Academic Positions

  • Present2016

    Becomes the convener of the EULAR recommendations for gout management.

    EULAR, recommendations for gout management.

  • 20161981

    Full time physician of Hôpital Lariboisière

    Hôpital Lariboisière, Rheumatoid Arthritis

  • 19811980

    Graduated from the University of Paris Medical School 5

    University of Paris Medical School 5, Graduate School

Education & Training

  • Pr. DPresent

    Paris 7 ( Paris Diderot ) University

    Paris 7 ( Paris Diderot )

  • Dr.1989

    Lariboisière Hospital

    Lariboisière Hospital

  • Chairman1993

    ART Vigo

    ART Vigo

  • co-Director1993

    French - Vietnamese Gout and Chronic Disease Research Center

    Vien Gut

Honors, Awards and Grants

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  • SCP 2014
    Distinguished Scientific Achievement Award
    image

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  • 2012-2013
    Ormond Family Faculty Fellow
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Outstanding Partner

professor of biostatistics and a recently elected member of Paris Diderot University board

Statistical analysis

Vien Gut Clinic

Patients data

University of Medicine and Pharmacy

Study protocol

Paris 7 ( Paris Diderot ) University

Research

Great Partner!

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Research Projects

  • image

    Hyperechoic deposits in the renal medulla are associated with severe gout and decreased egfr: a transversal study in 503 vietnamese patients

    1French-Vietnamese Gout Research Center, Vien Gut general clinic, Ho Chi Minh City, Viet Nam 2Rheumatology, hôpital Lariboisière, Paris, France 3Radiology, Cho Ray Hospital 4university of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam 5radiology, Hôpital Necker 6Biostatistics, hôpital Saint Louis, Paris, France

    Background: Renal medulla crystal deposits have been demonstrated by pathology in severe gout but little studied by ultrasound (US) scan.

    Objectives: To assess the frequency of hyperechoic renal medulla (HERM) in gouty patients and factors associated with their development.

    Methods: Renal US scan using a Ecube 9 echograph (Alpinion S. Korea), was performed in gout patients (ACR/EULAR criteria) consecutively seen at the Vien Gut general clinic, Ho Chi Minh City, Vietnam, and receiving no ULT at presentation. Age and sex of patients, gout features, associated diseases, serum (S) uric acid (UA), eGFR (MDRD), urinary lab stick parameters, urine UA/creatinine ratio, and fractional clearance of urate (FCU) were recorded. Patients with HERM were counted and compared with those who had no medullary deposits by the Wilcoxon rank sum test for continuous varables and the Fischer exact test for categorical variables. Multivariable logistic model was used to assess relation between variables at inclusion in the study and presence of medulla deposits.

    Results: 503 consecutive patients (500 males) were included. They had a median age of 46 years, median BMI of 25 kg/m2, median gout duration of 4 years. 280 (56%) had clinical tophi, 154 (31%) urate arthropathy, 28;56%) urolithiasis, 112 (22%) hypertension, 58 (11.5%) type 2 diabetes, 5 (1%) coronary heart disease. Their median eGFR was 78 ml/min, SUA 423 micromol/L, FCU 0.063, urine UA/creatinine ratio 0.253, urinary pH 6.

    Diffuse and bilateral HERM on the B mode with frequent twinkling artefacts on the Doppler mode was identified in 181 (36%) of the 503 patients. Univariate analysis showed that HERM associated with higher age, longer duration of gout, clinical tophi, urate arthropathy (p<0.0001 for each of the variables), higher uricemia (p=0.001), hypertension (p=0.0008), CHD (p=0.0006), lower eGFR (p<0.0001), leucocyturia (p=0.02), proteinuria (p=0.02). No association with US-diagnosed urolithiasis, hematuria, urine UA/creatinine ratio, FCU and urinary pH was found. In multivariate analysis, log of the duration of gout (0R: 2.22 (CI: 1.63–3.08), p<0.001), clinical tophi (OR: 8.21 (4.23–16.91) p<0.001), urate arthropathy (OR: 3.74 (2.18–6.52, p<0.001), and lower eGFR (OR: 0.86 (0.75–0.99) for each 10 ml/min decrease, p=0.04) were significantly associated with HERM.

    Conclusions: In our gout population, HERM was observed in 36% of patients,correlated with decreased renal function, and clearly associated with severe gout, but not with features of uric acic lithiasis.

    Disclosure of Interest: T. Bardin Consultant for: Grunnenthal, Ipsen Menarini, Astrazeneca, NovartisSobi, K. M. Tran: None declared, Q. D. Nguyen: None declared, N. H. Le : None declared, P. Richette Consultant for: Grunnenthal, Ipsen Menarini, Astrazeneca, NovartisSobi, P. Le Van: None declared, J.-M. Correas: None declared, M. Resche-Rigon: None declared

    DOI: 10.1136/annrheumdis-2018-eular.5027

  • image

    Effect of serum uric acid (SUA) on gout flares (GF) and tophi resolution in gout patients. pooled post hoc analysis of clear 1 & clear 2 trials

    F. Perez-Ruiz1, P. Richette2, R.G. Karra3, I. Wild3, H. Hagedorn3, P. Kandaswamy3, T. Bardin2

    Background: Gout is caused by crystal deposition due to persistent hyperuricemia. EULAR1 and other guidelines recommend a target sUA of <5–6 mg/dL (0.30 to 0.36 mmol/L) depending on severity. Despite physiological plausibility and abundant literature evidence there is an absence of consensus among physicians on the targets and necessity of long term urate lowering therapy (ULT)2.

    Objectives: To investigate the effects of sUA and target sUA <5–6 mg/dl with respect to the occurrence of GF, flares requiring treatment (GFRT) and the percent change in the area of tophi (TR) from baseline irrespective of treatment arms.

    Methods: Data of 1213 patients (PT) was pooled from CLEAR trials3&4, two randomised, double-blind, placebo-controlled Phase 3 studies that evaluated Lesinurad 200/400 mg daily in combination with allopurinol vs allopurinol. Prophylaxis for flares was given from baseline to month (M) 5. PT who met the sUA target of <5–6 mg/dl at M 6 and 12 were compared against those not on target with respect to the TR from baseline using a Wilcoxon test. In addition, the mean sUA measurements for PT with or without GFs and GFRT was compared at M 6 and 12 using a t-test.

    Results: PT with sUA on target <5–6 mg/dl showed a larger decrease (increase in percent reduction) in area of tophi with a difference of 27.9%, and 17.3% at M 12 only compared to the PT not on target (table 1). The mean sUA levels were 0.227 mg/dL lower for PT with GF and 0.389 mg/dL lower for PT with GFRT compared to PT without GF and GFRT at M 6 (table 2), but not at M 12.

    Abstract FRI0235 – Table 1 Percent Change from baseline Area of tophi vs. SUA on target <5–6 mg/dL at M 6 and 12

    sUA (mg/dL)

    n=M6/M12

    M6

    Median (Q1, Q3)

    p-value#

    M12

    Median (Q1, Q3)

    p-value#

    <5 (n=31/36)

    −22.1 (-46.4, 5.63)

    0.78

    −59.6 (-98.3,–27.5)

    0.01

    ≥5 (n=93/87)

    −22–2 (-56.7, 6.91)

    −31.7 (-77.4, 13.06)

     

    <6 (n=63/66)

    −23.8 (-56.7, 1.59)

    0.64

    −49.0 (-93.3,–12.9)

    0.06

    ≥6 (n=61/57)

    −19.2 (-42.5, 10.30)

    −31.7 (-60.1, 13.06)

     

    § Number of PT with a target tophus at baseline was small. # Wilcoxon test with H0: Mean ranks in categories are equal

    Abstract FRI0235 – Table 2 Mean sUA at M 6 and 12 by occurrence of GF and GFRT

    Mean sUA mg/dL (95% CI) M6

    p-value#

    Mean sUA (95% CI) M12

    p-value#

    GF Yes

    5.94 (5.80–6.07)

     

    5.92 (5.79–6.06)

     

    GF No

    5.71 (5.51–5.92)

     

    5.91 (5.64–6.17)

     

    Difference

    0.22 (−0.01–0.47)

    0.06

    0.01 (−0.28–0.31)

    0.91

    GFRT No

    5.91 (5.79–6.03)

     

    5.93 (5.80–6.05)

     

    GFRT Yes

    5.530 (5.23–5.83)

     

    5.83 (5,41–6.25)

     

    Difference

    0.38 (0.06–0.71)

    0.01

    0.09 (−0.34–0.53)

    0.65

    # T-test with H0: No difference in means

    Conclusions: These results confirm that sUA on target <5–6 mg/dl is essential for TR, and longer the control better the TR. The lower mean sUA levels for PT with GF and GFRT was observed at M6 and not at M 12, maybe owing to the fact that flares are common during the first months of ULT initiation and then taper off and urate deposits were more fragile and not completely dissolved. Also M 6 and 12 may not be optimal to observe statistically significant differences between treatments with respect to TR, GF and GFRT.

    References:

    1. Richette P, et al. Ann Rheum Dis 2017;76:29−42.
    2. Qaseem A, et al. Ann Intern Med 2017;166(1):58–68.
    3. Saag KG, et al. Arthritis Rheumatol 2017;69:203–12.
    4. Bardin T, et al. Ann Rheum Dis 2017;76:811–20.

    Disclosure of Interest: F. Perez-Ruiz Consultant for: Grünenthal, Menarini, Speakers bureau: Grünenthal, Menarini, P. Richette Consultant for: Grünenthal, Speakers bureau: Grünenthal, R. Karra Employee of: Grünenthal, I. Wild Employee of: Grünenthal, H. Hagedorn Employee of: Grünenthal, P. Kandaswamy Employee of: Grünenthal, T. Bardin Consultant for: Grünenthal

    DOI: 10.1136/annrheumdis-2018-eular.5565

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    Urate lowering to ACR-recommended targets allows significant improvement of severe gout. A monocentric experience in Vietnam, using a systematic treatment protocol

    Thomas Bardin1,2, Quang Nguyen Dinh1, Khoi Tran Minh1, Nghia Le Hieu1, Minh Duc3, Pascal Richette1, Matthieu Resche-Riggon2

    1 French – Vietnamese Research Center on Gout, Ho Chi Minh City, Vietnam - 2 University Paris Diderot, France - 3 University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam

    Rheumatology

    Background: Gout is frequent and severe in Vietnam, where urate-lowering drugs (ULD) are seldom used and many patients are treated by traditional herbal medicine. We looked at the effect of a T2T strategy using allopurinol on severe Vietnamese gout.

    Methods: 100 Vietnamese, ULD- free, crystal-proven gout patients (99 M, 1 F) with a eGFR > 60 ml/min, were prospectively followed after allopurinol introduction. The median age of patients was 47 years, median disease duration 10 years, median BMI 25 kg/m2; 91 patients had multiple clinical tophi, 32 had hypertension, 7 type 2 diabetes, 31 dyslipidemia, 47 coronary heart disease, 16 were on long term steroid. Treatment protocol included fullpatient information, titration of allopurinol up to obtaining a predefined SUA target (6 mg/dL in 5 patients and 5 mg/dL in 95), flare prophylaxis by colchicine (0.5 to 1mg/d) during the first months, and traditional herbal medicine. At each visit, gout flares from the last visit were counted using a daily diary, palpable tophus size was assessed using a Vernier caliper, SUA and eGFR were determined. Ultrasound (US) scan was performed at inclusion and every 3 months and allowed search for double contour (DC) at the knees and MTPs -which were found in all patients at baseline and classified into 4 classes (thick, medium, thin and none)- and measurement of a hand or foot index tophus. Quality of life (gout impact scale (GIS) and function were recorded at inclusion and after 12 months. The effect of SUA lowering was explored by comparing inclusion and 12-month data, in patients who reached the SUA targets and those who did not, using standard statistics.

     

     

    Background: Gout is frequent and severe in Vietnam, where urate-lowering drugs (ULD) are seldom used and many patients are treated by traditional herbal medicine. We looked at the effect of a T2T strategy using allopurinol on severe Vietnamese gout.

    Methods: 100 Vietnamese, ULD- free, crystal-proven gout patients (99 M, 1 F) with a eGFR > 60 ml/min, were prospectively followed after allopurinol introduction. The median age of patients was 47 years, median disease duration 10 years, median BMI 25 kg/m2; 91 patients had multiple clinical tophi, 32 had hypertension, 7 type 2 diabetes, 31 dyslipidemia, 47 coronary heart disease, 16 were on long term steroid. Treatment protocol included fullpatient information, titration of allopurinol up to obtaining a predefined SUA target (6 mg/dL in 5 patients and 5 mg/dL in 95), flare prophylaxis by colchicine (0.5 to 1mg/d) during the first months, and traditional herbal medicine. At each visit, gout flares from the last visit were counted using a daily diary, palpable tophus size was assessed using a Vernier caliper, SUA and eGFR were determined. Ultrasound (US) scan was performed at inclusion and every 3 months and allowed search for double contour (DC) at the knees and MTPs -which were found in all patients at baseline and classified into 4 classes (thick, medium, thin and none)- and measurement of a hand or foot index tophus. Quality of life (gout impact scale (GIS) and function were recorded at inclusion and after 12 months. The effect of SUA lowering was explored by comparing inclusion and 12-month data, in patients who reached the SUA targets and those who did not, using standard statistics.

    Results: 84 and 68 patients were seen at 6 and 12 months, respectively. Reasons for loss of follow-up were major improvement (12), alcoholism (2), long distance from the center (8), intercurrent disease or personal problem (9), and intolerance to allopurinol (4). The mean maximal dose of allopurinol was 520 (+165) mg/d and was reached after a median of 2 (+1.3) months. SUA target was obtained in 89 patients. Mean flare rate per month significantly declined from 2.5 on M1 (n=98) to 1.1 at M6 (n=84) (p<0.001), and 0.15 at M12 (n=68) (p<0.001), at a time when all patients were free of prophylactic colchicine, NSAIDs or steroid but remained under herbal treatment, with no significant difference between patients who were or were not at SUA targets. GIS significantly similarly strongly improved in all dimensions (p<0.02) except fear of side effects (p=0.13) and did not correlate with SUA target. Function significantly (p<0.004) improved, and even more in patients at target (p<0.001). Tophi (p<0.001 for both caliper and US measurements) and DC (p<0.03 for all locations) significantly decreased between inclusion and M12 and both decreases correlated with achievement of SUA target (p=0.004 for tophi, and <0.03 for DC disappearance).

    Conclusion: The T2T strategy strikingly improved patients. Tophi and DCs decreased, and function improved in correlation with achievement of SUA target. Flare rate dramatically decreased and GIS strongly improved but these did not correlate with SUA target achievement, suggesting anti-inflammatory effect of high dose allopurinol and/or herbal medicine.

    Introduction

    • The Vien Gut Medical center, in Ho Chi Minh City, Vietnam (VN) has been exclusively devoted to gout care for 10 years. An average of 4,000 gouty patients have been seen every  year.

    • About 1/3 of patients seen at the Vien Gut clinic suffer from severe, tophaceous gout (figure 1).

    • Up to 2015, gout was treated in this center by traditionnal, herbal medicine only.

    • In 2015 we introduced the use of urate-lowering drugs (ULDs) and decided to perform a prospective study of the effects of this therapeutic strategy

    Study Design

    • 100 patients were included in the study

    • Inclusion criteria:

    • Crystal proven gout

    • eGFR > 60 ml/min

    • Oral consentment to participate

    • The treatment protocol combined:

    • Allopurinol titration up to reaching the ACR and EULAR-recommended serum  uric acid (SUA) targets

    • Prophylactic colchicine (0.5-1mg/d) during the first months

    • Full education, repeated at each visit

    •Traditional herbal medicine treatment

    • Duration of the study: one year

    • Ethic committe approval:  
    University of Medicine and Pharmacy at Ho Chi Minh City (VN),

      Approval number: 198 of the year 2017

    Data Recording at Inclusion

    •Full medical history and physical examination

    •Number of fares in the preceding year

    •Assessment of urate arthropathies

    •Chart and count of clinical tophi

    •Vernier calliper measurement of 1 index tophus (hands or feet)

    •Digital photographs of hands and feet

    •Diet assesment, including alcohol and soda intake

    •ECG

    •Ultrasound (US) scan of MTPs, knees, liver, kidneys

    •Assesment of double contours (DC) according to 4 grades (fig 2) and measurement of an index tophus

    •Radiographs of urate arthropathies

    •Biological tests: SUA, eGFR (MDRD), FCU, CBC, CRP,  lipids, fasting glucose, CK, liver enzymes, urinary pH

    Prospective Follow-up Protocol

    - Patients were seen every month until the target uricemia was reached (< 6mg/L, or 5mg/L in patients with tophi or frequent flares (> 6/y), then at least at M3,6,9 and 12.

    - They filled out a diary, that included VAS for every joint and daily intake of drugs (fig 6)

    - At each visit

    •Patient weight, BP, pulse, any intercurrent illness were recorded

    •The number of flares was counted according to the diary information. Patients were instructed to automedicate early in case of flares. These were defined as an increase of joint VAS + NSAID, steroid or increased colchicine intake.

    •Digital photographs were taken of the hands and feet (Fig 3)

    •1 index hand/foot tophus was measured

    •SUA, eGFR, fasting glucose, CBC,  liver enzymes, CK, urine pH, FCU were measured

    •The number of remaining tablets were counted to assess drug adherence and diary coherence (all drugs were delivered by the Vien Gut pharmacy)

    - Supplementary data obtained at the M6 and M12 visits

    •Diet assessment

    •Gout impact scale

    •Function

    •US scan of the knees and feet

    •Double contour grading

    •Index tophus measurement

    •US scan of the liver

    •US scan of the kidney

    •Radiographs of the urate
    arthropathy-involved joints (Fig 4)

    •Blood lipid measurement

    Statistical Methods

    •Quantitative variables are described by their mean (SD) or median [Interquartile range]

    •Qualitative variables are described by their count and percentage

    •Tests between groups for qualitative variables were performed using Fisher test and McNemar test for paired data

    •Tests between groups for quantitative variables were performed using Wilcoxon test and Wilcoxon paired test for paired data

    •Correlation between measurements and target achievement of SUA at M3 were evaluated using random effect linear models.

    Results

     

     

    Currrent Teaching

    • Present1995

      Preclinical Endodnotics

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    • Present2003

      SELC 8160 Molar Endodontic Selective

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    • Present2010

      Endodontics Postdoctoral AEGD Program

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    Teaching History

    • 19971995

      Preclinical Endodnotics

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    • 20052003

      SELC 8160 Molar Endodontic Selective

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    • 20112010

      Endodontics Postdoctoral AEGD Program

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    • 20112010

      Endodontics Postdoctoral AEGD Program

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    • 20112010

      Endodontics Postdoctoral AEGD Program

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