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Introduction: Gout, a common comorbidity of chronic kidney disease (CKD), is associated with high morbidity and healthcare utilization. However, a large proportion of gout remains undermanaged or untreated which may lead to worse patient outcomes and greater healthcare costs. This study estimates the present and future health and economic burden of controlled and uncontrolled gout in a virtual United States (US) CKD population. Methods: A validated microsimulation model was used to project the burden of gout in patients with CKD in the USA through 2035. Databases were utilized to build a virtual CKD population of "individuals" with controlled or uncontrolled gout. Modelling assumptions were made on the basis of the literature, which was sparse in some cases. Health and economic outcomes with the current care (baseline) scenario were evaluated, along with potential benefits of urate-lowering intervention scenarios. Results: The prevalence of comorbid gout and CKD in the USA was projected to increase by 29%, from 7.9 million in 2023 to 9.6 million in 2035 in the baseline scenario. Gout flares, tophi, and comorbidity development were also projected to increase markedly through 2035, with the economic burden of gout in the CKD population subsequently increasing from $38.9 billion in 2023 to $47.3 billion in 2035. An increased use of oral urate-lowering therapies in undermanaged patients, and pegloticase use in patients refractory to oral urate-lowering therapies were also project to result in 744,000 and 353,000 fewer uncontrolled gout cases, respectively, by 2035. Marked reductions in complications and costs ensued. Conclusions: This study projected a substantial increase in comorbid gout and CKD. However, improved use of urate-lowering interventions could mitigate this growth and reduce the health and economic burdens of gout. [ABSTRACT FROM AUTHOR]

Gout is a debilitating form of inflammatory arthritis resulting from high serum urate. Close monitoring of serum urate, medications, and specific dietary choices are required for successful management, including a commitment to regular medical examinations and lifestyle modifications. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between industry‐sponsored meal payments and the prescribing patterns of brand‐name colchicines, namely Colcrys and Mitigare, among Medicare beneficiaries in the United States from 2014 to 2021. Methods: This cross‐sectional study utilized data from the Open Payments Database and Medicare Part D covering the years 2014 to 2021. The study included 54 836 physicians who submitted more than 10 colchicine claims. Exposure was defined as the receipt of one or more industry‐sponsored meals from the manufacturers of Colcrys or Mitigare. The primary outcomes included the likelihood of prescribing Colcrys and Mitigare, as well as the associated number of claims and Medicare expenditures. Results: Among 54 836 eligible physicians, 44.9% received meal payments from the Colcrys manufacturer, and 8.0% from the Mitigare manufacturer, over the eight‐year study period. The average meal payment value was $14.9 for Colcrys and $15.1 for Mitigare. The receipt of meal payments was significantly associated with an increased likelihood of prescribing Colcrys (odds ratio: 1.24 [95% CI: 1.21–1.27], p <.001) and Mitigare (odds ratio: 3.54 [95% CI: 2.98–4.20], p <.001). Each additional meal payment corresponded with a significant increase in Medicare expenditures: $55.4 (95% CI: $48.3–$62.5, p <.001) for Colcrys and $153.7 (95% CI: $17.7–$289.6, p =.03) for Mitigare. These associations remained consistent across different specialties and genders. Conclusion: This study reveals that receipt of meal payments from manufacturers of brand‐name colchicine was significantly associated with an increased rate of prescriptions for these brand‐name drugs, leading to higher Medicare expenditures in the United States. [ABSTRACT FROM AUTHOR]

Background: The co‐disease of depression and gout is becoming more common in the modern era. However, the relationship between the severity of depressive symptoms and gout prevalence and treatment rate was still unclear. Objective: This study aimed to determine the relationship between the prevalence, treatment rate of gout, and the severity of depression in the United States. Method: The cross‐sectional analysis of the 2007–2018 National Health and Nutrition Examination Survey (NHANES) for participants with depression was performed. According to their Patient Health Questionnaire‐9 (PHQ‐9) scores, participants were categorized as none, mild, moderate, moderately severe, and severe. To learn the correlation between the severity of depressive symptoms and the prevalence and treatment rate of gout using multivariate logistic regression to control for confounder interference. Results: A total of 25 022 patients were included in this study. As the severity of the depressive symptoms worsened (Mild, Moderate and Moderately severe), the risk of gout increased in non‐adjusted model and model 1,2,3 (p‐value for trend =.01 in non‐adjusted model, <.0001 in model 1, <.01 in models 2 and 3; prevalence group in Model 1, aOR1.71, 95% CI (1.40, 2.08) in the mild group, aOR1.68, 95% CI (1.19, 2.39) in the moderate group, aOR1.31,95% CI (0.82, 2.11) in the moderately severe group, aOR1.21, 95% CI (0.62, 2.38) in the severe group). However, the lower gout prevalence trend has no statistical significance after adjusting all factors in Model 4(p‐value for trend =.98). Compared with patients without depression, only a few patients received treatment, especially patients with severe depression (none, 80.1%; severe, 0.2%). The more severe the depression, the lower the treatment rate (p‐value for trend: non‐adjusted model, p <.001; model 1, p =.05; model 2, p =.02; model 3, p =.03). Conclusion: Compared with patients without depression, the patients with depression had a higher risk of gout. With the aggravation of depression, the prevalence of gout and the rate of treatment both were decreased. Patients with gout and depression need to receive multidisciplinary care after diagnosis. However, currently, treatment cannot meet the needs of the current patients. [ABSTRACT FROM AUTHOR]

Introduction: This drug utilization study evaluated the impact of 2019 label changes on real-world febuxostat utilization among patients with gout. We describe the numbers and proportions of patients initiating febuxostat as new users (allopurinol-naïve) or prevalent new users (prior allopurinol use) and data on febuxostat users with established cardiovascular disease (CVD) morbidities before, during, and after the 2019 label changes. Methods: This descriptive, non-interventional, cross-sectional study used data from two large administrative claims databases in the United States, the IQVIA PharMetrics Plus database and the Optum Research Database (ORD). The study population included patients with gout initiating febuxostat on or after June 1, 2016. Data were collected on febuxostat and allopurinol use, established CVD morbidities, comorbidities of interest, concomitant medications, and patient demographics. Results: In both databases, the total number of febuxostat users and proportion of patients who initiated febuxostat as new users both decreased during the study period. Of 13,848 patients in the PharMetrics Plus cohort, 42.7% were new users of febuxostat and 57.3% were prevalent new users. In the ORD cohort, 40.5% of the 10,198 patients were new users and 59.5% were prevalent new users. The most common established CVD morbidities in the 12 months prior to initiation of febuxostat were diabetes mellitus, ischemic heart disease, and heart failure/cardiomyopathy. Conclusions: Although the benefit–risk profile for febuxostat is considered favorable for the treatment of hyperuricemia in certain patients with gout, real-world febuxostat utilization decreased during the study period, presumably in response to the label change. [ABSTRACT FROM AUTHOR]

Background: The protective effects of allopurinol on physical function in older adults are not well understood, despite its potential to improve functional gains and reduce sarcopenia. This study aims to determine the association between allopurinol, persistent physical disability, and frailty in older gout patients. Methods: This analysis used data from a randomized trial in an older cohort, ASPirin in Reducing Events in the Elderly (ASPREE). ASPREE recruited 19,114 participants aged ≥65 years without prior cardiovascular events, dementia, or independence‐limiting physical disability at trial enrolment. This analysis examined the association of baseline and time‐varying allopurinol use with persistent physical disability and new‐onset frailty in participants with gout at baseline (self‐report or use of any anti‐gout medications). Frailty was measured using the Fried frailty phenotype (score ≥3/5) and a deficit accumulation frailty index (FI) (score >0.21/1.0). Multivariable Cox proportional‐hazards models were used for main analyses. Results: This analysis included 1155 gout participants, with 630 taking allopurinol at baseline and 525 not. During a median follow‐up of 5.7 years, 113 new allopurinol users were identified. Compared with nonusers, baseline allopurinol use was associated with a significant risk reduction of persistent physical disability (Adjusted HR 0.46, 95% CI 0.23–0.92, p = 0.03). The strength of the association was modestly attenuated in the time‐varying analysis (Adjusted HR 0.56, 0.29–1.08, p = 0.08). No significant associations with frailty measures were observed for either baseline allopurinol use (Fried frailty: Adjusted HR 0.83, 0.62–1.12; FI: Adjusted HR 0.96, 0.74–1.24) or time‐varying allopurinol use (Fried frailty: Adjusted HR 0.92, 0.69–1.24; FI: Adjusted HR 1.02, 0.78–1.33). Conclusions: Allopurinol use in older adults with gout is associated with a reduced risk of persistent physical disability but not associated with risk of frailty. [ABSTRACT FROM AUTHOR]

Objective: To assess 12‐month safety and efficacy of pegloticase + methotrexate (MTX) versus pegloticase + placebo (PBO) cotherapy in a PBO‐controlled, double‐blind trial (A randomized, double‐blind, placebo‐controlled, multicenter, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase [MIRROR RCT]). Methods: Patients with uncontrolled gout (serum urate level [SU] ≥7 mg/dl, oral urate‐lowering therapy failure or intolerance, and presence of one or more gout symptoms [one or more tophi, two or more flares in 12 months, gouty arthropathy]) were randomized 2:1 to receive pegloticase (8‐mg infusion every 2 weeks) with blinded MTX (oral 15 mg/week) or PBO for 52 weeks. Efficacy end points included proportion of responders (SU level <6 mg/dl for ≥80% of examined month) in the intent‐to‐treat population (ITT) (all randomized patients) during month 6 (primary end point), month 9, and month 12; proportion with resolution of one or more tophi (ITT); mean SU reduction (ITT); and time to SU‐monitoring pegloticase discontinuation. Safety was evaluated via adverse event reporting and laboratory values. Results: Month 12 response rate was significantly higher in patients cotreated with MTX (60.0% [60 of 100] vs. 30.8% [16 of 52]; difference: 29.1% [95% confidence interval (CI): 13.2%‐44.9%], P = 0.0003), with fewer SU discontinuations (22.9% [22 of 96] vs. 63.3% [31 of 49]). Complete resolution of one or more tophi occurred in 53.8% (28 of 52) versus 31.0% (9 of 29) of MTX versus PBO patients at week 52 (difference: 22.8% [95% CI: 1.2%‐44.4%], P = 0.048), more than at week 24 (34.6% [18 of 52] vs. 13.8% [4 of 29]). Consistent with observations through month 6, pharmacokinetic and immunogenicity findings showed increased exposure and lower immunogenicity of pegloticase when administered with MTX, with an otherwise similar safety profile. No infusion reactions occurred after 24 weeks. Conclusion: Twelve‐month MIRROR RCT data further support MTX cotherapy with pegloticase. Tophi resolution continued to increase through week 52, suggesting continued therapeutic benefit beyond month 6 for a favorable treatment effect. [ABSTRACT FROM AUTHOR]

Objective: To examine whether the cross‐sectional gene–diet interaction for prevalent hyperuricemia among women translates prospectively to risk of incident female gout. Methods: We analyzed the interaction between genetic predisposition and adherence to a healthy dietary pattern (i.e., Dietary Approaches to Stop Hypertension [DASH] score) on risk of incident female gout in 18,244 women from Nurses' Health Study (NHS; discovery) and 136,786 women from 3 additional prospective female cohorts from the US and UK (replication). Genetic risk score (GRS) was calculated from 114 urate‐associated loci. Results: In the NHS and replication cohorts, association between diet and gout risk was larger and stronger among women with higher genetic risk. In all cohorts combined, compared to women with an unhealthy DASH score (less than the mean score), multivariable relative risk (RR) for incident gout among women with a healthy DASH score (greater than/equal to the mean score) was 0.67 (95% confidence interval [95% CI] 0.60–0.76) among higher GRS (greater than/equal to the mean score) and 0.91 (0.78–1.05) among lower GRS (P for multiplicative interaction = 0.001); multivariable RR for higher versus lower GRS was 2.03 (95% CI 1.80–2.29) and 1.50 (95% CI 1.31–1.71) among unhealthy and healthy DASH score groups, respectively. Additive interaction was also significant, in both the discovery and replication cohorts (P < 0.001), with 51% of the excess risk attributable to the additive gene–diet interaction in all cohorts combined. Conclusion: The deleterious effect of genetic predisposition on risk of incident female gout was more pronounced among women with unhealthy diets, with nearly half the excess risk attributable to this gene–diet interaction. These data elucidate the important synergy of genetics and diet for female gout development. [ABSTRACT FROM AUTHOR]

Objectives Gout prevalence is reportedly ∼20% higher in US Black adults than Whites, but racial differences in emergency department (ED) visits and hospitalizations for gout are unknown. We evaluated the latest US national utilization datasets according to racial/ethnic groups. Methods Using 2019 US National Emergency Department Sample and National Inpatient Sample databases, we compared racial/ethnic differences in annual population rates of ED visits and hospitalizations for gout (primary discharge diagnosis) per 100 000 US adults (using 2019 age- and sex-specific US census data). We also examined rates of ED visits and hospitalizations for gout among all US ED visits/hospitalizations and mean costs for each gout encounter. Results Compared with White patients, the per capita age- and sex-adjusted rate ratio (RR) of gout primary ED visits for Black patients was 5.01 (95% CI 4.96, 5.06), for Asian patients 1.29 (1.26, 1.31) and for Hispanic patients 1.12 (1.10, 1.13). RRs for gout primary hospitalizations were 4.07 (95% CI 3.90, 4.24), 1.46 (1.34, 1.58) and 1.06 (0.99, 1.13), respectively. Corresponding RRs among total US hospitalizations were 3.17 (95% CI 2.86, 3.50), 3.23 (2.71, 3.85) and 1.43 (1.21, 1.68) and among total ED visits were 2.66 (95% CI, 2.50, 2.82), 3.28 (2.64, 4.08), and 1.14 (1.05, 1.24), respectively. RRs were largest among Black women. Costs for ED visits and hospitalizations experienced by race/ethnicity showed similar disparities. Conclusions These first nationwide data found a substantial excess in both gout primary ED visits and hospitalizations experienced by all underserved racial/ethnic groups, particularly by Black women, revealing an urgent need for improved care to eliminate inequities in gout outcomes. [ABSTRACT FROM AUTHOR]

Objectives To explore trends in risk factor control (hypertension, diabetes mellitus, hyperlipidaemia) in patients with gout and medication use among those whose risk factor control targets were not achieved. Methods We used the data from National Health and Nutrition Examination Survey (NHANES) between 2007–2008 and 2017–2018 for analyses. The study samples were weighted so that they could be representative of the non-institutionalized US population. We conducted a cross-sectional analysis to assess trends in risk factor control and medication use, and employed logistic regression analyses to explore patient characteristics associated with risk factor control. Results The prevalence of participants in whom blood pressure control target was achieved decreased from 64.6% in 2007–2008 to 55.3% in 2017–2018 (P -value for trend = 0.03). The percentage of participants whose glycaemic, lipid or all three risk factor control targets were achieved remained stable temporally (P  > 0.05). Some patient characteristics were significantly related to risk factor control, including age 45–64, age ≥65, Asian Americans, non-Hispanic Blacks, higher family income, and being overweight and obese. A trend towards increased use of glucose-lowering medication was found (from 71.0% in 2007–2008 to 94.7% in 2017–2018, P  < 0.01), while the prevalence of taking blood pressure-lowering and lipid-lowering medications remained stable (P  > 0.05). Conclusion Based on NHANES data, a significant trend towards decreased blood pressure control was observed in patients with gout, while glycaemic and lipid control levelled off. These findings emphasize that more endeavours are needed to improve management of cardiovascular risk factors in patients with gout. [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia (HUA) and gout have been demonstrated as independent risk factors for cardiovascular disease. The relationship between the recently updated Life's Essentials 8 (LE8), which measures ideal cardiovascular health (CVH), and HUA and gout remains unclear. The aim of this study was to explore the relationship between CVH and the prevalence of HUA and gout among a nationally representative sample of US adults., Methods: This study utilized cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) for the years 2007 to 2018. The CVH scores and their corresponding components were defined according to the guidelines established by the American Heart Association. The association between the LE8 score and both HUA and gout was assessed using weighted multivariable logistic and restricted cubic spline (RCS) models., Results: Among the 21,155 participants aged 20 years and older, the prevalence of HUA was 17.20% (95% CI, 16.05-18.36%), and the prevalence of gout was 3.58% (95% CI, 3.13-4.02%). After adjusting for potential confounders, compared to participants exhibiting low CVH, the multivariable adjusted odds ratio (OR) for HUA was 0.65 (95% CI, 0.56-0.75) in those with moderate CVH, and 0.25 (95% CI, 0.20-0.31) in those with high CVH. Additionally, compared to participants with low CVH, the multivariable adjusted OR for gout was 0.66 (95% CI, 0.53-0.81) in those with moderate CVH and 0.32 (95% CI, 0.20-0.50) in those with high CVH. The LE8 score exhibited a significant nonlinear negative association with HUA and linear negative correlation with gout. In subgroup analyses focusing on HUA, significant interactions were observed between LE8 score and age, sex, and CKD (P for interaction < 0.05). For gout, only a significant interaction between LE8 score and sex was observed (P for interaction < 0.05)., Conclusions: Among adults, there was a significant negative correlation between LE8 score and the prevalence of HUA and gout. Maintaining an ideal CVH may be beneficial in reducing the burden of HUA and gout., (© 2024. The Author(s).)

Background: The triglyceride glucose (TyG) index, defined as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2], provides insights into overall metabolic status. However, the association between the TyG index and gout has not been investigated. Therefore, this study explored the correlation between the TyG index and gout., Methods: Using data from the National Health and Nutrition Examination Survey, which was conducted from 2007 to 2018, this study investigated the relationship between the TyG index and gout. Demographic data and potential risk factors were analyzed and compared using t tests for continuous data and chi-square tests for categorical data. Logistic regression and subgroup analysis were performed to examine the association between the TyG index and gout., Results: A total of 14,924 participants were enrolled, among whom 726 (4.86%) were diagnosed with gout. Without controlling for any covariates, a significant positive correlation was observed between an elevated TyG index and increased risk of gout, with an odds ratio (OR) of 2.07 and a 95% confidence interval (CI) ranging from 1.76 to 2.43. After full adjustment, this association remained statistically significant, with an adjusted OR of 1.43 and a 95% CI from 1.14 to 1.80. Subgroup analyses revealed significant interactions, particularly for females (OR = 2.55; 95% CI: 2.00-3.26), individuals with no military service history (OR = 2.15; 95% CI: 1.66-2.43), and those without diabetes (OR = 2.00; 95% CI: 1.64-2.43)., Conclusion: A positive correlation was observed between the TyG index and gout. Consequently, further large-scale prospective studies are warranted for a comprehensive analysis of the role of the TyG index in gout., (© 2024. The Author(s).)

Introduction: Gout is a common type of inflammatory arthritis. Vitamin C is a potent antioxidant that neutralizes reactive oxygen species. However, the association between dietary vitamin C levels and gout remains unclear. This study evaluated the relationship between dietary vitamin C intake and gout., Methods: Cross-sectional data from individuals aged > 20 years who participated in the National Health and Nutrition Examination Survey between 2013 and 2018 were collected. Details on gout, dietary vitamin C intake, and several other essential variables were recorded., Results: There were 12589 participants, 5% (652/12589) of whom experienced gout. Compared with individuals with lower vitamin C consumption in the Q1 group (≤19.9 mg/day), the adjusted odds ratio(OR)values for dietary vitamin C intake and gout in the Q2 group (19.9-49.7 mg/day), Q3 group (49.7-110.375 mg/day), and Q4 group (≥110.375 mg/day) were 0.87 (95% confidence interval (CI): 0.69-1.1, P = 0.237), 0.81 (95% CI: 0.64-1.02, P = 0.076), and 0.77 (95% CI: 0.6-0.99, P = 0.042), respectively. Accordingly, the association between dietary vitamin C intake and gout exhibited an L-shaped curve (nonlinear, P = 0.245) in a restricted cubic spline. Subgroup analysis revealed significant interactions between vitamin C levels and gout according to sex ( P < 0.05). When we used data on dietary vitamin C from the second survey, we observed a similar inverse association between vitamin C intake and gout. The vitamin C was also negatively associated with hyperuricemia (OR, 0.94; 95% CI, 0.9-0.98, P =0.005). Compared with Q1, the adjusted OR values for dietary vitamin C and hyperuricemia in Q2, Q3, and Q4 were 0.77 (95% CI: 0.69-0.86, P = 0.65), 0.81 (95% CI: 0.72-0.91, P = 0.014), and 0.72 (95% CI: 0.64-0.81, P < 0.001), respectively. No association was observed between vitamin C supplementation and gout., Conclusion: The population-based data indicate that dietary vitamin C intake is inversely associated with gout. These findings support the potential role of vitamin C in preventing gout., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zou, Liu and Li.)

Background: Prevalence rates of hyperuricemia and gout are increasing. Clinical investigations of hyperuricemia-related risk factors aid in the early detection, prevention, and management of hyperuricemia and gout. Ongoing research is examining the association of obesity, dietary patterns, and blood pressure (BP) with serum uric acid (sUA). Methods: A cross-sectional study was conducted based on the National Health and Nutrition Examination Survey. The exposures included body mass index (BMI), dietary patterns, and BP. The outcome variable was sUA level. The weighted multivariate linear regression models and smooth curve fittings were used to assess the association of BMI, dietary patterns, and BP with sUA. Results: There was a significantly positive correlation between BMI and sUA (β = 0.059, 95% CI: 0.054 to 0.064, P < 0.00001). Overweight and obese individuals had higher sUA levels than those with the normal BMI (β = 0.451, 95% CI: 0.357 to 0.546, P < 0.00001; β = 0.853, 95% CI: 0.760 to 0.946, P < 0.00001; respectively). Dietary energy intake was positively correlated with sUA (β = 0.000, 95% CI: 0.000 to 0.000, P = 0.01057). Dietary intake of carbohydrate and fiber were negatively correlated with sUA (β = − 0.001, 95% CI: − 0.002 to − 0.000, P < 0.00001; β = − 0.008, 95% CI: − 0.011 to − 0.004, P = 0.00001; respectively). Moreover, systolic BP was positively correlated with sUA (β = 0.006, 95% CI: 0.003 to 0.009, P = 0.00002). However, no statistical differences were found about the associations of dietary intake of total sugars, protein, total fat, cholesterol, and diastolic BP with sUA. Conclusions: The current cross-sectional investigation of a nationally representative sample of US participants showed that BMI, dietary energy intake, and systolic BP were positively correlated with sUA levels; dietary carbohydrate and fiber intake were negatively correlated with sUA levels. The findings might be helpful for the management and treatment of hyperuricemia and gout. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance (IR) has been linked to the development of gout. The triglyceride glycemic (TyG) index is a useful biomarker of IR, and the evidences between TyG and gout are limited. Therefore, this study aimed to examine the association between the TyG index and gout in the United States (U.S)., Methods: The cross-sectional study was conducted among adults with complete TyG index and gout data in the 2007-2017 National Health and Nutrition Examination Survey (NHANES). The TyG index was calculated as fasting triglycerides (mg/dl) * fasting glucose (mg/dl)/2. Gout was assessed by self-report questionnaire (MCQ160n). Weighted chi-squared and weighted Student's t-test were used to assess group differences. Weighted multivariable logistic regression analysis, subgroup analysis, and interaction tests were used to examine the TyG index and gout association., Results: The final participants were 11,768; 5910 (50.32%) were female, 7784 (73.26%) were 18-60 years old, 5232 (69.63%) were white, and 573 (5.12%) had gout. After adjusting for all covariates, the TyG index was positively associated with gout; each unit increase in TyG index was associated with 40% higher odds of gout (odds ratio (OR), 1.40; 95% CI: 1.82-2.66; p < 0.0001). Participants in the highest TyG index tertile group were at high risk of gout (odds ratio (OR), 1.64; 95% CI: 1.06-2.54, p = 0.03) versus those in the lowest tertile group. Interaction tests showed no significant effect of age, race, marital status, PIR level, education, BMI, smoking status, drinking status, hypertension, and DM on this association between TyG index and gout (p for interaction > 0.05)., Conclusions: In this large cross-sectional study, our results suggested that a higher TyG index was associated with an increased likelihood of gout in U.S. adults. Our findings highlight that the TyG index is a reliable biomarker of IR; management of IR among adults may prevent or alleviate the development of gout; meanwhile, the TyG index may be a simple and cost-effective method to detect gout., (© 2024. The Author(s).)

Objectives: The weight-adjusted waist circumference index (WWI), a novel obesity indicator, gives better accuracy in assessing both muscle and fat mass. Our goal was to evaluate the relationship between WWI and the occurrence of hyperuricemia/gout among middle-aged and older adults in America., Methods: We analyzed the National Health and Nutrition Examination Survey (NHANES) data from the 2007-2014 cycles. Logistic regression analyses, subgroup analyses, and restricted cubic splines (RCS) were performed to evaluate the association between WWI and hyperuricemia/gout prevalence., Results: A total of 5332 adults aged 50 years and above were included in this study. The prevalence of hyperuricemia and gout was 23.20% and 6.70% respectively. The fourth quartile of WWI was associated with a 56% higher risk for hyperuricemia, compared with the first quartile (OR = 1.56, 95% CI 1.07-2.27, P trend < 0.001). A similar association was found between continuous WWI increase and OR of hyperuricemia in the fully adjusted model (OR = 1.35, 95% CI = 1.13-1.61, P < 0.05). However, WWI was not significantly associated with the prevalence of gout. The RCS model suggested a significant linear relationship between WWI and the risk of hyperuricemia/gout. Stratification analysis showed that the positive associations of WWI with the risk of hyperuricemia were more pronounced in participants who were women, aged 50-59, smokers, no physical activity, non-diabetes, hypertension, and hyperlipidemia., Conclusions: Our findings suggest a positive correlation between WWI and hyperuricemia among middle-aged and older adults in America. Employing WWI as a tool for hyperuricemia prevention may be meaningful. Key Points • Weight-adjusted waist circumference index is a new obesity evaluation index. • Weight-adjusted waist circumference index is associated with hyperuricemia not gout. • The association is more pronounced in participants who were women, aged 50-59, smokers, no physical activity, non-diabetes, hypertension, and hyperlipidemia., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: The Oxidative Balance Score (OBS) is a systematic tool to assess the effects of diet and lifestyle in relation to oxidative stress. The association between OBS and gout has not been reported previously. We conducted a cross-sectional study to investigate the complex association between OBS and gout in US adults., Methods: In all, 10 492 participants were included in this study. The exposure variable was OBS, which was scored by 16 dietary and four lifestyle factors. Multivariate logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were used to analyze the association between OBS and gout., Results: Compared with the lowest OBS quartile group (Q1), the multivariate corrected odds ratio (OR) (95% confidence interval [C]) for the highest quartile of OBS (Q4) was 0.72 (0.52-1.00) (p = .13 for trend); furthermore, the RCS showed a negative linear relationship between OBS and gout (p-nonlinear = .606)., Conclusion: In conclusion, the risk of gout is higher with high OBS. The prevalence of gout decreased with higher OBS. Diabetes may alter this negative correlation., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: The current study aimed to assess the relationships between oxidative balance score (OBS) and OBS subclasses (dietary and lifestyle OBS) with risks of hyperuricemia (HUA) and gout among American adults., Methods: Participants in the National Health and Nutrition Examination Survey from 2007 to 2018 were initially recruited and then the final sample was restricted to adults without missing values about serum uric acid, gout, OBS, and covariates. Rao-Scott adjusted chi-square test and analysis of variance were utilized to compare the baseline characteristics in adults of different quartiles of OBS, while the weighted stepped logistic regression models were used to explore the associations of overall, dietary, and lifestyle OBS with the risks of HUA and gout. Weighted restricted cubic spline analyses were conducted to explore the nonlinear dose-response associations., Results: The final sample consisted of 22,705 participants aged 20 years and older, which was representative of approximately 197.3 million non-institutionalized American adults. HUA and gout prevalence decreased with OBS quartiles. Compared with adults in the first quartile of OBS, those in the second (OR: 0.85, 95% CI: 0.72-0.99), third (OR: 0.71, 95% CI: 0.58-0.85), and fourth (OR: 0.48, 95% CI: 0.38-0.61) quartiles of OBS had reduced risks of hyperuricemia. Similarly, adults in the second (OR: 0.70, 95% CI: 0.51-0.97) quartile of OBS was associated with lower gout risk in comparison to adults in the lowest quartile. Regarding OBS subclasses, dietary and lifestyle OBS were both negatively correlated with the risk of HUA, and only higher lifestyle OBS was significantly associated with lower gout risk. Furthermore, the subgroup analyses and interaction effects also substantiated similar effects. Significant nonlinear dose-response relationships were observed between overall, dietary, and lifestyle OBS with HUA risk as well as that of lifestyle OBS with gout risk., Conclusion: This study strongly suggests the significant negative associations of OBS with HUA and gout in American adults and provides a dietary and lifestyle guideline to reduce the risks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wu, Deng, Nie, Tao, Li, Luo and Xia.)

The article focuses on the contribution of both genetic susceptibility and adherence to a healthy dietary pattern to incident female gout risk, addressing the exclusion of diabetes, hypertension, and chronic kidney disease from the multivariable models.

Background Cutaneous leishmaniasis (CL) is a neglected tropical disease causing an estimated 1 million new cases annually. While antimonial compounds are the standard of care worldwide, they are associated with significant adverse effects. Miltefosine, an oral medication, is United States (US) Food and Drug Administration approved to treat CL caused by Leishmania braziliensis , Leishmania guyanensis , and Leishmania panamensis. Evidence of efficacy in other species and side-effect profiles in CL has been limited. Methods Twenty-six patients with CL were treated with miltefosine at the US National Institutes of Health. Species included L. braziliensis (n = 7), L. panamensis (n = 5), Leishmania mexicana (n = 1), Leishmania infantum (n = 3), Leishmania aethiopica (n = 4), Leishmania tropica (n = 2), Leishmania major (n = 1), and unspeciated (n = 3). Demographic and clinic characteristics of the participants, response to treatment, and associated adverse events were analyzed. Results Treatment with miltefosine resulted in cure in 77 % (20/26) of cases, with cures among all species. Common adverse events included nausea/vomiting (97%) and lack of appetite (54%). Clinical management or dose reduction was required in a third of cases. Gout occurred in 3 individuals with a prior history of gout. Most laboratory abnormalities, including elevated creatinine and aminotransferases, were mild and normalized after treatment. Conclusions Our data suggest that miltefosine has good but imperfect efficacy to a wide variety of Leishmania species. While side effects were common and mostly mild to moderate, some resulted in discontinuation of therapy. Due to oral administration, broad efficacy, and manageable toxicities, miltefosine is a viable alternative treatment option for CL, though cost and lack of local availability may limit its widespread use. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To describe the levels and trends of point prevalence, annual incidence, and years lived with disability (YLD) for gout and its attributable risk factors in 195 countries and territories from 1990 to 2017 according to age, sex, and Sociodemographic Index (SDI; a composite of sociodemographic factors). Methods: Data were extracted from the Global Burden of Disease (GBD) 2017 study. A comprehensive systematic review of databases and the disease‐modeled analysis were performed by the GBD team at the Institute for Health Metrics and Evaluation, in collaboration with researchers and experts worldwide, to provide estimates at global, regional, and national levels during 1990 and 2017. Counts and age‐standardized rates per 100,000 population, along with 95% uncertainty intervals (95% UIs), were reported for point prevalence, annual incidence, and YLD. Results: Globally, there were ~41.2 million (95% UI 36.7 million, 46.1 million) prevalent cases of gout, with 7.4 million incident cases per year (95% UI 6.6 million, 8.5 million) and almost 1.3 million YLD (95% UI 0.87 million, 1.8 million) in 2017. The global age‐standardized point prevalence estimates and annual incidence rates in 2017 were 510.6 (95% UI 455.6, 570.3) and 91.8 (95% UI 81.3, 104.1) cases per 100,000 population, respectively, an increase of 7.2% (95% UI 6.4%, 8.1%) and 5.5% (95% UI 4.8%, 6.3%) from 1990. The corresponding age‐standardized YLD rate was 15.9 (95% UI 10.7, 21.8) cases per 100,000 persons, a 7.2% increase (95% UI 5.9%, 8.6%) from 1990. In 2017, the global point prevalence estimates for gout were higher in males, and higher prevalence was seen in older age groups and increased with age for both males and females. The burden of gout was generally highest in developed regions and countries. The 3 countries with the highest age‐standardized point prevalence estimates of gout in 2017 were New Zealand (1,394.0 cases [95% UI 1,290.1, 1,500.9]), Australia (1,171.4 cases [95% UI 1,038.1, 1,322.9]), and the US (996.0 cases [95% UI 923.1, 1,076.8]). The countries with the highest increases in age‐standardized point prevalence estimates of gout from 1990 to 2017 were the US (34.7% [95% UI 27.7%, 43.1%]), Canada (28.5% [95% UI 21.9%, 35.4%]), and Oman (28.0% [95% UI 21.5%, 34.8%]). Globally, high body mass index and impaired kidney function accounted for 32.4% (95% UI 18.7%, 49.2%) and 15.3% (95% UI 13.5%, 17.1%), respectively, of YLD due to gout in the 2017 estimates. The YLD attributable to these risk factors were higher in males. Conclusion: The burden of gout increased across the world from 1990 to 2017, with variations in point prevalence, annual incidence, and YLD between countries and territories. Besides improving the clinical management of disease, prevention and health promotion in communities to provide basic knowledge of the disease, risk factors, consequences, and effective treatment options (tailoring to high‐risk groups such as the middle‐aged male population) are crucial to avoid disease onset and hence to decrease the global disease burden. [ABSTRACT FROM AUTHOR]

Objectives The burden of gout has been increasing globally. However, little is known about the global, regional and national distribution and time trend of this disease. We present a comprehensive analysis of the Global Burden of Disease Study 2017 on gout burden estimates for 195 countries or territories between 1990 and 2017. Methods Age-standardized prevalence and disability-adjusted life-years of gout were reported between 1990 and 2017 in 195 countries and territories, and associations between these estimates and sociodemographic index (SDI) were further explored. Total and annual percent change between 1990 and 2017 were calculated to quantify the time trends of gout burden. Results Age-standardized prevalence rates (95% uncertainty interval) per 100 000 persons were 790.90 (706.10–881.90) and 253.49 (225.69–284.02) in 2017 in males and females, respectively. The annual percent change in age-standardized prevalence (males, 0.22%; females, 0.38%) and disability-adjusted life-years (males, 0.21%; females, 0.38%) of gout increased every year from 1990 to 2017, globally. The highest increase was detected in high-SDI countries, especially in high-income North America. A non-linear association was observed between burden of gout and SDI, with the lowest estimates of gout burden when SDI value was about 0.6. High BMI was the leading risk factor for the burden of gout. Conclusion These study results suggest a globally rising trajectory of gout burden between 1990 and 2017. More effective interventions, such as detailed and intensive dietary managements and other prevention strategies for reducing obesity, should be carried out to reverse this trend, especially in females and high-SDI countries. [ABSTRACT FROM AUTHOR]

Objective: To assess the risk of hypersensitivity reactions (HSRs) with allopurinol and febuxostat in a population-based study.Methods: We used the 5% Medicare beneficiary sample (≥65 years) from 2006 to 2012 to identify people with a newly filled prescription for allopurinol, febuxostat or colchicine. We used multivariable-adjusted Cox regression analyses to compare the hazard ratio (HR) of incident HSRs with allopurinol or febuxostat use versus colchicine use; separate analyses were done in people exposed to allopurinol. Propensity-matched analyses (5:1) compared hazards with allopurinol versus febuxostat.Results: Crude incidence rates of HSRs were as follows: allopurinol, 23.7; febuxostat, 30.7; and colchicine, 25.6 per 1000 person-years. Compared with colchicine, allopurinol, febuxostat and febuxostat+colchicine were associated with significantly higher HRs of HSRs, 1.32 (95% CI: 1.10 to 1.60) and 1.54 (95% CI: 1.12 to 2.12) and 2.17 (95% CI: 1.18 to 3.99), respectively. In propensity-matched analyses, febuxostat did not significantly differ from allopurinol; HR for HSRs was 1.25 (95% CI: 0.93 to 1.67). Compared with allopurinol start dose <200 mg/day, allopurinol start dose ≥300 mg/day, diabetes and female sex were associated with significantly higher hazard of HSRs, 1.27 (95% CI: 1.12 to 1.44), 1.21 (95% CI: 1.00 to 1.45) and 1.32 (95% CI: 1.17 to 1.48), respectively. The majority (69%) of HSRs occurred in the outpatient setting.Conclusions: Compared with colchicine, allopurinol and febuxostat similarly increased the risk of HSRs. Allopurinol and febuxostat did not differ from each other. In allopurinol users, starting dose, female sex and diabetes increased this risk, findings that need further study. [ABSTRACT FROM AUTHOR]

Objective: To examine whether a change in the presentation of incident gout happened over the last 20 years and to determine the risk of subsequent gout flares after an initial gout attack.Methods: All incident cases of gout were identified among residents of Olmsted County, Minnesota, diagnosed in 1989-1992 and 2009-2010 according to the earliest date fulfilling the 1977 American Rheumatism Association preliminary criteria, or the New York or Rome criteria for gout. Patients in both cohorts were then followed for up to 5 years. Cumulative incidence and person-year methods were used to compare flare rates, and conditional frailty models were used to examine predictors.Results: A total of 429 patients with incident gout (158 patients in 1989-1992 and 271 patients in 2009-2010) were identified and followed for a mean of 4.2 years. The majority of patients were male (73%) and the mean age (SD) at gout onset was 59.7 (17.3) years. Classic podagra decreased significantly from 74% to 59% (p < 0.001). Cumulative incidence of first flare was similar in both cohorts (62% vs 60% by 5 yrs in 1989-1992 and 2009-2010, respectively; p = 0.70), but overall flare rate was marginally higher in 2009-2010 compared to 1989-1992 (rate ratio: 1.24). Hyperuricemia (HR 1.59) and kidney disease (HR 1.34) were significant predictors of future flares.Conclusion: Gout flares were common in both time periods. Hyperuricemia and kidney disease were predictors of future flares in patients with gout. Podagra as a presentation of gout has become relatively less frequent in recent years. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives Several recent observations have suggested that the prevalence of gout may be increasing worldwide, but there are no recent data from the USA. We analysed the prevalence of hyperuricaemia and gout in the US population from 2007–08 to 2015–16. Methods We studied adults ⩾20 years of age from the National Health and Nutrition Examination Survey from 2007–08 to 2015–16. Persons with gout were identified from the home interview question 'Has a doctor or other health professional ever told you that you had gout?' Hyperuricaemia was defined as a serum urate level >0.40 mmol/l (6.8 mg/dl) (supersaturation levels at physiological temperatures and pH). Results In 2015–16, the overall prevalence of gout among US adults was 3.9%, corresponding to a total affected population of 9.2 million. Hyperuricaemia (>0.40 mmol/l or 6.8 mg/dl) was seen in 14.6% of the US population (estimated 32.5 million individuals). No significant trends were identified in the age-adjusted prevalence of gout and hyperuricaemia. Statistical comparisons between 2007–08 and 2015–16 age-adjusted rates were not significant. Conclusion While the age-adjusted prevalence of gout and hyperuricaemia has remained unchanged in the most recent decade from 2007–08 to 2015–16, the estimated total number of persons with self-reported gout has increased from 8.3 million to 9.2 million. The age-adjusted prevalence of hyperuricaemia has declined slightly, but the total number of affected individuals is virtually identical (32.5 million in 2015–16 compared with 32.1 million in 2007–08). [ABSTRACT FROM AUTHOR]

Although incidence and survival are frequent topics within the solid organ transplantation (SOT) literature, the size of the surviving SOT population is not well known. Existing studies of gout in patients with SOT have focused on the incident SOT population. This analysis was performed to characterize the prevalent SOT population and the prevalence of gout within it. This study includes the 2017 United States (US) population size of recipients of kidney, heart, liver, and lung transplants that was estimated by combining primary transplant recipient cohort sizes (1988-2017) with previously published survival rates for each annual cohort's time since transplantation (0-29 years). Gout among prevalent patients with SOT was assessed using Medicare and commercial claims. A total of 637,231 US patients received a primary kidney (393,953), liver (142,186), heart (66,637), or lung (34,455) transplant between 1988 and 2017. An estimated 356,000 (55.8%) recipients were alive in 2017 (233,000 kidney; 78,700 liver; 29,300 heart; 14,700 lung). Gout was identified in 11% of prevalent patients with SOT in 2016. Higher rates of gout were seen in recipients of kidney (13.1%) and heart (12.7%) compared to recipients of liver (6.7%) and lung (5.6%) (P <.0001 in both datasets). Active diagnosed gout prevalence in the US population without a SOT history was 1.1% in 2016. Hundreds of thousands of US patients are living with a transplanted organ today and these numbers are likely to increase. In patients with SOT, gout is a frequent comorbidity of which physicians should be aware. This study suggests a markedly higher rate of gout among transplant recipients compared to the general US population. • There is an estimated 356,000 surviving US patients of solid organ transplantation (SOT) as of 2017. • Kidney transplantation includes the largest population of patients at an estimated 233,000. • From Medicare and commercial claims analysis, gout prevalence among US patients of SOT is 11%. • Greater gout prevalence was seen in recipients of kidney and heart transplantations than in recipients of liver and lung transplantations. • All SOT populations had greater gout prevalence than the general US population. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine whether integrating concepts from the notes from the electronic health record (EHR) data using natural language processing (NLP) could improve the identification of gout flares., Methods: Using Medicare claims linked with EHR, we selected gout patients who initiated the urate-lowering therapy (ULT). Patients' 12-month baseline period and on-treatment follow-up were segmented into 1-month units. We retrieved EHR notes for months with gout diagnosis codes and processed notes for NLP concepts. We selected a random sample of 500 patients and reviewed each of their notes for the presence of a physician-documented gout flare. Months containing at least 1 note mentioning gout flares were considered months with events. We used 60% of patients to train predictive models with LASSO. We evaluated the models by the area under the curve (AUC) in the validation data and examined positive/negative predictive values (P/NPV)., Results: We extracted and labeled 839 months of follow-up (280 with gout flares). The claims-only model selected 20 variables (AUC = 0.69). The NLP concept-only model selected 15 (AUC = 0.69). The combined model selected 32 claims variables and 13 NLP concepts (AUC = 0.73). The claims-only model had a PPV of 0.64 [0.50, 0.77] and an NPV of 0.71 [0.65, 0.76], whereas the combined model had a PPV of 0.76 [0.61, 0.88] and an NPV of 0.71 [0.65, 0.76]., Conclusion: Adding NLP concept variables to claims variables resulted in a small improvement in the identification of gout flares. Our data-driven claims-only model and our combined claims/NLP-concept model outperformed existing rule-based claims algorithms reliant on medication use, diagnosis, and procedure codes., (© 2023 John Wiley & Sons Ltd.)

Benjamin Franklin, one of the founding fathers of the United States, was not just a politician and a political philosopher but an inventor with a scientific temperament. He was overweight and likely suffered from the consequences of metabolic syndrome including gout. He woke up with a gout attack on October 22, 1780 and wrote the "Dialogue Between Franklin and the Gout." His observations on the risk factors for gout are re-examined in the modern context 243 years later., Competing Interests: Disclosures: The authors have disclosed no financial or personal conflicts of interest, or financial support related to this work., (Copyright © 2023 Marshfield Clinic Health System.)

Gout is a the most common inflammatory arthritis in the United States. It is a significant cause of morbidity, disability, lost work days, and high healthcare utilization due to intermittent attacks, chronic inflammation, and joint damage. Despite our understanding of the prelude and pathophysiology of gout, hyperuricemia, it is still poorly misunderstood by patients and poorly managed by healthcare providers. Several parallel treatment paradigms have been developed by professional societies around the world based on the understanding of how hyperuricemia occurs, gout epidemiology, expert opinion, and clinical trials data in order to lower uric acid and eventually eliminate the patient's crystal burden. This review focuses on both the treatment of acute attacks, and more importantly, the long-term management of gout and the lowering of serum uric acid levels to a goal of < 6 mg/dl (0.360 mmol/l) or treating to target. Treating to a target serum uric acid goal is an opportunity to decrease morbidity and improve the quality of care of every gout patient. [ABSTRACT FROM AUTHOR]

Objective: To estimate the current prevalence rates and decadal trends of gout and hyperuricemia in the US, as well as the prevalence of urate‐lowering therapy (ULT) among gout patients, using 2007–2016 data from a nationally representative survey of American men and women (the National Health and Nutrition Examination Survey [NHANES]). Methods: Using data from 5,467 participants in the NHANES 2015–2016, we estimated the most recent prevalence rates of gout and hyperuricemia. When the NHANES was conducted, all participants were asked about their history of gout (as diagnosed by a health professional) and medication use. Hyperuricemia was defined as having a serum urate level of >7.0 mg/dl in men and >5.7 mg/dl in women. We examined decadal trends in these estimates using data from the NHANES 2007–2016 and investigated ULT usage trends using the NHANES 2007–14 (the most recent data available to date). Results: In 2015–2016, the prevalence of gout was 3.9% among adults in the US (9.2 million people), with 5.2% [5.9 million] in men and 2.7% [3.3 million] in women. Mean serum urate levels were 6.0 mg/dl in men and 4.8 mg/dl in women, and hyperuricemia prevalence rates were 20.2% and 20.0%, respectively. The prevalence rates of gout and hyperuricemia remained stable between 2007 and 2016 (P for trend > 0.05). The prevalence of ULT use among patients with gout was 33% in 2007–2014 and remained stable over time (P for trend > 0.05). Conclusion: In this nationally representative survey sample of adults in the US, the prevalence rates of gout and hyperuricemia remained substantial, albeit unchanged, between 2007 and 2016. Despite these rates, only one‐third of gout patients were receiving ULT. [ABSTRACT FROM AUTHOR]

Introduction/objective: While few studies with various types of outcomes and methodology have investigated the seasonality of gout, no internet data has been used in any study. This novel methodology may complement and extend the previous traditional data sources and has increasingly been used in investigating the seasonality of health conditions. Therefore, the objective of this study was to utilize the Google Trends data to test whether there is a seasonal variation in the internet searches for gout on a population basis.Methods: In this observational ecological study, the Google Trends was searched for the [gout] within the USA, the UK, Canada, Ireland, Australia, and New Zealand from January 01, 2004, to December 31, 2017, utilizing the "health" category.Results: The cosinor analyses revealed a statistically significant seasonal variation in relative search volume of the [gout] in the USA, the UK (p < 0.001), Canada (p < 0.001), Ireland (p < 0.001), Australia (p < 0.001), and New Zealand (p < 0.001), with a peak in the late spring/early summer months and trough in the late fall/early winter months. The peaks in late spring/early summer and troughs in late fall/early winter were out of phase by 6 months in the northern compared to the southern hemisphere countries.Conclusion: Another line of evidence from internet search query data showed a seasonal variation in gout, with a peak in the late spring/early summer months. Further studies aimed at elucidating the possible mechanisms behind seasonality in gout are needed. [ABSTRACT FROM AUTHOR]

The authors comment on a study published within the issue on the prevalence of gout and hyperuricaemia among U.S. adults in five periods of 1 year each. Topics covered include trends in the age-adjusted prevalence of gout and hyperuricaemia, gout as an independent risk factor for cardiovascular disease (CVD) and hyperuricaemia as a pathophysiologic mechanism of CVD, and arguments whether asymptomatic hyperuricaemia should be treated.

Objective: Observational data suggest that hyperuricemia and gout are associated with increased mortality, while allopurinol use is associated with reduced mortality. In addition, the protective effect of allopurinol may be dose dependent. The aim of the current study was to determine whether allopurinol dose escalation is associated with cause‐specific mortality in patients with gout. Methods: In this 10‐year observational, active‐comparator study of US Veterans with gout who initiated treatment with allopurinol, propensity score matching, Cox proportional hazards models, and competing risks regression analyses were used to assess differences in cause‐specific mortality between patients whose allopurinol dose was escalated (dose escalators) and those whose allopurinol dose was not escalated or was reduced (non‐escalators) over a 2‐year period. Results: Among the 6,428 dose escalators and 6,428 matched non‐escalators, there were 2,867 deaths during the observation period (40.4 deaths per 1,000 person‐years). Dose escalators experienced an increase in all‐cause mortality (hazard ratio [HR] 1.08, 95% confidence interval [95% CI] 1.01–1.17), with the effect sizes being similar for incidence of cardiovascular‐related deaths (HR 1.08, 95% CI 0.97–1.21) and cancer‐related deaths (HR 1.06, 95% CI 0.88–1.27), although neither reached statistical significance. Dose escalation to achieve the goal of lowering the serum urate (SU) level to <6.0 mg/dl was infrequent. At 2 years, 10% of dose escalators were receiving a final daily dose of >300 mg and 31% had achieved the SU goal. In a sensitivity analysis limited to dose escalators achieving the SU goal, there was a nonsignificant reduction of 7% in the hazard of cardiovascular‐related mortality (HR 0.93, 95% CI 0.76–1.14). Conclusion: This is the largest study to date to investigate the effects of allopurinol use on mortality and is the first to use a rigorous active‐comparator design. Dose escalation was associated with a small (<10%) increase in all‐cause mortality, thus showing that a strategy of allopurinol dose escalation, which in current real‐life practice is characterized by limited dose increases, is unlikely to improve the survival of patients with gout. [ABSTRACT FROM AUTHOR]

Objectives: To provide estimates of the cumulative incidence of gout according to baseline serum urate.Methods: Using individual participant data from four publicly available cohorts (Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, and both the Original and Offspring cohorts of the Framingham Heart Study), the cumulative incidence of clinically evident gout was calculated according to baseline serum urate category. Cox proportional hazards modelling was used to evaluate the relation of baseline urate categories to risk of incident gout.Results: This analysis included 18 889 participants who were gout-free at baseline, with mean (SD) 11.2 (4.2) years and 212 363 total patient-years of follow-up. The cumulative incidence at each time point varied according to baseline serum urate concentrations, with 15-year cumulative incidence (95% CI) ranging from 1.1% (0.9 to 1.4) for <6 mg/dL to 49% (31 to 67) for ≥10 mg/dL. Compared with baseline serum urate <6 mg/dL, the adjusted HR for baseline serum urate 6.0-6.9 mg/dL was 2.7, for 7.0-7.9 mg/dL was 6.6, for 8.0-8.9 mg/dL was 15, for 9.0-9.9 mg/dL was 30, and for ≥10 mg/dL was 64.Conclusions: Serum urate level is a strong non-linear concentration-dependent predictor of incident gout. Nonetheless, only about half of those with serum urate concentrations ≥10mg/dL develop clinically evident gout over 15 years, implying a role for prolonged hyperuricaemia and additional factors in the pathogenesis of gout. [ABSTRACT FROM AUTHOR]

Objective: Dual-energy CT (DECT) detects and quantifies monosodium urate (MSU) crystal deposition with high precision. This DECT study assessed crystal deposition in patients with gout treated with stable-dose allopurinol, and investigated potential clinical determinants for crystal deposition.Methods: Patients with gout treated with allopurinol ≥300 mg daily for at least 3 months were prospectively recruited from the USA and New Zealand, using monitored enrolment to include approximately 25% patients with palpable tophi and approximately 50% with serum urate (sUA) levels <6.0 mg/dL (<357µmol/L). MSU crystal deposition was measured in the hands/wrists, feet/ankles/Achilles and knees bilaterally. The presence and total volume of crystals were assessed by DECT and analysed according to sUA levels and gout characteristics.Results: Among 152 patients receiving allopurinol ≥300 mg/day for 5.1 years on average, 69.1% had crystal deposition on DECT, with a median total crystal volume of 0.16 cm3 (range: 0.01-19.53 cm3). The prevalence of crystal deposition ranged from 46.9% among patients with sUA <6.0 mg/dL and no palpable tophi to 90.0% among those with sUA ≥6.0 mg/dL and tophi. Total volume of crystal deposition was positively associated with sUA ≥6.0 mg/dL, gout flares within the past 3 months and tophi. Total volume of crystal deposition correlated positively with Patient Global Impression of Disease Activity scores.Conclusion: A substantial proportion of patients without palpable tophi have MSU crystal deposition, despite receiving allopurinol doses ≥300 mg/day for a considerable duration. Patients with higher sUA and clinical features of severe disease have a higher frequency and greater volume of MSU crystal deposition. [ABSTRACT FROM AUTHOR]

In November 2016, the American College of Physicians (ACP) published a clinical practice guideline on the management of acute and recurrent gout. This guideline differs substantially from the latest guidelines generated by the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) and 3e (Evidence, Expertise, Exchange) Initiative, despite reviewing largely the same body of evidence. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) convened an expert panel to review the methodology and conclusions of these four sets of guidelines and examine possible reasons for discordance between them. The G-CAN position, presented here, is that the fundamental pathophysiological knowledge underlying gout care, and evidence from clinical experience and clinical trials, supports a treat-to-target approach for gout aimed at lowering serum urate levels to below the saturation threshold at which monosodium urate crystals form. This practice, which is truly evidence-based and promotes the steady reduction in tissue urate crystal deposits, is promoted by the ACR, EULAR and 3e Initiative recommendations. By contrast, the ACP does not provide a clear recommendation for urate-lowering therapy (ULT) for patients with frequent, recurrent flares or those with tophi, nor does it recommend monitoring serum urate levels of patients prescribed ULT. Results from emerging clinical trials that have gout symptoms as the primary end point are expected to resolve this debate for all clinicians in the near term future. [ABSTRACT FROM AUTHOR]

Objective: Calcium pyrophosphate deposition disease (CPDD) is a common cause of acute and chronic arthritis, yet there are few large epidemiologic studies of CPDD. We sought to characterize CPDD in the national Veterans Affairs (VA) population.Methods: Using data from the Department of VA Corporate Data Warehouse, patients with International Classification of Diseases, Ninth Revision, codes for CPDD seen at any VA medical center from 2010 through 2014 were matched by age and sex with control patients without CPDD. We used multivariate analysis to compare the prevalence and odds ratios (ORs) of various comorbidities, substance use, medication exposures, and arthroplasties among patients with and without CPDD.Results: We identified 25,157 patients with CPDD, yielding a point prevalence of 5.2 per 1,000. The mean ± SD age was 68.1 ± 12.3 years, and 95% were male. The strongest positive associations with CPDD were hyperparathyroidism (OR 3.35 [95% confidence interval (95% CI) 2.96-3.79]), gout (OR 2.82 [95% CI 2.69-2.95]), osteoarthritis (OR 2.26 [95% CI 2.15-2.37]), rheumatoid arthritis (OR 1.88 [95% CI 1.74-2.03]), and hemochromatosis (OR 1.87 [95% CI 1.57-2.24]). Positive associations were also seen with higher odds for osteoporosis (OR 1.26 [95% CI 1.16-1.36]), hypomagnesemia (OR 1.23 [95% CI 1.16-1.30]), chronic kidney disease (OR 1.12 [95% CI 1.07-1.18]), and calcium supplementation (OR 1.15 [95% CI 1.06-1.24). Negative associations were seen with proton-pump inhibitors (OR 0.58 [95% CI 0.55-0.60]) and loop diuretics (OR 0.80 [95% CI 0.76-0.84]).Conclusion: Using a large national data set, we confirmed known associations with CPDD, provided support for positive associations with rheumatoid arthritis, hypomagnesemia, and osteoporosis, and suggested potential novel negative associations with commonly used medications. [ABSTRACT FROM AUTHOR]

Objective: To assess the health care burden of septic arthritis in the U.S. and examine the associated factors. Methods: We used the U.S. Nationwide Emergency Department Sample (NEDS) data of patients hospitalized with septic arthritis as the primary diagnosis from 2009–12 to assess time-trends. Multivariable-adjusted models assessed demographics, comorbidity and hospital characteristics as potential predictors of duration of hospitalization, total hospital (inpatient and ED) charges and discharge to home. Results: In 2009, 2010 and 2012 in the U.S., respectively, there were 13,087, 13,662 and 13,714 hospitalizations with septic arthritis as the primary diagnosis. Respective average hospital stay was 7.4 vs. 7.4 vs. 7.2 days; total hospital charges were $601 vs. $674 vs. $759 million; and proportion discharged home were 43% vs. 43% vs. 44%. Almost 25% each were discharged to a skilled facility or with home health. Age >50 years, Medicaid and self-pay as primary payer, Northeast U.S. hospital location, teaching hospital status, heart failure and diabetes were associated with longer hospitalization; hyperlipidemia, hypertension or gout were associated with a shorter hospital stay. Similar associations were noted for higher hospital charges. Age >50 years, higher income, Medicare insurance, heart failure, diabetes and longer hospital stay were associated with lower odds, and Western U.S. hospital location and gout with higher odds, of discharge to home. Conclusions: We noted an increase in hospital charges from 2009–12, but no time trends in duration or outcomes of hospitalization for septic arthritis. Comorbidity associations with outcomes indicate the potential for developing interventions to improve outcomes. [ABSTRACT FROM AUTHOR]

Objective: To assess the content and readability of online patient information resources against the current understanding of gout.Methods: An online survey was undertaken using Google UK, USA, Australia, and Canada. Information was assessed for content and accuracy on 19 key points regarding core content for gout patient information resources. Readability was assessed using the Flesch-Kincaid Reading Ease score. Fifteen randomly selected websites were reviewed by a blinded second observer.Results: A total of 85 websites were selected. More than 50% of the websites provided no information or had inaccuracies regarding the pathogenesis of gout. Most websites contained information on dietary and lifestyle modifications for treating gout and did not emphasize urate-lowering therapy (ULT) and its potential for cure. Over 75% of the websites had no/inaccurate information on the role of ULT or prophylaxis for preventing gout attacks on starting ULT. The majority of websites were difficult to read, with information in 68% of the websites rated at least fairly difficult.Conclusion: Only a few web-based patient information resources provide accurate and easy-to-read information on gout. This study will help physicians direct patients to currently reliable resources, but there is a need to improve many web-based patient information resources, which at present act as barriers to care. [ABSTRACT FROM AUTHOR]

Background: There are no published human studies investigating whether the use of allopurinol, the most commonly used medication for the treatment of hyperuricemia in gout, the most common type of inflammatory arthritis in adults, has any beneficial effects on ventricular electrophysiology. The objective of our study was to assess whether allopurinol use is associated with a reduction in the risk of ventricular arrhythmias (VA).Methods: We used the 5% random sample of Medicare beneficiaries from 2006-2012 to examine new allopurinol use and the risk of incident VA. Multivariable Cox regression analyses were adjusted for demographics (age, race, sex), comorbidity, cardiac medications, and conditions associated with VA. We calculated hazard ratios (HR) and 95% confidence intervals (CI).Results: Of the 28,755 episodes of new allopurinol use, 2538 were associated with incident VA (8.8%). Among patients with incident VA, 54% were male, 78% were White, 75% had gout as the underlying diagnosis, and the mean Charlson-Romano comorbidity score was 4.8. The crude incidence of VA per 1,000,000 person-days declined as the duration of allopurinol use increased: 1-180 days, 151; 181 days to 2 years, 105; and > 2 years, 85. In multivariable-adjusted analyses, compared to non-use, allopurinol use was associated with lower HR of VA of 0.82 (95% CI, 0.76-0.90). Compared to allopurinol non-use, longer allopurinol use durations were significantly associated with lower multivariable-adjusted HR for VA: 1-180 days, 0.96 (95% CI, 0.85-1.08); 181 days to 2 years, 0.76 (95% CI, 0.68-0.85); and > 2 years, 0.72 (95% CI, 0.60-0.87). Multiple sensitivity analyses adjusting for cardiac conditions, anti-arrhythmic drugs and alternate definitions confirmed our findings with minimal/no attenuation of estimates.Conclusion: Allopurinol use and use duration of more than 6 months were independently associated with a lower risk of VA. Future studies need to assess the pathophysiology of this potential benefit. [ABSTRACT FROM AUTHOR]

Background: Few studies, if any, have examined cardiovascular outcomes in patients with diabetes and gout. Both diabetes and gout are risk factors for cardiovascular disease. The objective of this study was to examine the effect of allopurinol on the risk of incident acute cardiovascular events in patients with gout and diabetes.Methods: We used the 2007-2010 Multi-Payer Claims Database (MPCD) that linked health plan data from national commercial and governmental insurances, representing beneficiaries with United Healthcare, Medicare, or Medicaid coverage. In patients with gout and diabetes, we assessed the current allopurinol use, defined as a new filled prescription for allopurinol, as the main predictor of interest. Our outcome of interest was the occurrence of the first Incident hospitalized myocardial infarction (MI) or stroke (composite acute cardiovascular event), after which observations were censored. We employed multivariable-adjusted Cox proportional hazards models that simultaneously adjusted for patient demographics, cardiovascular risk factors and other medical comorbidities. We calculated hazard ratios [HR] (95% confidence intervals [CI]) for incident composite (MI or stroke) acute cardiovascular events. We performed sensitivity analyses that additionally adjusted for the presence of immune diseases and colchicine use, as potential confounders.Results: There were 2,053,185 person days (5621.3 person years) of current allopurinol use and 1,671,583 person days (4576.5 person years) of prior allopurinol use. There were 158 incident MIs or strokes in current and 151 in prior allopurinol users, respectively. Compared to previous allopurinol users, current allopurinol users had significantly lower adjusted hazard of incident acute cardiovascular events (incident stroke or MI), with an HR of 0.67 (95% CI, 0.53, 0.84). Sensitivity analyses, additionally adjusted for immune diseases or colchicine use, confirmed this association.Conclusions: Current allopurinol use protected against the occurrence of acute cardiovascular events in patients with gout and diabetes. The underlying mechanisms for this potential cardio-protective effect of allopurinol need further exploration. [ABSTRACT FROM AUTHOR]

Objective Uric acid may be linked to bone health through its antioxidant or prooxidant effects, thereby affecting bone resorption and formation, or through its dual inhibition of vitamin D activation and parathyroid hormone production. Results of prior studies on the relationship between uric acid and bone mineral density have been conflicting. This prospective study was undertaken to examine the relationship between gout, a disease characterized by hyperuricemia and inflammation, and risk of hip or wrist fracture in women. Methods We conducted a prospective observational study of gout and risk of incident wrist and hip fracture in women participating in the Nurses' Health Study (n = 103,799 at baseline, with 14 years of follow-up for the wrist fracture analysis and 22 years of follow-up for the hip fracture analysis). Gout history and incident cases of wrist and hip fracture were assessed by biennial questionnaire. Cox proportional hazards models were used to simultaneously adjust for potential confounders. Results In this cohort, there were 3,769 incident wrist fractures (1990-2004) and 2,147 incident hip fractures (1990-2012), with 107 wrist fractures and 117 hip fractures occurring in participants with gout. In those women with a history of gout compared with women without gout, the multivariable-adjusted relative risk of wrist fracture was 1.12 (95% confidence interval [95% CI] 0.92-1.36) and the multivariable-adjusted relative risk of hip fracture was 1.38 (95% CI 1.14-1.68). Conclusion In women, a history of gout is associated with a modestly increased risk of hip fracture, but not significantly associated with a risk of wrist fracture. [ABSTRACT FROM AUTHOR]

Objective Lesinurad is a selective uric acid reabsorption inhibitor used for the treatment of gout in combination with a xanthine oxidase inhibitor. The Combining Lesinurad with Allopurinol Standard of Care in Inadequate Responders (CLEAR 1) study, a 12-month, multicenter, randomized, double-blind, placebo-controlled phase III trial, was conducted to investigate daily lesinurad (200 mg or 400 mg orally) added to allopurinol versus placebo plus allopurinol in patients with serum urate (UA) levels above a target of <6.0 mg/dl. Methods Patients receiving ≥300 mg of allopurinol (≥200 mg in those with moderate renal impairment) who had serum UA levels ≥6.5 mg/dl at screening and ≥2 gout flares during the previous year were studied. The primary end point was the proportion of patients achieving a serum UA level of <6.0 mg/dl at month 6. Key secondary end points were the mean gout flare rate requiring treatment (months 7-12) and the proportions of patients with complete resolution of ≥1 target tophus (month 12). Safety assessments included adverse events and laboratory data. Results The study patients (n = 603) were predominantly male and had a mean ± SD age of 51.9 ± 11.3 years, a gout duration of 11.8 ± 9.4 years, a baseline serum UA level of 6.94 ± 1.27 mg/dl, and were receiving an allopurinol dosage of 306.6 ± 59.58 mg/day. Lesinurad at doses of 200 mg or 400 mg added to allopurinol therapy significantly increased the proportions of patients who achieved serum UA target levels by month 6 as compared with those receiving allopurinol alone (54.2%, 59.2%, and 27.9%, respectively, P < 0.0001). Lesinurad was not significantly superior to allopurinol alone in terms of the secondary end points: rates of gout flares and complete resolution of tophi. Lesinurad was generally well-tolerated; the safety profile of the 200-mg dose was comparable to that of allopurinol alone, except for higher incidences of predominantly reversible elevations of serum creatinine levels. Conclusion Lesinurad added to allopurinol provided benefit as compared with allopurinol alone in reducing serum UA levels and represents a new treatment option for patients needing additional urate-lowering therapy. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of allopurinol dose/duration on the risk of renal failure in the elderly with allopurinol use.Methods: We used the 5% random Medicare claims data from 2006 to 2012. Multivariable-adjusted Cox regression analyses assessed the association of allopurinol dose/duration with subsequent risk of developing incident renal failure or end-stage renal disease (ESRD) (no prior diagnosis in last 183 days) in allopurinol users, controlling for age, sex, race and Charlson-Romano comorbidity index. HRs with 95% CIs were calculated. Sensitivity analyses considered a longer baseline period (365 days), controlled for gout or used more specific codes.Results: Among the 30 022 allopurinol treatment episodes, 8314 incident renal failure episodes occurred. Compared with 1-199 mg/day, allopurinol dose of 200-299 mg/day (HR 0.81; 95% CI 0.75 to 0.87) and ≥300 mg/day, 0.71 (0.67 to 0.76), had significantly lower hazard of renal failure in multivariable-adjustment model, confirmed in multiple sensitivity analyses. Longer allopurinol use duration was significantly associated with lower hazards in sensitivity analyses (365-day look-back; reference, <0.5 year): 0.5-1 year, 1.00 (0.88, 1.15); >1-2 years, 0.85 (0.73 to 0.99); and >2 years, 0.81 (0.67 to 0.98). Allopurinol ≥300 mg/day was also associated with significantly lower risk of acute renal failure and ESRD with HR of 0.89 (0.83 to 0.94) and 0.57 (0.46 to 0.71), respectively.Conclusions: Higher allopurinol dose is independently protective against incident renal failure in the elderly allopurinol users. A longer duration of allopurinol use may be associated with lower risk of incident renal failure. Potential mechanisms of these effects need to be examined. [ABSTRACT FROM AUTHOR]

Clinical prediction rules effectively diagnose gout without joint fluid analysis. The American College of Rheumatology clinical prediction rules, the most accurate rules developed for research purposes, have a sensitivity of 92%, specificity of 89%, positive likelihood ratio of 8.36, and negative likelihood ratio of 0.09. [ABSTRACT FROM AUTHOR]