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Gout: HELP
Articles from University of Michigan
Based on 23 articles published since 2008
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These are the 23 published articles about Gout that originated from University of Michigan during 2008-2019.
 
+ Citations + Abstracts
1 Guideline 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. 2012

Khanna, Dinesh / Khanna, Puja P / Fitzgerald, John D / Singh, Manjit K / Bae, Sangmee / Neogi, Tuhina / Pillinger, Michael H / Merill, Joan / Lee, Susan / Prakash, Shraddha / Kaldas, Marian / Gogia, Maneesh / Perez-Ruiz, Fernando / Taylor, Will / Lioté, Frédéric / Choi, Hyon / Singh, Jasvinder A / Dalbeth, Nicola / Kaplan, Sanford / Niyyar, Vandana / Jones, Danielle / Yarows, Steven A / Roessler, Blake / Kerr, Gail / King, Charles / Levy, Gerald / Furst, Daniel E / Edwards, N Lawrence / Mandell, Brian / Schumacher, H Ralph / Robbins, Mark / Wenger, Neil / Terkeltaub, Robert / Anonymous2310738. ·University of Michigan, Ann Arbor, MI, USA. ·Arthritis Care Res (Hoboken) · Pubmed #23024029.

ABSTRACT: -- No abstract --

2 Guideline 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. 2012

Khanna, Dinesh / Fitzgerald, John D / Khanna, Puja P / Bae, Sangmee / Singh, Manjit K / Neogi, Tuhina / Pillinger, Michael H / Merill, Joan / Lee, Susan / Prakash, Shraddha / Kaldas, Marian / Gogia, Maneesh / Perez-Ruiz, Fernando / Taylor, Will / Lioté, Frédéric / Choi, Hyon / Singh, Jasvinder A / Dalbeth, Nicola / Kaplan, Sanford / Niyyar, Vandana / Jones, Danielle / Yarows, Steven A / Roessler, Blake / Kerr, Gail / King, Charles / Levy, Gerald / Furst, Daniel E / Edwards, N Lawrence / Mandell, Brian / Schumacher, H Ralph / Robbins, Mark / Wenger, Neil / Terkeltaub, Robert / Anonymous2300738. ·University of Michigan, Ann Arbor, MI, USA. ·Arthritis Care Res (Hoboken) · Pubmed #23024028.

ABSTRACT: -- No abstract --

3 Review The impact of gout guidelines. 2015

Wise, Eric / Khanna, Puja P. ·Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA. ·Curr Opin Rheumatol · Pubmed #25784381.

ABSTRACT: PURPOSE OF REVIEW: This review discusses the impact of recent treatment guidelines for the management of gout and the barriers to treating gout patients. RECENT FINDINGS: Multiple guidelines for both the treatment and prevention of gout have been put forth in the last decade including those from the British Rheumatism Society; the European League Against Rheumatism; the Multinational Evidence, Expertise, Exchange Initiative; the Japanese Society of Gout and Nucleic Acid Metabolism; the American College of Rheumatology. These guidelines are designed to facilitate the management of gout by providers with key recommendations for the management of hyperuricemia, which is the greatest risk factor for developing gout. However, despite the extant guidelines, overall adherence to recommendations and uptake have been slow and initiation of urate-lowering therapy, titration of dosing, and monitoring of serum urate is infrequent. Greater education in proper management as well as increased awareness of new treatment strategies appear to be the primary reasons for this gap and offer avenues for improvement in management as well as areas for further research. SUMMARY: Gout remains a treatment challenge for both acute and chronic disease. Despite the availability of management guidelines, primary care providers are struggling with appropriate management of the disease. More research tools and strategies are needed to improve overall outcomes and quality of care.

4 Review Imaging as an Outcome Measure in Gout Studies: Report from the OMERACT Gout Working Group. 2015

Grainger, Rebecca / Dalbeth, Nicola / Keen, Helen / Durcan, Laura / Lawrence Edwards, N / Perez-Ruiz, Fernando / Diaz-Torne, Cesar / Singh, Jasvinder A / Khanna, Dinesh / Simon, Lee S / Taylor, William J. ·From the Department of Medicine, University of Otago Wellington, Wellington; Department of Medicine, University of Auckland, New Zealand; Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Medicine, University of Florida, Gainesville, Florida, USA; Rheumatology Division, Hospital Universitario Cruces and BioCruces Health Research Institute, Vizcaya; Division of Rheumatology, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham, Birmingham, Alabama; Division of Rheumatology, Department of Medicine, University of Michigan, Ann Arbor, Michigan; SDG LLC, Cambridge, Massachusetts, USA.R. Grainger, PhD, FRACP, Senior Lecturer, Rheumatologist, Department of Medicine, University of Otago Wellington; N. Dalbeth, MD, FRACP, Associate Professor, Department of Medicine, University of Auckland; L. Durcan, Rheumatology Fellow, MD, Mater Misericordiae University Hospital; H. Keen, PhD, Associate Professor, School of Medicine and Pharmacology, University of Western Australia; N.L. Edwards, MD, Professor of Medicine, Department of Medicine, University of Florida; F. Perez-Ruiz, MD, Professor, Rheumatology Division, Hospital Universitario Cruces and BioCruces Health Research Institute; C. Diaz-Torne, PhD, Associate Professor and Rheumatologist; J.A. Singh, MBBS, MPH, Associate Professor of Medicine; Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham; D. Khanna, MD, MSc, Associate Professor of Medicine, Division of Rheumatology, Department of Medicine, University of Michigan; L.S. Simon, MD, Principal Advisor, SDG LLC; W.J. Taylor, PhD, FRACP, Associate Professor and Rheumatologist, Department of Medicine, University of Otago Wellington. ·J Rheumatol · Pubmed #25641895.

ABSTRACT: OBJECTIVE: The gout working group at the Outcome Measures in Rheumatology (OMERACT) 12 meeting in 2014 aimed to determine which imaging modalities show the most promise for use as measurement instruments for outcomes in studies of people with chronic gout and to identify the key foci for future research about the performance of these imaging techniques with respect to the OMERACT filter 2.0. METHODS: During the gout session, a systematic literature review of the data addressing imaging modalities including plain radiography (XR), conventional computed tomography (CT), dual-energy computed tomography (DECT), magnetic resonance imaging (MRI), and ultrasound (US) and the fulfillment of the OMERACT filter 2.0 was presented. RESULTS: The working group identified 3 relevant domains for imaging in gout studies: urate deposition (tophus burden), joint inflammation, and structural joint damage. CONCLUSION: The working group prioritized gaps in the data and identified a research agenda.

5 Review Evolution of management of gout: a comparison of recent guidelines. 2015

Khanna, Puja P / FitzGerald, John. ·aDivision of Rheumatology, University of Michigan, Ann Arbor, Michigan bDavid Geffen School of Medicine, UCLA, Los Angeles, California, USA. ·Curr Opin Rheumatol · Pubmed #25611299.

ABSTRACT: PURPOSE OF REVIEW: There have been several guidelines on the management of gout over the last decade; however, inconsistencies between them create confusion for practitioners. This review highlights areas of agreement between guidelines and discusses data where disagreements exist. RECENT FINDINGS: For acute gout, the guidelines agree that anti-inflammatory treatment should start as soon as possible, preferably within 24 hours. Older guidelines preferred NSAIDs or colchicine over steroids, but newer ones leave the choice of agent to the physician. For colchicine, all guidelines recommend using low dose. Intra-articular, oral or intramuscular steroids are all described as effective. For management of hyperuricemia, indications for initiating urate-lowering therapy (ULT) have become more inclusive over the years by requiring lower burden of disease severity or including patient comorbidities. Probenecid has fallen out of favour with most guidelines favouring allopurinol over febuxostat. Although there is a disagreement about timing of initiation for ULT, guidelines recommend treating to target of serum urate (sUA) less than 6 mg/dl, and less than 5 mg/dl for patients with more severe disease. Concurrent anti-inflammatory prophylaxis has gained strong support over the years. SUMMARY: Most guidelines are in agreement with recommendations for management of gout and most changes have been directional and evolutionary.

6 Review Treatment of acute gout: a systematic review. 2014

Khanna, Puja P / Gladue, Heather S / Singh, Manjit K / FitzGerald, John D / Bae, Sangmee / Prakash, Shraddha / Kaldas, Marian / Gogia, Maneesh / Berrocal, Veronica / Townsend, Whitney / Terkeltaub, Robert / Khanna, Dinesh. ·Division of Rheumatology, University of Michigan, 300 North Ingalls, 7D13, Ann Arbor, MI 48109-5422. Electronic address: pkhanna@umich.edu. · Emory University, Atlanta, GA. · Rochester General Health System, Rochester, NY. · David Geffen School of Medicine, UCLA, Los Angeles, CA. · Division of Rheumatology, University of Michigan, 300 North Ingalls, 7D13, Ann Arbor, MI 48109-5422. · Division of Rheumatology, University of Michigan, 300 North Ingalls, 7D13, Ann Arbor, MI 48109-5422; Taubman Health Science Library, University of Michigan, 300 North Ingalls, 7D13, Ann Arbor, MI 48109-5422. · VAMC/UCSD, La Jolla, CA. ·Semin Arthritis Rheum · Pubmed #24650777.

ABSTRACT: OBJECTIVE: Acute gout is traditionally treated with NSAIDs, corticosteroids, and colchicine; however, subjects have multiple comorbidities that limit the use of some conventional therapies. We systematically reviewed the published data on the pharmacologic and non-pharmacologic agents used for the treatment of acute gouty arthritis. METHODS: A systematic search was performed using PubMed and Cochrane database through May 2013. We included only randomized controlled trials (RCTs) that included NSAIDs, corticosteroids, colchicine, adrenocorticotropic hormone (ACTH), interleukin-1 (IL-1) inhibitors, topical ice, or herbal supplements. RESULTS: Thirty articles were selected for systematic review. The results show that NSAIDs and COX-2 inhibitors are effective agents for the treatment of acute gout attacks. Systemic corticosteroids have similar efficacy to therapeutic doses of NSAIDs, with studies supporting oral and intramuscular use. ACTH is suggested to be efficacious in acute gout. Oral colchicine demonstrated to be effective, with low-dose colchicine demonstrating a comparable tolerability profile as placebo and a significantly lower side effect profile to high-dose colchicine. The IL-1β inhibitory antibody, canakinumab, was effective for the treatment of acute attacks in subjects refractory to and in those with contraindications to NSAIDs and/or colchicine. However, rilonacept was demonstrated to be not as effective, and there are no RCTs for the use of anakinra. CONCLUSION: NSAIDs, COX-2 selective inhibitors, corticosteroids, colchicine, ACTH, and canakinumab have evidence to suggest efficacy in treatment of acute gout.

7 Review Outcome measures in acute gout: a systematic literature review. 2014

Dalbeth, Nicola / Zhong, Cathy S / Grainger, Rebecca / Khanna, Dinesh / Khanna, Puja P / Singh, Jasvinder A / McQueen, Fiona M / Taylor, William J. ·From the Department of Medicine, University of Auckland, Auckland; Department of Medicine, University of Otago, Wellington, New Zealand; Division of Rheumatology, University of Michigan, Ann Arbor, Michigan; and Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham, Birmingham, Alabama, USA. ·J Rheumatol · Pubmed #24334652.

ABSTRACT: OBJECTIVE: Five core domains have been endorsed by Outcome Measures in Rheumatology (OMERACT) for acute gout: pain, joint swelling, joint tenderness, patient global assessment, and activity limitation. We evaluated instruments for these domains according to the OMERACT filter: truth, feasibility, and discrimination. METHODS: A systematic search strategy for instruments used to measure the acute gout core domains was formulated. For each method, articles were assessed by 2 reviewers to summarize information according to the specific components of the OMERACT filter. RESULTS: Seventy-seven articles and abstracts met the inclusion criteria. Pain was most frequently reported (76 studies, 20 instruments). The pain instruments used most often were 100 mm visual analog scale (VAS) and 5-point Likert scale. Both methods have high feasibility, face and content validity, and within- and between-group discrimination. Four-point Likert scales assessing index joint swelling and tenderness have been used in numerous acute gout studies; these instruments are feasible, with high face and content validity, and show within- and between-group discrimination. Five-point Patient Global Assessment of Response to Treatment (PGART) scales are feasible and valid, and show within- and between-group discrimination. Measures of activity limitations were infrequently reported, and insufficient data were available to make definite assessments of the instruments for this domain. CONCLUSION: Many different instruments have been used to assess the acute gout core domains. Pain VAS and 5-point Likert scales, 4-point Likert scales of index joint swelling and tenderness and 5-point PGART instruments meet the criteria for the OMERACT filter.

8 Review Advanced imaging in gout. 2013

Girish, Gandikota / Glazebrook, Katrina N / Jacobson, Jon A. ·Department of Radiology, University of Michigan Hospitals, 1500 E Medical Center Dr, TC 2910, Ann Arbor, MI 48109-0326, USA. ggirish@umich.edu ·AJR Am J Roentgenol · Pubmed #23971443.

ABSTRACT: OBJECTIVE: The purpose of this article is to describe the role of advanced imaging using ultrasound, CT, and MRI in the assessment and diagnosis of gout. CONCLUSION: Dual-energy CT can quantitatively identify monosodium urate crystal deposits with high sensitivity and specificity within joints, tendons, and periarticular soft tissues. There are several characteristic ultrasound imaging findings, which include visualization of echogenic monosodium urate crystal deposition, tophus, and adjacent erosions. MRI is sensitive in showing soft-tissue and osseous abnormalities of gout, although the imaging findings are not specific. Gout commonly involves specific joints and anatomic structures, and knowledge of these sites and imaging appearances are clues to the correct diagnosis.

9 Clinical Trial Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial. 2017

Dalbeth, Nicola / Jones, Graeme / Terkeltaub, Robert / Khanna, Dinesh / Kopicko, Jeff / Bhakta, Nihar / Adler, Scott / Fung, Maple / Storgard, Chris / Baumgartner, Scott / Perez-Ruiz, Fernando. ·University of Auckland, Auckland, New Zealand. · University of Tasmania, Hobart, Tasmania, Australia. · University of California, San Diego. · University of Michigan, Ann Arbor. · Ardea Biosciences, Inc., San Diego, California. · AstraZeneca Pharmaceuticals, Gaithersburg, Maryland. · Hospital Universitario Cruces, Baracaldo, Spain. ·Arthritis Rheumatol · Pubmed #28597604.

ABSTRACT: OBJECTIVE: To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12-month phase III trial in patients with tophaceous gout. METHODS: Patients with serum urate (UA) ≥8.0 mg/dl (≥6.0 mg/dl with urate-lowering therapy) and ≥1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients achieving a serum UA level of <5.0 mg/dl (month 6). The key secondary end point was the proportion of patients with complete resolution of ≥1 target tophus (month 12). Other end points included the percentage change in total target tophi area. Safety assessments included adverse events and laboratory data. RESULTS: Patients (n = 324) were predominantly male, with a mean age of 54.1 years. Significantly more patients achieved the serum UA target by month 6 with the addition of lesinurad 400 mg (76.1%; P < 0.0001), but not 200 mg (56.6%; P = 0.13), to the febuxostat therapy as compared with febuxostat alone (46.8%). At all other time points, significantly more patients in the lesinurad 200 mg group achieved the serum UA target. The number of patients with complete tophus resolution was not different between groups. Treatment with lesinurad (200 mg and 400 mg) plus febuxostat reduced the total target tophi area as compared with febuxostat alone (50.1% and 52.9% versus 28.3%, respectively; P < 0.05). Safety was generally comparable with that of febuxostat alone, except for higher rates of predominantly reversible elevations in the serum creatinine level, particularly with lesinurad 400 mg. CONCLUSION: Treatment with lesinurad in combination with febuxostat demonstrated superior lowering of serum UA levels as compared with febuxostat alone, with clinically relevant added effects on tophi and an acceptable safety profile with lesinurad 200 mg in patients with tophaceous gout warranting additional therapy.

10 Clinical Trial Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study). 2017

Bardin, Thomas / Keenan, Robert T / Khanna, Puja P / Kopicko, Jeff / Fung, Maple / Bhakta, Nihar / Adler, Scott / Storgard, Chris / Baumgartner, Scott / So, Alexander. ·Rhumatologie, Lariboisière Hospital, and Université Paris Diderot Sorbonne Cité, Paris, France. · Division of Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA. · Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA. · Biometrics, Ardea Biosciences, Inc., San Diego, California, USA. · Research & Development, Ardea Biosciences, Inc., San Diego, California, USA. · Research & Development, AstraZeneca Pharmaceuticals, Gaithersburg, Maryland, USA. · Medical Affairs, Ardea Biosciences, Inc., San Diego, California, USA. · Service de rhumatologie, Université de Lausanne, Lausanne, Switzerland. ·Ann Rheum Dis · Pubmed #27821644.

ABSTRACT: OBJECTIVES: Determine the efficacy and safety of daily lesinurad (200 or 400 mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial. METHODS: Patients on allopurinol ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0 mg/dL (<357 µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data. RESULTS: Patients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200 mg+allopurinol, in 9.5% of lesinurad 400 mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively. CONCLUSION: Lesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy. TRIAL REGISTRATION NUMBER: NCT01493531.

11 Article Gout: a patrician malady no more. 2018

Khanna, Puja P. ·Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-5422, USA. Electronic address: pkhanna@umich.edu. ·Lancet Diabetes Endocrinol · Pubmed #29571506.

ABSTRACT: -- No abstract --

12 Article Health care utilization in patients with gout: a prospective multicenter cohort study. 2017

Singh, Jasvinder A / Bharat, Aseem / Khanna, Dinesh / Aquino-Beaton, Cleopatra / Persselin, Jay E / Duffy, Erin / Elashoff, David / Khanna, Puja P. ·Department of Medicine at School of Medicine, and Division of Epidemiology at School of Public Health, University of Alabama at Birmingham (UAB), Faculty Office Tower 805B, 510 20th Street S, Birmingham, 35294, AL, USA. Jasvinder.md@gmail.com. · Medicine Service, Birmingham VA Medical Center, Birmingham, AL, USA. Jasvinder.md@gmail.com. · Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA. Jasvinder.md@gmail.com. · Medicine Service, Birmingham VA Medical Center, Birmingham, AL, USA. · University of Michigan, Ann Arbor, MI, USA. · VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA. · University of California, Los Angeles, CA, USA. · VA Ann Arbor Healthcare System, Ann Arbor, MI, USA. ·BMC Musculoskelet Disord · Pubmed #28569193.

ABSTRACT: BACKGROUND: All published studies of health care utilization in gout have been cross-sectional to date, and most used a patient-reported diagnosis of gout. Our objective was to assess health care utilization and its predictors in patients with physician-confirmed gout in a prospective cohort study. METHODS: In a multi-center prospective cohort study of U.S. veterans with rheumatologist-confirmed gout (N = 186; two centers), we assessed patient self-reported overall and gout-specific health care utilization with the Gout Assessment Questionnaire (GAQ) every 3-months for a 9-month period. Comparisons were made using the student's t test or the chi-square, Wilcoxon rank sum test or Fisher exact test, as appropriate. Mixed effects Poisson regression was used to assess potential correlates of gout-related health care utilization. RESULTS: Mean age was 64.6 years, 98% were men, 13% Hispanic or Latino, 32% were African-American, 6% did not graduate high school, mean serum urate was 8.3 and mean Deyo-Charlson score was 3.1. During the past year, mean gout-related visits were as follows: rheumatologist, 1.5; primary care physician, 2 visits; ≥1 inpatient visits, 7%; ≥1 ER visits, 26%; and urgent care/walk-in visit, 33%. In longitudinal analyses, African-American race and gout flares in the last 3 months were associated with significantly higher rate ratio of gout-related outpatient visits. African-American race and lack of college education were associated with significantly higher rate ratio for gout-related urgent visits and overnight stays. CONCLUSIONS: African-American race and recent gout flares were associated with higher outpatient utilization and African-American race and no college education with higher urgent or inpatient utilization. Future studies should examine whether modifiable predictors of utilization can be targeted to reduce healthcare utilization in patients with gout.

13 Article Racial differences in health-related quality of life and functional ability in patients with gout. 2017

Singh, Jasvinder A / Bharat, Aseem / Khanna, Dinesh / Aquino-Beaton, Cleopatra / Persselin, Jay E / Duffy, Erin / Elashoff, David / Khanna, Puja P. ·Medicine Service, Birmingham VA Medical Center Jasvinder.md@gmail.com. · Department of Medicine, School of Medicine. · Division of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL. · Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN. · Department of Medicine, University of Michigan, Ann Arbor, MI. · Department of Biostatistics, VA Greater Los Angeles Healthcare System. · Department of Medicine, University of California, Los Angeles, CA. · Department of Medicine, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA. ·Rheumatology (Oxford) · Pubmed #28028159.

ABSTRACT: OBJECTIVE: To compare the health-related quality of life (HRQOL) and the functional ability by race in patients with gout. METHODS: In a 9-month prospective cohort multicentre study, patients with gout self-reported race, dichotomized as Caucasian or African American (others excluded). We calculated HRQOL/function scores adjusted for age, study site and college education for Short Form-36 (SF-36; generic HRQOL), Gout Impact Scale (GIS; disease-specific HRQOL) and HAQ-disability index (HAQ-DI; functional ability). Longitudinally adjusted scores were computed using multivariable mixed-effect regression models with a random patient effect and fixed sequential visit effect (3-monthly visits). RESULTS: Compared with Caucasians (n = 107), African Americans (n = 60) with gout were younger (61.1 vs 67.3 years) and had higher median baseline serum urate (9.0 vs 7.9 mg/dl) (P < 0.01). African Americans with gout had worse HRQOL scores on three SF-36 domains, the mental component summary (MCS) and two of the five GIS scales than Caucasians [mean (se); P ⩽ 0.02 for all]: SF-36 mental health, 39.7 (1.1) vs 45.2 (0.9); SF-36 role emotional, 42.1 (4.2) vs 51.4 (4.2); SF-36 social functioning, 36.0 (1.1) vs 40.0 (0.9) (P = 0.04); SF-36 MCS, 43.2 (3.1) vs 50.0 (3.2); GIS unmet treatment need, 37.6 (1.6) vs 31.5 (1.4); and GIS concern during attacks, 53.3 (3.7) vs 47.4 (3.7). Differences between the respective HAQ-DI total scores were not statistically significant; 0.98 (0.1) vs 0.80 (1.0) (P = 0.11). Racial differences in SF-36 mental health, role emotional and MCS scales exceeded, and for HAQ-DI approached, the minimal clinically important difference thresholds. CONCLUSIONS: African Americans with gout have significantly worse HRQOL compared with Caucasians. Further research is necessary in the form of studies targeted at African Americans on how best to improve these outcomes.

14 Article Performance of Gout Impact Scale in a longitudinal observational study of patients with gout. 2016

Wallace, Beth / Khanna, Dinesh / Aquino-Beaton, Cleopatra / Singh, Jasvinder A / Duffy, Erin / Elashoff, David / Khanna, Puja P. ·Division of Rheumatology, University of Michigan, Ann Arbor, MI. · Department of Medicine/Division of Rheumatology, VA Greater Los Angeles Healthcare System, Los Angeles, CA. · Department of Medicine/Division of Rheumatology, University of Alabama and Birmingham VA, Birmingham, AL. · University of California Los Angeles Department of Medicine Statistics Core, Los Angeles, CA and. · Division of Rheumatology, University of Michigan, Ann Arbor, MI, Department of Medicine/Division of Rheumatology, Ann Arbor VA Medical Center, Ann Arbor, MI, USA pkhanna@med.umich.edu. ·Rheumatology (Oxford) · Pubmed #26888852.

ABSTRACT: OBJECTIVE: The aim was to evaluate the reliability, validity and responsiveness to change of the Gout Impact Scale (GIS), a disease-specific measure of patient-reported outcomes, in a multicentre longitudinal prospective cohort of gout patients. METHODS: Subjects completed the GIS, a 24-item instrument with five scales: Concern Overall, Medication Side Effects, Unmet Treatment Need, Well-Being during Attack, and Concern Over Attack. The total GIS score was calculated by averaging the GIS scale scores. HAQ-Disability Index (HAQ-DI), Short Form (SF)-36 physical and mental component summaries (PCS and MCS) and physician and patient gout severity assessments were also completed. Reliability was assessed with Cronbach's α. Baseline GIS scores were compared in subjects with and without gout attacks in the past 3 months using Wilcoxon rank sum tests. Multivariate linear regression was used to evaluate predictors of total GIS. Pearson's correlation coefficients 0.24-0.36 were considered moderate and >0.37 considered large. The effect size for responsiveness to change was interpreted as follows: 0.20-0.49 small, 0.50-0.79 medium and >0.79 large. RESULTS: In 147 subjects, reliability was acceptable for total GIS (0.93) and all GIS scales (0.82-0.94) except Medication Side Effects and Unmet Treatment Need. Total GIS and all scales except Medication Side Effects discriminated between subjects with and without recent gout attacks (P < 0.05). Total GIS showed moderate-to-large correlations with HAQ-DI, SF-36 PCS and MCS (0.33-0.46). Improvement in total GIS tracked with improved physician and patient severity scores. Worsening physician severity score and recent gout attack predicted worsening total GIS. CONCLUSION: Total GIS score is reliable, valid and responsive to change in patients with gout, and differentiates between subjects with and without recent gout attacks.

15 Article A world of hurt: failure to achieve treatment goals in patients with gout requires a paradigm shift. 2016

Khanna, Puja / Khanna, Dinesh / Storgard, Chris / Baumgartner, Scott / Morlock, Robert. ·a Department of Internal Medicine , University of Michigan , Ann Arbor , MI , USA. · b Research & Development, Ardea Biosciences, Inc. , San Diego , CA , USA. · c Medical Affairs, Ardea Biosciences, Inc. , San Diego , CA , USA. · d Health Outcomes, Ardea Biosciences, Inc. , San Diego , CA , USA. ·Postgrad Med · Pubmed #26578028.

ABSTRACT: BACKGROUND: Gout continues to be underdiagnosed and poorly managed despite the potential for cure. US and European management guidelines recommend treating to target serum urate (sUA) levels of <6 mg/dL (or <5 mg/dL to durably improve severe symptoms), with use of regular sUA monitoring, but studies suggest relatively poor adherence to these recommendations. This study investigates the real-world state of gout management in the United States by describing the characteristics of a large patient population treated in primary care and rheumatology settings. METHODS: A retrospective chart audit, conducted among 124 primary care physicians and 125 rheumatologists, included 1245 patients with gout. Physicians completed structured case report forms capturing 12 months of sUA laboratory values, flare counts, comorbidities, types and doses of treatment, treatment duration, diagnosis date, physician specialty and socio-demographic factors. Focusing on the xanthine oxidase inhibitors (n = 858), descriptive statistics and multivariate models characterized relationships between patient characteristics, disease control, and treatment. RESULTS: Only 83 (11%) patients achieved disease control, defined as a 12-month average sUA ≤6 mg/dL, no flares, and no tophi. Patients with greatest disease severity (defined as sUA >6 mg/dL, ≥2 flares per year, and tophi) were more likely to have kidney disease and other comorbidities. In a multivariate model, predictors of more severe gout were rheumatologist (vs primary care) management, febuxostat (vs allopurinol) use and presence of comorbid conditions. CONCLUSION: Our findings confirm the inadequacy of gout management in the real-world setting. Regular monitoring, including sUA measurement as recommended in guidelines, is important to assess gout control. Our analyses also demonstrate that patients with more severe gout are more likely to have comorbid conditions, be treated by a specialist and use newer therapies.

16 Article Development of Preliminary Remission Criteria for Gout Using Delphi and 1000Minds Consensus Exercises. 2016

de Lautour, Hugh / Taylor, William J / Adebajo, Ade / Alten, Rieke / Burgos-Vargas, Ruben / Chapman, Peter / Cimmino, Marco A / da Rocha Castelar Pinheiro, Geraldo / Day, Ric / Harrold, Leslie R / Helliwell, Philip / Janssen, Matthijs / Kerr, Gail / Kavanaugh, Arthur / Khanna, Dinesh / Khanna, Puja P / Lin, Chingtsai / Louthrenoo, Worawit / McCarthy, Geraldine / Vazquez-Mellado, Janitzia / Mikuls, Ted R / Neogi, Tuhina / Ogdie, Alexis / Perez-Ruiz, Fernando / Schlesinger, Naomi / Ralph Schumacher, H / Scirè, Carlo A / Singh, Jasvinder A / Sivera, Francisca / Slot, Ole / Stamp, Lisa K / Tausche, Anne-Kathrin / Terkeltaub, Robert / Uhlig, Till / van de Laar, Mart / White, Douglas / Yamanaka, Hisashi / Zeng, Xuejun / Dalbeth, Nicola. ·Auckland District Health Board, Auckland, New Zealand. · University of Otago, Wellington, New Zealand. · University of Sheffield, Sheffield, UK. · Schlosspark-Klinik, Charité, University Medicine Berlin, Berlin, Germany. · Hospital General de México, Mexico City, Mexico. · Christchurch Hospital, Christchurch, New Zealand. · Università di Genova, Genova, Italy. · Pedro Ernesto University Hospital, Rio de Janeiro, Brazil. · University of New South Wales and St Vincent's Hospital, Sydney, Australia. · University of Massachusetts Medical School, Worcester, and Corrona, LLC, Southborough. · Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK. · Rijnstate Hospital, Arnhem, The Netherlands. · Veterans Affairs Medical Center, Georgetown and Howard University Hospitals, Washington, DC. · University of California School of Medicine, San Diego. · University of Michigan, Ann Arbor. · University of Michigan and Ann Arbor VA Medical Center, Ann Arbor. · Taichung Veteran's General Hospital, Taichung, Taiwan. · Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. · Mater Misericordiae University Hospital and University College, Dublin, Ireland. · Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha. · Boston University School of Medicine, Boston, Massachusetts. · University of Pennsylvania, Philadelphia. · Hospital Universitario Cruces, OSI-EEC, and Biocruces Health Research Institute, Biscay, Spain. · Rutgers University Robert Wood Johnson Medical School, New Brunswick, New Jersey. · IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy. · University of Alabama at Birmingham and the Birmingham VA Medical Center, Birmingham. · Hospital General Universitario Elda, Elda, Spain. · Copenhagen University Hospital Glostrup, Glostrup, Denmark. · University of Otago, Christchurch, New Zealand. · University Hospital Carl Gustav Carus, Dresden, Germany. · University of California San Diego VA Medical Center, La Jolla. · National Advisory Unit on Rehabilitation in Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Universiteit Twente, Erschede, The Netherlands. · Waikato DHB and Waikato Clinical School, University of Auckland, Hamilton, New Zealand. · Tokyo Women's Medical University, Tokyo, Japan. · Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China. · University of Auckland and Auckland District Health Board, Auckland, New Zealand. ·Arthritis Care Res (Hoboken) · Pubmed #26414176.

ABSTRACT: OBJECTIVE: To establish consensus for potential remission criteria to use in clinical trials of gout. METHODS: Experts (n = 88) in gout from multiple countries were invited to participate in a web-based questionnaire study. Three rounds of Delphi consensus exercises were conducted using SurveyMonkey, followed by a discrete-choice experiment using 1000Minds software. The exercises focused on identifying domains, definitions for each domain, and the timeframe over which remission should be defined. RESULTS: There were 49 respondents (56% response) to the initial survey, with subsequent response rates ranging from 57% to 90%. Consensus was reached for the inclusion of serum urate (98% agreement), flares (96%), tophi (92%), pain (83%), and patient global assessment of disease activity (93%) as measurement domains in remission criteria. Consensus was also reached for domain definitions, including serum urate (<0.36 mm), pain (<2 on a 10-point scale), and patient global assessment (<2 on a 10-point scale), all of which should be measured at least twice over a set time interval. Consensus was not achieved in the Delphi exercise for the timeframe for remission, with equal responses for 6 months (51%) and 1 year (49%). In the discrete-choice experiment, there was a preference towards 12 months as a timeframe for remission. CONCLUSION: These consensus exercises have identified domains and provisional definitions for gout remission criteria. Based on the results of these exercises, preliminary remission criteria are proposed with domains of serum urate, acute flares, tophus, pain, and patient global assessment. These preliminary criteria now require testing in clinical data sets.

17 Article 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. 2015

Neogi, Tuhina / Jansen, Tim L Th A / Dalbeth, Nicola / Fransen, Jaap / Schumacher, H Ralph / Berendsen, Dianne / Brown, Melanie / Choi, Hyon / Edwards, N Lawrence / Janssens, Hein J E M / Lioté, Frédéric / Naden, Raymond P / Nuki, George / Ogdie, Alexis / Perez-Ruiz, Fernando / Saag, Kenneth / Singh, Jasvinder A / Sundy, John S / Tausche, Anne-Kathrin / Vaquez-Mellado, Janitzia / Yarows, Steven A / Taylor, William J. ·Boston University School of Medicine, Boston, Massachusetts, USA. · Viecuri Medical Center, Venlo, The Netherlands Radboud University Medical Center, Nijmegen, The Netherlands. · University of Auckland, Auckland, New Zealand. · Radboud University Medical Center, Nijmegen, The Netherlands. · University of Pennsylvania, Philadelphia, Pennsylvania, USA. · University of Otago, Wellington, New Zealand. · University of Florida, Gainesville, Florida, USA. · INSERM UMR 1132, Hôpital Lariboisière, AP-HP, and Université Paris Diderot, Sorbonne Paris Cité, Paris, France. · McMaster University Medical Centre, Hamilton, Ontario, Canada. · University of Edinburgh, Edinburgh, UK. · Hospital Universitario Cruces and BioCruces Health Research Institute, Vizcaya, Spain. · University of Alabama at Birmingham, Birmingham, Alabama, USA. · Birmingham VA Medical Center and University of Alabama at Birmingham, and Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · Duke University and Duke University Medical Center, Durham, North Carolina, USA Gilead Sciences, Foster City, California, USA. · University Hospital Carl Gustav Carus, Dresden, Germany. · Hospital General de Mexico, Mexico City, Mexico. · University of Michigan Health System, Chelsea. ·Ann Rheum Dis · Pubmed #26359487.

ABSTRACT: OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multi-criterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least one episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (ie, synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy CT, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSIONS: The new classification criteria, developed using a data-driven and decision-analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.

18 Article 2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. 2015

Neogi, Tuhina / Jansen, Tim L Th A / Dalbeth, Nicola / Fransen, Jaap / Schumacher, H Ralph / Berendsen, Dianne / Brown, Melanie / Choi, Hyon / Edwards, N Lawrence / Janssens, Hein J E M / Lioté, Frédéric / Naden, Raymond P / Nuki, George / Ogdie, Alexis / Perez-Ruiz, Fernando / Saag, Kenneth / Singh, Jasvinder A / Sundy, John S / Tausche, Anne-Kathrin / Vazquez-Mellado, Janitzia / Yarows, Steven A / Taylor, William J. ·Boston University School of Medicine, Boston, Massachusetts. · Viecuri Medical Center, Venlo, The Netherlands, and Radboud University Medical Center, Nijmegen, The Netherlands. · University of Auckland, Auckland, New Zealand. · Radboud University Medical Center, Nijmegen, The Netherlands. · University of Pennsylvania, Philadelphia. · University of Otago, Wellington, New Zealand. · University of Florida, Gainesville. · Frédéric Lioté, MD, PhD: INSERM UMR 1132, Hôpital Lariboisière, AP-HP, and Université Paris Diderot, Sorbonne Paris Cité, Paris, France. · McMaster University Medical Centre, Hamilton, Ontario, Canada. · University of Edinburgh, Edinburgh, UK. · Hospital Universitario Cruces and BioCruces Health Research Institute, Vizcaya, Spain. · University of Alabama at Birmingham. · Birmingham VA Medical Center and University of Alabama at Birmingham, and Mayo Clinic College of Medicine, Rochester, Minnesota. · Gilead Sciences, Foster City, California). · University Hospital Carl Gustav Carus, Dresden, Germany. · Hospital General de Mexico, Mexico City, Mexico. · University of Michigan Health System, Chelsea. ·Arthritis Rheumatol · Pubmed #26352873.

ABSTRACT: OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy computed tomography, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSION: The new classification criteria, developed using a data-driven and decision analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.

19 Article OMERACT endorsement of measures of outcome for studies of acute gout. 2014

Singh, Jasvinder A / Taylor, William J / Dalbeth, Nicola / Simon, Lee S / Sundy, John / Grainger, Rebecca / Alten, Rieke / March, Lyn / Strand, Vibeke / Wells, George / Khanna, Dinesh / McQueen, Fiona / Schlesinger, Naomi / Boonen, Annelies / Boers, Maarten / Saag, Kenneth G / Schumacher, H Ralph / Edwards, N Lawrence. ·From Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Medicine, University of Otago, Wellington; Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; SDG LLC, Cambridge, Massachusetts,; Duke University School of Medicine, Durham, North Carolina, USA, and Duke-National University of Singapore Graduate Medical School, Singapore; Schlosspark-Klinik Teaching Hospital of the Charité, University Medicine Berlin, Berlin, Germany; University of Sydney Institute of Bone and Joint Research and Department of Rheumatology, Royal North Shore Hospital, Sydney, Australia; Stanford University Division of Immunology and Rheumatology, Portolo Valley, California, USA; University of Ottawa, London, Ontario, Canada; University of Michigan Medical School, Ann Arbor, Michigan, USA; University of Auckland, Department of Molecular Medicine and Pathology, Grafton, Auckland, New Zealand; Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA; Maastricht University Medical Center, Division of Rheumatology, and Caphri Research Institute, University Maastricht; VU University Medical Center, Amsterdam, the Netherlands; University of Pennsylvania and Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Rheumatology, University of Florida, Gainsville, Florida, USA. ·J Rheumatol · Pubmed #24334651.

ABSTRACT: OBJECTIVE: To determine the extent to which participants at the Outcome Measures in Rheumatology (OMERACT) 11 meeting agree that instruments used in clinical trials to measure OMERACT core outcome domains in acute gout fulfill OMERACT filter requirements of truth, discrimination, and feasibility; and where future research efforts need to be directed. METHODS: Results of a systematic literature review and analysis of individual-level data from recent clinical studies of acute gout were presented to OMERACT participants. The information was discussed in breakout groups, and opinion was defined by subsequent voting in a plenary session. Endorsement was defined as at least 70% of participants voting in agreement with the proposition (where the denominator excluded those participants who did not vote or who voted "don't know"). RESULTS: The following measures were endorsed for use in clinical trials of acute gout: (1) 5-point Likert scale and/or visual analog scale (0 to 100 mm) to measure pain; (2) 4-point Likert scale for joint swelling; (3) 4-point Likert scale for joint tenderness; and (4) 5-point Likert scale for patient global assessment of response to treatment. Measures for the activity limitations domain were not endorsed. CONCLUSION: Measures of pain, joint swelling, joint tenderness, and patient global assessment in acute gout were endorsed at OMERACT 11. These measures should now be used in clinical trials of acute gout.

20 Article Tophi and frequent gout flares are associated with impairments to quality of life, productivity, and increased healthcare resource use: Results from a cross-sectional survey. 2012

Khanna, Puja P / Nuki, George / Bardin, Thomas / Tausche, Anne-Kathrin / Forsythe, Anna / Goren, Amir / Vietri, Jeffrey / Khanna, Dinesh. ·University of Michigan, MI, USA. ·Health Qual Life Outcomes · Pubmed #22999027.

ABSTRACT: BACKGROUND: The prevalence of gout is increasing, and most research on the associated burden has focused on serum urate (sUA) levels. The present study quantifies the impact of the presence of tophi and frequency of acute gout attacks on health-related quality of life (HRQOL), productivity, and healthcare resource utilization. METHODS: Patients with self-reported gout (n=620; 338 in US and 282 across France, Germany, and UK) were contacted based on inclusion in the 2010 US and EU National Health and Wellness Surveys (Kantar Health) and the Lightspeed Research ailment panel. Respondents were categorized into mutually-exclusive groups based on number of gout flares experienced in the past 12 months (0/don't recall, 1-2, 3, 4-5, 6+), current presence of tophi (none, 1+, or not sure), and sUA level awareness (yes, no). HRQOL (SF-12v2), healthcare provider visits in the last 6 months, and work productivity and activity impairment (WPAI) were compared across groups. RESULTS: Most patients were males, mean age of 61 years, who reported experiencing at least one acute gout flare in the past 12 months, and 12.3% (n=76) reported presence of tophi. Among the 27.7% (n=172) of patients who were aware of their sUA levels, higher sUA was associated with more flares and tophi. Decreased HRQOL was associated with more frequent flares and presence of tophi. In multivariable models predicting outcomes based on presence of tophi and number of flares, both flares (≥4) and tophi (≥1) were associated with HRQOL decrements on physical and mental component summary scores and health utilities (all p<0.05), after adjustment for age, gender, and time since diagnosis. Flares were also associated with greater activity impairment. CONCLUSIONS: Impairments associated with gout flares and presence of tophi, across patients in the US and EU, underscore the importance of effective management of this potentially curable condition.

21 Article Determinants of vascular function in patients with chronic gout. 2011

Brook, Robert D / Yalavarthi, Srilakshmi / Myles, James D / Khalatbari, Shokoufeh / Hench, Rita / Lustig, Susan / Marder, Wendy / Neidert, Adam / Kaplan, Mariana J. ·Divisions of Rheumatology and Cardiology, Department of Internal Medicine; the Michigan Institute for Clinical Research, University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA. ·J Clin Hypertens (Greenwich) · Pubmed #21366849.

ABSTRACT: Epidemiologic studies have proposed a relationship between hyperuricemia and cardiovascular (CV) risk. However, it is unclear whether uric acid (UA) is an independent risk factor for CV disease (CVD) after controlling for other predisposing conditions. Gout patients might have persistent systemic inflammation, which, in addition to hyperuricemia, may potentiate CVD. This study examined vascular function and markers of CV damage in gout patients when compared with healthy controls. Brachial artery flow-mediated dilatation, arterial compliance, and microvascular function were measured. Circulating apoptotic endothelial cells and endothelial progenitor cells were quantified by FACS and circulating biomarkers of CVD by enzyme-linked immunosorbent assay. Gout patients displayed significant increases in body mass index, C-reactive protein, UA, and triglycerides and decreases in high-density lipoprotein. There were no significant differences in other CV traditional risk factors, adhesion molecules, or chemokines. Gout patients did not differ from controls in vascular function. In univariate and multivariate analysis, UA was not associated with the quantified CV risk parameters. Despite an increase in several CV risk factors, inflammation, and UA, gout patients display normal endothelial function and no increases in biomarkers of CVD. These results do not support the notion that gout is an independent risk factor for premature CVD.

22 Article Expression and function of CXCL16 in a novel model of gout. 2010

Ruth, Jeffrey H / Arendt, Monica D / Amin, M Asif / Ahmed, Salahuddin / Marotte, Hubert / Rabquer, Bradley J / Lesch, Charles / Lee, Solhee / Koch, Alisa E. ·University of Michigan Medical School, Division of Rheumatology, 109 Zina Pitcher Place, 4023 BSRB Box 2200, Ann Arbor, MI 48109-2200, USA. jhruth@umich.edu ·Arthritis Rheum · Pubmed #20506383.

ABSTRACT: OBJECTIVE: To better define the activity of soluble CXCL16 in the recruitment of polymorphonuclear neutrophils (PMNs) in vivo, utilizing a novel animal model of gout involving engraftment of SCID mice with normal human synovial tissue (ST) injected intragraft with gouty human synovial fluid (SF). METHODS: For in vitro studies, a modified Boyden chemotaxis system was used to identify CXCL16 as an active recruitment factor for PMNs in gouty SF. Migration of PMNs could be reduced by neutralization of CXCL16 activity in gouty SF. For in vivo analyses, fluorescent dye-tagged PMNs were injected intravenously into SCID mice while, simultaneously, diluted gouty SF containing CXCL16, or depleted of CXCL16 by antibody blocking, was administered intragraft. In addition, the receptor for CXCL16, CXCR6, was inhibited by incubating PMNs with a neutralizing anti-CXCR6 antibody prior to injection into the mouse chimeras. Recruitment of PMNs to the gouty SF-injected normal human ST was then examined in this SCID mouse chimera system. RESULTS: CXCL16 concentrations were highly elevated in gouty SF, and PMNs were observed to migrate in response to CXCL16 in vitro. Normal human ST-SCID mouse chimeras injected intragraft with gouty SF that had been depleted of CXCL16 during PMN transfer showed a significant reduction of 50% in PMN recruitment to engrafted tissue as compared with that after administration of sham-depleted gouty SF. Similar findings were achieved when PMNs were incubated with a neutralizing anti-CXCR6 antibody before injection into chimeras. CONCLUSION: Overall, the results of this study outline the effectiveness of the human-SCID mouse chimera system as a viable animal model of gout, serving to identify the primary function of CXCL16 as a significant mediator of in vivo recruitment of PMNs to gouty SF.

23 Article Auricular tophi as the initial presentation of gout. 2009

Griffin, Garrett R / Munns, Justin / Fullen, Douglas / Moyer, Jeffrey S. ·Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Medical School, Ann Arbor, MI 48109, USA. gargriff@med.umich.edu ·Otolaryngol Head Neck Surg · Pubmed #19559981.

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