The GOUT-36 prediction rule for inpatient gout flare in people with comorbid gout: derivation and external validation.

OBJECTIVES: To develop and validate a gout flare risk stratification tool for people with gout hospitalized for non-gout conditions. METHODS: The prediction rule for inpatient gout flare was derived from a cohort of 625 hospitalized people with comorbid gout from New Zealand. The rule had four items: no pre-admission gout flare prophylaxis, no pre-admission urate-lowering therapy, tophus and pre-admission serum urate >0.36 mmol/l within the previous year (GOUT-36 rule). Two or more items are required for the classification of high risk for developing inpatient gout flares. The GOUT-36 rule was validated in a prospective cohort of 284 hospitalized people with comorbid gout from Thailand and China. RESULTS: The GOUT-36 rule had a sensitivity of 75%, specificity of 67% and area under the curve of 0.71 for classifying people at high risk for developing inpatient gout flares. Four risk groups were developed: low (no items), moderate (one item), high (two items) and very high risk (three or four items). In a population with frequent (overall 34%) in-hospital gout flares, 80% of people with very high risk developed inpatient flares while 11% with low risk had inpatient flares. CONCLUSION: The GOUT-36 rule is simple and sensitive for classifying people with high risk for inpatient gout flares. The rule may help inform clinical decisions and future research on the prevention of inpatient gout flares.

Disease activity is associated with LV dysfunction in rheumatoid arthritis patients without clinical cardiovascular disease.

OBJECTIVES: The cross-sectional study aimed to assess left ventricular systolic function using global longitudinal strain (GLS) by speckle-tracking echocardiography (STE) and arterial stiffness using cardio-ankle vascular index (CAVI) in Thai adults with rheumatoid arthritis (RA) and no clinical evidence of cardiovascular disease (CVD). METHODS: Confirmed RA patients were selected from a list of outpatient attendees if they were 18 years (y) without clinical, ECG and echocardiographic evidence of CVD, diabetes mellitus, chronic kidney disease, and excess alcoholic intake. Controls were matched with age and sex to a list of healthy individuals with normal echocardiograms. All underwent STE and CAVI. RESULTS: 60 RA patients (females = 55) were analysed. Mean standard deviation of patient and control ages were 50 ± 10.2 and 51 ± 9.9 y, respectively, and mean duration of RA was 9.0 ± 6.8 y. Mean DAS28-CRP and DAS28-ESR were 2.9 ± 0.9 and 3.4 ± 0.9, respectively. There was no between-group differences in left ventricular ejection fraction (LVEF), LV sizes, LVMI, LV diastolic function and CAVI were within normal limits but all GLSs values was significantly lower in patients vs. controls: 17.6 ± 3.4 vs 20.4 ± 2.2 (p = 0.03). Multivariate regression analysis demonstrated significant correlations between GLSs and RA duration (p = 0.02), and GLSs and DAS28-CRP (p = 0.041). CONCLUSIONS: Patients with RA and no clinical CV disease have reduced LV systolic function as shown by lower GLSs. It is common and associated with disease activity and RA disease duration. 2D speckle-tracking GLSs is robust in detecting this subclinical LV systolic dysfunction.

Clinical and immunological characteristics of antiphospholipid syndrome in an Asian population: a retrospective study.

OBJECTIVES: To describe the characteristics of patients with antiphospholipid syndrome (APS) in an Asian clinical practice setting. METHODS: We conducted a single-center, retrospective study of APS patients attending the rheumatology or hematology clinics, between January 2012 and December 2016. RESULTS: There were 450 patients suspected of having APS referred to our clinics. Seventy-four (16.4%) were diagnosed of APS, 51% of which were definite. Fifty-two (70%) patients were classified as primary APS, 50% of which were definite APS. The most common clinical manifestation was stroke (33%), followed by deep vein thrombosis of the lower extremities (30%) and pulmonary embolism (19%). Hypertension and the presence of at least one established cardiovascular risk factor were independently associated with stroke. Seven (9%) patients had multiorgan thrombosis as their first presentation of APS, 71% of which ultimately suffered from permanent organ damage or died of severe thrombosis, despite not fulfilling the criteria for 'definite' catastrophic APS (CAPS). Late fetal loss was the most prevalent obstetric complication. The majority of patients (79%) tested positive for lupus anticoagulant (LAC), while only 32% tested positive for anti-cardiolipin antibodies. Triple positive profile was documented in 14% of the cohort. Overall, recurrent thrombosis and bleeding complications were recorded in 9% and 28%, respectively. CONCLUSION: APS patients in central Thailand demonstrated high prevalence of stroke, late fetal loss, LAC positivity, and multiorgan thrombosis at first presentation, leading to poor outcomes.

Disease activity is associated with LV dysfunction in rheumatoid arthritis patients without clinical cardiovascular disease

Abstract Objectives: The cross-sectional study aimed to assess left ventricular systolic function using global longitudinal strain (GLS) by speckle-tracking echocardiography (STE) and arterial stiffness using cardio-ankle vascular index (CAVI) in Thai adults with rheumatoid arthritis (RA) and no clinical evidence of cardiovascular disease (CVD). Methods: Confirmed RA patients were selected from a list of outpatient attendees if they were 18 years (y) without clinical, ECG and echocardiographic evidence of CVD, diabetes mellitus, chronic kidney disease, and excess alcoholic intake. Controls were matched with age and sex to a list of healthy individuals with normal echocardiograms. All underwent STE and CAVI. Results: 60 RA patients (females = 55) were analysed. Mean standard deviation of patient and control ages were 50 ± 10.2 and 51 ±9.9 y, respectively, and mean duration of RA was 9.0 ± 6.8 y. Mean DAS28-CRP and DAS28-ESR were 2.9 ± 0.9 and 3.4 ± 0.9, respectively. There was no between-group differences in left ventricular ejection fraction (LVEF), LV sizes, LVMI, LV diastolic function and CAVI were within normal limits but all GLSs values was significantly lower in patients vs. controls: 17.6 ± 3.4 vs 20.4 ± 2.2 (p = 0.03). Multivariate regression analysis demonstrated significant correlations between GLSs and RA duration (p = 0.02), and GLSs and DAS28-CRP (p = 0.041). Conclusions: Patients with RA and no clinical CV disease have reduced LV systolic function as shown by lower GLSs. It is common and associated with disease activity and RA disease duration. 2D speckle-tracking GLSs is robust in detecting this subclinical LV systolic dysfunction.

Estrogen receptor beta expression and prognosis of diffuse large B cell lymphoma.

OBJECTIVES: Estrogen receptor beta (ERß)-selective agonists inhibited B cell lymphoma growth in animal models. However, a recent study found that higher ERß expression in tissue from diffuse large B cell lymphoma (DLBCL) patients indicated a poorer survival. This study aimed to determine the ERß expression in DLBCL tissue using immunohistochemistry and correlate with clinical outcomes. METHODS: Diagnostic tissues from newly diagnosed adult DLBCL patients treated with Rituximab-Cyclophosphamide/Doxorubicin/Vincristine/Prednisolone were counted for ERß1-expressing cells. Nodal lymphoma (N = 41) was analyzed separately from extra-nodal DLBCL (N = 31). RESULTS: On immunohistochemistry, ERß1 was expressed in 73.6% of cases with the median expressing cells of 20%. For nodal lymphoma, high ERß expression (≥25%) was associated with poorer event free survival (EFS) independent of the international prognostic index with the adjusted hazard ratio (HR) of 2.49 (95% Confidence interval (CI) 1.03-6.00, P = 0.042). On the contrary, high ERß expression (≥25%) was associated with superior outcomes in extra-nodal DLBCL with the adjusted HR of 0.25 (95% CI 0.09-0.75, P = 0.013) for EFS and adjusted HR of 0.29 (95% CI 0.10-0.85, P = 0.024) for overall survival in multivariate analyses. CONCLUSION: ERß1 protein expression represented opposite prognostic factors in nodal vs. extra-nodal DLBCL.

2016 updated Thai Rheumatism Association Recommendations for the use of biologic and targeted synthetic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.

AIM: In June 2015, the Thai Rheumatism Association (TRA) approved an update of its recommendation for the use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) and targeted synthetic (tsDMARD) in the treatment of rheumatoid arthritis (RA) to cover those currently available in Thailand (etanercept, infliximab, golimumab, rituximab, tocilizumab, abatacept and tofacitinib). METHOD: A search of the literature was performed between January 2000 and June 2015. Existing RA recommendations, in relation to the use of bDMARDs and tsDMARD, were identified and evaluated by the AGREE II instrument prior to their use as a 'guide' for developing this TRA recommendation. An additional literature search was performed in order to answer specific clinical questions that could not be found in existing guidelines. RESULT: Thirteen recommendations were developed. They covered the use of RA classification criteria, the aim of RA treatment, when to initiate bDMARDs/tsDMARD or taper or switch them to other medications, as well as monitoring these drugs during their use. In addition, specific issues including their use and vaccination, malignancies, pregnancy and lactation, and perioperative period also were addressed. Public hearings were performed at the annual meeting of the TRA and of the Royal College of Physicians of Thailand. The recommendations were distributed to other professional associations related to RA management, as well as government sectors associated with the reimbursement policy, prior to development of the final version. CONCLUSION: These recommendations will help Thai rheumatologists prescribe bDMARDs and tsDMARD more appropriately when treating RA patients.

Outcome of Treatment in Gouty Arthritis Patients: A Retrospective Study.

BACKGROUND: Effective treatment in gouty arthritis can prevent joint and renal damage. Target serum uric acid levels of < 6 mg/dl and < 5 mg/dl are recommended in gouty arthritis and those with tophi, respectively. OBJECTIVE: To evaluate: (i) whether patients achieved recommended serum uric acid target and assess influencing factors and (ii) renal function between patients who achieved and not achieved the goal. MATERIAL AND METHOD: The medical records of gouty arthritis patients treated in outpatient department at Thammasat University Hospital between January 2013 and December 2013 were reviewed. Patients were divided into adequately (ATG) and inadequately treated groups (ITG) based on the ACR uric acid criteria after six months of treatment. Factors associated with inadequate treatment were explored and post treatment renal function compared between A and ITGs. RESULTS: Of 139 patients, 46 (33%) achieved target serum uric acid concentrations. Alcoholic consumption was the significant factor influencing the outcome. 75.5% of patients were followed-up > 1 month for second evaluation of uric acid and most of them not receiving dosage up-titration even though not achieving the target. Both groups had similar alterations of renal function after treatment (p = 0.68). CONCLUSION: Most patients failed to achieve recommended uric acid targets. Alcohol consumption was identified as a key risk factorfor a suboptimal outcome. The treat-to-target approach should be underlined. Other risk factors should be explored prospectively.

Comprehensibility, reliability, validity, and responsiveness of the Thai version of the Health Assessment Questionnaire in Thai patients with rheumatoid arthritis.

INTRODUCTION: The Health Assessment Questionnaire Disability Index (HAQ-DI) is a commonly used instrument to assess functional status of patients with rheumatoid arthritis (RA). Translations and adaptations of the HAQ-DI have been carried out for use with RA patients in several countries. The objective of this study was to evaluate the psychometric properties of the Thai version of the HAQ-DI (Thai HAQ) in Thai patients with RA. METHODS: Comprehensibility of the Thai HAQ was assessed by 126 patients with RA from 6 medical centers in Thailand. Another group of 115 patients with active RA was enrolled to test the reliability (internal reliability and 1-week test-retest reliability), construct validity (correlations with other measures of RA disease activity), floor and ceiling effects, and sensitivity to change of the Thai HAQ at 3 months of treatment with disease-modifying antirheumatic drugs. RESULTS: More than 98% of the patients regarded the Thai HAQ as comprehensible. The internal consistency of the Thai HAQ was satisfactory with the overall Cronbach alpha of 0.91. The test-retest reliability of the Thai HAQ was acceptable with the intraclass correlation coefficient of 0.89. Moderate correlations between the Thai HAQ and other outcomes of RA disease activity were observed, except erythrocyte sedimentation rate, with the Spearman correlation coefficients ranging from 0.42 to 0.57. The responsiveness of the Thai HAQ was moderate, with a standardized response mean of 0.75 (95% confidence interval 0.56 to 0.94). CONCLUSIONS: The Thai HAQ is comprehensible, reliable, valid and sensitive to change in the evaluation of functional status of Thai patients with RA. The Thai HAQ is an essential tool to measure treatment effects and progression of disability in RA patients and should be applied in both clinical trials and routine clinical care settings.

Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus.

A genomic region on distal mouse chromosome 1 and its syntenic human counterpart 1q23-42 show strong evidence of harboring lupus susceptibility genes. We found evidence of linkage at 1q32.2 in a targeted genome scan of 1q21-43 in 126 lupus multiplex families containing 151 affected sibpairs (nonparametric linkage score 2.52, P = 0.006). A positional candidate gene at 1q32.2, complement receptor 2 (CR2), is also a candidate in the murine Sle1c lupus susceptibility locus. To explore its role in human disease, we analyzed 1,416 individuals from 258 Caucasian and 142 Chinese lupus simplex families and demonstrated that a common three-single-nucleotide polymorphism CR2 haplotype (rs3813946, rs1048971, rs17615) was associated with lupus susceptibility (P = 0.00001) with a 1.54-fold increased risk for the development of disease. Single-nucleotide polymorphism 1 (rs3813946), located in the 5' untranslated region of the CR2 gene, altered transcriptional activity, suggesting a potential mechanism by which CR2 could contribute to the development of lupus. Our findings reveal that CR2 is a likely susceptibility gene for human lupus at 1q32.2, extending previous studies suggesting that CR2 participates in the pathogenesis of systemic lupus erythematosus.

Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus.

OBJECTIVE: To study 5 type I interferon (IFN)-inducible genes (LY6E, OAS1, OASL, MX1, and ISG15) in patients with systemic lupus erythematosus (SLE) and to correlate expression levels with disease activity and/or clinical manifestations. METHODS: Peripheral blood cells were obtained from 48 SLE patients, 48 normal controls, and 22 rheumatic disease controls, and total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real-time polymerase chain reaction, standardized to a housekeeping gene, and summed to an IFN score. Disease activity was determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) composite. RESULTS: Each gene was highly expressed in SLE patients compared with normal controls (P < or = 0.0003) or disease controls (P < or = 0.0008 except for MX1). IFN scores were positively associated with the SELENA-SLEDAI instrument score (P = 0.001), the SELENA-SLEDAI flare score (P = 0.03), and the physician's global assessment score (P = 0.005). Compared with patients without nephritis, lupus nephritis patients had higher IFN scores (overall P < 0.0001), especially during active renal disease. IFN scores were weakly associated with neurologic manifestations. Elevated IFN scores were positively associated with the current presence of anti-double-stranded DNA (anti-dsDNA) antibodies (P = 0.007) or hypocomplementemia (P = 0.007). LY6E expression levels distinguished active from inactive lupus nephritis (P = 0.02) and were positively associated with proteinuria (P = 0.009). CONCLUSION: The 5 IFN-inducible genes were highly expressed in SLE patients, and increased levels were correlated with disease activity defined by several methods. IFN scores, or LY6E levels, were elevated in lupus nephritis patients, especially during active renal disease, and in patients with anti-dsDNA antibody positivity and hypocomplementemia. IFN scores, or LY6E levels, may be useful as a biomarker for lupus nephritis therapy.

Clinical manifestations of patients with hyperuricemia.

OBJECTIVE: To study the clinical manifestations of patients with hyperuricemia in King Chulalongkorn Memorial Hospital. METHOD: A cross sectional study of 188 hyperuricemic patients was done at King Chulalongkorn Memorial Hospital. History, physical examination, and blood samples were drawn to assess complete blood count (CBC), blood urea nitrogen (BUN), creatinine (Cr), liver function test (LFT), and serum uric acid in all patients. RESULTS: Most of the patients (92%) were male, more than 50 years old (69%), the mean age of the patients was 56.7 +/- 12.1 years old. All of the female patients were more than 50 years old. Symptomatic hyperuricemia was found in 93%, the mean duration of symptoms was 63.2 +/- 66.3 months. The mean of the serum uric acid level was 10.0 +/- 2.9 mg/dl. Associated diseases were found in 46% of the patients, and 30% of these patients had more than one disease. Hypertension was the most common followed infrequency by dyslipidemia, diabetes mellitus, ischemic heart disease, and chronic obstructive pulmonary disease consecutively. Renal impairment was detected in about one-third of the patients. CONCLUSION: This study shows that hyperuricemia is common in elderly, male patients. Associated diseases and renal impairment can befoundfrequently, and the patients should be monitored.

Efficacy of benzbromarone compared to allopurinol in lowering serum uric acid level in hyperuricemic patients.

This study was aimed to evaluate the efficacy of benzbromarone compared to allopurinol in lowering serum uric acid level in hyperuricemic patients with normal renal function (serum creatinine < or = 1.5). The authors conducted a crossover study consisting of two four-week treatment periods of allopurinol 300 mg/day and benzbromarone 100 mg/day separated by a four-week washout period. Fourteen patients with mean age and duration of hyperuricemia of 60.78 +/- 8.62 and 6.93 +/- 3.69 years, respectively, were recruited and all completed our study protocol. This study was a crossover design consisting of two four-week treatments of allopurinol and benzbromarone separated by a four-week washout period. The serum uric acid level was reduced from 9.89 +/- 1.43 mg/dl to 5.52 +/- 0.83 mg/dl and from 9.53 +/- 1.48 to 4.05 +/- 0.87 mg/dl by allopurinol and benzbromarone, respectively. The efficacy of benzbromarone in lowering serum uric acid level was significantly superior to allopurinol (p=0.005). No patient reported clinical side effects during treatment with either drug. In conclusion, the authors have shown that benzbromarone is more effective than allopurinol in the reduction of serum uric acid levels in hyperuricemic patients with normal renal function.