Blockades in the Pathway of Specialty Care in Rheumatoid Arthritis: A Report Based on Indian Rheumatology Association Database.

AIM: The study aims to identify factors influencing referral patterns and delays in rheumatoid arthritis (RA) patients across clinical settings in India. MATERIALS AND METHODS: A prospective, multicenter, observational study collected data from eight centers using the Indian Rheumatology Association (IRA) database. Patient-related factors and referral factors were determined based on patient narration. The modified PRASAD scale categorized patients' socioeconomic status. RESULTS: The study included 4,643 RA patients from eight centers. Data from 35 patients were excluded due to inconsistent reporting of diagnosis and delay. Lack of awareness was the predominant factor causing the delay in referral. Approximately, 39% of patients were referred to the rheumatology specialty within 6 months of disease onset, while 26% reported later, and 34% reported over 2 years. Referral delays were linked to socioeconomic factors in Madhya Pradesh (21.43%) and West Bengal (28.57%). Lack of awareness about the disease and rheumatology specialty was highest in West Bengal (100%), followed by Delhi and Rajasthan (93.70%). Misconceptions about modern medicine, reluctance to refer patients to the rheumatologist, and previous treatment by other specialities were other factors influencing referral delay. Primary care clinicians' unawareness of the rheumatology specialty was the primary reason for referral delay in Gujarat (33.56%) and Delhi and Rajasthan (25.18%). CONCLUSION: Both patient and healthcare professional-related factors contribute to referral delays in RA patients. Major factors causing referral delays include reluctance to refer and inadequate knowledge about rheumatology among primary care physicians and the general public. Patients' education and occupation also influence the timing of referrals to specialty care.

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.

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.

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.

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.

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.

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.

High IL-6 and low IL-15 levels mark the presence of TB infection: A preliminary study.

The host immune response, apart from mycobacterial factors, is a significant determinant in the development of tuberculosis (TB). The purpose of the study was to examine whether the differential serum profiles of cytokines IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-15, IFN-γ, TGF-ß, and TNF-α could discriminate between TB patients and healthy controls and provide insights into pathogenesis. Serum samples from TB patients, TB patient contacts and healthy controls were collected and analyzed by ELISA. The cytokine concentrations obtained were stratified into three groups: below detection limit (BDL), low values, and high values. The differences in cytokine concentrations were analyzed by Fisher's exact test. The statistically significant results were interpreted based on post-hoc analysis of the chi square contingency table using the adjusted residual method. Among the assayed cytokines, there was a statistically significant difference in the detection levels of IL-6, IL-15 and IFN-γ. Levels of IL-1ß, IL-2, IL-4, IL-10, TGF-ß and TNF-α did not vary. Post-hoc analysis of the significant results revealed that dynamic changes in the BDL and high values of cytokines influenced the post-infection cytokine milieu in the study subjects. The study concludes that altered balance in the levels of serum cytokines can be indicative of TB pathogenesis. Hence, profiling of dynamic changes in cytokines would facilitate effective TB diagnostic and treatment strategies.

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.

Neutrophil-lymphocyte ratio, pain perception, and disease activity score may serve as important predictive markers for sustained remission in rheumatoid arthritis.

The implementation of new treatment strategies based on current recommendations has enabled a greater number of patients with rheumatoid arthritis (RA) to achieve remission. However, there are no definite predictors of sustained remission. Moreover, the absence of clear consensus on the time of withdrawal or reduction of treatment further adds to the treatment burden. This pilot study was intended to evaluate the prognostic potential of various RA-related parameters. All the enrolled subjects (n=124) were clinically evaluated on the basis of various parameters including age, gender, duration of illness before the initiation of disease-modifying anti-rheumatic drugs, tender and swollen joints (28 joints), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin percentage, lymphocyte count, total white-blood cell counts, and neutrophil to lymphocyte ratio (NLR). Student's t-test and discriminant function analysis were performed. The specificity of all parameters and their best possible cut-off to predict relapse were calculated using the receiver operating characteristic (ROC) analysis. A significant difference in terms of pain perception, NLR, tendency to have a significant tender joint count and absolute lymphocyte counts was identified between the patients in sustained remission and those in relapse. The ROC analysis indicated that NLR was consistent in predicting remission. CRP, ESR, and/or disease activity score may not be very effective in differentiating patients with sustainable remission/low disease activity. NLR along with patient's perception of pain may assist in predicting sustained remission.

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.

Clinical profiling, treatment characteristics and outcome in Behcet's Disease (BD)-A retrospective cohort study from Karnataka Rheumatology Association (KRA).

BACKGROUND: Behcet's disease (BD) has a heterogeneous and unpredictable phenotype that differs in various geographical areas. OBJECTIVE: To describe the clinical phenotype & outcome of Behcet's disease(BD) from Karnataka, India and compare them with large cohorts from endemic regions. METHODS: Databases of practising rheumatologists from Karnataka were reviewed to retrieve clinical characteristics, course of illness, prescribing information and outcome at last follow-up of patients clinically diagnosed as BD. The classification criteria, namely revised International criteria for Behcet's disease (rICBD) and International study group (ISG) criteria were applied. Outcome was defined as complete or partial remission, persistent disease or relapse. RESULTS: We included 72 patients, equal gender distribution and mean age 37.4 ± 12.8 years from 8 rheumatology centres. Commonest presentations were recurrent oral aphthosis 58(80.6%), genital ulcers 36(50%) and ocular manifestations 40(55.6%). Three-quarters [51/72(70.8%)] fulfilled rICBD criteria whereas only half [36/72(50%)] fulfilled ISG criteria. Apart from glucocorticoids [53/72(73.6%)], frequently prescribed therapies were colchicine 39(54.2%) and azathioprine 35(48.6%). Eleven-patients received biologics(anti-TNF-α) and JAK inhibitors to treat severe organ involvement. HLA-B*51 and pathergy tests were positive in 27/45(60%) and 12/34(35.3%) patients respectively. Outcomes were documented in 94.4%(68/72) patients at median follow-up of 24 (12;36) months. Majority [46/68(67.6%)] had complete remission, 17/68(25%) had partial remission, 4/68(5.9%) had persistent while 1/68(1.5%) had relapsing course. CONCLUSION: Majority of BD patients had orogenital aphthosis and ocular manifestations and an excellent response to treatment. Key Points • In our region, Behçet's Disease primarily manifests with recurrent oral aphthae and ocular involvement, with comparatively lower incidence of severe genital ulcers and neurological involvement than in endemic regions. • Apart from glucocorticoids, colchicine and azathioprine are the most commonly used agents. Biologics and JAK inhibitors are prescribed infrequently, primarily in cases of severe organ involvement. • A significant proportion of patients achieved either complete or partial remission during follow-up, with no observed mortality suggesting a milder disease course and better outcome compared to endemic regions. • Gender, HLA-B*51 status, and pathergy response did not exert any significant influence on the clinical profile or outcome in BD patients in Karnataka.

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.

Serum levels of interleukin-13 and interferon-gamma from adult patients with asthma in Mysore.

Serum protein analysis for noninvasive quantification of airway inflammation in asthma is a promising research tool in the field of lung diseases. Cytokines are believed to have major role in inflammatory process of the airways of the lung. There is an imbalance between T-helper (Th)-2 cells, which secrete interleukin (IL)-4 and interleukin (IL)-13, and Th1 cells, which secrete interferon (IFN)-gamma in asthma. To test the hypothesis that serum IL-13 and IL-4 levels may be elevated whereas IFN-gamma would be decreased in this cohort of patients, a property that could make them possible candidate biomarkers in determining asthma occurrence and severity, we measured concentrations of IL-4, IL-13 and IFN-gamma in serum samples of 88 subjects (44 normal, 12 with mild asthma, 16 with moderate asthma, and 16 with severe asthma). Serum Levels of IL-4, IL-13, and IFN-gamma were determined by an enzyme-linked immune-sorbent assay (ELISA). Median serum level of IFN-gamma in asthmatic patients was 8.0 pg/ml, while it was 11.4 pg/ml in healthy controls. However, the difference was not significant. Among the different age groups in whom IFN-gamma was assessed, the highest median value in both cases and controls was observed in the age group of 31-40 years. The median serum level of IL-13 was 40.0 pg/ml in asthmatic patients and 58.25 pg/ml in healthy controls. The difference was not significant. On subgroup analysis, no significant difference of IFN-gamma and IL-13 between asthma of different severities was observed. The study also revealed nonsignificant difference of serum cytokines with the duration of asthma, number of allergens, and severity of sensitization. Normal serum levels of IFN-gamma and IL-13 in asthmatic patients suggest their neutral role in the inflammatory process; however, more studies are required to establish the effect of these cytokines in adulthood asthma in different ethnic populations.

Moderate regular exercises reduce inflammatory response for physical stress.

Exercises induce pro-inflammatory cytokines. We assessed the effect of different grades of exercises on inflammatory cytokine response. Twenty healthy volunteers performed a single bout of moderate exercise, a single bout of strenuous exercise and one month regular moderate exercise using standardized 10m Shuttle Walk Test. Interleukin-6 (IL-6) and Tumour Necrosis Factor Alpha (TNF-alpha) were estimated by Sandwich ELISA method after each exercise regime. Statistics were run using SPSS software version 11.0, Systat software. Repeated measures ANOVA has been used for analysis of IL-6 values and Friedman test has been used for analyzing TNF-alpha and IL-6 values. Twenty healthy volunteers (18 to 30 years) were chosen for this study. The mean and SEM of plasma levels (pg/ml) of IL-6 before exercise was 10.70 +/- 1.11 pg/ml, whereas, after acute moderate exercise and acute strenuous exercise it was 12.00 +/- 1.09 pg/ml and 13.35 +/- 0.89 pg/ml respectively. interestingly, after one month of moderate exercise the values decreased to; 8.80 +/- 0.65 pg/ml. Mean and SEM of TNF-alpha before exercise was 121.78 +/- 29.06 pg/ml. With acute moderate exercise and after acute strenuous exercise the values were 132.90 +/- 35.75 pg/ml and 112.05 +/- 29.89 pg/ml respectively. After one month moderate exercise the levels decreased to 94.95 +/- 27.29 pg/ml. The observed changes in both IL-6 and TNF-alpha levels before and after both moderate and strenuous exercise were statistically significant. Although there was a slight decrease in the value of both the cytokines after one month of regular moderate exercise compared to baseline value, the difference in the values was not statistically significant. However, both IL-6 and TNF-alpha levels showed overall statistically significant difference among the different grades of exercise. Plasma IL-6 and TNF-alpha increase with acute moderate exercise and IL-6 increases further with acute strenuous exercise. Their levels tend to fall below baseline with one month of regular moderate exercise indicating that regular moderate exercise has beneficial effects.

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.

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.