. We identified several novel particle types in synovial fluid analysis, including calcium carbonate crystals, deposited carotenoids, microplastics, and three types of Maltese cross birefringent objects. CONCLUSION: iRPolM can easily identify CPP crystals with a strong diagnostic performance. PLM alone is not specific enough to reliably resolve complicated cases, and the implementation of Raman spectroscopy in rheumatology practice can be of benefit to patients with suspected CPPD.

Safety and Outcome of High-Flow Nasal Oxygen Therapy Outside ICU Setting in Hypoxemic Patients With COVID-19.

OBJECTIVE: High-flow nasal oxygen (HFNO) therapy is frequently applied outside ICU setting in hypoxemic patients with COVID-19. However, safety concerns limit more widespread use. We aimed to assess the safety and clinical outcomes of initiation of HFNO therapy in COVID-19 on non-ICU wards. DESIGN: Prospective observational multicenter pragmatic study. SETTING: Respiratory wards and ICUs of 10 hospitals in The Netherlands. PATIENTS: Adult patients treated with HFNO for COVID-19-associated hypoxemia between December 2020 and July 2021 were included. Patients with treatment limitations were excluded from this analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included intubation and mortality rate, duration of hospital and ICU stay, severity of respiratory failure, and complications. Using propensity-matched analysis, we compared patients who initiated HFNO on the wards versus those in ICU. Six hundred eight patients were included, of whom 379 started HFNO on the ward and 229 in the ICU. The intubation rate in the matched cohort ( n = 214 patients) was 53% and 60% in ward and ICU starters, respectively ( p = 0.41). Mortality rates were comparable between groups (28-d [8% vs 13%], p = 0.28). ICU-free days were significantly higher in ward starters (21 vs 17 d, p < 0.001). No patient died before endotracheal intubation, and the severity of respiratory failure surrounding invasive ventilation and clinical outcomes did not differ between intubated ward and ICU starters (respiratory rate-oxygenation index 3.20 vs 3.38; Pa o2 :F io2 ratio 65 vs 64 mm Hg; prone positioning after intubation 81 vs 78%; mortality rate 17 vs 25% and ventilator-free days at 28 d 15 vs 13 d, all p values > 0.05). CONCLUSIONS: In this large cohort of hypoxemic patients with COVID-19, initiation of HFNO outside the ICU was safe, and clinical outcomes were similar to initiation in the ICU. Furthermore, the initiation of HFNO on wards saved time in ICU without excess mortality or complicated course. Our results indicate that HFNO initiation outside ICU should be further explored in other hypoxemic diseases and clinical settings aiming to preserve ICU capacity and healthcare costs.

Diaphragm excursions as proxy for tidal volume during spontaneous breathing in invasively ventilated ICU patients.

There is a need to monitor tidal volume in critically ill patients with acute respiratory failure, given its relation with adverse clinical outcome. However, quantification of tidal volume in non-intubated patients is challenging. In this proof-of-concept study, we evaluated whether ultrasound measurements of diaphragm excursion could be a valid surrogate for tidal volume in patients with respiratory failure. Diaphragm excursions and tidal volumes were simultaneously measured in invasively ventilated patients (N = 21) and healthy volunteers (N = 20). Linear mixed models were used to estimate the ratio between tidal volume and diaphragm excursion. The tidal volume-diaphragm excursion ratio was 201 mL/cm in ICU patients [95% confidence interval (CI) 161-240 mL/cm], and 361 (294-428) mL/cm in healthy volunteers. An excellent association was shown within participants (R2 = 0.96 in ICU patients, R2 = 0.90 in healthy volunteers). However, the differences between observed tidal volume and tidal volume as predicted by the linear mixed models were considerable: the 95% limits of agreement in Bland-Altman plots were ± 91 mL in ICU patients and ± 396 mL in healthy volunteers. Likewise, the variability in tidal volume estimation between participants was large. This study shows that diaphragm excursions measured with ultrasound correlate with tidal volume, yet quantification of absolute tidal volume from diaphragm excursion is unreliable.

Antibodies against angiotensin II receptor type 1 and endothelin A receptor are increased in COVID-19 patients.

Background: Increased titers of autoantibodies targeting the G-protein-coupled receptors angiotensin II type 1 receptor (AT1R) and endotelin-1 type A receptor (ETAR) are associated with severe coronavirus disease 2019 (COVID-19) infection. The aim of this study was to determine whether 1) these antibodies are specifically related to COVID-19 disease pathogenesis or increased during any severe respiratory illness, 2) if they are formed during illness, and 3) if they correlate with inflammatory markers or long-term symptoms. Methods: Antibodies against AT1R, ETAR, and antinuclear antibodies (ANAs) were measured in n=40 prospectively enrolled COVID-19 patients and n=207 COVID-19 patients included in a biobank. Clinical and laboratory findings were prospectively and retrospectively assessed in both cohorts, and results were combined for analysis. The presence of auto-antibodies against AT1R or ETAR in peripheral blood was compared between hospitalized patients with COVID-19 and controls (n=39). Additionally, AT1R and ETAR titers were compared between patients with an unfavorable disease course, defined as intensive care admission and/or death during hospital admission (n=121), to those with a favorable disease course (n=126). A subset of intubated patients with severe COVID-19 were compared to intubated patients with acute respiratory distress syndrome (ARDS) due to any other cause. Results: Significantly increased AT1R and ETAR antibody titers were found in COVID-19 patients compared to controls, while titers were equal between favorable and unfavorable COVID-19 disease course groups. On ICU, intubated patients with COVID-19 had significantly increased AT1R and ETAR titers compared to patients with ARDS due to any other cause. The titers did not correlate with baseline inflammatory markers during admission or with diffusion capacity, cognitive impairment, or fatigue measured at 3 months follow-up. Conclusions: In patients hospitalized for COVID-19, antibodies against AT1R and ETAR are increased compared to controls and patients with ARDS due to other causes than COVID-19. The baseline antibody titers do not correlate with inflammatory markers or long-term symptoms in this study.

Test characteristics of Raman spectroscopy integrated with polarized light microscopy for the diagnosis of acute gouty arthritis.

OBJECTIVES: We studied the performance of Raman spectroscopy integrated with polarized light microscopy (iRPolM) as a next-generation technique for synovial fluid analysis in gout. METHODS: This is a prospective study, including consecutive synovial fluid samples drawn from any peripheral swollen joint. Diagnostic accuracy was compared to the 2015 ACR/EULAR Gout classification criteria as a reference test and to polarized light microscopy (PLM) analysis by a rheumatologist. Synovial fluid was analysed with iRPolM after unblinding the PLM results. RESULTS: Two hundred unselected consecutive patient samples were included in this study. Validation against clinical criteria: 67 patients were classified as gout according to 2015 ACR/EULAR classification criteria. Compared to the 2015 ACR/EULAR gout classification criteria, iRPolM had a sensitivity of 77.6% (95% CI: 65.8-86.9), specificity of 97.7% (95% CI: 93.5-99.5), positive predictive value (PPV) of 94.5% (95% CI: 84.9-98.2), negative predictive value (NPV) of 89.7% (95% CI: 84.7-93.1), an accuracy of 91.0% (95% CI: 86.2-94.6), a positive likelihood ratio of 34.4 (95% CI: 11.16-106.10) and a negative likelihood ratio of 0.23 (95% CI: 0.15-0.36). Validation against PLM: 55 samples were positive for MSU according to PLM. The interrater agreement between PLM and iRPolM was near perfect (к=0.90). The sensitivity of iRPolM to identify MSU in PLM-positive samples was 91.2% (95% CI: 80.7-97.1), the specificity was 97.6% (95% CI: 93.0-99.5), the PPV was 94.6% (95% CI: 85.0-98.2), NPV was 96.0% (95% CI: 91.2-98.2) and the accuracy was 95.6% (95% CI: 91.4-98.2). The positive likelihood ratio was 37.4 (95% CI: 12.20-114.71), and the negative likelihood ratio was 0.09 (95% CI: 0.04-0.21). CONCLUSION: iRPolM is a promising next-generation diagnostic tool for rheumatology by diagnosing gout with high specificity, increased objectivity, and a sensitivity comparable to PLM.

The 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score >56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

Airborne virus shedding of the alpha, delta, omicron SARS-CoV-2 variants and influenza virus in hospitalized patients.

Airborne transmission is an important transmission route for the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological data indicate that certain SARS-CoV-2 variants, like the omicron variant, are associated with higher transmissibility. We compared virus detection in air samples between hospitalized patients infected with different SARS-CoV-2 variants or influenza virus. The study was performed during three separate time periods in which subsequently the alpha, delta, and omicron SARS-CoV-2 variants were predominant. In total, 79 patients with coronavirus disease 2019 (COVID-19) and 22 patients with influenza A virus infection were included. Collected air samples were positive in 55% of patients infected with the omicron variant in comparison to 15% of those infected with the delta variant (p < 0.01). In multivariable analysis, the SARS-CoV-2 omicron BA.1/BA.2 variant (as compared to the delta variant) and the viral load in nasopharynx were both independently associated with air sample positivity, but the alpha variant and COVID-19 vaccination were not. The proportion of positive air samples patients infected with the influenza A virus was 18%. In conclusion, the higher air sample positivity rate of the omicron variant compared to previous SARS-CoV-2 variants may partially explain the higher transmission rates seen in epidemiological trends.

Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout.

OBJECTIVE: To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. METHODS: A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease. RESULTS: The PRS was associated with earlier age at gout onset in men (ß = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; ß = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; ß = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (ß = 0.07 [95% CI -2.32, 2.45] in European women; ß = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; ß -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (ß = -2.42 [95% CI -3.37, -1.46] and ß = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (ß = -1.79 [95% CI -4.74, 1.16]). CONCLUSION: Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.

Development and usability of a web-based patient-tailored tool to support adherence to urate-lowering therapy in gout.

BACKGROUND: The aim of this study is to develop and assess usability of a web-based patient-tailored tool to support adherence to urate-lowering therapy (ULT) among gout patients in a clinical setting. METHODS: The content of the tool was based on the Integrated Change (I-Change) model. This model combines various socio-cognitive theories and assumes behavioral change is a result of becoming aware of the necessity of change by integrating pre-motivational, motivational, and post-motivational factors. An expert group (five gout experts, three health services researchers, and one health behavior expert) was assembled that decided in three meetings on the tool's specific content (assessments and personalized feedback) using information from preparatory qualitative studies and literature reviews. Usability was tested by a think aloud approach and validated usability questionnaires. RESULTS: The I-Change Gout tool contains three consecutive sessions comprising 80 questions, 66 tailored textual feedback messages, and 40 tailored animated videos. Navigation through the sessions was determined by the patients' intention to adapt suboptimal ULT adherence. After the sessions, patients receive an overview of the personalized advices and plans to support ULT adherence. Usability testing among 20 gout patients that (ever) used ULT and seven healthcare professionals revealed an overall score for the tool of 8.4 ± 0.9 and 7.7 ± 1.0 (scale 1-10). Furthermore, participants reported a high intention to use and/or recommend the tool to others. Participants identified some issues for further improvement (e.g. redundant questions, technical issues, and text readability). If relevant, these were subsequently implemented in the I-Change Gout tool, to allow further testing among the following participants. CONCLUSION: This study provides initial support for the usability by patients and healthcare professionals of the I-Change Gout tool to support ULT adherence behavior.

Development of a patient decision aid for the initiation of urate-lowering therapy in gout patients.

AIM: Shared decision-making improves patients' experiences with care, satisfaction with management decisions and possibly health outcomes. This study describes the development of a decision aid (DA) that supports patients with gout and their physicians in a face-to-face clinical setting to (a) decide whether or not to (re)start urate-lowering therapy (ULT) and (b) agree on the preferred ULT. METHODS: Recommendations of the International Patient Decision Aid Standards group guided the development. A steering group of experts in gout and health services research specified the scope. Nominal group technique meetings were organised in which patients ranked the importance of preidentified potential characteristics/attributes of ULT and discussed further needs regarding the DA. A literature search was conducted to collect evidence on gout outcomes with and without ULT. Subsequently, the DA prototype was designed and adjusted using feedback from the steering group and results of cognitive debriefing interviews among five gout patients. RESULTS: The final DA consists of six pages. First, the DA clarifies the decision at stake and describes gout including its risk factors, the role of lifestyle and treatment of flares. Next, risk of future flares with and without ULT in relation to serum uric acid levels is described and visualised. Relevant attributes of ULT are presented in an option grid distinguishing first-line and second-line ULT. Finally, patients' believes and preferences are explicitly addressed before making the shared decision. CONCLUSION: This study provides initial support for usability of a DA for gout patients eligible for starting ULT.

[Gout: an overview of diagnostics and treatment]. / Jicht.

Gout is characterized by acute arthritis due to the deposition of urate crystals in joints in a state of hyperuricemia. Gout is a clinical diagnosis and can be confirmed with a joint aspiration to examine the synovial fluid with a polarized light microscopy. If a joint aspiration is not feasible or inconclusive, ultrasound or Dual Energy Computed Tomography (DECT) can be considered. Pharmacological treatment of gout consists of treating acute flares with anti-inflammatory drugs and, if indicated, of urate lowering therapies (ULT). (Inter)national rheumatology guidelines recommend the use of ULT indefinite by a treat-to-target approach, but there is discussion whether (certain) patients might also be treated by a treat-to-avoid-symptoms approach. Two large Dutch trials are comparing these strategies in gout patients. Most gout patients have cardiovascular and metabolic comorbidities and therefore an indication for cardiovascular risk assessment.

Model-based cost-effectiveness analyses comparing combinations of urate lowering therapy and anti-inflammatory treatment in gout patients.

OBJECTIVES: To assess the cost-effectiveness of various combinations of urate lowering therapy (ULT) and anti-inflammatory treatment in the management of newly diagnosed gout patients, from the Dutch societal perspective. METHODS: A probabilistic patient-level simulation estimating costs and quality-adjusted life years (QALYs) comparing gout and hyperuricemia treatment strategies was performed. ULT options febuxostat, allopurinol and no ULT were considered. Flare treatments naproxen, colchicine, prednisone, and anakinra were considered. A Markov Model was constructed to simulate gout disease. Health states were no flare, and severe pain, mild pain, moderate pain, or no pain in the presence of a flare. Model input was derived from patient level clinical trial data, meta-analyses or from previously published health-economic evaluations. The results of probabilistic sensitivity analyses were presented using incremental cost-effectiveness ratios (ICERs), and summarized using cost-effectiveness acceptability curves (CEACs). Scenario analyses were performed. RESULTS: The ICER for allopurinol versus no ULT was €1,381, when combined with naproxen. Febuxostat yielded the highest utility, but also the highest costs (€4,385 vs. €4,063 for allopurinol), resulting in an ICER of €25,173 when compared to allopurinol. No ULT was not cost-effective, yielding the lowest utility. For the gout flare medications, comparable effects on utility were achieved. Combined with febuxostat, naproxen was the cheapest option (€4,404), and anakinra the most expensive (€4,651). The ICER of anakinra compared to naproxen was €818,504. Colchicine and prednisone were dominated by naproxen. CONCLUSION: Allopurinol and febuxostat were both cost-effective compared to No ULT. Febuxostat was cost-effective in comparison with allopurinol at higher willingness-to-pay thresholds. For treating gout flares, colchicine, naproxen and prednisone offered comparable health economic implications, although naproxen was the favoured option.

Outcomes of Care Among Patients With Gout in Europe: A Cross-sectional Survey.

OBJECTIVE: To assess health- and patient-centered outcomes in gout across Europe, and explore patient-, care-, and country-level characteristics associated with these outcomes. METHODS: Patients with self-reported physician-diagnosed gout from 14 European countries completed an online survey. Multivariable mixed-effect logistic and linear regressions were computed for health outcomes (gout flare recurrence) and patient-centered outcomes (patient satisfaction with current medication, and unaddressed goals), accounting for clustering within countries. The role of patient-, care-, and country-level factors was explored. RESULTS: Participants included 1029 patients, predominantly diagnosed by a general practitioner (GP). One or more gout flares were reported by 70% of patients and ≥ 3 flares by 32%. Gout patients reported 1.1 ± 1.2 unaddressed goals, and 80% were satisfied with current medication. Patients with ≥ 3 and ≥ 1 flares were less likely to be treated with urate-lowering therapy (ULT) (OR 0.52, 95% CI 0.39-0.70 and OR 0.38, 95% CI 0.28-0.53, respectively), but more likely to have regular physician visits (OR 2.40, 95% CI 1.79-3.22 and OR 1.77, 95% CI 1.30-2.41). Three or more gout flares were also associated with lower satisfaction (OR 0.39, 95% CI 0.28-0.56) and more unaddressed goals (ß 0.36, 95% CI 0.19-0.53). Notwithstanding, the predicted probability of being satisfied was still between 57% and 75% among patients with ≥ 3 flares but who were not receiving ULT. Finally, patients from wealthier and Northern European countries more frequently had ≥ 3 gout flares. CONCLUSION: Across Europe, many patients with gout remain untreated despite frequent reported flares. Remarkably, a substantial proportion of them were still satisfied with gout management. A better understanding of patients' satisfaction and its role in physicians' gout management decisions is warranted to improve quality of care and gout outcomes across Europe.

Sex Differences in the Clinical Profile Among Patients With Gout: Cross-sectional Analyses of an Observational Study.

OBJECTIVE: Research findings in gout result predominantly from studies about men and might not be generalizable to women. To improve insight into sex differences in gout, our study compared clinical characteristics and comorbidities of female and male patients with gout, and explored the influence of menopause on these differences. METHODS: Data from patients referred to 2 rheumatology clinics and diagnosed with gout were used. Clinical characteristics and comorbidities of each sex were compared univariately. Sex difference in comorbidities were further explored in multivariate logistic regression analyses adjusting for age, BMI, smoking, and alcohol consumption in both the total group and in those with gout onset ≥ 55 years (as a surrogate for menopausal state). RESULTS: There were 954 patients, including 793 (83%) men, included. Women were on average older (65 vs 62 yrs), were more often obese (54% vs 36%), had a higher serum uric acid (sUA) level (0.53 vs 0.49 mmol/L), used diuretics more often (60% vs 30%), and consumed alcohol less frequently (47% vs 72%). Additionally, women more frequently had reduced renal function (64% vs 31%), hypertension (78% vs 56%), heart failure (23% vs 12%), and type 2 diabetes (39% vs 17%; all P < 0.05). In those with gout onset ≥ 55 years, differences in comorbidities were less pronounced and disappeared after adjusting for lifestyle. CONCLUSION: Our study confirmed sex differences in clinical characteristics and comorbidities among newly diagnosed patients with gout, and revealed that sex differences in comorbidities among those with gout onset beyond the age of female menopause were strongly attenuated and fully explained by lifestyle.