Assessment of the efficacy of alkaline water in conjunction with conventional medication for the treatment of chronic gouty arthritis: A randomized controlled study.

BACKGROUND: Chronic gouty arthritis, a prevalent metabolic disorder, has prompted interest in the role of diet and lifestyle in its management. This study examines alkaline water as a non-pharmacological adjunct to traditional medicine, hypothesizing its positive effects on uric acid levels and gout symptoms. METHODS: In this research, 400 chronic arthritis patients from Guangdong Hydropower Hospital (September 2021-September 2023) were randomly assigned to groups receiving varying concentrations of alkaline water alongside conventional Western medicine, or Western medicine alone. A 1-year follow-up involved assessments using visual analogue scales, joint swelling scores, functional assessment scales, and biochemical markers (serum uric acid, creatinine, urea nitrogen) for comprehensive evaluation. RESULTS: Pain relief: High-concentration alkaline water significantly reduced VAS pain scores posttreatment (P < .05). Joint swelling: Greatest improvement observed in high-concentration group (P < .001). Daily activity capability: Notable enhancements in daily activity scores in experimental groups (P < .05). Range of joint motion: All groups showed significant improvement posttreatment (P < .05). Inflammatory markers: Experimental groups experienced a notable decrease in C-reactive protein, especially in the low concentration group (P < .001). Erythrocyte sedimentation rate decreases were marginal and not statistically significant (P > .05). Interleukin-1ß and tumor necrosis factor-α levels significantly decreased, particularly in the low concentration group. Serum uric acid levels: Significant reduction in serum uric acid observed in all alkaline water groups (P < .05), contrasting with the control group. CONCLUSION: Alkaline water, particularly at high concentrations, effectively alleviated pain, reduced joint swelling, enhanced daily activities, and improved joint motion in chronic gouty arthritis treatment. It significantly reduced key inflammatory markers (C-reactive protein, interleukin-1ß, tumor necrosis factor-α) and serum uric acid levels, suggesting its potential as a valuable adjunct in gout management. The limited impact on erythrocyte sedimentation rate warrants further investigation.

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease: the ALL-HEART RCT and economic evaluation.

Background: Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol. Objective: To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease. Design: Prospective, randomised, open-label, blinded endpoint multicentre clinical trial. Setting: Four hundred and twenty-four UK primary care practices. Participants: Aged 60 years and over with ischaemic heart disease but no gout. Interventions: Participants were randomised (1 : 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care. Main outcome measures: The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis. Results: From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm (n = 2979) or the usual care arm (n = 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21); p = 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20); p = 0.77. The pre-specified health economic analysis plan was to perform a 'within trial' cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval -0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective. Limitations: The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis. Conclusions: The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout. Future work: The effects of allopurinol on cardiovascular outcomes in patients with ischaemic heart disease and co-existing hyperuricaemia or clinical gout could be explored in future studies. Trial registration: This trial is registered as EU Clinical Trials Register (EudraCT 2013-003559-39) and ISRCTN (ISRCTN 32017426). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in Health Technology Assessment; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.

The purpose of the ALL-HEART study was to determine whether giving allopurinol to people with ischaemic heart disease (also commonly known as coronary heart disease) would reduce their risk of having a heart attack, stroke or of dying from cardiovascular disease. Allopurinol is a medication usually given to patients with gout to prevent acute gout flares. It is not currently used to treat ischaemic heart disease. We randomly allocated people aged over 60 years with ischaemic heart disease to take up to 600 mg of allopurinol daily (in addition to their usual care) or to continue with their usual care. We then monitored participants for several years and recorded any major health events such as heart attacks, strokes and deaths. We obtained most of the follow-up data from centrally held electronic hospital admissions and death records, making the study easier for participants and more cost-efficient. We asked participants in both groups to complete questionnaires to assess their quality of life during the study. We also collected data to determine whether there was any economic benefit to the NHS of using allopurinol in patients with ischaemic heart disease. There was no difference in the risk of heart attacks, strokes or death from cardiovascular disease between the participants given allopurinol and those in the group continuing their usual care. We also found no difference in the risks of other cardiovascular events, deaths from any cause or quality-of-life measurements between the allopurinol and usual care groups. The results of the ALL-HEART study suggest that we should not recommend that allopurinol be given to people with ischaemic heart disease to prevent further cardiovascular events or deaths.

Standardization of interstitial lung disease assessment by ultrasound: results from a Delphi process and web-reliability exercise by the OMERACT ultrasound working group.

OBJECTIVES: Over the last years ultrasound has shown to be an important tool for evaluating lung involvement, including interstitial lung disease (ILD) a potentially severe systemic involvement in many rheumatic and musculoskeletal diseases (RMD). Despite the potential sensitivity of the technique the actual use is hampered by the lack of consensual definitions of elementary lesions to be assessed and of the scanning protocol to apply. Within the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group we aimed at developing consensus-based definitions for ultrasound detected ILD findings in RMDs and assessing their reliability in dynamic images. METHODS: Based on the results from a systematic literature review, several findings were identified for defining the presence of ILD by ultrasound (i.e., Am-lines, B-lines, pleural cysts and pleural line irregularity). Therefore, a Delphi survey was conducted among 23 experts in sonography to agree on which findings should be included and on their definitions. Subsequently, a web-reliability exercise was performed to test the reliability of the agreed definitions on video-clips, by using kappa statistics. RESULTS: After three rounds of Delphi an agreement >75 % was obtained to include and define B-lines and pleural line irregularity as elementary lesions to assess. The reliability in the web-based exercise, consisting of 80 video-clips (30 for pleural line irregularity, 50 for B-lines), showed moderate inter-reader reliability for both B-lines (kappa = 0.51) and pleural line irregularity (kappa = 0.58), while intra-reader reliability was good for both B-lines (kappa = 0.72) and pleural line irregularity (kappa = 0.75). CONCLUSION: Consensus-based ultrasound definitions for B-lines and pleural line irregularity were obtained, with moderate to good reliability to detect these lesions using video-clips. The next step will be testing the reliability in patients with ILD linked to RMDs and to propose a consensual and standardized protocol to scan such patients.

Trends in healthcare utilization by patients with gout: A cross-sectional study using Health Insurance Review and Assessment Service data.

This study aimed to analyze the distribution of gout patients and the utilization of healthcare services in South Korea to provide valuable recommendations to clinicians and policymakers. A cross-sectional study was conducted. Claims data from the Health Insurance Review and Assessment Service spanning 2010 to 2019 were utilized, and a sample of 69,680 patients was included in the study. The incidence of gout was observed to be high in male patients over the age of 40, with most patients receiving outpatient care for gout management. Nonsteroidal anti-inflammatory drugs and urate-lowering agents were the most frequently prescribed medications, with prescriptions for colchicine and febuxostat increasing among urate-lowering agents. Musculoskeletal disorders were found to be the most common comorbidities among gout patients. Although the total costs of gout management increased, there was no significant increase in cost per patient. This study provides insights into the current state of healthcare utilization for gout patients in South Korea and trends in the disease burden and use of medications. The findings have crucial implications for clinicians and policymakers involved in decision-making regarding the management and treatment of gout.

Gout in Native Hawaiian Patients in Hawai'i: Clinical Characteristics and Disparities.

OBJECTIVE: The purpose of this study was to investigate differences in clinical characteristics and health care use of Native Hawaiian and White patients with gout. METHODS: We performed a retrospective chart review of Native Hawaiian and White patients with gout treated from 2011 to 2017 within a large health care system in Hawai'i. We compared demographic characteristics, clinical outcomes, and risk factors for gout. We used multivariable logistic regression to identify predictive factors of emergency department visits. RESULTS: We identified 270 Native Hawaiian patients with gout and 239 White patients with gout. The Native Hawaiian patients were younger on average (54.0 vs 64.0 years; P < 0.0001) and had an earlier onset of disease (50.0 vs 57.0 years; P < 0.0001). Native Hawaiian patients with gout had higher mean (7.58 vs 6.87 mg/dL; P < 0.0001) and maximum (10.30 vs 9.50 mg/dL; P < 0.0001) serum urate levels compared to White patients with gout. Native Hawaiian patients with gout also had a greater number of tophi (median 2.00 vs 1.00; P < 0.0001). Native Hawaiians patients with gout were 2.7 times more likely to have frequent (≥1) emergency department visits than White patients with gout. Native Hawaiian patients with gout were less likely to have a therapeutic serum urate ≤6.0 mg/dL and had lower rates of rheumatology specialty care. CONCLUSION: Native Hawaiian patients have a higher disease burden of gout, with earlier disease onset and more tophi. Native Hawaiian patients with gout are more likely to use emergency services for gout and have lower rates of rheumatology specialty care compared to White patients. Future studies are needed to promote culturally appropriate preventive care and management of gout in Native Hawaiians.

Comparison of clinical and economic evaluation between selected generic and original febuxostat tablets in Chinese gout patients with hyperuricemia: A real-world multicenter retrospective study.

Generic febuxostat tablets were listed in China's third-round centralized drug procurement program. However, there are no sufficient data available on the use of febuxostat in a real-world setting. This study aimed to compare the efficacy, safety, and cost of selected generic febuxostat with original febuxostat in primary gout and hyperuricemia. Medical records at 3 tertiary hospitals from January 2014 to February 2022 were retrospectively analyzed. Propensity score matching was used to balance the distribution of baseline characteristics. The proportion of patients achieving target serum uric acid (SUA) levels at 12 weeks, the percent changes from baseline in SUA, adverse drug reactions, and the cost of febuxostat therapy were assessed. A total of 221 patients were recruited and 57 pairs of patients were 1:1 matched in the 2 groups. There was no statistically significant difference in the proportion of patients achieving a target SUA levels below 300 µmol/L, the percent changes of SUA decreased from baseline, and the incidence of adverse drug reactions between the 2 groups (all P > .05). The daily febuxostat cost in the generic group were significantly lower than that in original group (P < .05). Based on the results of this study, the clinical efficacy of selected generic febuxostat is comparable to that of original febuxostat for gout with hyperuricemia. No serious adverse reactions were reported in the 2 groups, and generic febuxostat is more economical than the original febuxostat.

Improving the accuracy of automated gout flare ascertainment using natural language processing of electronic health records and linked Medicare claims data.

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.

The Role of Ultrasound Semi-Quantitative Scoring in the Diagnosis and Assessment of Gout and Hyperuricemia.

OBJECTIVES: To develop an ultrasound semi-quantitative scoring system for the diagnosis and evaluation of gout and hyperuricemia. METHODS: This study included 348 male patients: 81 patients with asymptomatic hyperuricemia, 182 patients with gout, and 85 patients with other arthritis. Clinical data were collected, ultrasound was detected, gout activity score was calculated to assess disease activity, and statistical analysis was performed. RESULTS: Monosodium urate crystal deposition and subclinical arthritis were detected in 17 patients with asymptomatic hyperuricemia, with lesions concentrated in the metatarsophalangeal joint, ankle and peroneus-longus and brevis at rate of 91.8%. Gout was significantly higher than non-gouty arthritis in crystal scores (sum scores of double contour, aggregates, and tophi), but not in inflammation scores (sum scores of synovial hypertrophy, power Doppler [PD] activity, and tenosynovitis) and bone erosion. The optimal cut-off score for the diagnosis of gout by the crystal score was 2. The sensitivity, specificity, and AUC were 95.4%, 97.1%, and .965, respectively. Gout flare had higher inflammation scores than intercritical gout, while bone erosion scores were lower than intercritical gout. The active gout patients had higher ultrasound scores of tophi, bone erosion, and PD activity than the remission group (P < .001). The sensitivity, specificity and area under the receiver operating characteristic curve (AUC) for the identification with high disease activity gout by ultrasound semi-quantitative composite score were 76.2%, 84.2%, and .812, respectively. CONCLUSION: Ultrasound helps early identification of patients at risk in asymptomatic hyperuricemia. Ultrasound semi-quantitative scoring allows for more objective and accurate assessment of gout lesions, correlates with disease activity, and helps in the diagnosis and assessment of gout.

Analysis of appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors as the first-line urate-lowering therapy in patients with gout using the Korean Health Insurance Review and Assessment Service database.

INTRODUCTION: We investigated the appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) in patients with gout. This was a nationwide population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database. METHODS: Patients with gout aged ≥20 years who were newly initiated on XOIs, such as allopurinol or febuxostat, from July 2015 to June 2017 and received these medications for ≥6 months were analyzed and followed up until June 2019. Persistence of XOIs was compared according to the 6-month duration of colchicine prophylaxis. For additional subgroup analysis, we also compared the persistence of XOIs according to the 3-month duration of colchicine prophylaxis. RESULTS: This study included 43 926 patients. The frequencies of patients with gout receiving colchicine prophylaxis for ≥6 months and ≥3 months were 6.3% and 7.6%, respectively. Allopurinol (65.2%) was prescribed more frequently than febuxostat (34.8%). During the study period, 23 475 patients (53.4%) stopped using XOIs. Colchicine prophylaxis for ≥6 months did not significantly reduce the risk of XOI discontinuation in multivariable Cox regression models. Colchicine prophylaxis for ≥3 months was significantly associated with a lower risk of non-persistence to XOIs after adjusting for confounding factors (hazard ratio = 0.95, p = .041). CONCLUSION: Our data suggest that at least 3 months of colchicine prophylaxis may be more appropriate than at least 6 months in terms of maximizing the persistence of XOIs in patients with gout.

Proton pump inhibitor use associated with an increased risk of gout: A population-based case-control study.

OBJECTIVES: In previous reports, proton pump inhibitor (PPI) use increased the risk of gout. However, there is no epidemiological study investigating this association. We aimed to examine the potential impact of PPI treatment on the risk of developing gout. METHODS: A population-based case-control study was performed using a Longitudinal Health Insurance Database 2000 from Taiwan (population 23 million). We identified gout cases and non-gout controls through propensity score matching at 1:1, which was matched by sex and age. We used a conditional logistic regression model to estimate an odds ratio and 95% confidence intervals (CI) for gout population versus controls. RESULTS: Esomeprazole increased the risk of gout after adjusting confounding variables (adjusted odds ratio [aOR] 1.3; 95% CI 1.0-1.6). The risk of gout was highest within 30 days of PPI treatment (aOR 1.7; 95% CI 1.4-1.9) and attenuated thereafter. The risk of gout was increased among female users of PPI compared with male users (aOR 2.2; 95% CI 1.7-2.8). The aOR of gout in people with PPI use was higher in middle-aged individuals (41-60 years: aOR 2.1; 95% CI 1.7-2.7) than in the older group (≥60 years: aOR 1.8; 95% CI 1.5-2.2). CONCLUSIONS: Our findings provide population-level evidence for the hypothesis that PPI treatment is positively associated with the risk of developing gout. Further research on the mechanism underlying this association is warranted.

Changes in Prescription Drug and Health Care Use Over 9 Years After the Large Drug Price Increase for Colchicine.

Importance: Prescription drug prices are a leading concern among patients and policy makers. There have been large and sharp price increases for some drugs, but the long-term implications of large drug price increases remain poorly understood. Objective: To examine the association of the large 2010 price increase in colchicine, a common treatment for gout, with long-term changes in colchicine use, substitution with other drugs, and health care use. Design, Setting, and Participants: This retrospective cohort study examined MarketScan data from a longitudinal cohort of patients with gout with employer-sponsored insurance from 2007 through 2019. Exposures: The US Food and Drug Administration's discontinuation of lower-priced versions of colchicine from the market in 2010. Main Outcomes and Measures: Mean price of colchicine; use of colchicine, allopurinol, and oral corticosteroids; and emergency department (ED) and rheumatology visits for gout in year 1 and over the first decade of the policy (through 2019) were calculated. Data were analyzed between November 16, 2021, and January 17, 2023. Results: A total of 2 723 327 patient-year observations were examined from 2007 through 2019 (mean [SD] age of patients, 57.0 [13.8] years; 20.9% documented as female; 79.1% documented as male). The mean price per prescription of colchicine increased sharply from $11.25 (95% CI, $11.23-$11.28) in 2009 to $190.49 (95% CI, $190.07-$190.91) in 2011, a 15.9-fold increase, with the mean out-of-pocket price increasing 4.4-fold from $7.37 (95% CI, $7.37-$7.38) to $39.49 (95% CI, $39.42-$39.56). At the same time, colchicine use declined from 35.0 (95% CI, 34.6-35.5) to 27.3 (95% CI, 26.9-27.6) pills per patient in year 1 and to 22.6 (95% CI, 22.2-23.0) pills per patient in 2019. Adjusted analyses showed a 16.7% reduction in year 1 and a 27.0% reduction over the decade (P < .001). Meanwhile, adjusted allopurinol use rose by 7.8 (95% CI, 6.9-8.7) pills per patient in year 1, a 7.6% increase from baseline, and by 33.1 (95% CI, 32.6-33.7) pills per patient through 2019, a 32.0% increase from baseline over the decade (P < .001). Moreover, adjusted oral corticosteroid use exhibited no significant change in the first year, then increased by 1.5 (95% CI, 1.3-1.7) pills per patient through 2019, an 8.3% increase from baseline over the decade. Adjusted ED visits for gout rose by 0.02 (95% CI, 0.02-0.03) per patient in year 1, a 21.5% increase, and by 0.05 (95% CI, 0.04-0.05) per patient through 2019, a 39.8% increase over the decade (P < .001). Adjusted rheumatology visits for gout increased by 0.02 (95% CI, 0.02-0.03) per patient through 2019, a 10.5% increase over the decade (P < .001). Conclusions and Relevance: In this cohort study among individuals with gout, the large increase in colchicine prices in 2010 was associated with an immediate decrease in colchicine use that persisted over approximately a decade. Substitution with allopurinol and oral corticosteroids was also evident. Increased ED and rheumatology visits for gout over the same period suggest poorer disease control.

Trends in Prevalence of Gout Among US Asian Adults, 2011-2018.

Importance: Gout disparities among Black individuals in the US have recently been explained by socioclinical factors; however, no information is available among Asian individuals living in Western countries, despite their disproportionately worsening metabolic health. Objective: To determine the prevalence of gout and serum urate concentrations according to race and ethnicity and to explore the association of social determinants of health and clinical factors. Design, Setting, and Participants: This is a population-based, cross-sectional analysis. Data from a nationally representative sample of US adults were obtained from the National Health and Nutrition Examination Survey (NHANES) (2011-2018) in which Asian race data were collected (primary). Data from the UK Biobank (2006-2021) were used for replication of the Asian vs White differences. Data analysis was performed from December 2021 to September 2022. Main Outcomes and Measures: Race-specific gout prevalence and serum urate levels. Results: A total of 22 621 participants from NHANES (2011-2018) were included in the analysis (mean [SD] age, 49.8 [17.8] years; 10 948 male participants [48.4%]). In 2017 to 2018, gout affected 12.1 million US individuals, with its crude prevalence increasing from 3.6% (95% CI, 2.8%-4.5%) in 2011 to 2012 to 5.1% (95% CI, 4.2%-5.9%) in 2017 to 2018 (P for trend = .03); this trend was no longer significant after age adjustment (P for trend = .06) or excluding Asian individuals (P for trend = .11). During the same period, age- and sex-adjusted prevalence among Asian Americans doubled from 3.3% (95% CI, 2.1%-4.5%) to 6.6% (95% CI, 4.4%-8.8%) (P for trend = .007) to numerically exceed all other racial and ethnic groups in 2017 to 2018, with age- and sex-adjusted odds ratio (ORs) of 1.61 (95% CI, 1.03-2.51) and a socioclinical factor-adjusted multivariable OR of 2.62 (95% CI, 1.59-4.33) for Asian vs White individuals. The latest age- and sex-adjusted gout prevalence among US individuals aged 65 years and older was 10.0% among White individuals and 14.8% among Asian individuals (including 23.6% of Asian men). Serum urate concentrations also increased between 2011 and 2018 among US Asian individuals (P for trend = .009). The Asian vs White disparity was also present in the UK Biobank. Conclusions and Relevance: The findings of this study suggest that the prevalence of gout among Asian individuals numerically surpassed that for all other racial and ethnic groups in 2017 to 2018. This Asian vs White disparity did not appear to be associated with socioclinical factors.

Global, regional and national burdens of gout in the young population from 1990 to 2019: a population-based study.

OBJECTIVE: To use data from the Global Burden of Disease (GBD) Study 2019 to report the global, regional and national rates and trends of annual incidence, point prevalence and years lived with disability (YLD) for gout in adolescents and young adults aged 15-39 years. METHODS: We conducted a serial cross-sectional study of gout burden in the young population aged 15-39 years using data from GBD Study 2019. We extracted rates per 100 000 population of incidence, prevalence and YLD of gout, then calculated their average annual percentage changes (AAPCs) at the global, regional and national level between 1990 and 2019 by sociodemographic index (SDI). RESULTS: The global gout prevalent cases in individuals aged 15-39 years was 5.21 million in 2019, with the annual incidence substantially increasing from 38.71 to 45.94 per 100 000 population during 1990-2019 (AAPC 0.61, 95% CI 0.57 to 0.65). This substantial increase was observed in all SDI quintiles (low, low-middle, middle, high-middle and high) and every age subgroup (15-19, 20-24, 25-29, 30-34 and 35-39 years). Males accounted for 80% of the gout burden. High-income North America and East Asia were facing a substantial increase in gout incidence and YLD simultaneously. Elimination of high body mass index can reduce 31.74% of the gout YLD globally in 2019, which varied from 6.97% to 59.31% regionally and nationally. CONCLUSION: Gout incidence and YLD in the young population grew simultaneously and substantially in both developed and developing countries. Improving representative national-level data on gout, interventions for obesity and awareness in young populations are strongly suggested.

Assessment of Cardiovascular Disease Among Predominantly Black Gout Patients.

INTRODUCTION: Although the association between gout and cardiovascular disease (CVD) has been extensively studied, scarce data are available for the Black population. We aimed to assess the association between gout and CVD in a predominantly Black urban population with gout. METHODS: A cross-sectional analysis was performed between a gout cohort and an age-/sex-matched control group. Clinical parameters and 2D echocardiograms were reviewed for the patients with gout and heart failure (HF). The primary outcome studied includes the prevalence and strength of association between gout and CVD. Secondary outcomes studied includes strength of association of gout and HF categorized by ejection fraction, mortality, and HF readmissions. RESULTS: Four hundred seventy-one patients with gout had a mean age of 63.7 ± 0.5 years; 89% were Black, 63% were men, and mean body mass index was 31.3 ± 0.4 kg/m 2 . Hypertension, diabetes mellitus, and dyslipidemia were present in 89%, 46%, and 52%, respectively. Compared with controls, patients with gout had significantly higher rates of angina, arrhythmia, coronary artery disease/stents, myocardial infarction, coronary artery bypass graft surgery, cerebrovascular accident, and peripheral vascular disease. The adjusted odds ratio for CVD was 2.9 (95% confidence interval, 1.9-4.5; p < 0.001). Gout patients had a higher prevalence of HF with 45% (n = 212) compared with controls with 9.4% (n = 44). Adjusted odds ratio for HF risk was 7.1 (95% confidence interval, 4.7-10.6; p < 0.01). CONCLUSIONS: Gout in a predominantly Black population confers 3 times the CVD risk and 7 times HF-specific risk compared with age- and sex-matched cohort. Further research is needed to confirm our findings and to develop interventions to reduce morbidity associated with gout.

Dynamic assessment of the double contour sign by ultrasonography helps to distinguish between gout and calcium pyrophosphate deposition disease.

OBJECTIVE: To test whether the double contour (DC) sign has a different dynamic behaviour in gout and calcium pyrophosphate deposition (CPPD) and whether the dynamic assessment of the DC sign increases its accuracy in gout diagnosis. METHODS: This cross-sectional analysis included patients with gout meeting the 2015 ACR/EULAR classification criteria and patients with crystal-proven diagnosis of CPPD. Hyaline cartilages were explored by ultrasound (US) to detect the DC sign (ie, abnormal hyperechoic band over the superficial margin of hyaline cartilages) and its dynamic behaviour during joint movement was evaluated ((ie, movement of the DC sign together with subchondral bone (DC sign), or in the opposite direction (pseudo DC sign)). RESULTS: Eighty-one patients with gout and 84 patients with CPPD underwent US assessment. Among them, 47 patients with gout and 9 patients with CPPD had evidence of the DC sign. During dynamic assessment, in all 47/47 patients with gout there was a DC sign. Conversely, in 7/9 (77.8%) patients with CPPD, there was a pseudo DC sign (p<0.01).The presence of DC sign during static assessment had a sensitivity, specificity and accuracy of 58.0% (95% CI 46.5% to 68.9%), 89.3% (95% CI 80.6% to 95.0%) and 73.9% (95% CI 66.5% to 80.5%) for gout, respectively. The dynamic evaluation improved the DC sign's diagnostic performance (p=0.01) as the specificity (97.6% (95% CI 91.7% to 99.7%)) and the accuracy (78.2% (95% CI 71.1% to 84.2%)) increased without loss in sensitivity. CONCLUSION: The dynamic US assessment of the DC sign may help to differentiate the DC sign due to MSU crystals from the pseudo DC sign seen in CPPD, as they move in opposite directions.

Comparative Safety of Gout Treatment Strategies on Cardiovascular Outcomes Using Observational Data: Clone-censor-weight Target Trial Emulation Approach.

BACKGROUND: We sought to examine the cardiovascular safety of intensive treat-to-target serum urate strategies for gout using Medicare claims data linked to electronic health record laboratory data. METHODS: We selected patients with gout who initiated urate-lowering therapy. We emulated a hypothetical trial comparing the rate of major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) among seven different strategies over 24 months. Three aspects were considered in defining increasingly intensive strategies: (1) continuation of urate-lowering therapy, (2) serum urate monitoring, and (3) modification of urate-lowering therapy when serum urate >6 mg/dl. We applied the "clone-censor-weight" method to account for baseline and time-varying confounding. RESULTS: We identified 4402 patients with gout who initiated urate-lowering therapy (mean age 77; male 60%). During a total of 6611 person-years (PY) of follow-up under usual care, the rate of major cardiovascular events (first and recurrent) was 4.5/100 PY (95% CI = 4.0, 5.1). The rate ratios (RRs) suggested reductions (RR point estimates 0.88-0.84) compared with usual care. All 95% CIs were imprecise, but their upper bounds excluded substantial increase in RRs. RRs were closer to 1.0 for the analysis focusing on the first major adverse cardiovascular event during follow-up and on comparison to the strategy requiring continuation of urate-lowering therapy (but not necessarily titration). CONCLUSIONS: Our treatment strategy trial emulation did not find increased risk of major adverse cardiovascular events with intensive urate-lowering strategies. Results may provide reassurance of the cardiovascular safety of intensive treat-to-target serum urate strategies recommended by rheumatology societies.

A lifetime economic research of universal HLA-B*58:01 genotyping or febuxostat initiation therapy in Chinese gout patients with mild to moderate chronic kidney disease.

OBJECTIVE: To evaluate Chinese long-term economic impact of universal human leukocyte antigen B (HLA-B)*58:01 genotyping-guided urate-lowering therapy or febuxostat initiation therapy for gout patients with mild to moderate chronic kidney disease (CKD) from perspective of healthcare system. METHODS: A Markov model embedded in a decision tree was structured including four mutually exclusive health states (uncontrolled-on-therapy, controlled-on-therapy, uncontrolled-off-therapy, and death). Mainly based on Chinese real-world data, the incremental costs per quality-adjusted life years (QALYs) gained were evaluated from three groups (universal HLA-B*58:01 testing strategy, and no genotyping prior to allopurinol or febuxostat initiation therapy) at 25-year time horizon. All costs were adjusted to 2021 levels based on Chinese Consumer Price Index and were discounted by 5% annually. One-way and probability sensitivity analysis were performed. RESULTS: Among these three groups, universal HLA-B*58:01 genotyping was the most cost-effective strategy in base-case analysis according to Chinese average willingness-to-pay threshold of $37 654.50 per QALY. The based incremental cost-effectiveness ratio was $31784.55 per QALY, associated with 0.046 additional QALYs and $1463.81 increment costs per patient at a 25-year time horizon compared with no genotyping prior to allopurinol initiation strategy. Sensitivity analysis showed 64.3% robustness of these results. CONCLUSION: From Chinese perspective of healthcare system, HLA-B*58:01 genotyping strategy was cost-effective for gout patients with mild to moderate CKD in mainland China, especially in the most developed area, such as Beijing and Shanghai. Therefore, we suggest China's health authorities choose the genotyping strategy and make different recommendations according to the differences of local conditions.

Health and Economic Outcomes Associated With Musculoskeletal Disorders Attributable to High Body Mass Index in 192 Countries and Territories in 2019.

Importance: The degree to which health and economic outcomes of musculoskeletal disorders are attributable to high body mass index (BMI) has not been quantified on a global scale. Objective: To estimate global health and economic outcomes associated with musculoskeletal disorders-low back pain (LBP), gout, and osteoarthritis attributable to high BMI in 2019. Design, Setting, and Participants: This cross-sectional study used data of 192 countries and territories from the Global Burden of Diseases, Injuries, and Risk Factors Study, World Health Organization Global Health Expenditure, World Bank, and International Labour Organization databases. Data analyses were conducted from February 24 to June 16, 2022. Main Outcomes and Measures: Prevalence, years lived with disability (YLDs), health care costs, and productivity losses due to morbidity from LBP, gout, and osteoarthritis attributable to high BMI by region and country. Prevalence and YLDs were calculated with the population attributable fraction approach. The economic burden, including health care costs and productivity losses due to morbidity, was also quantified. Health care costs borne by the public, private, and out-of-pocket sectors were estimated based on their corresponding payment shares. Productivity losses were estimated based on the output per worker. A sensitivity analysis was conducted to arrive at the base, minimum, and maximum estimates (ie, uncertainty interval [UI]) by using the mean, lower, and upper bounds of all input variables. Results: High BMI was estimated to be responsible for 36.3 million (UI, 18.4-61.0 million), 16.9 million (UI, 7.5-32.5 million), and 73.0 million (UI, 32.4-131.1 million) prevalent cases of LBP, gout, and osteoarthritis, respectively, which accounted for 7.3 million (UI, 3.0-15.0 million) YLDs across 192 countries and territories in 2019. Globally, the YLDs of musculoskeletal disorders attributable to high BMI accounted for 1.0% of all-cause YLDs in the working-age population aged 15 to 84 years. The global total costs of musculoskeletal disorders attributable to high BMI reached $180.7 billion (UI, $83.8-$333.1 billion), including $60.5 billion (UI, $30.7-$100.5 billion) in health care costs and $120.2 billion (UI, $53.1-$232.7 billion) in productivity losses. In terms of the global health care costs, 58.9% ($35.6 billion; UI, $17.8-$59.6 billion) was borne by the public sector, 24.0% ($14.5 billion; UI, $7.8-$23.2 billion) by the private sector, and 17.1% ($10.3 billion; UI, $5.1-$17.6 billion) by the out-of-pocket sector. On average, the total costs accounted for 0.2% of global gross domestic product. Great inequalities in the disease and economic burden existed across regions and countries. Nearly 80% of global health care (82.4%) and morbidity-related costs (82.9%) were paid by high-income countries, whereas more than 60% (61.4%) of global YLDs occurred in middle-income countries. Conclusions and Relevance: In this cross-sectional study of 192 countries and territories, a substantial amount of the health and economic impact of musculoskeletal disorders was attributable to high BMI. Developing effective policies and active participation from health professionals to prevent excessive weight gain are needed. More available estimates are also needed to facilitate a global analysis.