An Emergency Department-based system intervention to improve osteoporosis screening for older adults at high-risk of fracture.

Falls and osteoporosis are risk factors for fragility fractures. Bone mineral density (BMD) assessment is associated with better preventative osteoporosis care, but it is underutilized by those at high fracture risk. We created a novel electronic medical record (EMR) alert-driven protocol to screen patients in the Emergency Department (ED) for fracture risk and tested its feasibility and effectiveness in generating and completing referrals for outpatient BMD testing after discharge. The EMR alert was configured in 2 tertiary-care EDs and triggered by the term "fall" in the chief complaint, age (≥65 years for women, ≥70 years for men), and high fall risk (Morse score ≥ 45). The alert electronically notified ED study staff of potentially eligible patients. Participants received osteoporosis screening education and had BMD testing ordered. From November 15, 2020 to December 4, 2021, there were 2,608 EMR alerts among 2,509 patients. We identified 558 patients at high-risk of fracture who were screened for BMD testing referral. Participants were excluded for: serious illness (N = 141), no documented health insurance to cover BMD testing (N = 97), prior BMD testing/recent osteoporosis care (N = 58), research assistant unavailable to enroll (N = 53), concomitant fracture (N = 43), bedridden status (N = 38), chief complaint of fall documented in error (N = 38), long-term care residence (N = 34), participation refusal (N = 32), or hospitalization (N = 3). Of the 16 participants who had BMD testing ordered, 7 scheduled and 5 completed BMD testing. EMR alerts can help identify subpopulations who may benefit from osteoporosis screening, but there are significant barriers to identifying eligible and willing patients for screening in the ED. In our study targeting an innovative venue for osteoporosis care delivery, only about 1% of patients at high-risk of fracture scheduled BMD testing after an ED visit. Adequate resources during and after an ED visit are needed to ensure that older adults participate in preventative osteoporosis care.

Defining the key clinician skills and attributes for competency in managing patients with osteoporosis and fragility fractures.

Osteoporosis and fragility fractures are managed by clinicians across many medical specialties. The key competencies of clinicians delivering bone health care have not been systematically established. We aimed to develop a decision rule to define the threshold of adequate skills and attributes associated with clinical competency in bone health for a clinician serving as a referral source for bone health care. Using a modified-Delphi method, we invited clinicians with expertise in treating osteoporosis and representatives of patient advocacy groups focused on bone health to create a list of desirable characteristics of a clinician with bone health competency. Characteristics were defined as "attributes" with "levels" within each attribute. Participants prioritized levels by perceived importance. To identify the cut points for defining adequate competency, participants next ranked 20 hypothetical clinicians defined by various levels of attributes from highest to lowest likelihood of having adequate bone health competency. Lastly, we conducted a discrete choice experiment (DCE) to generate a weighted score for each attribute/level. The threshold for competency was a priori determined as the total weighted score at which ≥70% of participants agreed a clinician had adequate bone health competency. Thirteen participants generated lists of desirable characteristics, and 30 participants ranked hypothetical scenarios and participated in the DCE. The modified-Delphi exercise generated 108 characteristics, which were reduced to 8 categories with 20 levels with associated points. The maximum possible score was 25 points. A summed threshold score of >12 points classified a clinician as having adequate bone health competency. We developed a numeric additive decision rule to define clinicians across multiple specialties as having adequate competency in managing bone health/osteoporosis. Our data provide a rigorously defined criteria for a clinician with competency in bone health and can be used to quantitate the skills of clinicians participating in bone health research and clinical care.

Osteoporosis and fragility fractures are managed by clinicians across many medical specialties. The key skills of clinicians delivering bone health care have not been systematically established. We invited clinicians with expertise in treating osteoporosis and representatives of patient advocacy groups focused on bone health to create a list of desirable characteristics of a clinician with bone health competency. Participants next ranked 20 hypothetical clinicians defined by various characteristics from highest to lowest likelihood of having adequate bone health competency. Lastly, we generated a weighted score for each characteristic. The threshold for competency was determined as the total weighted score at which ≥70% of participants agreed a clinician had adequate bone health competency. The maximum possible score was 25 points, and a summed threshold score of >12 points classified a clinician as having adequate bone health competency. Our data provide a rigorously defined criteria for a clinician with competency in bone health and can be used to quantitate the skills of clinicians participating in bone health research and clinical care.

Examination of monosodium urate crystal depletion and bone erosion remodeling during pegloticase treatment in patients with uncontrolled gout: exploratory dual-energy computed tomography findings from MIRROR RCT.

OBJECTIVE: Monosodium-urate (MSU) crystal deposits can be visualized and quantified with dual-energy CT (DECT). Pegloticase lowers serum urate (SU) in uncontrolled gout patients, with methotrexate (MTX) co-therapy recommended to increase SU-lowering response rate and decrease infusion reaction risk. The literature on serial DECT-imaging during pegloticase+MTX co-therapy is sparse, with only 2 prior cases of rapid MSU deposition depletion with subsequent bone-erosion remodeling reported from a small open-label trial. Here, we report DECT findings during pegloticase treatment in a larger number of patients from a randomized controlled trial to confirm bone-erosion remodeling that follows MSU depletion with pegloticase. The influence of length-of-therapy is also explored. METHODS: Patients received pegloticase (8mg every 2-weeks)+MTX (15mg/week orally) or pegloticase+placebo (PBO) during the MIRROR RCT trial. A subset underwent DECT-imaging on Day1 (first pegloticase infusion) and at Week 14, 24, and 52. Patients with paired baseline-Week52 images were included. Imaged regions with baseline MSU-crystal volume (VMSU) <0.5cm3 were excluded to minimize artifact contributions. VMSU and bone erosion remodeling were assessed. RESULTS: Eight patients (6 MTX, 2 PBO) were included. Included patients had received 52-weeks (5 MTX), 42-weeks (1 PBO), and 6-weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU <6mg/dL on allopurinol (n=2)/febuxostat (n=1). At Week52, VMSU had markedly decreased in both the pegloticase+MTX and pegloticase+PBO treatment groups, with faster depletion during pegloticase therapy. Bone-erosion remodeling was observed in 29/42 (69%) evaluated erosions: 29 (69%) size decrease, 4 (9.5%) recortication, 3 (7.1%) new bone formation. CONCLUSION: Rapid VMSU depletion pegloticase therapy was observed with concomitant bone remodeling within 1-year. Following pegloticase discontinuation, VMSU reduction slowed or stopped even when SU was maintained <6mg/dL with oral ULT. CLINICAL TRIAL REGISTRATION: NCT03994731.

Response rates for lumbar spine, total hip, and femoral neck bone mineral density in men treated with abaloparatide: results from the ATOM study.

Osteoporosis in men is an underappreciated public health issue, accounting for approximately 30% of the societal burden of osteoporosis. Although the prevalence of osteoporosis in men is lower, fracture-related morbidity and mortality rates exceed those of women. Abaloparatide is a synthetic, 34-amino acid peptide with homology to human parathyroid hormone-related protein (PTHrP), which favors bone formation by selective activation of PTH receptor type 1. In the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM; NCT03512262) trial, 228 men with primary or hypogonadism-associated osteoporosis were randomized to receive subcutaneous injections of abaloparatide 80 µg or placebo. Abaloparatide significantly improved LS, TH, and FN BMD when compared with placebo. In this prespecified analysis, the proportion of men with a percent change from baseline of >0%, >3%, and > 6% in BMD at the LS, TH, and FN at 3, 6, and 12 mo and/or a shift in T-score category (based on LS and TH T-scores) at 12 mo was compared between the abaloparatide and placebo groups in ATOM. There were significantly more men with a BMD gain of >3% at all 3 anatomical sites in the abaloparatide than placebo group at month 6 (18/122 [14.8%] vs 1/70 [1.4%], P = .002) and at month 12 (38/119 [31.9%] vs 1/66 [1.5%], P < .0001). At month 3, more men treated with abaloparatide than placebo had a > 3% BMD increase at the LS (82/134 [61.2%] vs 21/68 [30.9%], P < .0001). A greater proportion of men treated with abaloparatide had an improvement in T-score category from osteoporosis to low BMD or normal when compared with placebo. In conclusion, use of abaloparatide compared with placebo for 12 mo resulted in significant and rapid improvements in BMD in men with osteoporosis from the ATOM study.

Changes in the Workforce Characteristics of Providers Who Care for Adult Patients With Rheumatologic and Musculoskeletal Disease in the United States.

OBJECTIVE: The aim of this study was to describe the adult rheumatology workforce in the United States, assess change in rheumatology providers over time, and identify variation in rheumatology practice characteristics. METHODS: Using national Medicare claims data from 2006 to 2020, clinically active rheumatology physicians and advanced practice providers (APPs) were identified. Each calendar year was used for inclusion, exclusion, and analysis, and providers were determined to be entering, exiting, or stable based upon presence or absence in the prior or subsequent years of data. Characteristics (age, gender, practice type, rural, and region) of rheumatologists were determined for 2019 and in mutually exclusive study periods from 2009 to 2011, 2012 to 2015, and 2016 to 2019. The location of rheumatology practice was determined by billing tax identification and mapped. Demographics of physicians exiting or entering the rheumatology workforce were compared separately to those stable by logistic regression. RESULTS: The clinically active adult rheumatology workforce identified in US Medicare in 2019 was 5,667 rheumatologists and 379 APPs. From 2009 to 2020, the number of rheumatologists increased 23% and the number of APPs increased 141%. There was an increase in female rheumatologists over time, rising to 43% in 2019. Women and those employed by a health care system were more likely to exit, and those in a small practice or in the South were less likely to exit. CONCLUSION: The overall number of clinically active rheumatology providers grew more than 20% over the last decade to a high of 6,036 in 2020, although this rate of growth appears to be flattening off in later years.

Risk of fracture in women with glucocorticoid requiring diseases is independent from glucocorticoid use: An analysis on a nation-wide database.

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common cause of secondary osteoporosis. However, glucocorticoid requiring diseases pose a risk themselves for fracture. The aim of the present study was to determine the risk of fracture associated with variety of glucocorticoid requiring diseases independently from glucocorticoid use and other risk factors for osteoporosis. METHODS: We conducted a retrospective cross-sectional analysis of a nation-wide cohort (DeFRACalc79 database). We used multivariable regression analysis adjusting for several risk factors for fracture and glucocorticoid intake to estimate the independent role of glucocorticoid requiring illnesses on fracture risk. RESULTS: We found that patients with rheumatoid arthritis, connective tissue diseases, chronic obstructive pulmonary disease (COPD) and neurological diseases were at greater risk of vertebral or hip fracture (crude ORs 1.31, 1.20, 1.92 and 2.97 respectively). After adjusting for potential confounders COPD and neurological diseases remained significantly associated with an increased risk of vertebral or hip fractures (aORs 1.33, 95 % CI 1.18-1.49 and 2.43, 95 % CI 2.17-2.74). Rheumatoid arthritis, COPD, IBD and neurological diseases also significantly increased the risk of non-vertebral, non-hip fractures (aORs 1.23, 1.42, 1.52 and 1.94 respectively). CONCLUSION: Some glucocorticoid requiring diseases were independently associated with an increased risk of fractures. COPD and neurological diseases with both vertebral and non-vertebral fracture risk while RA and IBD were independently associated only with non-vertebral, non-hip fractures.

GLUCOCORTICOIDS IN CHRONIC DISEASE: THE GOOD, THE BAD, THE BONE.

Despite the advent of more targeted therapies, glucocorticoids (steroids) remain in chronic use (defined as > 3 months or more) by an estimated 0.5% of the population. Steroids yield symptomatic benefits for systemic and local inflammation as well as disease-modifying properties in rheumatoid arthritis, the most common disorder for their chronic use. Despite their many benefits, steroids have been associated with a myriad of common side effects. Observational studies of steroid safety are limited by confounding by indication, and randomized controlled trials have been too short and too small to understand their true safety profile. Glucocorticoid-induced osteoporosis (GIOP) occurs in a time- and dose-dependent way and is associated with both a reduction in bone formation and an increase in bone resorption. Numerous anti-osteoporotic therapies have efficacy for improving bone health among chronic glucocorticoid users, but implementation science approaches are needed to achieve adequate GIOP prevention and to reduce fracture outcomes.

A multi-step approach to develop a "storytelling" intervention to improve patient gout knowledge and improve outpatient follow-up.

Background: "Storytelling" interventions influence knowledge, attitudes and behavior to promote chronic disease management. We aimed to describe the development of a video "storytelling" intervention to increase gout knowledge and promote adherence to medications and follow-up care after an acute gout flare visit in the emergency department. Methods: We developed a direct-to-patient storytelling intervention to mitigate modifiable barriers to gout care and promote outpatient follow-up and medication adherence. We invited adult patients with gout as storytellers. We utilized a modified Delphi process involving gout experts to identify key themes to guide development of an intervention. Using a conceptual model, we selected stories to ensure delivery of evidence-based concepts and to maintain authenticity. Results: Our video-based storytelling intervention consisted of segments addressing modifiable barriers to gout care. Four diverse gout patients were recruited as storytellers and interviewed with questions that covered gout diagnosis and care. Eleven international gout experts from diverse geographic locations generated and ranked items they considered important messages to promote outpatient gout care follow-up and treatment adherence. Filmed videos were truncated into segments and coded thematically. Distinct segments that captured desired messages were combined to form a cohesive narrative story based on gout patient experiences that conveyed evidence-based strategies to manage gout. Conclusions: Using the Health Belief Model, we developed a culturally appropriate narrative intervention containing "storytelling" that can be tested as an approach to improve gout outcomes. The methods we describe may be generalizable to other chronic conditions requiring outpatient follow-up and medication adherence to improve outcomes.

A Randomized, Double-Blind, Placebo-Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12-Month Findings.

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.

Pegloticase efficacy and safety in kidney transplant recipients; results of the phase IV, open-label PROTECT clinical trial.

INTRODUCTION: Kidney transplant (KT) recipients have a high prevalence and severity of gout. Pegloticase (pegylated recombinant uricase) rapidly metabolizes serum uric acid (sUA), and its efficacy is not impacted by kidney function. METHODS: This open-label, Phase 4 trial (PROTECT NCT04087720) examined safety and efficacy of pegloticase in 20 participants with KT > 1 year prior to enrollment and with uncontrolled gout (sUA ≥7 mg/dL, intolerance/inefficacy to urate lowering therapy, and ≥1 of the following: tophi, chronic gouty arthritis, ≥2 flares in past year) and functioning KT (estimated glomerular filtration rate [eGFR] ≥15 mL/min/1.73 m2 ) on stable immunosuppression therapy. RESULTS: The primary endpoint was sUA response during month 6 (sUA < 6 mg/dL for ≥80% of time). The study enrolled 20 participants (mean ± SD); age: 53.9 ± 10.9 years, time since KT: 14.7 ± 6.9 years, sUA: 9.4 ± 1.5 mg/dL, gout duration: 8.4 ± 11.6 years; all on ≥2 stable doses of immunosuppression agents. Pegloticase (8 mg intravenous every 2 weeks) in KT recipients with uncontrolled gout showed a high response rate of 89% (16/18 responders). Two participants discontinued treatment solely due to COVID-19 concerns prior to month 6 were not included in the primary analysis. Pegloticase exposures were higher than those historically observed with pegloticase monotherapy, and no anaphylaxis or infusion reaction events occurred during the study. CONCLUSIONS: This improved response rate to pegloticase in the KT population reflects observations from other trials and reports on immunomodulation with pegloticase. As the KT population has a high prevalence of gout and limitations with oral urate lowering medication options, these findings suggest a potential option for uncontrolled gout therapy in KT participants.

Hypertension severity, apparent treatment resistant hypertension and hyperuricemia in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

BACKGROUND: Prior studies have identified an association between hypertension and hyperuricemia; however, there has been limited research on the association between hypertension severity and hyperuricemia. METHOD: We studied 997 Black and white adults with serum urate data from the reasons for geographic and racial differences in stroke (REGARDS) study. Hypertension was defined as SBP ≥ 140 mmHg or DBP ≥ 90 mmHg or self-reported use of antihypertensive medication. Apparent treatment-resistant hypertension (aTRH) was defined as a SBP ≥ 140 mmHg or DBP ≥ 90 mmHg with concurrent use of three classes of antihypertensive medications, or taking four or more classes of antihypertensive medication regardless of BP level. Controlled BP was defined as SBP <140 mmHg and DBP <90 mmHg. RESULTS: Overall 5.9% of participants had aTRH and 36.6% had hyperuricemia, defined as serum urate >7.0 mg/dl for men and >6.0 mg/dl for women. After full multivariable adjustment, the odds ratio (OR) for hyperuricemia associated with hypertension was 1.60 [95% confidence interval (95% CI): 1.06-2.40]. Compared to participants not taking antihypertensive medication, the ORs for hyperuricemia for participants taking one, two and three classes of antihypertensive medication without aTRH were 1.98 (95% CI: 1.23-3.20), 2.08 (95% CI: 1.25-3.43), 4.31 (95% CI: 2.07-8.97), respectively, and 3.96 (95% CI: 1.75-8.96) for aTRH. Compared to participants without hypertension, the odds ratios for hyperuricemia were 1.67 (95% CI: 1.08-2.58) and 1.46 (95% CI: 0.88-2.44) among those with hypertension with and without controlled BP, respectively. Diuretic use was associated with a higher odds of hyperuricemia. CONCLUSION: This study suggests that individuals taking more classes of antihypertensive medication may benefit from monitoring for hyperuricemia.

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.

Serum Urate-Lowering Efficacy and Safety of Tigulixostat in Gout Patients With Hyperuricemia: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Trial.

OBJECTIVE: To evaluate the safety and efficacy of the nonpurine xanthine oxidase inhibitor tigulixostat for lowering serum urate level in gout patients with hyperuricemia. METHODS: We conducted a multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding trial. After screening, gout patients with hyperuricemia were randomly assigned, after appropriate washout, to receive daily oral administration of 50 mg, 100 mg, or 200 mg of tigulixostat, or placebo for 12 weeks. Colchicine gout flare prophylaxis was administered to all patients. The primary end point was the proportion of patients with a serum urate level <5.0 mg/dl at week 12. RESULTS: A total of 143 patients were randomized to receive tigulixostat 50 mg (n = 34), 100 mg (n = 38), or 200 mg (n = 37), or placebo (n = 34). A significantly greater proportion of patients in the tigulixostat groups achieved the target serum urate level <5.0 mg/dl at week 12 (47.1% in the 50 mg group, 44.7% in the 100 mg group, and 62.2% in the 200 mg group) compared to the placebo group (2.9%) (P < 0.0001). The mean percentage change in serum urate level from baseline was also significantly greater in the tigulixostat groups (-38.8% to -61.8%) than in the placebo group at all time points (P < 0.0001). The rate of gout flares requiring rescue treatment ranged from 9.4% to 13.2% in the tigulixostat and placebo groups. The incidence of adverse events was 50.0% to 56.8% across all groups, and their severity was mild or moderate. CONCLUSION: Tigulixostat significantly lowered serum urate compared to placebo at all doses studied with an acceptable safety profile.

Nationwide racial/ethnic disparities in US emergency department visits and hospitalizations for gout.

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.

Development and Validation of an Emergency Department Electronic Medical Record Gout Flare Alert.

OBJECTIVE: Patients with acute gout are frequently treated in the emergency department (ED) and represent a typically underresourced and understudied population. A key limitation for gout research in the ED is the timely ability to identify acute gout patients. Our goal was to refine a multicriteria, electronic medical record alert for gout flares and to determine its diagnostic characteristics in the ED. METHODS: The gout flare alert used electronic medical record data from ED nursing notes and was triggered by the term 'gout' preceding past medical history in the chief complaint, the term 'gout' and a musculoskeletal problem in the chief complaint, or the term 'gout' in the problem list and a musculoskeletal chief complaint. We validated its diagnostic properties to assess presence/absence of gout through manual medical record review using adjudicated expert consensus as the gold standard. RESULTS: In January 2020, we analyzed 202 patient records from 2 university-based EDs; from these records, 57 patients were identified by our gout flare alert, and 145 were identified by other means as potentially having an acute gout flare. The gout flare alert's positive predictive value was 47% (95% confidence interval [95% CI] 34-60%), negative predictive value was 94% (95% CI 90-98%), sensitivity was 75% (95% CI 61-89%), and specificity was 82% (95% CI 76-88%). The diagnostic properties were similar at both institutions. CONCLUSION: Our multicomponent gout flare alert had reasonable sensitivity and specificity, albeit a modest positive predictive value. An electronic gout flare alert may help enable the conduct of gout research in the ED setting.

Interactions Between Genetic Risk and Diet Influencing Risk of Incident Female Gout: Discovery and Replication Analysis of Four Prospective Cohorts.

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.

A Randomized, Placebo-Controlled Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings.

OBJECTIVE: To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout in a randomized, placebo-controlled, double-blind trial. METHODS: This study included adults with uncontrolled gout, defined as serum urate ≥7 mg/dl, oral urate-lowering therapy failure or intolerance, and presence of ongoing gout symptoms including ≥1 tophus, ≥2 flares in the past 12 months, or gouty arthritis. Key exclusion criteria included MTX contraindication, current immunosuppressant use, G6PDH deficiency, and estimated glomerular filtration rate <40 ml/minute/1.73 m2 . Patients were randomized 2:1 to 52 weeks of pegloticase (8 mg biweekly) with either oral MTX (15 mg/week) or placebo. The primary end point was the proportion of treatment responders during month 6 (defined as serum urate <6 mg/dl for ≥80% of visits during weeks 20-24). Efficacy was evaluated in all randomized patients (intent-to-treat population), and safety was evaluated in all patients receiving ≥1 blinded MTX or placebo dose. RESULTS: A total of 152 patients were randomized, 100 to receive pegloticase plus MTX, 52 to receive pegloticase plus placebo. Significantly higher treatment response occurred during month 6 in the MTX group versus the placebo group (71.0% [71 of 100 patients] versus 38.5% [20 of 52 patients], respectively; between-group difference 32.3% [95% confidence interval 16.3%, 48.3%]) (P < 0.0001 for between-group difference). During the first 6 months of pegloticase plus MTX or pegloticase plus placebo treatment, 78 (81.3%) of 96 MTX patients versus 47 (95.9%) of 49 placebo patients experienced ≥1 adverse event (AE), most commonly gout flare (64 [66.7%] of 96 MTX patients and 34 [69.4%] of 49 placebo patients). Reports of AEs and serious AEs were comparable between groups, but the infusion reaction rate was considerably lower with MTX cotherapy (4.2% [4 of 96 MTX patients, including 1 patient who had anaphylaxis]) than with placebo cotherapy (30.6% [15 of 49 placebo patients, 0 who had anaphylaxis]) (P < 0.001). Antidrug antibody positivity was also lower in the MTX group. CONCLUSION: MTX cotherapy markedly increased pegloticase response rate over placebo (71.0% versus 38.5%) during month 6 with no new safety signals. These findings verify higher treatment response rate, lower infusion reaction incidence, and lower immunogenicity when pegloticase is coadministered with MTX.

Risk for osteoporosis and fracture with glucocorticoids.

Glucocorticoid use is ubiquitous and is associated with multiple adverse reactions. Among them, osteoporosis and bone fractures are of our concern. In this review, we present current evidence on the effect of glucocorticoids on bone mineral density and the risk of fractures, the mechanisms underlying those effects, and the recommendations for monitoring and treating patients who take them. The bone mineral density of the lumbar spine and total hip is lower, and the risk of fractures is higher in glucocorticoid users than non-users. These effects have a rapid onset, are dose-dependent, and improve soon after discontinuation of glucocorticoids. They also appear to occur even with non-systemic routes of administration and with low doses. Glucocorticoids reduce bone mineral density by increasing osteoclast activity and decreasing osteoblast and osteocyte activity. Calcium metabolism and parathyroid hormone activity are less important than was initially thought. Treatment decisions are on risk stratification using clinical, radiographic, and prediction tools. Our armamentarium for the treatment and prevention of glucocorticoid-induced osteoporosis includes calcium and vitamin D, bisphosphonates, recombinant parathyroid hormone, monoclonal antibodies against receptor activator of nuclear factor kappa-B ligand, and hormone treatments.