Pharmacokinetic review of janus kinase inhibitors and its clinical implications for the management of rheumatoid arthritis.

INTRODUCTION: In the realm of autoimmune rheumatic diseases, understanding JAK inhibitors (JAKi) nuances is vital. Baricitinib, tofacitinib, upaacitinib, filgotinib, and peficitinib exhibit subtle yet impactful pharmacokinetic (PK) and pharmacodynamic (PD) variations. AREAS COVERED: This narrative review critically assesses PK and PD distinctions among globally approved JAKi for rheumatoid arthritis, which primarily guide clinical decisions in autoimmune diseases, particularly rheumatoid arthritis. It explores the intricate JAK-STAT signaling pathway, offering insights into JAKs' roles in inflammation, hematopoiesis, and immune homeostasis. Emphasis on PK parameters, including absorption, distribution, metabolism, and excretion, along with CYP3A4 drug interactions, is highlighted. The review underscores integrating PK and PD properties, considering patient-specific factors like hepatic and renal clearance, for judicious JAKi selection in RA and related autoimmune conditions. The literature has been collected from all available databases based on the review question. EXPERT OPINION: Integrating PK and PD properties with patient-specific factors is pivotal for judicious JAKi selection. Recognizing disparities in PK and PD across diseases, ethnicities, and environmental factors is crucial for personalized JAKi choices. This expert opinion underscores the significance of a second compartment analysis, elucidating the interplay between PK and PD and its impact on JAKi efficacy.

Osteoporosis in Rheumatology.

Introduction: Osteoporosis is a common diagnosis and comorbidity observed in patients with rheumatic diseases. It is frequently associated with conditions such as rheumatoid arthritis, spondyloarthropathy, systemic lupus erythematosus, and other autoimmune rheumatic diseases. Conclusion: The incidence of osteoporosis is influenced by factors such as uncontrolled disease, prolonged and higher doses of steroid use, immobility, advanced age, and postmenopausal status. Achieving good control of the underlying disease, minimizing or avoiding the use of steroids for extended periods, and ensuring adequate supplementation of vitamin D and calcium are crucial in reducing the incidence of osteoporosis. Regular screening and appropriate management of osteoporosis can significantly decrease the associated morbidity and mortality.

Prevalence of LTBI in patients with autoimmune diseases and accuracy of IGRA in predicting TB relapse.

OBJECTIVES: The current study evaluated latent tuberculosis infection (LTBI) positivity in a cohort of Indian subjects and the accuracy of IFN-gamma release assay (IGRA) in predicting tuberculosis (TB) reactivation. METHODS: This cross-sectional, retrospective chart-based study considered patients diagnosed with autoimmune rheumatic diseases (AIRDs), especially those who received treatment with biologics or targeted synthetic (ts)DMARDs. The patients had undergone LTBI screening and IGRA test. The study excluded patients with inadequate information and those who had undergone test exclusively for diagnostic purpose. Statistical analyses were carried out for descriptive, demographic and clinical variables. Accuracy and error rate in predicting the absence of TB reactivation were calculated for IGRA test. RESULTS: The study selected 943 patients who had undergone IGRA pre-screening prior to the initiation of biologics or tsDMARDs with a mean age of 42.93 ± 14.01 years and male-to-female ratio of 1:2.08. RA was the most common primary diagnosis (43.16%). The proportion of subjects who received single, double and triple or more DMARDs or immune suppressants were 54.35%, 33.33% and 7.69%, respectively. Among the selected subjects, 125 patients were LTBI positive and 816 were negative. All patients, except one who tested positive at baseline, received antitubercular prophylaxis. Accuracy of IGRA in predicting the absence of TB reactivation was 99.6%, with an error rate of 0.46. CONCLUSION: LTBI screening is beneficial in AIRDs patients prior to the prescription of biologics or tsDMARDs. IGRA is ideal for identifying patients with increased likelihood of developing TB upon receiving biologics or tsDMARDs with reasonable accuracy.

A prospective longitudinal study evaluating the influence of immunosuppressives and other factors on COVID-19 in autoimmune rheumatic diseases.

BACKGROUND: We conducted this study to identify the influence of prolonged use of hydroxychloroquine (HCQ), glucocorticoids and other immunosuppressants (IS) on occurrence and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs). METHODS: This was a prospective, multicenter, non-interventional longitudinal study across 15 specialist rheumatology centers. Consecutive AIRD patients on treatment with immunosuppressants were recruited and followed up longitudinally to assess parameters contributing to development of COVID-19 and its outcome. RESULTS: COVID-19 occurred in 314 (3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR 129, 219) days. Long term HCQ use had no major impact on the occurrence or the outcome of COVID-19. Glucocorticoids in moderate dose (7.5-20 mg/day) conferred higher risk (RR = 1.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk factors such as male sex (RR = 1.51), coexistent diabetes mellitus (RR = 1.64), pre-existing lung disease (RR = 2.01) and smoking (RR = 3.32) were the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the strongest risk factor being pre-existing lung disease (RR = 6.36, p = 0.01). Incidence (17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh (Kerala)) and case fatality (4.1% vs 1.3% (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was significantly higher (p < 0.001) compared to the general population of the corresponding geographic region. CONCLUSIONS: Immunosuppressants have a differential impact on the risk of COVID-19 occurrence in AIRD patients. Older age, males, smokers, hypertensive, diabetic and underlying lung disease contributed to higher risk. The incidence rate and the case fatality rate in AIRD patients is much higher than that in the general population.

Prediction of daily and cumulative cases for COVID-19 infection based on reproductive number (R0) in Karnataka: a data-driven analytics.

To estimate the reproductive number (R0) of the coronavirus in the present scenario and to predict the incidence of daily and probable cumulative cases, by 20 August, 2020 for Karnataka state in India. The model used serial interval with a gamma distribution and applied 'early R' to estimate the R0 and 'projections' package in R program. This was performed to mimic the probable cumulative epidemic trajectories and predict future daily incidence by fitting the data to existing daily incidence and the estimated R0 by a model based on the assumption that daily incidence follows Poisson distribution. The maximum-likelihood (ML) value of R0 was 2.242 for COVID-19 outbreak, as on June 2020. The median with 95% CI of R0 values was 2.242 (1.50-3.00) estimated by bootstrap resampling method. The expected number of new cases for the next 60 days would progressively increase, and the estimated cumulative cases would reach 27,238 (26,008-28,467) at the end of 60th day in the future. But, if R0 value was doubled the estimated total number of cumulative cases would increase up to 432,411 (400,929-463,893) and if, R0 increase by 50%, the cases would increase up to 86,386 (80,910-91,861). The probable outbreak size and future daily cumulative incidence are largely dependent on the change in R0 values. Hence, it is vital to expedite the hospital provisions, medical facility enhancement work, and number of random tests for COVID-19 at a very rapid pace to prepare the state for exponential growth in next 2 months.

Post COVID Inflammation Syndrome: Different Manifestations Caused by the Virus.

BACKGROUND: Incidence of viral pneumonia has been reported in several patients diagnosed with COVID-19. The infection has also been linked to the development of inflammatory syndromes and related clinical manifestations. RESULT: The present study discusses four cases of COVID infection showing varying clinical features. The post-COVID inflammation syndrome was associated with non-specific inflammation and post viral arthritis in three cases. One other subject had vasculitis leading to central retinal artery occlusion. CONCLUSION: As the number of cases of COVID-19 cases has been increasing globally, it is advisable that physicians consider the possibility of post-COVID manifestations while examining patients with non-specific inflammation. A short course of NSAIDs and hydroxychloroquine regimen has been found to be beneficial for alleviating symptoms, and in rare cases with organ threatening inflammation, steroids may be required.

Potential of neutrophil to lymphocyte ratio in predicting sustained remission in rheumatoid arthritis compared to other immune activation markers.

Background & objectives: Cells and cell proportions may indicate the equilibrium status of the immune system. The present study was conducted to evaluate the role of cytokines and the immunocompetent cells as biomarkers of remission in rheumatoid arthritis (RA) patients intended to withdraw or reduce disease-modifying anti-rheumatic drug (DMARD) treatment. Methods: This prospective observational study involved newly diagnosed and treated RA patients who fulfilled 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. The patients were classified based on disease activity score (DAS)28-C-reactive protein (CRP)(3) score into remission (≤2.6) and treatment-naïve/active (>2.6) groups. Remission patients were followed up for six months and were reclassified into those in sustained remission (≤2.6) and relapse (>2.6) based on the DAS28-CRP(3) score. Various cytokines and cell surface markers were quantitated using whole blood samples, and the CD3+/CD19+ and FOXP3+/CD4+ ratios were calculated. The clinical, demographic, cytokine and cellular phenotype characteristics were compared between remission and treatment-naïve groups. The factors associated with sustained remission were verified. Results: Of the 72 patients, 52 were in remission and 20 were DMARD naïve and had active disease. Duration of illness, interleukin-6 (IL-6) and IL-10 were significantly different between remission and treatment naïve/active disease patients. Increased likelihood for achieving sustained remission was noted in RA patients with baseline NLR ≤2. Other demographic/clinical variables and cell phenotypes, namely age, gender, duration of illness, CD3+, CD4+, FOXP3+, CD19+, CD3+/CD19+, FOXP3+/CD4+ and cytokines - IL-6 and IL-10 were not associated with sustained remission. Interpretation & conclusions: The present preliminary study highlighted the potential of NLR in predicting sustained remission in RA patients with a cut-off <2. Further study with a large sample size should be done to confirm this finding.

Influence of disease duration and socioeconomic factors on the prevalence of infection and hospitalization in rheumatoid arthritis: KRAC study.

AIM: The use of healthcare resources by rheumatoid arthritis (RA) patients can be related to the presence of disease, comorbid conditions, use of steroids, and the combined use of immunosuppressants. This study evaluated the risk factors associated with infection and hospitalization in RA. METHODS: This multicenter, cross-sectional study enrolled 3247 RA subjects fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism criteria to examine the prevalence of hospitalization and episodes of documentable non-tubercular infections as a part of the "Karnataka rheumatoid arthritis comorbidity" study (KRAC). The study included 2081 subjects and 1166 were excluded due to incomplete data. Demographic, clinical and treatment variables were collected, and the events related to infections and hospitalization were extracted from the medical records. Comparative analysis and multivariate logistic regression were performed. RESULTS: Around 22% of the subjects had hospitalizations and 2.9% had infections. Infections were pertaining to dental (1.3%), urinary tract (1.6%) and candidiasis (0.2%). Skin- and soft tissue-related infections were found in 1.8% and 0.3% of patients, respectively. Increased need of hospitalization in RA patients was associated with advanced age (≥60 years), lower education, family income, and longer duration of RA. Presence of comorbidity, usage of three or more disease-modifying anti-rheumatic drugs (DMARDs) and family income influenced the likelihood of infection. Dental infections were less likely in working subjects and more likely in patients with increased disease duration, higher family income, comorbidities and those between the age group 40-59 years. Urinary tract infection was associated with DMARD usage. CONCLUSION: Patient-specific risk factors should be considered to improve treatment strategies and to reduce the risk of infection and hospitalization in RA patients.

The Differential Influence of Immunological Process of Autoimmune Disease on Lipid Metabolism: A Study on RA and SLE.

Metabolic parameters like uric acid, lipids and homocysteine are influenced by immunopathological mechanisms underlying the autoimmune disease processes. The current study examined the differences in these parameters and the correlation between inflammatory and metabolic variables in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. The cross-sectional prospective study included 24 treatment-naïve patients with moderate to severe diseases-15 subjects had RA and 9 had SLE. Atherogenic index of plasma (AIP) was used to assess the cardiovascular risk of the patients. Spearman's correlation was performed to verify the relationship between inflammatory and metabolic parameters. A two-tailed P < 0.05 was considered statistically significant for all the analysis. SLE patients had higher uric acid levels, very low density lipoprotein-cholesterol, total cholesterol/high density lipoprotein-cholesterol ratio (TC/HDL-C) and logarithmic ratio of triglycerides to HDL-cholesterol (log[TG/HDL-C]) than RA. Whereas, reduced total lymphocyte count, lipoprotein(a), and low density lipoprotein cholesterol were noted in the former than latter group. Majority of the SLE patients had increased risk of cardiovascular diseases (> 0.24 AIP score) and RA patients in comparison had lower risk. Correlation among serum uric acid, lipid profile constituents and AIP was noted. The immunological process of SLE has greater impact on the metabolic parameters. Higher uric acid levels are suggestive of dysfunctional lipid profile. Understanding the implications of risk factors and its inflammatory role in autoimmune processes may assist in disease management.

Incidence of infection other than tuberculosis in patients with autoimmune rheumatic diseases treated with bDMARDs: a real-time clinical experience from India.

Biologic disease-modifying anti-rheumatic drugs (bDMARD) have transformed the treatment paradigm of chronic autoimmune rheumatic diseases (ARDs), but they are often associated with adverse drug reactions. The present study evaluated the frequency, characteristics and type of infections, other than tuberculosis (TB), in ARD patients receiving bDMARDs. The multicentre, cross-sectional, retrospective, observational study was conducted across 12 centers in Karnataka, India, between January to August 2016. The study included patients receiving bDMARD therapy for various ARDs. Outcome variables considered were any infection, minor infections and major infections, other than TB. Clinical variables were compared between infection and no infection group, and the increase in the likelihood of infection with respect to various clinical variables was assessed. The study involved 209 subjects with a median (range) age of 41 (16-84) years and male to female ratio of 0.97:1. A total of 29 (13.88%) subjects developed infection following bDMARD therapy, out of whom a majority had minor infection (n = 26). The likelihood of developing any infection was noted to be more in subjects receiving anti-TNF (golimumab, P = 0.03) and those on three or more conventional synthetic (cs) DMARDs (P < 0.01). Infection risk was higher in patients with systemic lupus erythematosus (P = 0.04), other connective tissue disease (P < 0.01) and in patients with comorbidities (P = 0.13). The risk of infection was associated with the use of anti-TNF therapy and more than three csDMARDs, co morbidities and Adds such as systemic lupus erythematosus and connective tissue disease.

Biologics and risk of tuberculosis in autoimmune rheumatic diseases: A real-world clinical experience from India.

AIM: Tuberculosis (TB) is one of the major adverse events of concern associated with the use of biologics for managing autoimmune inflammatory rheumatic diseases (AIRDs). The study presents the data on incidence of TB in relation to biologic used, screening test and TB prophylaxis in a real-world setting. METHODS: The cross-sectional, observational, retrospective study was conducted across 12 centres in Karnataka, India. The study included patients receiving biologics therapy for AIRDs, established based on the respective diagnostic criteria. The development of TB after receiving biologic therapy and other clinical variables and the predictability of the test performed for latent TB were evaluated. RESULTS: One hundred and ninety-five AIRDs patients with an average age of 41 years were initiated on biologic therapy. Twenty-one patients were latent TB positive and were given antitubercular prophylaxis, prior to biologics treatment. During follow-up, seven patients belonging to the negative test group (n = 174) developed TB. The negative predictive values noted for Mantoux test (n = 120) and quantiFERON TB gold test (n = 178) were 96.52% and 96.25%, respectively. Patients on anti-tumor necrosis factor were more likely to develop TB. Presence of comorbidities and steroid use increased the likelihood of developing TB by 1.5 and 4.6 times, respectively. CONCLUSION: Close monitoring of patients receiving biologics is essential for early identification of adverse events, especially in test negative patients. Prophylaxis can effectively reduce the risk of developing TB in patients positive for screening.

Factors influencing remission in rheumatoid arthritis patients: results from Karnataka rheumatoid arthritis comorbidity (KRAC) study.

AIM: To study the prevalence of remission in rheumatoid arthritis (RA) patients and the influence of different factors like literacy, socioeconomic status, presence of comorbidity and treatment strategy in achieving remission. METHODS: The study involved 1990 RA patients who were recruited for the Karnataka Rheumatoid arthritis comorbidity (KRAC) study. Based on the factors evaluated, the study participants were classified as follows: age, < 30 years, 30-39 years, 40-49 years, 50-59 years and ≥ 60 years; educational status, illiterate/no formal education, high school or less, graduate, post-graduate and doctorate; family income (₹ per annum), < 50 000, 50-100 000, 100-500 000, and > 500 000; duration of illness prior (DOIP): ≤ 6 months, 6-24 months, 24-120 months and > 120 months. Joint counts were performed by a rheumatologist or trained joint assessor. To assess the treatment outcome, the disease activity score was calculated using the Disease activity Score of 28 joints - erythrocyte sedimentation rate (DAS 28-3 ESR). RESULTS: As per the DAS 28-3 ESR score, around 20% (n = 397) of the study subjects achieved remission. The corresponding mean ± SD of DAS 28-3 ESR noted for remission and non-remission groups were 2.13 ± 0.42 and 4.32 ± 1.28. The majority of the patients were treated with double disease-modifying anti-rheumatic drugs (DMARDs) (60.7%). The likelihood of remission was found to be more in patients who reported DOIP ≤ 6 months. Furthermore, the chances of remission reduced with increase in patient's age and the highest remission rate was noted for 30-39 years age group (59%), followed by 40-49 years (35.4%) and 50-59 years (19.7%). CONCLUSION: The prevalence of remission noted was around 20%. Early treatment, escalating dose of DMARDs, and patient counseling are important contributing factors for attaining remission.

Characterization of neutrophil-to-lymphocyte ratio as a measure of inflammation in rheumatoid arthritis.

OBJECTIVES: The neutrophil to lymphocyte ratio (NLR) is one of the well-recognized sensitive measures of inflammation. This cross-sectional observational study was aimed at characterizing the relationship of NLR with the inflammatory markers erythrocyte sedimentation rate (ESR), C-reative protein (CRP), Disease Activity Score of 28 joints (DAS28)-CRP(3), joint counts and quality measures of rheumatoid arthritis (RA). MATERIALS AND METHODS: Patients with RA were recruited in two phases. The following were assessed for all patients: joint count, pain by visual analogue scale (VAS), complete blood count, ESR, CRP and quality index assessment using the Short Form health survey (SF-36) questionnaire. A subgroup analysis was also performed to evaluate the association between NLR and cytokines. RESULTS: Four hundred and eighty-nine subjects were recruited. Distribution of NLR values corresponded with DAS28-CRP(3) rather than CRP and ESR. A significant difference in VAS, swollen joint counts (SJC-28), inflammatory parameters and general health outcome measures was observed among the NLR groups. A weak correlation was observed between NLR and RA disease measures. It had least bias at lower ranges with DAS28-CRP(3) than CRP and ESR. The NLR cut-off value of 1.4 classified the patients in deep remission with 90% specificity, 24% sensitivity, likelihood ratio positive (LR+) 2.46 and likelihood ratio negative (LR-) 0.84. CRP was a significant baseline predictor of NLR. A significant influence of interleukin-6 on CRP was noted. CONCLUSION: In contrast to the traditional markers, NLR may serve as a less expensive and effective measure of inflammation in RA. Its efficacy is comparable to that of CRP and it is not impacted by the cytokines influencing CRP and ESR.

Influence of cytokine status on insulin resistance and circulating endothelial progenitor cells in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder caused by insulin resistance (IR) and elevated blood glucose level, may lead to endothelial dysfunction. This can result in the development of various vascular complications, even in clinically controlled glycemic state. AIM: It has been experimentally proven that cytokine influences both IR and endothelial progenitor cell (EPC) dysfunction in T2DM patients. The present study evaluated the effect of clinical and metabolic risk factors and cytokine levels on IR and EPC, which are used as critical early biomarkers for estimating the risks associated with T2DM. METHODS: The study involved 58 T2DM patients. They were further subdivided into three groups based on IR score: 32 (55.17%) with normal, 11 (18.97%) with mild-moderate and 15 (25.86%) with severe IR. The relationship of clinical, metabolic and immune mediators with IR and EPCs was verified. RESULTS: HbA1c% was significantly elevated in severe (P=0.022) and mild-moderate IR groups (P= 0.012) than the normal group. The IR normal group had significantly elevated TNF levels compared to mild-moderate and severe groups. The regression analysis indicated that patients with increased body mass index (BMI) were 19.5% more likely to be significantly associated with severe IR. Association studies demonstrated that IL6 and IL10 values correlated with EPCs. CONCLUSION: IL6 and IL10 were associated with circulating EPCs than IR and other clinical characteristics including glycemic control (glycated hemoglobin). TNF-α was associated with IR, but had no relationship with EPCs. The effect of cytokine status on IR and circulating EPCs in T2DM may indicate the risk of vascular complications.

Comorbidities and related factors in rheumatoid arthritis patients of south India- Karnataka Rheumatoid Arthritis Comorbidity (KRAC) study.

The aim was to study the prevalence of comorbidities in rheumatoid arthritis (RA) patients in everyday clinical practice and their association with disease-specific and demographic factors. The multi-center study recruited 3,247 (at 14 centers, and 265) were excluded due to incomplete data. The number of subjects considered for the analysis was 2982. The mean (±standard deviation) age was 48.98±12.64 years and the male-to-female ratio was 1:5. The data was collected based on a pre-structured pro forma by trained clinical research associates through interview and verification of charts and reports available in the patient records. The following comorbidities were studied: cardiovascular disease, hypertension, diabetes mellitus, hypercholesterolemia, thyroid disease, psychiatric diseases like depression, and pulmonary disease. Hypertension (20.7%), diabetes mellitus (14.4%) and thyroid disease (18.3%) were the most prevalent comorbidities. Hypercholesterolemia (5.3%), pulmonary diseases (2.1%), cardiovascular diseases (0.2%) and depression (0.03%) were prevalent in ≤5% of the study population. The overall presence of comorbidity increased with age and reduced with the duration of illness prior (DOIP). The age, gender, and DOIP differed significantly between groups with and without hypercholesterolemia. Females had a statistically increased prevalence of thyroid disease. The prevalence of comorbidities in RA patients from south India is around 40% and the incidence of comorbidity increased with age. As per the literature evidence, the prevalence in the current study subjects was higher when compared to prevalence of similar diseases occurring in the general south Indian population.

Role of vitamin D supplementation in improving disease activity in rheumatoid arthritis: An exploratory study.

AIM: The aim of this exploratory study is to estimate the relationship between vitamin D (vit D) deficiency and active rheumatoid arthritis (RA), and the role of supplementation in improving disease activity. METHOD: A randomized recruitment, consent screening, open-label interventional study was conducted in patients who fulfilled American College of Rheumatology/European League Against Rheumatism 2010 criteria for diagnosing RA and on stable disease-modifying anti-rheumatic drugs (DMARDs) for 3 months. Serum vit D levels and Disease Activity Score of 28 joints/C-reactive protein (DAS28-CRP) disease activity status were estimated at the first visit. Subjects with low vit D levels and DAS28-CRP > 2.6 were supplemented with vit D for 12 weeks, and were assessed for improvement in disease activity and serum vit D levels. RESULTS: One hundred and fifty RA patients of mean age 49 ± 12.1 years, mean duration of illness 78 ± 63 months, and on treatment with DMARDs for 44 ± 39 months were recruited for the study. Of these, 73 (49%) subjects were found to have DAS28-CRP > 2.6 and serum vit D below 20 ng/mL. The patients received vit D supplement of 60 000 IU/week for 6 weeks, followed by 60 000 IU/month for a total duration of 3 months. Disease activity and vit D status were assessed for 59 (80.8%) patients who reported at the end of 12 weeks of treatment. Mean DAS28-CRP of these patients showed a statistically significant improvement from 3.68 ± 0.93 at baseline to 3.08 ± 1.11 after supplementation (P = 0.002). Serum vit D levels improved from 10.05 ± 5.18 to 57.21 ± 24.77 ng/mL (P < 0.001) during the period. CONCLUSION: Supplementation of vit D in RA patients with persisting disease activity and vit D deficiency contributed to significant improvement in disease activity within a short duration.

Reduced incidence of extra-articular manifestations of RA through effective disease control: Karnataka Rheumatoid Arthritis Comorbidity (KRAC) study.

AIM: To estimate the prevalence of extra-articular manifestations (EAM) in rheumatoid arthritis (RA) patients and the impact of demographic, clinical and treatment factors. METHOD: The study was carried out as a part of 'Karnataka Rheumatoid arthritis comorbidity (KRAC) study' conducted at 14 centers across Karnataka, India between September 2014 and July 2015. The data were collected by trained clinical research associates using a structured pro forma, under the supervision of the consulting rheumatologists. Based on the factors evaluated, the study participants were classified as follows: age, < 30 years, 30-39 years, 40-49 years, 50-59 years and ≥ 60 years; and duration of illness prior to visiting rheumatologist (DOIP), ≤ 6 months, > 6 months-2 years, 2-10 years and > 10 years. The Disease Activity Score of 28 joints-3 (erythrocyte sedimentation rate) score was calculated for each patient by three variable methods. RESULTS: The total number of patients considered for the study after exclusion was 1716. The subjects had a mean (SD) age of 48.1 (12.71) years, the male-to-female ratio was 1 : 5, and median (range) of duration of RA was 48 (0.5-484) months. The prevalence of EAM noted was around 13%. EAM were more likely during the first 2 years of the disease (odds ratio [OR]: 1.465; P = 0.047) and increased with longer DOIP. The incidence was less in patients with low disease activity (OR: 0.657) and worse with the presence of deformities (OR: 2.1). CONCLUSION: The study corroborates the current concept of effective disease control to reduce the incidence/likelihood of EAM in RA patients.

Nanoscale Three-Dimensional Microstructural Characterization of an Sn-Rich Solder Alloy Using High-Resolution Transmission X-Ray Microscopy (TXM).

Three-dimensional (3D) nondestructive microstructural characterization was performed using full-field transmission X-ray microscopy on an Sn-rich alloy, at a spatial resolution of 60 nm. This study highlights the use of synchrotron radiation along with Fresnel zone plate optics to perform absorption contrast tomography for analyzing nanoscale features of fine second phase particles distributed in the tin matrix, which are representative of the bulk microstructure. The 3D reconstruction was also used to quantify microstructural details of the analyzed volume.