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Uric acid is a toxin retained with advancing kidney disease. Clinical manifestations of hyperuricemia include gout and systemic inflammation that are associated with increased risk of cardiovascular mortality. As many as one-third of all patients with chronic kidney disease have a history of gout, yet <25% of these patients are effectively treated to target serum urate levels of ≤6 mg/dl. A major reason for ineffective management of gout and hyperuricemia is the complexity in managing these patients, with some medications contraindicated and others requiring special dosing, potential drug interactions, and other factors. Consequently, many nephrologists do not primarily manage gout despite it being a common complication of chronic kidney disease, leaving management to the primary physician or rheumatologist. We believe that kidney specialists should consider gout as a major complication of chronic kidney disease and actively manage it in their patients. Here, we present insights from nephrologists and rheumatologists for a team approach to gout management that includes the nephrologist., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objective: Despite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout., Methods: We conducted a 16-week randomized nonmasked parallel-group trial in Denmark, randomly assigning (one-to-one) individuals with obesity and gout to a low-energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale-assessed pain and fatigue., Results: Between December 1, 2018, and June 1, 2019, 61 participants were included in the intention-to-treat population and randomly assigned to the intensive diet group (n = 29) or control diet group (n = 32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (-15.4 vs -7.7 kg; difference -7.7 kg [95% confidence interval -10.7 to -4.7], P < 0.001). Despite results being potentially in favor of a low-energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial., Conclusion: An intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain., (© 2024 American College of Rheumatology.)

Objective: The selection and reporting of core outcome measures in clinical trials is essential for patients, researchers, and healthcare providers for clinical research to have an impact on healthcare. In this systematic scoping review, we aimed to quantify the extent to which gout clinical trials are collecting and reporting data in accordance with the core outcome domains from Outcome Measures in Rheumatology (OMERACT) published in 2009 applicable for both acute and chronic trials and evaluate the reporting according to the core domains before and after the 2009 OMERACT endorsement., Methods: We searched multiple databases PubMed, EMBASE, the Cochrane Library including the Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews (CDSR) and www., Clinicaltrials: gov for randomized controlled trials (RCTs) allocating people with gout versus an active pharmacological gout treatment or a control comparator (no date limitation). We extracted the data in accordance with the core outcome sets, focusing individually on core outcome domains and the core outcome measurements for acute and chronic trials, respectively. In this study 'Acute trials' reflect studies that describe interventions for short term management of gout flares, and 'chronic trials' describe interventions for long-term urate lowering therapy in the management of gout., Results: From 8,522 records identified in the database search, 134 full text papers were reviewed, and 71 trials were included, of which 36 were acute and 35 were chronic. Only 3 of 36 (8%) acute trials reported all five core domains and none of the 35 included chronic trials reported all 7 core domains. In the acute trials, twenty-seven unique measurement instruments across the 5 core domains were identified. For chronic trials there were 31 unique measurement instruments used across the 7 core domains. Serum urate was reported in 100% of the chronic trials and gout flares in 80%. However, other core domains were reported in <30% of chronic trials. In particular the patient-important domains such as HR-QOL, patient global assessment and activity limitations were rarely reported. A broad variety of different measurement instruments were used to assess each endorsed core domain, a minority of trials used the OMERACT endorsed instruments. For acute trials, the number reporting on all core domains was consistently low and no change was detected before and after the endorsement of the core domains in 2009. None of the included chronic trials reported on all 7 endorsed core domains at any time., Conclusion: In this study we found a low adherence with the intended endorsed (i.e., core) outcome domains for acute and chronic gout studies which represents a poor uptake of the global OMERACT efforts for the minimum of what should be measured in clinical trials. In addition, there is a significant variation in how the OMERACT endorsed outcome domains have been measured. This systematic review demonstrates the need for continuous encouragement among gout researchers to adhere to OMERACT core domains as well as further guidance on outcome measurements reporting., Registration: Prospero: CRD42019151316., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This single-center clinical study identifies clusters of different phenotypes and pathophysiology subtypes of patients with gout and associated comorbidities., Methods: Patients clinically diagnosed with gout were enrolled between January 2018 and December 2019. Hierarchical cluster analyses were performed using clinical data or biological markers, inflammatory markers, and oxidative stress pathway metabolites assayed from serum and plasma samples. Subgroup clusters were compared using ANOVA for continuous data and chi-square tests for categorical data., Results: Hierarchical cluster analysis identified 3 clusters. Cluster 1 (C1; n = 24) comprised dyslipidemia, hypertension, and early-onset gout, without tophi. Cluster 2 (C2; n = 25) comprised hypertension, dyslipidemia, nephrolithiasis, and obesity. Cluster 3 (C3; n = 39) comprised multiple comorbidities and tophi. Post hoc comparisons of data obtained from samples of patients in C1, C2, and C3 revealed significant differences in the levels of oxidative stress and inflammation-related markers, including 3-nitrotyrosine, tumor necrosis factor, C-reactive protein, interleukin (IL) 1β, IL-6, platelet-derived growth factor (PDGF)-AA, and PDGF-BB. Reclustering patients based on all markers as well as on the biological markers that significantly differed among the initial clusters identified similar clusters., Conclusion: Oxidative stress and inflammatory marker levels may affect the development and clinical manifestations (ie, clinical phenotypes) of gout. Measuring oxidative stress and levels of inflammatory cytokines is a potential adjunctive tool and biomarker for early identification and management of gout., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: To examine the associations of changes in serum urate (SU) with health-related quality of life (HRQOL) in gout., Methods: We used the first 6-months of data from four interventional trials and one observational, open-label study of urate-lowering therapy (ULT) use. HRQOL were assessed at baseline and every 3-months, and SU was measured monthly. Primary outcome measures were Short-form 36 physical and mental component summary scores, Health Assessment Questionnaire Disability Index (HAQ-DI), Sheehan Disability Scale (SDS), Patient Global Assessment, and pain scores in the last week. Linear mixed models for each outcome were adjusted as appropriate for current SU, change in urate in the last month, number of flare-affected days in the last month, baseline BMI, age, comorbidities, sex, ethnicity, trial/study and treatment combination, and tophi status (fixed effects); subject, and the trial/study month were random effects., Results: Higher current SU correlated with reduced physical and mental HRQOL, and increased SDS and pain but not with HAQ-DI score. In the first 6-months of new/escalating ULT use, absolute change in SU levels associated with poorer outcomes on the HAQ-DI scale (β (95% CI) = 0.013 (0.007-0.019)) and poorer outcomes on SDS, SF-36 MCS, patient global and pain scales. Reduction of SU associated with poorer outcomes in all six measures., Conclusion: High SU levels were associated with poorer HRQOL, pain and Sheehan disability score. Recent SU level fluctuations are associated with poorer outcomes, primarily driven by a reduction in SU. Clinical emphasis on slow rather than fast SU reduction and the routine use of effective, anti-inflammatory medications at ULT initiation/escalation may avoid short-term poor outcomes., Competing Interests: Declaration of Competing Interests JAS has received consultant fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc., Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology. JAS has received institutional research support from Zimmer Biomet Holdings. JAS received food and beverage payments from Intuitive Surgical Inc./Philips Electronics North America. JAS owns stock options in TPT Global Tech, Vaxart pharmaceuticals, Atyu biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris Pharmaceuticals, Enzolytics Inc., Seres Therapeutics, Tonix Pharmaceuticals Holding Corp., and Charlotte's Web Holdings, Inc. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JAS is on the speaker's bureau of Simply Speaking. JAS is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organization that develops outcome measures in rheumatology and receives arms-length funding from 8 companies. JAS is a member of the veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS served as a member of the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response Criteria subcommittee. AMJ has received research support from Bristol Myers Squibb. JR, EC, and BN have no conflicts. Other authors (RT, SN, and TRM) declare no relevant conflicts. There are no non-financial competing interests for any of the other authors., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To examine the incidence, time trends, and outcomes of alcohol use disorder (AUD) hospitalizations in people with gout, rheumatoid arthritis (RA), fibromyalgia, osteoarthritis, or low back pain (LBP)., Methods: We used the US National Inpatient Sample data from 1998 to 2016. We examined the rates of AUD hospitalizations in musculoskeletal diseases (MSDs), based on the presence of diagnostic codes for AUD in the primary and MSDs in a secondary position. Multivariable-adjusted (age, sex, race, and income) health care utilization and in-hospital mortality were compared by the presence/absence of MSDs, using linear or logistic regression., Results: Alcohol use disorder hospitalizations increased over the 19-year study period from 1998 to 2014 to 3-fold higher in gout, osteoarthritis, or LBP; 3.5-fold in RA; and 4.5-fold in fibromyalgia. Compared with AUD hospitalizations in people without each respective MSD, adjusted total hospital charges were $3913 higher in people with gout and $1368 to $1614 lower for osteoarthritis, fibromyalgia, or LBP over the study period (all significant) and not significantly different for RA. The adjusted odds of hospital stay of more than 3 days were significantly higher for all 5 MSDs, with odds ratio ranging 1.10 for LBP to 1.34 for gout. The adjusted odds of in-hospital mortality were significantly lower for all 5 MSDs, with odds ratio ranging from 0.21 for fibromyalgia to 0.50 for gout., Conclusions: In a national US study, the rate of AUD hospitalizations increased in all 5 MSDs. Providers and patients with MSDs should be counseled regarding the risk and impact of alcohol use. Interventions to reduce AUD hospitalization-associated health care burden in MSD are needed., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Medication adherence in gout is suboptimal, and the lack of effective interventions to address it presents a huge challenge. Medication adherence and gout outcomes are worse in racial/ethnic minorities. The objective of this paper was to provide the details of the study protocol for randomized, controlled trial (RCT) in African Americans (AAs) with gout that will test the effectiveness of a culturally appropriate gout storytelling intervention., Methods: The SToRytelliing to Improve Disease outcomes in Gout (STRIDE-GO) study will be a 12-month, multicenter, open-label RCT that will assess the effect of a culturally appropriate gout storytelling in at least 300 AA veterans with gout. Participants will be randomized to gout-storytelling intervention vs. a stress reduction video in a 1:1 ratio. The primary outcome is urate-lowering therapy (ULT) adherence measured with MEMSCap™, an electronic monitoring system (efficacy, 6 months; sustenance of efficacy, 12 months). Secondary outcomes include gout flares, serum urate (SU), gout-specific health-related quality of life [HRQOL], self-reported ULT adherence, patient satisfaction with treatment, and patient understanding of the intervention. AA veterans with gout who met the 1977 Preliminary American College of Rheumatology (ACR) classification criteria for gout, currently prescribed an oral ULT medication (allopurinol or febuxostat) for at least 6 months, and not using a pillbox to redistribute their medications, will be invited to an in-person study visit. After the study coordinators obtain informed consent, and ensure that participants meet the inclusion criteria, the eligible participants will be provided with their current ULT in a MEMSCap™ bottle for the 1-month run-in period and asked to return to the clinic in 1 month. ULT adherence with MEMSCap™ will be recorded at a 1-month return visit. Interested participants will complete the baseline assessments, randomized using the computerized system to either gout-storytelling intervention or a stress reduction intervention video arm and watch the respective video in-clinic. Patients will be interviewed on the phone at 2 and 4 months regarding the viewing of the videos at home at each time. Participants will be assessed in-clinic at 3, 6, 9, and 12 months; MEMSCap™ data and patient surveys will be captured at each visit. For any missed visit, assessments will be completed on the phone and MEMSCap™ data captured at the next in-clinic visit., Discussion: The study will assess the efficacy of a behavioral intervention to improve ULT adherence in minority populations with gout., Trial Registration: ClinicalTrials.gov NCT02741700. Registered on 14 September 2018., (© 2021. The Author(s).)

Serum urate (SU) is the most common primary efficacy outcome in trials of urate-lowering therapies for gout. Despite this, it is not formally considered a validated surrogate outcome. In this paper we will outline the definitions of biomarkers and surrogate outcome measures, respectively as well as the available frameworks and challenges in the assessment of the validity of serum urate as a surrogate in gout (i.e. a reasonable replacement for gout symptoms)., Competing Interests: Declaration of Competing Interest MBM: No conflicts declared, RC: No conflicts declared, JAS: Has received consultant fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc., Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology. JAS owns stock options in TPT Global Tech, Vaxart pharmaceuticals and Charlotte's Web Holdings, Inc. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JAS is on the speaker's bureau of Simply Speaking. JAS is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organization that develops outcome measures in rheumatology and receives arms-length funding from 12 companies. JAS serves on the FDA Arthritis Advisory Committee. JAS is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and the Criteria subcommittee. Director of the University of Alabama at Birmingham (UAB) Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS previously served as a member of the following committees: member, the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response, ND: Reports consulting fees from AstraZeneca, Dyve BioSciences, Selecta, Horizon, and Arthrosi, speaker fees from Abbvie and Janssen, and research grants from Amgen and AstraZeneca, outside the submitted work. ORCID: 0000-0003-3485-0006, KS: Reports he is an Investigator for Horizon, Sobi, LG, Dyve and consulting fees from Horizon, WJT: No conflicts declared ORCID 0000-0001-6075-8479, TN: No conflicts declared. ORCID 000-002-9515-1711, MK: No conflicts declared ORCID 0000-0002-6445-8526, BMP: No conflicts declared, GMM: No conflicts declared, BJS: Is the senior Methodologist. ORCID 0000-0002-7686-2585, CDT: No conflicts declared. ORCID 0000-0001-6275-7699, SKT: No conflicts declared, RG: personal fees from Pfizer, Cornerstones, Jannsen, and Novartis. AA: No conflicts declared, ML: No conflicts declared, AG: No conflicts declared ORCID 0000-0001-7365-7212, LSS: Serves as a consultant to Horizon Therapeutics. He serves on the Executive of OMERACT and is Chair of the Finance Committee of OMERACT and Co-Chair of It's Business Advisory Committee., AN: No conflicts declared, SMN: No conflicts declared, ML: No conflicts declared, PT: No conflicts declared ORCID 00000-0001-5062-0556, LKS: No conflicts declared ORCID 0000-0003-0138-2912, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Urate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs)., Methods: In a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence., Results: The 306 male AA veterans with gout who met the eligibility criteria were randomized to the gout-storytelling intervention (n = 152) or stress reduction video (n = 154); 261/306 (85%) completed the 1-year study. The mean age was 64 years, body mass index was 33 kg/m 2 , and gout disease duration was 3 years. ULT adherence was similar in the intervention vs. control groups: 3 months, 73% versus 70%; 6 months, 69% versus 69%; 9 months, 66% versus 67%; and 12 months, 61% versus 64% (p > 0.05 each). Secondary outcomes (gout flares, serum urate and gout-specific health-related quality of life [HRQOL]) in the intervention versus control groups were similar at all time points except intervention group outcomes were better for the following: (1) number of gout flares at 9 months were fewer, 0.7 versus 1.3 in the previous month (p = 0.03); (2) lower/better scores on two gout specific HRQOL subscales: gout medication side effects at 3 months, 32.8 vs. 39.6 (p = 0.02); and unmet gout treatment need at 3 months, 30.9 vs. 38.2 (p = 0.003), and 6 months, 29.5 vs. 34.5 (p = 0.03), respectively., Conclusions: A culturally appropriate gout-storytelling intervention was not superior to attention control for improving gout outcomes in AAs with gout., Trial Registration: Registered at ClinicalTrials.gov NCT02741700., (© 2021. The Author(s).)

Objective: To examine the accuracy of dual-energy CT (DECT) vs ultrasound or their combination for the diagnosis of gout., Methods: Using prospectively collected data from an outpatient rheumatology clinic at a tertiary-care hospital, we examined the diagnostic accuracy of either modality alone or their combination, by anatomical site (feet/ankles and/or knees), for the diagnosis of gout. We used two standards: (i) demonstration of monosodium urate crystals in synovial fluid (gold), and (ii) modified (excluding DECT and ultrasound) 2015 ACR-EULAR gout classification criteria (silver)., Results: Of the 147 patients who provided data, 48 (33%) had synovial fluid analysis performed (38 were monosodium urate-crystal positive) and mean symptom duration was 9.2 years. One hundred (68%) patients met the silver standard. Compared with the gold standard, diagnostic accuracy statistics for feet/ankles DECT, feet/ankles ultrasound, knees DECT and knees ultrasound were, respectively: sensitivity: 87%, 84%, 91% and 58%; specificity: 100%, 60%, 87% and 80%; positive predictive value: 100%, 89%, 97% and 92%; negative predictive value: 67%, 50%, 70% and 33%; area under the receiver operating characteristic curve: 0.93, 0.72, 0.89 and 0.66. Combining feet/ankles DECT with ultrasound or knees DECT with ultrasound led to a numerically higher sensitivity compared with DECT alone, but overall accuracy was lower. Similarly, combining imaging knees to feet/ankles also yielded a numerically higher sensitivity and negative predictive values compared with feet/ankles DECT alone, without differences in overall accuracy. Findings were replicated compared with the silver standard, but with lower numbers., Conclusions: Feet/ankles or knees DECT alone had the best overall accuracy for gout diagnosis. The DECT-US combination or multiple joint imaging offered no additional increase in overall diagnostic accuracy., (Published by Oxford University Press on behalf of the British Society for Rheumatology 2021. This work is written by US Government employees and is in the public domain in the US.)

Hypertension, obesity, chronic kidney disease and type 2 diabetes are comorbidities that have very high prevalence among persons with hyperuricemia (serum urate > 6.8 mg/dL) and gout. Here we use multivariate genetic models to test the hypothesis that the co-association of traits representing hyperuricemia and its comorbidities is genetically based. Using Bayesian whole-genome regression models, we estimated the genetic marker-based variance and the covariance between serum urate, serum creatinine, systolic blood pressure (SBP), blood glucose and body mass index (BMI) from two independent family-based studies: The Framingham Heart Study-FHS and the Hypertension Genetic Epidemiology Network study-HyperGEN. The main genetic findings that replicated in both FHS and HyperGEN, were (1) creatinine was genetically correlated only with urate and (2) BMI was genetically correlated with urate, SBP, and glucose. The environmental covariance among the traits was generally highest for trait pairs involving BMI. The genetic overlap of traits representing the comorbidities of hyperuricemia and gout appears to cluster in two separate axes of genetic covariance. Because creatinine is genetically correlated with urate but not with metabolic traits, this suggests there is one genetic module of shared loci associated with hyperuricemia and chronic kidney disease. Another module of shared loci may account for the association of hyperuricemia and metabolic syndrome. This study provides a clear quantitative genetic basis for the clustering of comorbidities with hyperuricemia., (© 2021. The Author(s), under exclusive licence to European Society of Human Genetics.)

Objective: To study the epidemiology of serious infections in patients hospitalized with gout., Methods: We identified patients with gout hospitalized with a primary diagnosis of pneumonia, sepsis/bacteremia, urinary tract infection (UTI), skin and soft tissue infections (SSTIs), or opportunistic infections (OIs) in a US National Inpatient Sample from 1998 to 2016 and examined factors associated with utilization and mortality., Results: We noted 1,140,085 hospitalizations of patients with serious infections and gout (11% of all hospitalizations of patients with gout; 1998-2000 [8.9%], 2015-2016 [14.5%]). Compared to patients without gout, patients with gout hospitalized with serious infections were older (median age 65 versus 74 years), more of them had a Charlson-Deyo comorbidity index score ≥2 (42% versus 65%), and fewer were female (53% versus 35%) or non-White (40% versus 35%), respectively. The most common infection was pneumonia (52%) in 1998-2000 and sepsis (52%) in 2015-2016. Median hospital charges and hospital stays were higher for patients with sepsis and OIs in 2015-2016 ($41,000-$42,000; 5.1-5.5 days) versus those with UTI, pneumonia, or SSTIs ($15,000-$17,000; 3.0-3.9 days). Compared to patients with sepsis, the multivariable-adjusted odds of health care utilization and in-hospital mortality were significantly lower for patients with UTI, SSTIs, and pneumonia, and non-home discharge or in-hospital mortality were lower in patients with OIs. Among patients hospitalized with infections, older age, Medicaid coverage, a higher Charlson-Deyo comorbidity index score, Black race, and Northeast and nonrural hospital location were associated with significantly higher health care utilization and mortality, while female sex, Medicare insurance, and lower income were associated with higher utilization., Conclusion: Given an increasing rate of serious infections, especially sepsis and pneumonia, in individuals with gout, development of effective interventions targeting factors associated with health care utilization and mortality will improve outcomes and reduce burden., (© 2020, American College of Rheumatology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Objective: To examine opioid use disorder (OUD)-related hospitalizations and associated healthcare utilization outcomes in people with 5 common musculoskeletal diseases (MSD)., Methods: We used the US National Inpatient Sample (NIS) data from 1998 to 2014 to examine the rates of OUD hospitalizations (per 100,000 NIS claims overall), time trends, and outcomes in 5 common rheumatic diseases: gout, rheumatoid arthritis (RA), fibromyalgia (FM), osteoarthritis (OA), and low back pain (LBP)., Results: OUD hospitalization rate per 100,000 total NIS claims in 1998-2000 vs 2015-2016 (and increase) were as follows: gout, 0.05 vs 1.88 (36-fold); OA, 0.68 vs 10.22 (14-fold); FM, 0.53 vs 6.98 (12-fold); RA, 0.30 vs 3.16 (9.5-fold); and LBP, 1.17 vs 7.64 (5.5-fold). The median hospital charges and hospital stays for OUD hospitalizations were as follows: gout, $18,363 and 2.5 days; RA, $17,398 and 2.4 days; FM, $15,772 and 2.1 days; OA, $16,795 and 2.4 days; and LBP, $13,722 and 2.0 days. In-hospital mortality rates ranged from 0.9% for LBP and FM to 1.7% for gout with OUD hospitalizations. Compared to those without each MSD, age-, sex-, race-, and income-adjusted total hospital charges (inflation-adjusted) for OUD hospitalizations with each rheumatic disease were as follows: gout, $697 higher; OA, $4759 lower; FM, $2082 lower; RA, $1258 lower; and LBP, $4944 lower., Conclusion: OUD hospitalizations increased in all 5 MSD studied, but the rate of increase differed. Awareness of these OUD hospitalization trends in 5 MSD among providers, policy makers, and patients is important. Development and implementation of interventions, policies, and practices to potentially reduce OUD-associated effects in people with rheumatic diseases is needed., (Copyright © 2021 by the Journal of Rheumatology.)

Objective: To develop a Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) common language definition of gout, with the goal of increasing public understanding and awareness, and ensure consistent and understandable messages about gout., Methods: A G-CAN working group that included patients, physicians and nongovernmental organisation (NGO) representatives was formed to develop a common language definition of gout for use with the public, media, healthcare providers and stakeholders. A literature search and interviews with patients, healthcare workers and stakeholders informed development of the definition. Following consultation with G-CAN members and partners, the definition was endorsed by the G-CAN board., Results: The G-CAN common language definition of gout describes the epidemiology, pathophysiology, symptoms and impact, risk factors, comorbidities, management and healthcare and workforce considerations. Detailed information is provided to support the content of the definition. After the publication of the English-language version, the definition will be available for translation into other languages by G-CAN members., Conclusion: G-CAN has developed a concise and easily understandable statement describing gout in language that can be used in conversations with the lay public, media, NGOs, funders, healthcare providers and other stakeholders., Competing Interests: Competing interests: ND reports personal fees and non-financial support from Abbvie, personal fees from Horizon, Janssen, Dyve, Selecta and Arthrosi, grants from Amgen, grants and personal fees from AstraZeneca and personal fees from Hengrui, outside the submitted work. G-CAN is a global gout research consortium, non-profit, supported at arms length by annual funding support from pharma. In the last 36 months, pharma donor support to G-CAN was provided by Horizon, Astra-Zeneca, SOBI, Takeda, CymaBay, Selecta and LG. RT reports other than from G-CAN, during the conduct of the study; personal fees from Astra-Zeneca, SOBI, Horizon, Selecta and grants from Astra-Zeneca, outside the submitted work. JAS has received consultant fees from Crealta/Horizon, Medisys, Fidia, UBM LLC, Trio Health, Medscape, WebMD, Adept Field Solutions, Clinical Care Options, Clearview Healthcare Partners, Putnam Associates, Focus Forward, Navigant Consulting, Spherix, Practice Point Communications, the National Institutes of Health and the American College of Rheumatology. JAS owns stock options in TPT Global Tech, Vaxart Pharmaceuticals and Charlotte’s Web Holdings, Inc. JAS previously owned stock options in Amarin, Viking and Moderna Pharmaceuticals. JAS is on the speaker’s bureau of Simply Speaking. JAS is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organisation that develops outcome measures in rheumatology and receives arms-length funding from 12 companies. JAS serves on the FDA Arthritis Advisory Committee. JAS is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and the Director of the University of Alabama at Birmingham (UAB) Cochrane Musculoskeletal Group Satellite Centre on Network Meta-analysis. JAS previously served as a member of the following committees: member, the American College of Rheumatology’s (ACR) Annual Meeting. MJB reports grants from Healthwise, a non-profit, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To assess rheumatologists' views and practices related to shared decision-making (SDM) in gout treatment. We performed a cross-sectional electronic survey of rheumatologists at U.S. Veterans Affairs (VA) medical centers, assessing views and practices related to SDM in gout. Of the 154 VA rheumatology providers eligible, 90 responded (response rate, 58%). Fifty-eight percent were female, the mean age was 51 years (standard deviation, 9.6), 42% had > 20 years of experience in medical practice. Rheumatologists reported routinely offering a choice to their patients for (1) starting urate-lowering therapy (ULT) for gout vs. doing nothing (70%); (2) choosing NSAIDs, corticosteroids, or colchicine for the treatment of acute flares (67%); and (3) choosing NSAIDs, corticosteroids, or colchicine for anti-inflammatory prophylaxis when starting ULT (51%). Very few rheumatologists offered choice regarding (4) choosing allopurinol vs. febuxostat as the first ULT (16%) and (5) taking daily ULT long-term vs. intermittently (15%). Rheumatologists perceived that a large proportion of patients were often or sometimes unsure of the best choice for these five decisions, 34%, 76%, 76%, 52%, and 54%, respectively. Similar proportions of rheumatologists felt that patients were uninformed about both medication benefits and risks, unclear about the personal importance of the benefits and risks, and unsupported in decision-making. For the five decisions respectively, rheumatologists supported SDM with patients in 76%, 56%, 58%, 27%, and 25%. The majority of VA rheumatologists incorporated SDM in several gout treatment decisions. Rheumatologists also recognized that patients need better support to participate in SDM in gout. Key Points: • Rheumatologists offered shared decision-making to gout patients for 3 key treatment decisions. • Rheumatologists perceived that many patients were unsure of the best choice for these decisions. • Rheumatologists felt that patients were uninformed about medication benefits/risks and unsupported in decision-making.

Objective: To investigate the factors associated with discordance between patient and physician on the presence of a gout flare., Methods: Patients' self-reports of current gout flares were assessed with the question, 'Are you having a gout flare today?' which was then compared with a concurrent, blinded, physician's assessment. Based on agreement or disagreement with physicians on the presence of a gout flare, flares were divided into concordant and discordant groups, respectively. Within the discordant group, two subgroups-patient-reported flare but the physician disagreed and physician-reported flare but the patient disagreed-were identified. The factors associated with discordance were analysed with multivariable logistic regression analysis., Results: Of 268 gout flares, 81 (30.2%) flares were discordant, with either patient or physician disagreeing on the presence of a flare. Of the discordant flares, in 57 (70.4%) the patient reported a flare but the physician disagreed. In multivariable logistic regression analysis adjusted for demographics, disagreement among patients and physicians on the presence of a gout flare was associated with lower pain scores at rest [odds ratio (OR) for each point increase on 0-10 point pain scale 0.81 (95% Wald CI 0.73, 0.90), P < 0.0001] and less presence of joint swelling [OR 0.24 (95% CI 0.10, 0.61), P = 0.003] or joint warmth [OR 0.39 (95% CI 0.20, 0.75), P = 0.005]., Conclusion: Although patients and physicians generally agree about the presence of gout flare, discordance may occur in the setting of low pain scores and in the absence of swollen or warm joints., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To determine the relationship between gout flare rate and self-categorization into remission, low disease activity (LDA), and patient acceptable symptom state (PASS)., Methods: Patients with gout self-categorized as remission, LDA, and PASS, and reported number of flares over the preceding 6 and 12 months. Multinomial logistic regression was used to determine the association between being in each disease state (LDA and PASS were combined) and flare count, and self-reported current flare. A distribution-based approach and extended Youden index identified possible flare count thresholds for each state., Results: Investigators from 17 countries recruited 512 participants. Remission was associated with a median recalled flare count of zero over both 6 and 12 months. Each recalled flare reduced the likelihood of self-perceived remission compared with being in higher disease activity than LDA/PASS, by 52% for 6 months and 23% for 12 months, and the likelihood of self-perceived LDA/PASS by 15% and 5% for 6 and 12 months, respectively. A threshold of 0 flares in preceding 6 and 12 months was associated with correct classification of self-perceived remission in 58% and 56% of cases, respectively., Conclusion: Flares are significantly associated with perceptions of disease activity in gout, and no flares over the prior 6 or 12 months is necessary for most people to self-categorize as being in remission. However, recalled flare counts alone do not correctly classify all patients into self-categorized disease activity states, suggesting that other factors may also contribute to self-perceived gout disease activity., (Copyright © 2021 by the Journal of Rheumatology.)

Although effective and low-cost urate-lowering therapy has been available for decades, inequities in gout management exist. Despite high impact of disease, rates of urate-lowering therapy prescription are low in women, in African-Americans in the United States, in Māori (Indigenous New Zealanders), and in Pacific peoples living in Aotearoa/New Zealand. Social determinants of health, barriers to accessing the health care system, health literacy demands, stigmatization, and bias contribute to inequities in gout burden and management. Approaches that focus on building health literacy and delivering culturally safe care lead to improved outcomes in gout, and offer important solutions to achieve health equity., Competing Interests: Disclosure A.G. Guillén and L. Te Karu have no disclosures. J.A. Singh has received consultant fees from Crealta/Horizon, MediSYS, Fidia, UBM LLC, Trio health, Medscape, WebMD, Clinical Care options, Clearview health care partners, Putnam associates, Focus forward, Navigant consulting, Spherix, Practice Point communications, the National Institutes of Health, and the American College of Rheumatology (ACR). J.A. Singh owns stock options in Amarin pharmaceuticals and Viking therapeutics. J.A. Singh is on the speaker’s bureau of Simply Speaking. J.A. Singh is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 12 companies. J.A. Singh serves on the Food and Drug Administration Arthritis Advisory Committee. J.A. Singh is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. J.A. Singh is the editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. J.A. Singh previously served as a member of the following committees: member, the ACR Annual Meeting Planning Committee and Quality of Care Committees; the Chair of the ACR Meet-the-Professor, Workshop, and Study Group Subcommittee; and the cochair of the ACR Criteria and Response Criteria subcommittee. N. Dalbeth has received fees from Janssen, AbbVie, CymaBay, AstraZeneca, Crealta, Takeda, Kowa, Horizon, Hengrui, Dyve Biosciences, Arthrosi, Selecta, bpac, the Health Research Council of New Zealand, UpToDate, Oxford University Press, the Pharmaceutical Society of New Zealand, the Spanish Society for Rheumatology, the Asia Pacific Gout Consortium, and the ACR. Her institution has received research grants from the Health Research Council of New Zealand, the Auckland Medical Research Foundation, PHARMAC, AstraZeneca, and Amgen., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to report patient-centered outcomes and finalization of key study procedures from a 9-month pilot internet randomized controlled trial of cherry extract versus diet modification., Methods: We randomized 84 people with physician-confirmed gout in an internet study to cherry extract (n = 41) or dietitian-assisted diet modification for gout (n = 43). All study outcomes were collected via internet and phone calls. We finalized key study procedures. We assessed acceptability and feasibility of the intervention and satisfaction with study website., Results: Study participant satisfaction with the intervention was high. The intervention was perceived as easy, enjoyable, understandable, and helpful (scores 65-88 for all; higher = better). The amount of time spent for the study was acceptable. Participant satisfaction with website interaction and content was very high; 85% or more were moderately to extremely satisfied. Significantly lower total calories, total carbohydrate, and saturated fat intake were noted at 6 months in the diet modification versus cherry extract group; differences were insignificant at 9 months. Six of the 8 Health Assessment Questionnaire sections/domains improved significantly from baseline to 9 months in cherry extract versus 2 Health Assessment Questionnaire sections/domains in the diet modification group. Key study procedures were finalized for a future trial, including an internet diet assessment tool, gout flare assessment, provider confirmation of gout diagnosis, patient reporting of classification criteria, and centralized laboratory-assisted serum urate testing., Conclusions: High patient acceptability and feasibility of study/intervention and finalization of key study procedures indicate that hypothesis-testing internet gout trials of cherry extract and/or diet modification can be conducted in the future.

Objective: To assess patient perceptions of gout management goals., Methods: We conducted a cross-sectional Internet survey of people who visited the Gout and Uric Acid Education Society's website to assess patient/respondent perception of gout management goals. We used chi-square test for categorical or t-test for continuous variables., Results: Among the 320 survey respondents with physician-diagnosed gout, mean age was 57 (SD, 13.4) years, 72% were male, 77% White; mean gout duration was 7.6 years (SD, 11), gout flares in the last year were 5.2 (SD, 6.1), and medical comorbidities were common, 2.7 (SD, 2.6). Two-thirds respondents each reported very severe or severe symptoms from gout and that gout ranked among the top two health conditions with a negative impact on quality of life. During a clinic visit, only one-third of respondents' physicians spent 50% of more of the time discussing gout treatment. Only 54% respondents were prescribed ULT by their healthcare provider. By patient preference, the best life-long gout treatment strategies were the lowering of the serum urate level and the control of gout symptoms (62%) followed by serum urate lowering (32%). Respondents considered the following as the most important things for making gout treatment satisfactory: (1) patient education; (2) effective physician-patient communication; (3) diet and lifestyle modification; (4) serum urate monitoring and target achievement; (5) pain management and flare prevention; and (6) medication management., Conclusions: Patient identification of gout symptom control and serum urate level monitoring as the most important treatment goals is informative for clinicians and guideline developers.

Objective: To review the epidemiology of gout and associated comorbidities., Methods: We review the key published studies of the epidemiology of gout and associated comorbidities., Results: The prevalence of gout ranged 1-4% worldwide and incidence ranged 0.1-0.3%. Gout is more common in men vs. women by 3:1 to 10:1. Gout incidence and prevalence increased by each decade of life, with prevalence increasing to 11-13% and incidence increasing to 0.4% in people older than 80 years. Racial minorities in the U.S., New Zealand Māori, Han Chinese and some ethnic groups in Asia have a higher prevalence of gout. Comorbidities are common in people with gout and complicate its management and disease outcomes. Hypertension is present in up to three-quarters of gout patients and could be in the causal pathway of its association with cardiovascular disease and stroke. Chronic kidney disease of stage 3 or greater severity is present in many patients with gout. Appropriate management can improve both gout and stabilize chronic kidney disease. Whether the association of gout with metabolic syndrome and diabetes is causal is still controversial. Given the biological anti-oxidant effect of serum urate, the association of gout with neurodegenerative disorders is being actively explored., Conclusions: Gout is the most common inflammatory arthritis in adults worldwide, with a disproportionate burden of disease in men, the elderly and racial/ethnic minorities. Comorbidities in gout are very common and add further to the disease morbidity and make its management challenging., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations., Methods: Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional., Results: Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended., Conclusion: Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout., (© 2020, American College of Rheumatology.)

Objective: The aim of this study was to conduct a 9-month pilot Internet randomized controlled trial (RCT) of cherry extract and diet modification in gout to assess the feasibility of an Internet study and obtain effect estimates., Methods: After providing online informed consent in response to Internet advertisements and social media or clinic flyers, 84 people with physician-confirmed gout were randomized to either cherry extract 3,600 mg/d (n = 41) or dietitian-assisted diet modification for gout (n = 43). All study outcomes were collected via Internet and phone calls. The primary objective was the feasibility of an Internet study, and secondary objectives were to obtain effect estimates for gout flares, functional ability assessed with the Health Assessment Questionnaire (HAQ), and adverse events (AEs) for future trials., Results: Of the 84 people randomized, overall completion rates were more than 80% for most study procedures up to 6 months and similar for the 2 active comparators. Improvements were seen in gout flares and HAQ scores in cherry extract and diet modification groups at 9 months compared with baseline: gout flares per month, 0.22 versus 0.36 (p = 0.049) and 0.28 versus 0.31 (p = 0.76); proportion with any gout flare, 56% versus 98% (p < 0.0001) and 65% versus 98% (p = 0.0002); and mean ± standard deviation HAQ score, 0.28 ± 0.54 versus 0.55 ± 0.68 (p = 0.001) and 0.23 ± 0.40 versus 0.48 ± 0.61 (p = 0.06), respectively. Any AEs and gastrointestinal symptoms/AEs at 9 months in cherry extract and diet modification groups were 3% versus 0% and 28% versus 27%, respectively., Conclusions: An Internet gout RCT is feasible for nonpharmacological gout treatments. A hypothesis-testing, large Internet RCT of cherry extract versus placebo is needed.

Background: Gout has been associated with a higher risk for coronary heart disease (CHD) and stroke in some prior studies. Few studies have assessed the association of gout with incident heart failure (HF)., Methods: We analyzed data from 5713 black and white men and women ≥ 65.5 years of age in the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study who had Medicare coverage without a history of HF, CHD, or stroke at baseline between 2003 and 2007. Gout was defined by ≥ 1 hospitalization or ≥ 2 outpatient visits with a diagnosis code for gout in Medicare claims prior to each participant's baseline study examination. REGARDS study participants were followed for HF hospitalization, CHD, stroke, and all-cause mortality as separate outcomes through December 31, 2016. Analyses were replicated in a random sample of 839,059 patients ≥ 65.5 years of age with Medicare coverage between January 1, 2008, and June 30, 2015, who were followed through December 31, 2017., Results: Among REGARDS study participants included in the current analysis, the mean age at baseline was 72.6 years, 44.9% were men, 31.4% were black, and 3.3% had gout. Over a median follow-up of 10.0 years, incidence rates per 1000 person-years among participants with and without gout were 13.1 and 4.4 for HF hospitalization, 16.0 and 9.3 for CHD, 9.3 and 8.2 for stroke, and 55.0 and 37.1 for all-cause mortality, respectively. After multivariable adjustment for sociodemographic variables and cardiovascular risk factors, hazard ratios (95% CI) comparing participants with versus without gout were 1.97 (1.22, 3.19) for HF hospitalization, 1.21 (0.79, 1.84) for CHD, 0.83 (0.48, 1.43) for stroke, and 1.08 (0.86, 1.35) for all-cause mortality. The multivariable-adjusted hazard ratio for HF hospitalization with reduced and preserved left ventricular ejection fraction among participants with versus without gout was 1.77 (95% CI 0.83, 3.79) and 2.32 (95% CI 1.12, 4.79), respectively. The multivariable-adjusted hazard ratio for heart failure hospitalization associated with gout among the 839,059 Medicare beneficiaries was 1.32 (95% CI 1.25, 1.39)., Conclusion: Among older adults, gout was associated with an increased risk for incident HF but not for incident CHD, incident stroke, or all-cause mortality.

Objective: To assess factors associated with the ability to achieve and maintain target serum urate (SU) with allopurinol in patients with gout., Methods: We used US Veterans Affairs (VA) databases from 2002-2012. Eligible patients had ≥ 1 inpatient or ≥ 2 outpatient visits with a diagnostic code for gout, filled a new index allopurinol prescription, had at least 1 posttreatment SU level measured, and met the 12-month observability rule. Treatment successes were defined as the achievement of postindex SU < 6 mg/dl (success 1) and postindex SU < 6 mg/dl that was sustained (success 2)., Results: Of the 198,839 unique patients with allopurinol use, 41,153 unique patients (with 47,072 episodes) and 17,402 unique patients (with 18,323 episodes) were eligible for analyses for success 1 and success 2; 42% each achieved (success 1) or achieved and maintained postindex SU < 6 mg/dl (success 2). In multivariable-adjusted models, factors associated with significantly higher odds of both outcomes were older age, normal body mass index, Deyo-Charlson index score of 0, rheumatologist as the main provider rather than non-rheumatologist, midwestern US location for the healthcare facility, a lower hospital bed size, military service connection for medical conditions of 50% or more (a measure of healthcare access priority), longer distance to the nearest VA facility, and lower preindex SU., Conclusion: We identified novel factors associated with maintaining SU < 6 mg/dl based on a theoretical model. Several potentially modifiable factors can be targeted by individual/provider/systems interventions for improving successful achievement and maintenance of target SU in patients with gout.

Objective: There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout., Methods: A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions., Results: The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus)., Conclusion: Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice., Competing Interests: Competing interests: AKT has received speaking fees and honoraria for advisory boards from Berlin Chemie Menarini, Novartis, Grünenthal and AstraZeneca. JAS has received consultant fees from Crealta/Horizon, Medisys, Fidia, UBM LLC, Medscape, WebMD, the National Institutes of Health and the American College of Rheumatology. JAS owns stock options in Amarin pharmaceuticals and Viking therapeutics. JAS is a member of the executive of OMERACT, an organisation that develops outcome measures in rheumatology and receives arms-length funding from 36 companies. JAS is a member of the Veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS previously served as a member of the following committees: member, the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response Criteria subcommittee. ND has received speaking fees from Pfizer, Horizon, Janssen, and AbbVie, consulting fees from Horizon, AstraZeneca, Dyve Biosciences, Hengrui, and Kowa, and research funding from Amgen and AstraZeneca., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: In the absence of previous studies, our objective was to assess whether gout was associated with an increase or decrease in the risk of Sjogren's Syndrome (SS) in older adults, 65 years or older., Methods: We used the 5% Medicare claims from 2006-2012. A multivariable Cox regression model assessed the association of gout with incident SS adjusting for age, sex, race, Charlson-Romano comorbidity index, and the use of medications for cardiovascular diseases (statins, beta-blockers, diuretics, ACE-inhibitors) and gout (allopurinol, febuxostat). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated., Results: There were 3,186 new cases of SS in the study cohort with crude incidence rates of SS of 30/100,000 person-years in patients without gout and 49/100,000 person-years in patients with gout. Multivariable-adjusted analyses showed that gout was independently associated with a higher hazard ratio of SS of 1.73 (95% CI, 1.45, 2.06). Sensitivity analyses that substituted continuous Charlson-Romano comorbidity index score with categorized score (model 2) or individual comorbidities plus three common cardiovascular diseases (hypertension, hyperlipidemia, and coronary artery disease; model 3), confirmed the main study findings with minimal attenuation of hazard ratio, 1.70 (95% CI, 1.43, 2.02) and 1.48 (95% CI, 1.25, 1.77), respectively. Younger age, female sex, White race and higher comorbidity score were associated with a higher hazard of SS., Conclusions: Gout was associated with more than 1.7-fold higher risk of incident SS in adults 65 years or older. This finding needs to be reproduced and the underlying mechanisms for this association need further study., (Published by Elsevier Masson SAS.)

Aims: Gout is associated with a higher risk of atrial fibrillation (AF). Comparative effectiveness of allopurinol or febuxostat for reducing the AF risk is unknown, which was our study's main objective., Methods and Results: We used the 5% Medicare Beneficiary cohort (≥65 years) from 2006 to 2012 to identify people with a new filled prescription for allopurinol or febuxostat, with a baseline period of 365 days without respective medication and without AF. We used 5:1 propensity-matched Cox regression analyses to assess whether allopurinol use differed from febuxostat use regarding the hazard ratio (HR) of incident AF. We found 25 732 eligible episodes in 23 135 beneficiaries. Of these, 2311 incident allopurinol or febuxostat use episodes (9%) ended in incident AF with crude incidence rates of 8.0 and 10.5 per 100 person-years, respectively. In propensity-matched analyses, compared with allopurinol, febuxostat was associated with higher HR of AF, 1.25 [95% confidence interval (CI) 1.05-1.48]. Compared with allopurinol <200 mg/day, febuxostat 80 mg/day was associated with significantly higher HR of AF, 1.62 (95% CI 1.16-2.27), but not febuxostat 40 mg/day or higher allopurinol doses. Compared with 1-180 days of allopurinol use, febuxostat use for 1-180 days was associated with significantly higher HR of AF, 1.36 (95% CI 1.10-1.67), but longer durations were not., Conclusion: Febuxostat was associated with a higher risk of AF compared with allopurinol in older adults. Increased AF risk was noted with febuxostat 80 mg/day dose and was most evident in the first 6 months of use. These findings need replication., (Published by Oxford University Press on behalf of the European Society of Cardiology 2019. This work is written by US Government employees and is in the public domain in the US.)

To assess if gout is associated with a higher risk of incident chronic pain. This study used the 2006-2012 Medicare claims data. We used multivariable-adjusted Cox regression analyses to examine the association of pre-existing diagnosis of gout with incident (new) diagnosis of chronic pain, adjusting for demographics, medical comorbidity, and use of common medications for cardiovascular disease and gout. Sensitivity analyses substituted Charlson-Romano score with a categorical variable or each Charlson-Romano comorbidity. There were 1,321,521 eligible people, of whom 424,518 developed incident chronic pain. Crude incidence rates of chronic pain were as follows: gout, 158.1 per 1000 person-years and no gout, 64.5 per 1000 person-years. In multivariable-adjusted Cox regression analyses, gout was associated with higher hazard ratio of chronic pain, 2.02 (95% CI, 1.98, 2.05), confirmed in sensitivity analyses 1.96 (95% CI, 1.93, 1.99) (model 2) and 1.77 (95% CI, 1.74, 1.80) (model 3). No meaningful differences were found by gender and race in subgroup analyses; slightly lower hazard of chronic pain with gout was seen in oldest people. Use of allopurinol or febuxostat was associated with lower risk of chronic pain, 0.79 (95% CI, 0.77, 0.82; model 1) and 0.72 (95% CI, 0.56, 0.92; model 1). Gout was associated with a doubling of the risk of chronic pain and gout treatments with reduction in the risk. Efforts must be made to optimize gout control, so that chronic pain can be avoided as a long-term sequalae of gout and when present, treated early and appropriately. Key points • Gout was associated with twofold higher risk of incident (or new) diagnosis of chronic pain. • Gout treatments were associated with a lower chronic pain risk. • Increased risk of chronic pain with gout was similar across age, race, and sex. • Studies should examine if optimal gout control with treat-to-target approach can reduce the risk of chronic pain in people with gout.

Cardiovascular disease affects more than 90 million Americans. Recent studies support an increased cardiovascular disease risk in inflammatory conditions, such as gout. Increased serum urate levels, or hyperuricemia, are a precursor to gout. Data from meta-analyses have shown hyperuricemia to be linked to hypertension and coronary heart disease. Similarly, gout has been associated with an increased risk of myocardial infarction, cerebrovascular accidents, and death from cardiovascular disease in randomized clinical trials. Urate-lowering therapy reduces serum urate and may decrease systemic inflammation, generation of oxidative species, and reverses endothelial dysfunction through hyperuricemia-dependent or hyperuricemia-independent pathways. Cardioprotective benefits of allopurinol, a first-line agent for the treatment of gout, have been demonstrated to potentially prevent myocardial infarction, stroke, atrial fibrillation, and other cardiovascular diseases in observational studies in select populations. Randomized controlled trials (RCTs) have also examined the role of newer urate-lowering therapies, such as febuxostat and lesinurad, and their risk of cardiovascular-specific mortality in comparison to allopurinol. A large post-marketing study of febuxostat vs. allopurinol showed higher all-cause and cardiovascular-specific mortality in the febuxostat group than in the allopurinol group; a major study limitation was that large numbers of patients were lost to follow-up or discontinued treatment. RCTs are required to assess the comparative effectiveness of urate-lowering therapies, validate findings of observational studies, and to determine which subgroup populations of gout are most likely to benefit from appropriate long-term urate-lowering therapy. This review examines the data for increased cardiovascular disease in gout and potential underlying mechanisms (including hyperuricemia, inflammation, endothelial dysfunction, oxidative stress) and the effect of urate-lowering therapy on cardiovascular disease.

Background: Hyperuricemia and gout have been linked to chronic kidney disease (CKD). Whether the increased risk of CKD in gout is due to shared risk factors such as hypertension, diabetes or heart disease, or due to gout itself is not known. Studies in older adults, who tend to have a high incidence of CKD, are limited. Our objective was to assess whether gout was associated with incident CKD in older adults., Methods: Using the 5% random sample of Medicare claims, we assessed whether gout is associated with higher risk of incident (new) CKD in adults 65 years or older, using multivariable-adjusted Cox regression analyses, adjusting for demographics (age, gender, race), medical comorbidity and common medications. We calculated hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses varied comorbidity variable (models 2, 3), or limited CKD to the most specific codes., Results: Of the 1,699,613 eligible people, 168,065 developed incident CKD; 150,162 people without gout and 17,903 people with gout. Respective crude incidence rates were 15.6 vs. 78.1 per 1000 person-years. We found that gout was associated with a higher risk of incident CKD in multivariable-adjusted analyses, HR was 3.05 (95% CI, 2.99, 3.10), with minimal attenuation in sensitivity analyses, with HR 2.96 (95% CI, 2.91, 3.01) (model 2, categorical Charlson-Romano) and 2.59 (95% CI, 2.54, 2.63) (model 3, individual Charlson-Romano comorbidities plus hypertension, heart disease, obesity, coronary artery disease). Sensitivity analyses that limited the CKD diagnostic codes to more specific codes, confirmed findings from the main models with respective HRs of 3.10 (95% CI, 3.05, 3.15; Model 1), 3.03 (95% CI, 2.97, 3.08; Model 2) and 2.60 (95% CI, 2.56, 2.65; Model 3)., Conclusion: Gout was associated with a 3-fold higher risk of CKD, confirmed in multiple sensitivity analyses. Future studies should provide insights into underlying mechanisms that are responsible for an increased CKD risk in gout.

Purpose of Review: Recent studies have produced evidence regarding the patient perspectives in gout including from disease experience to disease outcomes. Therefore, an overview on the topic can help improve our understanding of the patient experience., Recent Findings: This article explores several aspects of the patient perspective including the impact of gout on a patient's life, patient knowledge and beliefs regarding gout and its treatments, patient-perceived barriers to optimal medication adherence in gout and patient's perception of their gout. This article also summarizes any evidence of the association of patient perceptions to patient outcomes in gout., Summary: A recognition of patient perspectives in gout has the potential to positively impact clinical care for gout. Discussion of disease impact, misperceptions about benefits/harms of urate-lowering therapy (ULT), and patient values/preferences regarding pharmacological and nonpharmacological treatments can lead to a better shared decision-making and improved outcomes in gout. These findings emphasize the importance of inclusion of patient perspective not only in clinical care and quality improvement and research initiatives but also in the design and implementation of the research agenda in gout. Inclusion of patient-reported outcomes in clinical research is likely to improve its relevance to patients with gout.

Objectives: To assess whether gout is associated with a higher or lower risk of a new diagnosis of giant cell arteritis (GCA) in older adults, adjusting for known risk factors of GCA., Methods: We used the 5% Medicare claims to conduct a multivariable Cox regression analyses to assess the association of gout with incident GCA in adults 65 years or older adjusting for age, gender, race (known risk factors for GCA) and Charlson-Romano comorbidity score, the use of medications for cardiovascular diseases (statins, beta-blockers, diuretics, ACE-inhibitors) and gout (allopurinol, febuxostat). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated., Results: There were 3004 incident cases (new diagnosis) of GCA with crude incidence rates of GCA of 28.0/100,000 person-years in patients without gout and 63.8/100,000 person-years in patients with gout. Multivariable-adjusted analyses showed that preexisting gout was associated with a higher risk of incident/new GCA diagnosis with a hazard ratio of 2.05 (95% CI: 1.76, 2.40), confirmed in sensitivity analyses that substituted continuous Charlson-Romano comorbidity score with categorized score or individual comorbidities (plus hypertension, hyperlipidemia, and coronary artery disease). Older age, female gender, white race and higher comorbidity index, were also associated with a higher hazard of GCA. Subgroup analyses did not show any significant variation of the association of preexisting gout with incident GCA by age, race or sex., Conclusions: Gout was associated with more than 2-fold higher risk of incident GCA in older adults, independent of known risk factors of GCA. Future studies should explore the underlying mechanisms for this association., (Published by Elsevier Masson SAS.)

Objective: The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout., Methods: Experts in gout (n = 130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labeling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting., Results: There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (≥80%) was achieved for the labels of 8 disease elements through the Delphi exercise; the remaining 3 labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion, and podagra. Participants at the face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label "chronic gout" should not be used., Conclusion: Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout etiology, pathophysiology, and clinical presentation. The Gout, Hyperuricemia, and Crystal-Associated Disease Network recommends the use of these labels when describing the basic disease elements of gout., (© 2018, American College of Rheumatology.)

Background: Limited information exists regarding sleep disorders in gout. Our objective was to assess the burden of sleep disorders in people with gout., Methods: A brief anonymized Internet survey of people with physician-diagnosed gout who visited a gout education website assessed the frequency of sleep problems, sleep quality over the past 24 h (0 = best possible sleep, 10 = worst possible sleep), daytime sleepiness on a typical day (0 = none and 10 = most sleepy during the day), sleep quantity (number of hours of sleep), and the frequency of snoring or gasping, and snorting or stopping breathing during the sleep, using validated questionnaires, including the NHANES 2016 sleep questionnaire. We used Chi-square test to compare the categorical and t test the continuous variables., Results: Of the 454 website visitors who clicked the survey, 320 survey respondents reported physician-diagnosed gout. Mean age was 57 years (standard deviation [SD], 13.4), 72% were male, 77% were White, and mean gout duration was 7.6 (SD, 11). Of the respondents, 23% reported doctor-diagnosed sleep disorder (sleep apnea, 17%; sleep study ordered, diagnosis pending, 4%; other sleep disorder 2%). A mean 6.7 h of sleep per night was reported (SD, 1.3). Eighty-six percent reported snoring during sleep and 45% reported having snorted, gasped, or stopped breathing while asleep. Two thirds of the patients reported feeling sleepy during the day, at least 3-4 times a month or more. Sleep quality was 5.5 (SD, 2.6), and daytime sleepiness was 3.5 (SD, 2.6) on a 0-10 scale (higher = worse)., Conclusions: People with physician-diagnosed gout reported frequent sleep disorders and daytime sleepiness in an Internet survey. More in-depth studies are needed to better understand the association of gout with sleep disorders.

Background: In the presence of limited available data, our objective was to assess the association of gout with the risk of incident Parkinson's disease (PD) in adults 65 years or older., Methods: We used the 5% random sample of Medicare claims data from 2006 to 2012 to examine the association of gout with incident PD. The multivariable Cox regression model adjusted for demographics, comorbidity, and common cardiovascular disease and gout medications. We calculated hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses adjusted for comorbidity categorically, or individually and for additional cardiovascular comorbidities., Results: In a cohort study, 1.72 million Medicare beneficiaries were eligible. The mean age was 75 years (standard deviation [SD], 7.6), 58% were female, 86% were White and 37% had Charlson-Romano comorbidity index score of ≥2. We found that 22,636 people developed incident PD, 1129 with gout and 21,507 without gout. The respective crude incidence rates of incident PD were 3.7 vs. 2.2 per 1000 person-years. We found that gout was associated with 1.14-times higher hazard ratio (95% CI, 1.07, 1.21) of PD in the main analysis; findings were confirmed in sensitivity analyses. We noted that the risk differed slightly by age; ages 65-75, 75-85 and > 85 had hazard ratios of incident PD with gout of 1.27 (95% CI, 1.16, 1.39), 1.07 (95% CI, 0.97, 1.16) and 0.97 (95% CI, 0.79, 1.20), respectively, but no gender or race differences were noted., Conclusions: Gout was associated with a higher risk of incident PD in older adults, with the risk being significant in the age group 65-75 years. Future studies need to assess the mechanisms of this increased risk.

We used the 5% random Medicare claims from Americans 65 years or older from 2006-2012 to examine the association of gout with the risk of developing incident (new) depression using multivariable-adjusted Cox proportional hazards model, adjusting for demographics (age, race, sex), common cardiovascular medications, allopurinol, and febuxostat and medical comorbidity. Of the 1.69 million people, 142,596 developed depression. In multivariable-adjusted analyses, gout was independently associated with 42% higher hazard of depression in older adults, confirmed in sensitivity analyses. This finding suggests the gout patients should be screened for depression and may trigger research to assess the role of inflammation and oxidative stress pathways in older people with depression., (Copyright © 2018. Published by Elsevier B.V.)

Background: Conflicting data in the literature raise the question whether gout, independent of its treatment, increases the risk of dementia in the elderly. Our objective was to assess whether gout in older adults is associated with the risk of incident dementia., Methods: We used the 5% Medicare claims data for this observational cohort study. We used multivariable-adjusted Cox proportional hazard models to assess the association of gout with a new diagnosis of dementia (incident dementia), adjusting for potential confounders/covariates including demographics (age, race, sex), comorbidities (Charlson-Romano comorbidity index), and medications commonly used for cardiac diseases (statins, beta-blockers, diuretics, and angiotensin converting enzyme (ACE)-inhibitors) and gout (allopurinol and febuxostat)., Results: In our cohort of 1.71 million Medicare beneficiaries, 111,656 had incident dementia. The crude incidence rates of dementia in people without and with gout were 10.9 and 17.9 per 1000 person-years, respectively. In multivariable-adjusted analyses, gout was independently associated with a significantly higher hazard ratio of incident dementia, with a HR of 1.15 (95% CI, 1.12, 1.18); sensitivity analyses confirmed the main findings. Compared to age 65 to < 75 years, age 75 to < 85 and ≥ 85 years were associated with 3.5 and 7.8-fold higher hazards of dementia; hazards were also higher for females, black race or people with higher medical comorbidity., Conclusion: Gout was independently associated with a 15% higher risk of incident dementia in the elderly. Future studies need to understand the pathogenic pathways involved in this increased risk.

Objective: There are no qualitative studies of sleep in gout; the aim of this study was to examine the impact of gout on sleep., Methods: Nine nominal groups were conducted, oversampling for African-Americans and women with gout. Patients discussed and rank-ordered their concerns., Results: Nine nominal groups with 46 gout patients were conducted with mean age, 61 years (s.d. 10.6) and gout duration, 14.9 years (s.d. 12); 63% were men, 46% African-American, 52% married, 46% retired and 63% were allopurinol users. The most frequently cited highly ranked concerns could be divided into three categories. The first category, character of sleep interruption, included the concerns: severe and complete sleep interruption by gout flare pain (nine groups); and inability to get rapid eye movement sleep (one group). The second category, causes of sleep interruption, included: inability to get into a comfortable position during sleep (six groups); anxiety and depression associated with severe gout pain (seven groups); sleep interruption by moderate chronic joint pain (three groups); frequent trips to the bathroom interfering with sleep (two groups); gout medication side effects (four groups); frequent trips to the emergency room (one group); joint swelling with physical/functional deficit interfering with sleep (two groups); and flare pain interfering with sleep apnoea management (two groups). The final category, consequences of sleep interruption, included: effect on daily functioning (two groups); worsens other health conditions, which then affect sleep (four groups); and cumulative effect on sleep (one group)., Conclusion: Gout has significant impact on sleep quantity, quality and architecture. Sleep disruption due to gout has several pathways and significant consequences.

Objectives: The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical trials., Methods: Multiple databases through October 2017 were searched. Randomized controlled trials comparing any ULT in people with gout with any control or placebo, ≥three months duration were included. Open label extension (OLE) trial data were included in secondary analyses. Standardized data elements were extracted independently by two reviewers., Results: Ten RCTs and 3 OLE studies were identified. From the RCTs (maximum duration 24 months) meta-regression did not reveal an association between the relative risk of a gout flare and the difference in proportions of individuals with SU < 6mg/dL (P = 0.47; R 2 = 8%). In a post hoc analysis, the ratio of the time in months at which the proportion of individuals having a flare was reported/time in months at which the proportion of individuals with SU < 6mg/dL was reported was calculated and studies where the ratio was <2 were excluded. Using the remaining 6 studies there was an association between proportion of individuals achieving SU < 6mg/dL and gout flares (over patient years). Duration of ULT was inversely associated with the proportion of patients experiencing a flare. Study duration and variability in reporting of outcomes limited the analysis. Observational studies supported the trend of fewer flares in those with lower SU., Conclusions: Based on aggregate clinical trial-level data an association between SU and gout flare could not be confirmed. However, based on observational ecological study design data-including longer duration extension studies-SU < 6mg/dL was associated with reduced gout flares., (Copyright © 2018 Elsevier Inc. All rights reserved.)