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To examine whether the cross-sectional gene-diet interaction for prevalent hyperuricemia among women translates prospectively to risk of incident female gout.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 US and UK (replication). Genetic risk score (GRS) was calculated from 114 urate-associated loci.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 with women with unhealthy DASH score (mean), multivariable relative risk (mRR) for incident female gout among women with healthy DASH score (≥mean) was 0.67 (95% CI 0.60-0.76) among higher GRS (≥mean) and 0.91 (0.78-1.05) among lower GRS (P multiplicative interaction=0.001); mRR for higher vs. lower GRS was 2.03 (1.80-2.29) and 1.50 (1.31-1.71) among unhealthy and healthy DASH score groups, respectively. Additive interaction was also significant, in both the discovery and replication cohorts (P0.001), with 51% of the excess risk attributable to the additive gene-diet interaction in all cohorts combined.The deleterious effect of genetic predisposition on risk of incident female gout was more pronounced among women with unhealthy diet, 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. This article is protected by copyright. All rights reserved.

Background/Purpose Disordered osteoclast activity has been implicated in the pathogenesis of gouty bone erosion. We sought to determine if the addition of denosumab (a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand - RANKL) to intensive urate-lowering therapy (ULT) improves gouty bone erosion. Methods Open-label, parallel-group pilot randomized controlled trial in which 20 participants with gout with at least one confirmed conventional radiographic foot bone erosion were assigned in a 1:1 allocation to receive denosumab (60 mg subcutaneous every 6 months) added to intensive ULT (serum urate ≤5 mg/dL or 300 µmol/L at the time of randomization and continued for the duration of the study), or intensive ULT alone. The primary outcome was the change in the bilateral foot and ankle computed tomography (CT) bone erosion score from baseline to 12 months, assessed by an experienced musculoskeletal radiologist blinded to study assignment. Secondary outcomes included change in serum C-terminal telopeptide (CTX), and patient reported outcomes of pain and function. Results Although serum CTX declined markedly in the denosumab/ULT group compared with the ULT alone group, there was no interval change in CT erosion score in either the denosumab/ULT or ULT alone group after one year of follow-up. Other secondary outcomes did not differ between groups. There were two severe adverse events: One patient developed atrial fibrillation (on denosumab/ULT) and another atrial flutter (on ULT alone). Conclusions In this pilot study, denosumab did not offer additional benefit to intensive urate lowering therapy for gouty bone erosion.

BackgroundUrate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs).MethodsIn a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence.ResultsThe 306 male AA veterans with gout who met the eligibility criteria were randomized to the gout-storytelling intervention (n= 152) or stress reduction video (n= 154); 261/306 (85%) completed the 1-year study. The mean age was 64 years, body mass index was 33 kg/m2, and gout disease duration was 3 years. ULT adherence was similar in the intervention vs. control groups: 3 months, 73% versus 70%; 6 months, 69% versus 69%; 9 months, 66% versus 67%; and 12 months, 61% versus 64% (p> 0.05 each). Secondary outcomes (gout flares, serum urate and gout-specific health-related quality of life [HRQOL]) in the intervention versus control groups were similar at all time points except intervention group outcomes were better for the following: (1) number of gout flares at 9 months were fewer, 0.7 versus 1.3 in the previous month (p= 0.03); (2) lower/better scores on two gout specific HRQOL subscales: gout medication side effects at 3 months, 32.8 vs. 39.6 (p= 0.02); and unmet gout treatment need at 3 months, 30.9 vs. 38.2 (p= 0.003), and 6 months, 29.5 vs. 34.5 (p= 0.03), respectively.ConclusionsA culturally appropriate gout-storytelling intervention was not superior to attention control for improving gout outcomes in AAs with gout.Trial registrationRegistered atClinicalTrials.govNCT02741700

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.

Background Previous studies have noted significant variation in serum urate (sUA) levels, and it is unknown how this influences the accuracy of hyperuricemia classification based on single data points. Despite this known variability, hyperuricemic patients are often used as a control group in gout studies. Our objective was to determine the accuracy of hyperuricemia classifications based on single data points versus multiple data points given the degree of variability observed with serial measurements of sUA. Methods Data was analyzed from a cross-over clinical trial of urate-lowering therapy in young adults without a gout diagnosis. In the control phase, sUA levels used for this analysis were collected at 2–4 week intervals. Mean coefficient of variation for sUA was determined, as were rates of conversion between normouricemia (sUA ≤6.8 mg/dL) and hyperuricemia (sUA > 6.8 mg/dL). Results Mean study participant (n = 85) age was 27.8 ± 7.0 years, with 39% female participants and 41% African-American participants. Mean sUA coefficient of variation was 8.5% ± 4.9% (1 to 23%). There was no significant difference in variation between men and women, or between participants initially normouricemic and those who were initially hyperuricemic. Among those initially normouricemic (n = 72), 21% converted to hyperuricemia during at least one subsequent measurement. The subgroup with initial sUA n = 54) was much less likely to have future values in the range of hyperuricemia compared to the group with screening sUA values between 6.0–6.8 (n = 18) (7% vs 39%, p = 0.0037). Of the participants initially hyperuricemic (n = 13), 46% were later normouricemic during at least one measurement. Conclusion Single sUA measurements were unreliable in hyperuricemia classification due to spontaneous variation. Knowing this, if a single measurement must be used in classification, it is worth noting that those with an sUA of Trial registration Data from parent study ClinicalTrials.gov Identifier: NCT02038179.

OBJECTIVE To evaluate the efficacy and safety of anakinra compared to triamcinolone in the treatment of gout flares. METHODS Patients for whom nonsteroidal antiinflammatory drugs and colchicine were not suitable treatments were enrolled in this multicenter, randomized, double-blind study with follow-up for up to 2 years. The study was designed to assess superiority of anakinra (100 or 200 mg/day for 5 days) over triamcinolone (40 mg in a single injection) for the primary end point of changed patient-assessed pain intensity in the most affected joint (scored on a visual analog scale of 0-100) from baseline to 24-72 hours. Secondary outcome measures included: safety, immunogenicity, and patient- and physician-assessed global response. RESULTS One hundred sixty-five patients were randomized to receive anakinra (n = 110) or triamcinolone (n = 55). The median age was 55 years (range 25-83), 87% were men, the mean disease duration was 8.7 years, and the mean number of self-reported flares during the prior year was 4.5. A total of 301 flares were treated (214 with anakinra; 87 with triamcinolone). Anakinra in both doses and triamcinolone provided clinically meaningful reduction in patient-assessed pain intensity in the first and subsequent flares. For the first flare, the mean decline in pain intensity from baseline to 24-72 hours for total anakinra and triamcinolone was -41.2 and -39.4, respectively (P = 0.688). Anakinra performed better than triamcinolone for most secondary end points. There were no unexpected safety findings. The presence of antidrug antibodies was not associated with adverse events or altered pain reduction. CONCLUSION Anakinra was not superior to triamcinolone for the primary end point, but had comparable efficacy in pain reduction and was favored for most secondary end points. Anakinra is an effective option for gout flares when conventional therapy is unsuitable.

BACKGROUND: Osteoporosis medication use is suboptimal. Simple interventions personalized to a patients’ stage of readiness are needed to encourage osteoporosis medication use. OBJECTIVES: To estimate interrelationships of sociodemographic factors, perceived fracture risk, health literacy, receipt of medication information, medication trust and readiness to use osteoporosis medication; and apply observed relationships to inform design specifications for a clinical decision support application that can be used for personalized patient counseling. METHODS: Data from a national sample of older women (n = 1759) with self-reported history of fractures and no current use of osteoporosis medication treatment were used to estimate an acceptable path model that describes associations among key sociodemographic characteristics, health literacy, perceived fracture risk, receipt of osteoporosis medication information within the past year, trust in osteoporosis medications, and readiness to use osteoporosis medication. Path model results were used to inform an application for personalized patient counseling that can be easily integrated into clinical decision support systems. RESULTS: Increased age (β = 0.13), trust for medications (β = 0.12), higher perceived fracture risk (β = 0.21), and having received medication information within the past year (β = 0.21) were all positively associated with readiness to use osteoporosis medication (p < 0.0001). Whereas, health literacy (β = − 0.09) was inversely associated with readiness to use osteoporosis medication (p < 0.0001). Using these results, a brief 6-item question set was constructed for simple integration into clinical decision support applications. Patient responses were used to inform a provider dashboard that integrates a patient’s stage of readiness for osteoporosis medication use, predictors of readiness, and personalized counseling points appropriate to their stage of readiness. CONCLUSION: Content of counseling strategies must be aligned with a patient’s stage of readiness to use treatment. Path modeling can be effectively used to identify factors for inclusion in an evidenced-based clinical decision support application designed to assist providers with personalized patient counseling and osteoporosis medication use decisions.

Abaloparatide significantly increased bone mineral density (BMD) in women with postmenopausal osteoporosis and decreased risk of vertebral, nonvertebral, and clinical fractures compared with placebo. The Abaloparatide for the Treatment of Men with Osteoporosis (ATOM; NCT03512262) study evaluated the efficacy and safety of abaloparatide compared with placebo in men. Eligible men aged 40 to 85 years with osteoporosis were randomized 2:1 to daily subcutaneous injections of abaloparatide 80 μg or placebo for 12 months. The primary endpoint was change from baseline in lumbar spine BMD. Key secondary endpoints included BMD change from baseline at the total hip and femoral neck. A total of 228 men were randomized (abaloparatide, n = 149; placebo, n = 79). Baseline characteristics were similar across treatment groups (mean age, 68.3 years; mean lumbar spine BMD T-score, -2.1). At 12 months, BMD gains were greater with abaloparatide compared with placebo at the lumbar spine (least squares mean percentage change [standard error]: 8.48 [0.54] versus 1.17 [0.72]), total hip (2.14 [0.27] versus 0.01 [0.35]), and femoral neck (2.98 [0.34] versus 0.15 [0.45]) (all p 0.0001). The most common (≥5%) treatment-emergent adverse events were injection site reaction, dizziness, nasopharyngitis, arthralgia, bronchitis, hypertension, and headache. During 12 months of abaloparatide treatment, men with osteoporosis exhibited rapid and significant improvements in BMD with a safety profile consistent with previous studies. These results suggest abaloparatide can be considered as an effective anabolic treatment option for men with osteoporosis. © 2022 Radius Health Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Objective.To determine the association of serum urate (SU) levels with sudden cardiac death and incident coronary heart disease (CHD), separately, among adults without a history of CHD.Methods.We conducted a case-cohort analysis of Black and White participants aged ≥ 45 years enrolled in the REason for Geographic And Racial Differences in Stroke (REGARDS) study without a history of CHD at baseline between 2003 and 2007. Participants were followed for sudden cardiac death or incident CHD (i.e., myocardial infarction [MI] or death from CHD excluding sudden cardiac death) through December 31, 2013. Baseline SU was measured in a random sample of participants (n = 840) and among participants who experienced sudden cardiac death (n = 235) or incident CHD (n = 851) during follow-up.Results.Participants with higher SU levels were older and more likely to be male or Black. The crude HR (95% CI) per 1 mg/dL higher SU level was 1.26 (1.14–1.40) for sudden cardiac death and 1.17 (1.09–1.26) for incident CHD. After adjustment for age, sex, race, and cardiovascular risk factors, the HR (95% CI) per 1 mg/dL higher SU level was 1.19 (1.03–1.37) for sudden cardiac death and 1.05 (0.96–1.15) for incident CHD. HRs for sudden cardiac death were numerically higher among participants aged 45–64 vs ≥ 65 years, without vs with diabetes, and among those of White vs Black race, although P values for effect modification were all ≥ 0.05.Conclusion.Higher SU levels were associated with an increased risk for sudden cardiac death but not with incident CHD.

OBJECTIVE To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect. METHODS We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and

Objective Disagreement exists between rheumatology and primary care societies regarding gout management. This paper describes a formal process for gathering input from stakeholders in the planning of a trial to compare gout management strategies. Methods We recruited patients, nurses, physician assistants, primary care clinicians, and rheumatologists to participate in a modified Delphi panel (mDP) to provide input on design of a trial focused on optimal management for primary care patients with gout. The 16 panelists received a plain-language briefing document that discussed the rationale for the trial, key clinical issues in gout, and aspects of trial design. The panelists also received information and considerations on nine voting questions (VQs), judged to be the key design questions. Cognitive interviews with panelists ensured that the VQs were understood by the range of panelists involved in the mDP. Panelists were asked to score all VQs from 1 (definitely no) to 9 (definitely yes). Two voting rounds were conducted-round 1 by email and round 2 by video conference. Results The VQs were modified through the cognitive interviews. The round 1 voting resulted in consensus on eight items, with consensus defined as median voting score in the same tercile (1-3, 4-6 or 7-9). Re-voting at the meeting (round 2) reached consensus on the remaining item. Conclusion An mDP with various stakeholders facilitated consensus on the design of a trial of different management strategies for chronic gout. This method may be useful for designing trials of clinical questions with substantial disagreement across stakeholders.

Summary: This post hoc analysis of a randomized, double-blind study of postmenopausal women with osteoporosis found that there were early increases in bone turnover markers and decreases in bone mineral density after discontinuation of long-term alendronate. These findings might help guide treatment decisions, including monitoring after alendronate withdrawal. Introduction: The short-term effects of discontinuing long-term bisphosphonates are poorly characterized. This post hoc analysis investigated 1–12-month changes in bone mineral density (BMD) and bone turnover markers (BTM) after alendronate (ALN) discontinuation. Methods: Data were from a randomized, double-blind trial of MK-5442 (calcium-sensing receptor antagonist) following oral bisphosphonates, with placebo and continued ALN controls (ClinicalTrials.gov NCT00996801). Postmenopausal women with osteoporosis had received oral bisphosphonate (≥ 3–4 preceding years; ALN for the 12 months pre-screening), continuing on ALN 70 mg/week (n = 87) or placebo (n = 88). Results: At 12 months, least-squares mean percent changes from baseline BMD (placebo vs. ALN) were lumbar spine (LS): – 0.36 vs. 1.29, total hip: – 1.44 vs. 0.46, and femoral neck (FN): – 1.26 vs. – 0.08 (all P < 0.05). BTM levels increased by 1–3 months, to 12 months, with placebo vs. ALN (P < 0.001). FN BMD decline was greater in the placebo subgroup with higher urinary N-terminal cross-linked telopeptides of type I collagen/creatinine [uNTx/Cr] (P < 0.01), and higher serum N-terminal pro-peptide of type 1 collagen [P1NP] levels (P < 0.05), at baseline. There was a trend toward greater FN BMD loss with higher BTM levels at 3 and/or 6 months. Younger age and higher LS BMD at baseline were associated with greater LS BMD loss at 12 months (P = 0.04 and < 0.01, respectively); higher baseline FN BMD predicted greater FN BMD loss (P = 0.04). Conclusion: Early changes in BTM levels and BMD were observed after discontinuation of long-term ALN. Further characterization of factors associated with patients’ risk of bone loss upon bisphosphonate discontinuation is warranted.

The study aimed to utilize machine learning (ML) approaches and genomic data to develop a prediction model for bone mineral density (BMD) and identify the best modeling approach for BMD prediction. The genomic and phenotypic data of Osteoporotic Fractures in Men Study (n = 5130) was analyzed. Genetic risk score (GRS) was calculated from 1103 associated SNPs for each participant after a comprehensive genotype imputation. Data were normalized and divided into a training set (80%) and a validation set (20%) for analysis. Random forest, gradient boosting, neural network, and linear regression were used to develop BMD prediction models separately. Ten-fold cross-validation was used for hyper-parameters optimization. Mean square error and mean absolute error were used to assess model performance. When using GRS and phenotypic covariates as the predictors, all ML models’ performance and linear regression in BMD prediction were similar. However, when replacing GRS with the 1103 individual SNPs in the model, ML models performed significantly better than linear regression (with lasso regularization), and the gradient boosting model performed the best. Our study suggested that ML models, especially gradient boosting, can improve BMD prediction in genomic data.

To investigate whether serum urate levels, number of gout flares, and tophi burden are related to death from cardiovascular (CV) causes after treatment with febuxostat or allopurinol in patients with gout from the Cardiovascular Safety of Febuxostat or Allopurinol in Patients With Gout and Cardiovascular Comorbidities (CARES) trial.Patients were randomly assigned to receive febuxostat (40 mg or 80 mg once daily, according to serum urate levels at week 2) or allopurinol titrated in 100-mg increments from 200-400 mg or 300-600 mg (with dose determined according to kidney function). Changes from baseline in serum urate level, gout flares, and tophus resolution were key exploratory efficacy parameters in the overall population and in subgroups of patients who died and those who did not die from a CV-related cause. The latter subgroup included patients who died due to non-CV causes and those who did not die due to any cause.Patients received treatment with febuxostat (n = 3,098) or allopurinol (n = 3,092) for a median follow-up period of 32 months (for a maximum of 85 months). In the overall population, mean serum urate levels were lower in those receiving febuxostat compared with those receiving allopurinol at most study visits. There were no associations between serum urate levels and death from CV causes with febuxostat. The number of gout flares requiring treatment was higher within 1 year of treatment with febuxostat compared with allopurinol (mean incidence of gout flares per patient-years of exposure 1.33 versus 1.20), but was comparable thereafter and decreased overall throughout the study period (mean incidence of gout flares per patient-years of exposure 0.35 versus 0.34 after 1 year of treatment; overall mean incidence 0.68 versus 0.63) irrespective of whether the patient died from a CV-related cause. Overall, 20.8% of patients had ≥1 tophus at baseline; tophus resolution rates were similar between treatment groups, with cumulative resolution rates of50%.In the CARES trial, febuxostat and allopurinol (≤600 mg doses) had comparable efficacy in patients with gout and CV disease, and there was no evidence of a relationship between death from CV causes and serum urate levels, number of gout flares, or tophus resolution among the patients receiving febuxostat.

Introduction: The Living Donor Navigator (LDN) program is one of several initiatives designed to help transplant candidates identify living donors with the help of a friend or family member advocate to speak on their behalf. More than half of advocates in the LDN program were the spouse or parent of the candidate and served in a caregiving role. Caregivers for patients awaiting transplantation have reported poorer quality of life than the general population, suggesting more support is needed for this vulnerable group. The purpose of this study was to understand whether the LDN program met the needs of advocates who were also caregivers for the transplant candidate. Methods: We performed a supplementary secondary qualitative analysis of a parent study conducted December 2017-January 2018 with 9 advocates who participated in the LDN program. Transcripts were reanalyzed from focus group discussions, concentrating on comments about caregiving or made by caregivers. Using manual coding and reflexive thematic analysis, we identified broad codes and major themes. Findings: Our re-analysis revealed one theme overlapping with our previous analysis (Support) and 2 new themes specific to caregiver advocates: Quality of Life and Fear. Caregivers agreed that the LDN program equipped them with tools to address these areas and best serve their simultaneous caregiver/advocate roles. Discussion: These analyses demonstrated that those who served as advocate and caregiver derived a benefit from the LDN program but had distinct needs from other advocates. These findings can inform continued refinement of the program and expansion to support needs of caregiver

Summary The use of bone turnover marker (BTM) testing for patients with osteoporosis in the USA has not been well characterized. This retrospective US-based real-world data study found BTM testing has some association with treatment decision-making and lower fracture risk in patients with presumed osteoporosis, supporting its use in clinical practice. Introduction The purpose of this study was to characterize bone turnover marker (BTM) testing patterns and estimate their clinical utility in treatment decision-making and fragility fracture risk in patients with osteoporosis using a retrospective claims database. Methods Data from patients aged ≥ 50 years with newly diagnosed osteoporosis enrolled in the Truven MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Co-ordination of Benefits databases from January 2008 to June 2018 were included. Osteoporosis was ascertained by explicit claims, fragility fracture events associated with osteoporosis, or prescribed anti-resorptive or anabolic therapy. BTM-tested patients were 1:1 propensity score matched to those untested following diagnosis. Generalized estimating equation models were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for testing versus no testing on both treatment decision-making and fragility fracture. Results Of the 457,829 patients with osteoporosis, 6075 were identified with ≥ 1 BTM test following diagnosis; of these patients, 1345 had a unique treatment decision made ≤ 30 days from BTM testing. The percentage of patients receiving BTM tests increased significantly each year (average annual % change: + 8.1%; 95% CI: 5.6–9.0; p = 0.01). Patients tested were significantly more likely to have a treatment decision (OR: 1.14; 95% CI: 1.13–1.15), and testing was associated with lower odds of fracture versus those untested (OR: 0.87; 95% CI: 0.85–0.88). Conclusion In this large, heterogeneous population of patients with presumed osteoporosis, BTM testing was associated with treatment decision-making, likely leading to fragility fracture reduction following use. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-020-05734-0.

Objective This ancillary study examined the impact of depressive symptoms on the effectiveness of a urate‐lowering therapy in the context of a clinical trial. Methods Participants included 67 adults (ages 18–40) with elevated blood pressure who were enrolled in a double‐blind, randomized, crossover clinical trial evaluating the effectiveness of allopurinol (300 mg/d) versus placebo to decrease blood pressure. Depressive symptoms were measured at the beginning of each 4‐week phase with the Center for Epidemiological Studies Depression scale (CESD‐10). Serum urate (sUA) was assessed at the beginning and end of each treatment phase. Compliance to treatment was measured by having detectable oxypurinol levels. Linear regressions tested associations between depressive symptoms and change in sUA in each phase, adjusting for sex and race. Logistic regression predicted compliance from depressive symptoms. Results Participants had a mean age of 27 years and were 64% male and 39% African American. sUA levels decreased during the allopurinol treatment period but did not change during the placebo period. Higher depressive symptoms at pretreatment were associated with an attenuated urate‐lowering response during the allopurinol phase (β = 0.24, p < 0.05), but had no effect on sUA changes during the placebo phase. Depressive symptoms were not associated with treatment compliance assessed by oxypurinol levels. Conclusion Depressive symptoms were associated with reduced efficacy of allopurinol treatment for hyperuricemia in a clinical trial targeting hypertension. Studies evaluating the efficacy of urate‐lowering therapies may benefit from screening for depressive symptoms.

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

Uric acid is the final byproduct of purine metabolism. The loss of the enzyme that hydrolyzes uric acid to allantoin was lost, leading to a decrease in uric acid excretion and its further accumulation. The buildup of uric acid leads to damage in different organ systems, including the cardiovascular system. With the increasing burden of cardiovascular disease worldwide, a growing body of evidence has addressed the relationship between urate, cardiovascular outcomes, and gout medication cardiovascular safety.The treatment of gout reduces joint damage and it can also lessen CV morbidity. Allopurinol shows CV safety profile when compared to other ULTs. Evidence supporting CV safety with the use of colchicine and IL-1 agents is promising and research needs to be conducted to further assess this outcome.

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

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk offuture fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the riskfor second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring foradverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). (c) 2019 American Society for Bone and Mineral Research. (Less)

BACKGROUND Fractures associated with postmenopausal osteoporosis (PMO) are associated with pain, disability, and increased mortality. A recent, nationwide evaluation of racial difference in outcomes after fracture has not been performed. OBJECTIVE To determine if 1-year death, debility, and destitution rates differ by race. DESIGN Observational cohort study. SETTING US Medicare data from 2010 to 2016. PARTICIPANTS Non-Hispanic black and white women with PMO who have sustained a fragility fracture of interest: hip, pelvis, femur, radius, ulna, humerus, and clinical vertebral. MEASUREMENTS Outcomes included 1-year: (1) mortality, identified by date of death in Medicare vital status information, (2) debility, identified as new placement in long-term nursing facilities, and (3) destitution, identified as becoming newly eligible for Medicaid. RESULTS Among black and white women with PMO (n = 4,523,112), we identified 399,000 (8.8%) women who sustained a major fragility fracture. Black women had a higher prevalence of femur (9.0% vs 3.9%; P

Introduction:The updated common rule, for human subjects research, requires that consents “begin with a ‘concise and focused’ presentation of the key information that will most likely help someone make a decision about whether to participate in a study” (Menikoff, Kaneshiro, Pritchard. The New England Journal of Medicine. 2017; 376(7): 613–615.). We utilized a community-engaged technology development approach to inform feature options within the REDCap software platform centered around collection and storage of electronic consent (eConsent) to address issues of transparency, clinical trial efficiency, and regulatory compliance for informed consent (Harris, et al. Journal of Biomedical Informatics 2009; 42(2): 377–381.). eConsent may also improve recruitment and retention in clinical research studies by addressing: (1) barriers for accessing rural populations by facilitating remote consent and (2) cultural and literacy barriers by including optional explanatory material (e.g., defining terms by hovering over them with the cursor) or the choice of displaying different videos/images based on participant’s race, ethnicity, or educational level (Phillippi, et al. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 2018; 47(4): 529–534.).Methods:We developed and pilot tested our eConsent framework to provide a personalized consent experience whereby users are guided through a consent document that utilizes avatars, contextual glossary information supplements, and videos, to facilitate communication of information.Results:The eConsent framework includes a portfolio of eight features, reviewed by community stakeholders, and tested at two academic medical centers.Conclusions:Early adoption and utilization of this eConsent framework have demonstrated acceptability. Next steps will emphasize testing efficacy of features to improve participant engagement with the consent process.

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

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).

ObjectivesTo provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

Previous studies do not widely support hyperuricemia as a risk factor for stroke and other cardiovascular diseases. We assessed the relationship between hyperuricemia and ischemic stroke (≈900 cases) using a large data set from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). We employed a case-cohort design (incident stroke cases and randomly selected cohort participants) and weighted Cox-proportional hazard models to estimate the association of serum urate level ≥6.8 mg/dL (ie, hyperuricemia) and 6.0 to

In a randomized clinical trial in patients initiating glucocorticoid therapy (GC-I) or on long-term therapy (GC-C), denosumab every 6 months increased spine and hip bone mineral density at 12 and 24 months significantly more than daily risedronate. The aim of this study was to evaluate the effects of denosumab compared with risedronate on bone strength and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in GC-I and GC-C. A subset of 110 patients had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia at baseline and at 12 and 24 months. Cortical and trabecular microarchitecture were assessed with standard analyses and failure load (FL) with micro-finite element analysis. At the radius at 24 months, FL remained unchanged with denosumab and significantly decreased with risedronate in GC-I (-4.1%, 95% confidence interval [CI] -6.4, -1.8) and, in GC-C, it significantly increased with denosumab (4.3%, 95% CI 2.1, 6.4) and remained unchanged with risedronate. Consequently, FL was significantly higher with denosumab than with risedronate in GC-I (5.6%, 95% CI 2.4, 8.7, p < 0.001) and in GC-C (4.1%, 95% CI 1.1, 7.2, p = 0.011). We also found significant differences between denosumab and risedronate in percentage changes in cortical and trabecular microarchitectural parameters in GC-I and GC-C. Similar results were found at the tibia. To conclude, this HR-pQCT study shows that denosumab is superior to risedronate in terms of preventing FL loss at the distal radius and tibia in GC-I and in increasing FL at the radius in GC-C, based on significant differences in changes in the cortical and trabecular bone compartments between treatment groups in GC-I and GC-C. These results suggest that denosumab could be a useful therapeutic option in patients initiating GC therapy or on long-term GC therapy and may contribute to treatment decisions in this patient population. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). PG reports grants from Amgen, grants and other from AbbVie, grants from Celgene, grants from Lilly, grants from Merck, grants from Pfizer, grants from Roche, grants from UCB, grants from Fresenius, grants from Mylan, and grants from Sandoz outside the submitted work. BR reports personal fees from Scanco Medical AG outside the submitted work. EL reports personal fees from Amgen; personal fees from Lilly; grants, personal fees, and nonfinancial support from Celgene; personal fees from Expanscience; personal fees from AbbVie; personal fees from Sublimed; grants, personal fees, and non-financial support from UCB; and grants, personal fees, and non-financial support from MSD outside the submitted work. BO reports personal fees from Raffo, personal fees from Baliarda, personal fees from Shire, personal fees from Takeda, personal fees from Gador, personal fees from Amgen, and personal fees from Ultragenyx outside the submitted work. RC reports grants from Amgen during the conduct of the study; grants and personal fees from UCB; personal fees from Lilly; personal fees from BMS; personal fees from AbbVie; personal fees from Pfizer; grants and personal fees from Chugai; personal fees from Sanofi; personal fees from Novartis; and grants and other from Fresenius Kiabi outside the submitted work. AC is employed by Amgen and has equity in Amgen. SH is an employee of and has equity in Amgen. KGS reports grants from Amgen, Horizon Pharma, Swedish Orphan Biovitrum AB, Shanton Pharma Co. LTD, Dyve Bioscience, and LG Chem outside the submitted work. JPB reports grants from Amgen, grants from UCB, and grants from Lilly the outside the submitted work. All authors had full access to the data, and there were no restrictions regarding content to include in the manuscript. This study was funded by Amgen Inc. Authors’ roles: Investigation: PG, OM, EL, BO, RC, and KGS. Formal analysis: KE, AC, and SH. Writing—original draft: PG and MB. Writing—review & editing: PG, MB, BR, OM, EL, BO, RC, KE, AC, SH, KGS, and JPB.

Haiyan Qu,1 Stuart L Silverman,2 Richard M Shewchuk,1 Jeffrey R Curtis,3 Shamly Austin,4 Susan L Greenspan,5 Jeri W Nieves,6 Ryan C Outman,3 Amy H Warriner,3 Nelson B Watts,7 Kenneth G Saag3 1Department of Health Services Administration, University of Alabama at Birmingham, Birmingham, AL, USA; 2Cedars-Sinai, Los Angeles, CA, USA; 3Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 4Research, Development, & Analytics, Highmark Wholecare, Pittsburgh, PA, USA; 5Division of Geriatric Medicine, University of Pittsburgh, Pittsburgh, PA, USA; 6Department of Epidemiology, Columbia University, New York, NY, USA; 7Mercy Health, Cincinnati, OH, USACorrespondence: Haiyan Qu, Department of Health Services Administration, University of Alabama at Birmingham, SHPB 580D, 1716 9th Ave. S., Birmingham, AL, 35294-1212, USA, Tel +1 205996-4940, Email hyqu@uab.eduObjective: Interventions to initiate medication and increase adherence for postmenopausal women who have had a fragility fracture were not always successful. The purpose of this study was to derive an empirical framework for patient-identified barriers to osteoporosis medication initiation and adherence from physician experts.Methods: A cognitive mapping approach involving nominal group technique (NGT) meetings and a card sorting and rating task were used to obtain formative data. We first conducted four NGT meetings with 18 women patients who were not on osteoporosis treatment to identify barriers to osteoporosis medication, then invited 27 osteoporosis physicians to sort and rate 25 patients identified barriers. Descriptive analysis, multidimensional scaling analysis, and hierarchical cluster analysis were applied for data analysis.Results: A two-dimensional five-cluster cognitive map was derived to provide an organizational framework for understanding patients perceived barriers to medication initiation and adherence. The five clusters were concerns about side effects, experience of side effects, lifestyle changes, medication access and complexity, and patient uncertainty about treatment and trust in the provider. The two dimensions were interpreted as internal to patients (X-axis) and external to patients (Y-axis).Conclusions/Implications: Views of patients solicited in a structured format provided directions to help in designing interventions to improve osteoporosis medication initiation and adherence.Keywords: nominal group technique, cognitive mapping, patient barriers, osteoporosis treatment, medication initiation, medication adherence

Gout is the most common form of inflammatory arthritis affecting millions of persons around the world. Painful flares and tophaceous deposits are debilitating, reduce quality of life and put strain on health-care systems.This review provides an overview of the treatment of gout flares and lowering serum urate. First line agents are discussed with emphasis on emerging evidence. Novel therapies are also covered.Lifestyle modifications form a part of gout prevention. NSAIDs, colchicine, and glucocorticoids are first line agents for gout flares. The IL-1β antagonists are highly effective for arresting flares but their cost-effectiveness render them salvage therapies. Allopurinol is an agent of first choice for urate lowering therapy. In Southeast Asian and Black populations, screening for HLA*B58:01 mutation is a cost-effective approach to decrease the occurrence of allopurinol hypersensitivity syndrome. Febuxostat is another efficacious urate lowering therapy, but has received a U.S. FDA black box warning for cardiovascular safety. Novel uricosurics are a class for continued drug development; verinurad and arhalofenate are agents with future promise. For patients with recalcitrant gout, pegloticase is effective. Its immunogenicity significantly threatens the achievement of sustained urate lowering responses. Abrogating pegloticase's immunogenicity with immunomodulatory co-therapy may lend to sustained efficacy.

Little is known about satisfaction with different modes of telemedicine delivery. The objective of this study was to determine whether patient satisfaction with phone-only was noninferior to video visits.We conducted a parallel group, randomized (1:1), single-blind, noninferiority trial in multispecialty clinics at a tertiary academic medical center. Adults age ≥ 60 years or with Medicare/Medicaid insurance were eligible. Primary outcome was visit satisfaction rate (9 or 10 on a 0-10 satisfaction scale). Noninferiority was determined if satisfaction with phone-only (intervention) versus video visits (comparator) was no worse by a -15% prespecified noninferiority margin. We performed modified intent-to-treat (mITT) and per protocol analyses, after adjusting for age and insurance.200 participants, 43% Black, 68% women completed surveys. Visit satisfaction rates were high. In the mITT analysis, phone-only visits were noninferior by an adjusted difference of 3.2% (95% CI, -7.6% to 14%). In the per protocol analysis, phone-only were noninferior by an adjusted difference of -4.1% (95% CI, -14.8% to 6.6%). The proportion of participants who indicated they preferred the same type of telemedicine visit as their next clinic visit were similar (30.2% vs 27.9% video vs phone-only, p = 0.78) and a majority said their medical concerns were addressed and would recommend a telemedicine visit.Among a group of diverse, established older or underserved patients, the satisfaction rate for phone-only was noninferior to video visits. These findings could impact practice and policies governing telemedicine.

Background/objective Patient, provider, and system factors can contribute to chronic care management and outcomes. Few studies have examined these multilevel associations with osteoporosis care and outcomes. We examined how key process and structural factors at the patient, primary care physician (PCP), and primary care clinic (PCC) levels were associated with guideline concordant osteoporosis pharmacotherapy, daily calcium intake, vitamin D supplementation, and weekly exercise sessions at 52 weeks following enrollment in a cluster randomized controlled trial. Methods We conducted a secondary analysis of observational data from 1 site of the trial. The study sample included 1996 men and women ≥ 50 years of age at the time of recruitment following completion of a dual-energy x-ray absorptiometry (DXA) scan and who had complete data at baseline and 52 weeks. Our primary independent variable was "relationship continuity": the DXA-ordering provider was the patient's PCP. Hierarchical linear and logistic regression accounted for patient, provider, and primary care clinic characteristics. Results In multivariable regression analyses, relationship continuity (ie, the PCP ordered the study DXA) was associated with higher average daily calcium intake and likelihood of vitamin D supplementation at 52 weeks. No PCP or primary care clinic factors were associated with osteoporosis care. Conclusions The relationship continuity, in which the provider ordering a DXA is the patient's PCP and therefore also presents the results of a DXA, may help to promote patient behaviors associated with good bone health.

Serum urate (SU) is the most common primary efficacy outcome in trials of urate-lowering therapies for gout. Despite this, it is not formally considered a validated surrogate outcome. In this paper we will outline the definitions of biomarkers and surrogate outcome measures, respectively as well as the available frameworks and challenges in the assessment of the validity of serum urate as a surrogate in gout (i.e. a reasonable replacement for gout symptoms).