BackgroundThe 2019 WHO strategy to reduce snakebite burden emphasises the need for fostering research on snakebite treatments. A core outcome set (COS) is a consensus minimal list of outcomes that should be measured in research on a particular condition. We aimed to develop a COS for snakebite research in South Asia, the region with the highest burden.MethodsWe used data from a systematic review of outcomes to develop a long list of outcomes which were rated in two rounds of online Delphi survey with healthcare providers, patients and the public, and potential COS users to develop a COS for intervention research on snakebite treatments in South Asia for five intervention groups. Subsequently, meetings, consultations and workshops were organised to reach further consensus. We defined the consensus criteria a priori.ResultsOverall, 72 and 61 people, including patients and the public, participated in round I and round II of the Delphi, respectively. Consensus COSs (including definition and time points) were developed for interventions that prevent adverse reaction to snake antivenom (three outcomes), specifically manage neurotoxic manifestations (five outcomes), specifically manage haematological manifestations (five outcomes) and those that act against snake venom (seven) outcomes. A priori criteria for inclusion in COS were not met for COS on interventions for management of the bitten part.ConclusionThe COS contributes to improving research efficiency by standardising outcome measurement in South Asia. It also provides methodological insights for future development of COS, beyond snakebite.

INTRODUCTION:Standard triglyceride assays may overestimate true triglyceride concentrations due to endogenous glycerol interference, particularly in type 2 diabetes, where enhanced lipolysis elevates circulating free glycerol. We compared glycerol-blanked and non-blanked triglyceride assays in patients with type 2 diabetes to quantify analytical bias and assess impact on cardiovascular risk indices. METHODS:This cross-sectional study enrolled 200 patients with type 2 diabetes and 200 healthy control individuals. Serum triglyceride levels were measured using glycerol-blanked (Sekisui) and nonblanked (Beckman Coulter) enzymatic assays. Bias assessment, correlation analysis, and impact on atherogenic index of plasma were evaluated. RESULTS:Median nonblanked triglyceride values were substantially higher than glycerol-blanked triglyceride values in control individuals (129.5 vs 120.95 mg/dL, P = .02) and patients with type 2 diabetes (158.5 vs 136.85 mg/dL, P = .0019). Overestimation was greater in patients (median difference, 16.1 mg/dL) than in control individuals (9.95 mg/dL, P = .0001). Bland-Altman analysis showed higher mean (SD) bias in patients with type 2 diabetes (-21.25 [41.51] mg/dL) than in control individuals (-13.26 [31.26] mg/dL). The triglyceride- glycerol-blanked triglyceride difference correlated with glycated hemoglobin values in individuals with type 2 diabetes (ρ = 0.141, P = .0473). DISCUSSION:Glycerol-blanked triglyceride assays provide more accurate lipid assessment in type 2 diabetes, improving cardiovascular risk stratification and therapeutic decision-making.

The saw-scaled viper Echis carinatus, one of the "Big Four" causes of snakebites in India, is found from Sri Lanka to eastern Iraq. To investigate clinical reports regarding the limited efficacy of Indian polyvalent antivenom (IPAV) against envenomation in Echis carinatus sochureki (ECS) in northwestern India, we obtained 22 snakes from three locations in Rajasthan and identified 148-174 toxin isoforms belonging to 21-25 toxin families in their venom using a bottom-up proteomics approach. All samples showed a high abundance of snake venom metalloproteinases (SVMPs), particularly SVMP class III. Other major components were phospholipases A2, L-amino-acid oxidases, snake venom serine proteases and snaclecs (C-type lectins). Variation in venom composition among locations in Rajasthan, compared to E. c. carinatus (ECC) from southern India, was primarily due to differences in the relative abundance of these toxin families. Recognition of all venom components by IPAV was poor at lower antivenom concentrations. Notably, SVMP classes II and III were poorly recognized at all venom-to-antivenom ratios in all ECS venoms, and a plasma clotting assay revealed poor neutralization of procoagulant activity. This collaborative study highlights the need for the development of regional antivenoms to effectively treat snakebites in northwestern India.

BACKGROUND:India experiences the highest snakebite burden globally, with 58 000 predicted deaths annually. The central Indian state of Madhya Pradesh is thought to have a substantial snakebite burden and provides compensation to families who can demonstrate by postmortem and hospital treatment reports that their relatives have died due to snakebite. This study represents the first report on the frequency of distribution of compensation for snakebite deaths in Madhya Pradesh. METHODS:Statewide snakebite death compensation data from 2020-2021 and 2021-2022, provided by the Madhya Pradesh health authorities, were analysed alongside interviews with 15 families that described the events that ultimately led to their compensation claims. RESULTS:Compensation was paid to a total of 5728 families, with a total value equating to 22 912 Lakhs (approximately US${\$}$27.94 million). Families described commonly recognised snakebite risk factors and behaviours in the events that resulted in their relatives' deaths. CONCLUSIONS:The snakebite burden in Madhya Pradesh is significant, both in terms of mortality and economic expenditure of the state. Sustained investment in preventative interventions, as well as monitoring of the rate of compensation payouts due to snakebite death as a measure of intervention effectiveness, should be considered to substantially reduce snakebite incidence and mortality.

BACKGROUND:Snakebite is a neglected tropical disease that causes significant morbidity and mortality in India. In this study, we describe the clinical characteristics and outcomes of Echis carinatus sochureki envenoming from Western Rajasthan. We document the clinical ineffectiveness of the currently available Indian polyvalent antivenom in managing E. c. sochureki envenoming. METHODS:In this ambispective study, conducted from 14 April 2019 to 15 April 2024, we enrolled all patients presenting to our emergency department at a tertiary care centre in Jodhpur, Rajasthan, with a history of snakebite. After they provided informed consent, the demographic details, bite geo-location, bite-to-antivenom time, antivenom dose, coagulation profile, mortality and duration of hospital stay of those patients with E. c. sochureki envenoming were recorded. RESULTS:Of 210 patients screened, 105 had E. c. sochureki envenoming, 103 venom-induced consumption coagulopathy, 36 (34.3%) local bleeding and 55 (52.3%) systemic bleeding. The median bite-to-antivenom time was 2 (IQR: 1.13-4.0) h. The median antivenom dose was 22 (IQR: 10-30) vials. Of 92 patients who received antivenom, 63 (68.4%) were unresponsive. Total antivenom dose and geographical location (West zone) were significant predictors of antivenom unresponsiveness. Fifty-three of 70 patients (75.7%) had delayed hypofibrinogenaemia. The mean hospital stay was 8.3±7.1 d with nine (8.6%) mortalities. CONCLUSIONS:Our study highlights the alarming finding of poor antivenom response to E. c. sochureki envenoming, with significant clinical bleeding and delayed coagulopathy. There is an urgent need for region-specific antivenom in Western India.

The receptor for Advanced Glycation End Products (RAGE) gene polymorphism influences matrix metalloproteinase 9 (MMP-9) levels and its expression, but their genetic impact on the risk of nephropathy in type 2 Diabetes Mellitus remains unexplored in the north Indian population. This study examined the role of RAGE and MMP-9 polymorphisms and their circulating level among type 2 Diabetes patients with nephropathy. The case-control study included 100 type 2 Diabetes patients with nephropathy and 100 healthy controls. Biochemical parameters were measured using a clinical chemistry analyzer, and RAGE and MMP-9 polymorphisms were genotyped using a pre-designed TaqMan 5′ nuclease assay and real-time PCR. The circulating levels of AGE, soluble RAGE, and MMP-9 were estimated using an enzyme-linked immunosorbent assay (ELISA). The MMP-9 and AGEs levels were significantly increased and sRAGE was decreased in DN compared to control. The rs184003 TT genotype and T allele of RAGE was associated with the risk of nephropathy (OR: 5.65 (1.5–21.1), p < 0.014). The 1704G > T, TT + GT genotypes showed increased levels of blood glucose, HbA1c, LDL, TC, TG and UACR compared to GG carrier The MMP-9, -1562 C/T was not significantly associated with susceptibility to DN. However, TT + TC genotypes of MMP-9 showed increased blood glucose, HbA1c and SBP compared to CC carriers. Linear regression analysis showed that increased TAG (P = 0.046) and lower sRAGE (P = 0.001) levels were predictors of increased UACR. This study suggested that the TT genotype and T allele of rs184003 RAGE is associated with the risk of nephropathy in patients with T2DM. We also found that increased TAG and lower sRAGE levels were predictive factors for increased albuminuria in DN.

Background: Overweight rheumatoid arthritis (RA) patients are known to have less joint space narrowing progression (JSN). Early RA cartilage damage may be influenced by body mass index (BMI) and fat distribution [1]. Obesity diminishes the likelihood of attaining remission in RA and has adverse effects on disease activity and patient-related outcomes (PROs) during therapy [2]. Objectives: To study the relationship between BMI and whole-body DEXA parameters including fat mass, lean mass, fat mass index, lean mass index, and fat mass percentage with radiographic erosions and serum RANK ligand and osteoprotegerin (OPG) ratio and to study the relationship between radiographic erosions, serum RANKL/OPG ratio with PROs [Indian Health Assessment Questionnaire for disability, PROMIS fatigue score, Pittsburgh Sleep Quality Index, Patient Health Questionnaire 9 for depression and Rheumatoid Arthritis Impact of Disease (RAID) score]. Methods: This cross-sectional study was conducted after Ethics Committee approval in patients with RA at our rheumatology clinic from March 2022 to September 2023, in Jodhpur, India. After obtaining informed written consent, demographic, clinical, anthropometric, and treatment details of the patients were collected. Whole body DEXA was done using a DEXA scanner (Hologic Corp, model no - Horizon A S/N 303237M), and X-rays of bilateral hands and feet were done. Serum levels of RANKL and OPG were determined using ELISA kits. Bivariate correlation analysis between BMI, fat mass, lean mass, fat mass index, lean mass index, and fat mass percentage with radiographic erosion parameters and serum RANKL: OPG ratio was done. Bivariate correlation analysis was also done between erosion parameters (radiographic erosion and RANKL: OPG ratio) and PROs. Results: We enrolled 144 patients in the study with a mean age of 46.41±13.23 years and 75.4% were females. The mean BMI was 23.7±5.0 kg/m2. Whole-body DEXA was done for 102 patients. The median fat mass, lean mass, fat mass index, lean mass index, and fat mass percentage in the study population were 22.83±11.10 kg, 33.04±10.70 kg, 9.60±4.90 kg/m2, 13.90±3.20 kg/m2 and 39.80±9.60 % respectively. RANKL: OPG ratios were calculated for 75 patients and the median was 1.2975±2.07. The median joint erosions, JSN, and joint destruction were 5.0±8.0, 15.0±8.5, and 0.0±1.0 respectively. A significant negative correlation was seen between joint erosions and BMI (r = -0.349, p = 0.008), fat mass (r = -0.281, p = 0.034), lean mass (r = -0.291, p = 0.036), and lean mass index (r = -0.363, p = 0.005). JSN and total number of destroyed joints inversely correlated with lean mass index (r = -0.265, p = 0.047 and r = -0.309, p = 0.019 respectively). A negative correlation nearing significance was seen between the RANKL: OPG ratio and BMI (r = -0.187, p = 0.061) (Table 1). No significant correlation was obtained between radiographic erosion parameters, serum RANKL: OPG ratio, and PROs. Conclusion: Obesity affects the progression of erosions in patients with RA. Radiographic erosion parameters were inversely correlated with BMI and whole body fat mass. Hormonal processes have been proposed as potential explanations for how BMI affects radiographic progression; while further research is needed to confirm the same. REFERENCES: [1] Rydell E, Forslind K, Nilsson J-Å, Karlsson M, Åkesson KE, Jacobsson LTH, et al. Predictors of radiographic erosion and joint space narrowing progression in patients with early rheumatoid arthritis: a cohort study. Arthritis Res Ther. 2021 Jan 14;23(1):27.[2] Liu, Y., Hazlewood, G.S., Kaplan, G.G., Eksteen, B. and Barnabe, C. (2017), Impact of Obesity on Remission and Disease Activity in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Arthritis Care & Research, 69: 157165. https://doi.org/10.1002/acr.22932 Acknowledgements: NIL. Disclosure of Interests: None declared.

Background: Remission in rheumatoid arthritis (RA) is a state with an absence of disease activity. Remission at 6 months has been shown to predict future good outcomes such as arresting radiographic progression and better functional status at 12 and 24 months. ACR EULAR has endorsed Boolean2.0 in the revised remission criteria in 2022. Comparison of performance of various commonly used remission criteria (Disease Activity Score 28 (DAS28 ESR), Disease Activity Score 28 CRP (DAS28 CRP), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Boolean, Boolean2.0 and BooleanX in patients with RA from India and its association to Patient Related Outcomes (PROs) is not studied. In this study, we compare the various remission criteria in patients with RA from India and explore its association with PROs. Objectives: To compare the performance of various remission criteria in patients with RA, validate the newly endorsed Boolean-based remission criteria, and explore its relationship with PROs in RA. Methods: In this prospective hospital-based study, we enrolled patients with RA attending our Rheumatology Clinic at Jodhpur, India after Ethics Committee approval. Patients were assessed clinically after informed written consent and different ACR EULAR disease activity scores (DAS28, SDAI, CDAI, Boolean, Boolean2.0, and BooleanX) and various PROs Visual Analogue Scale (VAS) for pain, PROMIS® fatigue score, Indian Health Assessment Questionnaire (IHAQ) disability index, Patient Health Questionnaire (PHQ-9) depression score, Pittsburgh Sleep Quality Index (PSQI) and Rheumatoid Arthritis Impact of Disease (RAID) scores were obtained at enrollment and 6 months. Agreement between Boolean-based and index-based criteria were analyzed using kappa analysis at enrollment and 6 months. Bivariate correlation analysis and binary logistic regression analysis were done to correlate between various remission criteria and PROs at enrollment and 6 months. Results: Out of 155 participants, 83.87% were females with a median age of 46.7±12.1 years. Out of these, 32 patients (20.64%) belonged to early RA while 123 (79.35%) patients had established RA. At enrolment, 11.61% (n = 18) were on biologicals, 29.1% (n = 45) on methotrexate, and 59.35% (n = 92) on combination Disease-modifying Antirheumatic Drugs (DMARDs). The proportion of patients in remission at 6 months using DAS28-ESR was 81.30%, DAS28-CRP was 76.10%, SDAI was 67.10%, CDAI was 69.60%, Boolean was 40.20% and Boolean2.0 was 65.10% (Figure 1). In our study, all remission criteria showed agreement between each other. Boolean2.0 showed more remission rates compared to Boolean1.0 and a substantial level of agreement between SDAI and CDAI at 6 months (Table 1). Our study showed a significant reduction in DAS28-ESR, DAS28-CRP, SDAI, and CDAI at 6 months and similarly a significant reduction in VAS, PROMIS® fatigue score, IHAQ, PSQI, PHQ-9, and RAID at 6 months following starting treatment. However, none of the PROs revealed any correlation with remission criteria at enrollment and 6 months following initiation of treatment. Conclusion: This study provides evidence of external validation of the newly proposed modification of the Boolean ACR/EULAR remission criteria. Our results replicate the findings that a Boolean definition using 2 cm as the threshold for patient global assessment of disease activity (Boolean2.0) yields better agreement than Boolean1.0. With the validation of Boolean2.0 in our settings, our data support the revised ACR/EULAR remission criteria as a target in clinical practice in India. None of the remission criteria can replace PROs and thus, PROs should be measured separately in assessing treatment targets. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background: Platyceps ventromaculatus is a non-front-fanged colubrid snake of unknown medical significance. In this study, we highlight the clinical manifestations and outcomes of P. ventromaculatus bites. We also emphasise the need to create awareness among clinicians and the public for its potential to be confused with serious venomous bites such as Echis carinatus sochureki. Methods: This series is part of an ongoing observational clinical study from our tertiary care hospital in Jodhpur, India on the profile and outcomes of snakebite envenoming. Data was collected after approval from Institute Ethics Committee. The date and time of the bite, geographical location, type of human-snake conflict, time-toreach a healthcare facility, antivenom used (dose), and outcomes were recorded. We retrospectively examined our clinical data for images suggestive of P. ventromaculatus and present the clinical details of these patients. The photographs were identified utilising taxonomic keys for species identification. Results: A total of four images and three patients with bites due to P. ventromaculatus were identified. The clinical effects included mild local erythema, pain, transient local bleeding, and edema. All bites occurred during daylight hours, 2 during agricultural activities, and one at home. Twenty-minute Whole Blood Clotting Test was persistently prolonged for 12 h after the bite in one patient. All patients were treated symptomatically, observed at the emergency department, and discharged within 24 h. None of the patients received antivenom. Conclusions: To our knowledge, P. ventromaculatus has so far not been reported to result in envenoming or medically significant bites. This study highlights that Platyceps bite can present with clinically significant local and possibly systemic findings that may lead to confusion with saw-scaled viper (Echis) envenoming. Clinicians must receive appropriate training so as to be aware and recognize regional snake species that do not require antivenom so as to avoid unnecessary antivenom administration.

Background: Rheumatoid arthritis (RA) affects over 10 million individuals in India. Along with the disease activity scales assessing the severity of the disease, patient-reported outcomes (PRO) are equally important in managing RA. Rheumatoid arthritis impact of disease (RAID) score is a valuable tool for assessing the impact of RA from the patient's perspective. However, validating RAID scores in Hindi is essential to improve the accessibility of patients with RA who face challenges with the English version. This not only enhances accessibility but also streamlines the process, reducing the burden on both the healthcare system and patients in rheumatology clinics across India. Objectives: To validate the Hindi version of RAID (H-RAID) score and to determine its relationship with other disease activity scores Methods: After Ethics Committee approval, a cross-sectional study was conducted at the rheumatology clinic in our tertiary care teaching hospital, in Jodhpur, India. The translation process included - back translation, expert reviews, pre-testing, face validation, content validation, and cognitive interviews with patients. Demographic details were collected along with an assessment of disease activity score 28 (DAS28), patient global assessment of disease activity (PtGA), pain visual analogue scale (VAS), H-RAID, and Indian health assessment questionnaire (IHAQ). Internal consistency was assessed using Cronbach alpha and correlation with DAS28 and IHAQ was performed. Confirmatory Factor Analysis (CFA) using LaVan and Sem Tools R packages was performed to confirm the factor structure of H-RAID. Results: RAID was translated into Hindi with the help of language experts and face and content validation was done with experts in the field and suggested changes were made. The content validation index (n=10 experts) was calculated as 0.96. Cognitive interviews were done in patients with RA. The final version of H-RAID was then administered to the patients enrolled. A total of 238 patients with RA were enrolled with a mean age of 47.6 ± 11.9 years and 88.7% were females. Out of 238 patients, 55 (23.1%) were in remission (DAS28-CRP <2.6) while 41 (17.2%) had low disease activity (DAS28-CRP 2.6-3.2), 116 (48.7%) had moderate disease activity (DAS28-CRP 3.2-5.1), and 26 (10.9%) had high disease activity (DAS28-CRP >5.1). The median H-RAID score was 4.09 (Figure 1). Internal consistency calculated using Cronbach alpha was 0.858. H-RAID correlated positively with disease activity score, DAS28-CRP (r = 0.385, p <0.001), PtGA scores (r = 0.530, p <0.001), pain VAS (r = 0.639, p <0.001), and established PRO - IHAQ (r = 0.532, p <0.001). Confirmatory Factor Analysis resulted in an acceptable model fit after adjustments with non-multicollinear factors and factor loadings exceeding the 0.3 cutoff (CFA value ranging from 0.45 to 0.79) compared to the initial Model 1 (Figure 2). The CFA of the single-factor model of RAID, the model did not fit the data. Modification Indices (MI, sometimes called a LaGrange Multiplier) estimated the amount by which the chi-square would be reduced if a single parameter restriction were to be removed from the model. After the inclusion of 3 correlated residuals (Item 1- Item 2, Item 3- Item 5 and Item 4- Item 6) to the model, the CFA showed an acceptable model fit (Figure 2). The factors were not multicollinear because all r values were less than 0.85, which indicated good discrimination between the factors. The factor loadings for all items exceeded the cut-off value of 0.3 (0.45 to 0.79). Conclusion: H-RAID is a valid tool for assessing the impact of RA across various dimensions of individuals' lives in the Indian context. REFERENCES: [1] Dougados, M., Brault, Y., Logeart, I. et al. Defining cut-off values for disease activity states and improvement scores for patient-reported outcomes: the example of the Rheumatoid Arthritis Impact of Disease (RAID). Arthritis Res Ther 14, R129 (2012). https://doi.org/10.1186/ar3859 Acknowledgements: Prof. Pankaj Bhardwaj, Academic Head School of Public Health and Prof. Mahendra Kumar Garg, Head of Department of Internal Medicine. Disclosure of Interests: None declared.

Background: The economic burden of Rheumatoid arthritis (RA) relates to the cost of the treatment which is significant for the individual and also for the health care and social care system. Assessing the economic impact of RA on patients is an important prerequisite for allocating resources and managing the disease from the health system perspective. Objectives: The study aimed to determine the economic burden of the illness and assess the quality of life in patients with RA in our setting. Methods: After Institutional Ethics Committee approval, a cross-sectional study was conducted at the rheumatology clinic at All India Institute of Medical Sciences (AIIMS), Jodhpur, India. The data collection tool used to estimate the Cost of Illness (COI) of patients with RA included a semi-structured, pretested questionnaire and individual patient interviews after receiving the consent. Disease activity was calculated using the Disease Activity Score (DAS28-CRP). The quality of life of the patients was analyzed based on the EQ-5D-5L questionnaire. The EQ-5D is a descriptive and visual analog scale (VAS) framework that measures health in 5 dimensions, such as mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression. Results: A total of 225 patients were enrolled. The mean age group was 47.8 ± 12.7 years and about 79.6% were females. Occupational status - 85 (82.2%) were unemployed, followed by skilled workers (8.9%), semiskilled workers (6.7%), and semi-professionals (2.2%). The majority (92.9%) of patients were married. About 28.9% of patients belonged to the upper middle class, 24.9% to the middle class, 20.4% to the upper class, 17.4% to the lower middle class, and 8.4% to the lower class based on their per capita income (Table 1). A total of 139 patients had DAS28-CRP calculated, of whom, 30 (13.3%) were in remission, 8 (3.6%) had low disease activity, 66 (29.3%) had moderate disease activity and 35 (15.6%) had high disease activity.The annual median (IQR) for the total direct cost of the RA patients was Indian Rupee (INR) 18005 (12907-25393)/ EUR 198.7. The annual median indirect cost (IQR) for the loss of productivity was INR 2800 (1500-4000)/ EUR 30.9. The annual median (IQR) for total cost (direct cost + indirect cost) was INR 19076 (13602-27776)/ EUR 210.5 (Table 2). Indirect costs were mainly calculated for loss of productivity for patients and their caregivers. A total of 118 (52.4%) patients were using health insurance. Among those insured, 44% were under an insurance scheme under the Government of India, 4.9% were government employees, 3.1% were using other insurance schemes and 1.8% of patients were using private insurance. The median (IQR) EQ- 5D utility score was 0.56 (0.17- 0.74). Conclusion: The total cost of disease as well as indirect cost was lower as compared to other studies, the probable reason for which could be the subsidized treatment at AIIMS, a tertiary care teaching institute under the Government of India. More than 60% of the patients experienced slight and moderate problems in each domain of the EQ-5D 5L tool. The median EQ-5D utility score was comparatively lower in comparison to that of other countries [1]. Hence it is vital to diagnose and control the disease at an early stage to control the economic burden on the patient and to plan therapeutic and rehabilitation interventions considering various parameters of quality of life. This study will help advance our knowledge of the costs incurred by patients with RA and is expected to serve as a reference for future health-related policy development. REFERENCES: [1] Haridoss M, Bagepally BS, Natarajan M. Health-related quality of life in rheumatoid arthritis: Systematic review and meta-analysis of EuroQoL (EQ-5D) utility scores from Asia. Int J Rheum Dis. 2021 Mar;24(3):314-326. doi: 10.1111/1756-185X.14066. Epub 2021 Jan 23. PMID: 33486900. Acknowledgements: Prof. Pankaj Bhardwaj, Academic Head School of Public Health and Prof. Mahendra Kumar Garg, Head of Department of Internal Medicine. Disclosure of Interests: None declared. Table 2Direct cost and indirect cost incurred by patients with RA in the last one yearCodeCost ComponentsMedian (INR/ EUR)IQRDCTTotal Direct cost18005/ 198.7(12907-25393)ICTTotal Indirect cost2800/ 30.9(1500 -4000)TCTotal cost of disease19076/ 210.5(13602-27776)RA: Rheumatoid Arthritis; INR - Indian Rupee; EUR - Euro; IQR - Interquartile

Background: Systemic autoimmune rheumatic disease-associated pulmonary arterial hypertension (SARD-PAH) is a major contributor to mortality. Few studies have explored the clinical profile and outcomes of this condition in India. Objectives: To describe the profile of SARD-PAH of the patients attending the rheumatology clinic at our centre, and to assess the response to therapy at 6 months from the diagnosis of PAH. Methods: We analysed the 4-year records of SARD-PAH patients who had at least 6 months of follow-up echocardiographic data since the diagnosis of PAH. Patients were diagnosed with SARD-PAH if they had definite evidence of a systemic autoimmune rheumatic disease, and echocardiographic PAH as defined by a right ventricular systolic pressure (RVSP) ≥30 mmHg and no pulmonary valve pathology. We used echocardiographic data as right heart catheterisation is not available at our centre, and is available only in a few centres across the country. Demographic data, diagnoses, clinical manifestations, details of autoantibodies, echocardiographic data at baseline and at 6 months, as well as details of therapy, were retrieved. Patients were considered to be responders if they had a decline in RVSP by ≥15mmHg or normalisation of pressures as measured by echocardiogram at 6 months. Results: Twenty-one patients were included, 86% were females with a median age of 42 years. The most common diagnosis was an overlap syndrome (43%), followed by mixed connective tissue disorder and systemic sclerosis (each 19%). Interstitial lung disease was present in 48% of patients. The median baseline RVSP was 47mm Hg, and at 6 months it was 36mm Hg (for n= 15 patients), while 6 patients had a qualitative report of normal RVSP. No patient had LV dysfunction either at baseline or at follow-up. No patient had chronic thromboembolic pulmonary hypertension.Fifteen (71%) patients responded to therapy. Almost all patients (95%) had received anti-PAH therapy, and almost all of them (95%) received immunosuppression for any indication. Conclusion: We describe one of the first SARD-PAH cohorts from India with follow-up data. Our study shows that most patients (71%) respond to appropriate anti-PAH measures and immunosuppression. Long-term, prospective follow-up studies are required to better understand this condition in our population and to design appropriate therapy. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.Table 1Baseline data of patients. (Values in brackets indicate percentages unless indicated otherwise)All patients (n=21)Responders (n=15)Non-responders(n=6)Age in yearsMedian(IQR)42(16)42(18.5)40.5 (21.5)Females18 (86)13 (87)5 (83)DiagnosisOverlap syndrome9 (43)8 (53)1 (17)Systemic sclerosis4 (19)2 (13)2 (33)MCTD4 (19)4 (27)0 (0)SLE2 (10)0 (0)2 (33)RA1 (5)0 (0)1 (17)Antisynthetase syndrome1(5)1 (7)0 (0)Associated clinical featuresInterstitial lung disease10 (48)7 (47)3 (50)Raynaud’s phenomenon16 (76)13 (87)3 (50)Myositis7 (33)7 (47)0 (0)Arthritis/ arthralgia12 (57)9 (60)3 (50)Cutaneous manifestations13 (62)9 (60)4(67)Renal manifestations3 (14)3 (20)0 (0)Antiphospholipid syndrome2 (10)2 (13)0 (0) Table 2Echocardiographic data and therapy details. (Values in brackets indicate percentages unless indicated otherwise)All patients (n=21)Responders (n=15)Non-responders(n=6)Baseline RVSP in mm HgMedian (IQR)47 (13)45 (11)51(12.5)6-month RVSP in mm HgMedian (IQR)36 (31)[n=15]29 (2)[n=9]68(30.5)[n=6]Anti-PAH therapyNone1 (5)0 (0)1 (17)Nifedipine alone5 (24)4 (27)1 (17)Tadalafil alone1 (5)1 (7)0 (0)Nifedipine and Tadalafil9 (43)7 (47)2 (33)Ambrisentan and Tadalafil1 (5)1 (7)0 (0)Nifedipine,Tadalafil and Ambrisentan4 (19)2 (13)2 (33)ImmunosuppressionSteroids11 (52)8 (53)3 (50)Methotrexate8 (38)7 (47)1 (17)Mycophenolate Mofetil5 (24)4 (27)1 (17)Cyclophosphamide4 (19)3 (20)1 (17)Rituximab3 (14)2 (13)1 (17)Azathioprine1 (5)1 (7)0 (0)No IS drug1 (5)0 (0)1 (17)Single IS drug10 (48)7 (47)3 (50)Two IS drugs8 (38)6 (40)2 (33)Three IS drugs2 (10)2 (13)0 (0)

Background: Empathy is an attribute that involves understanding the patient combined with a capacity to communicate this understanding with an intention to help (1). Empathy in clinical care has been associated with better outcomes for the patients and lower disease activity is associated with a higher degree of trust in physicians in rheumatology (2). Jefferson Scale of Patient's Perceptions of Physician Empathy (JSPPPE) is a validated instrument that assesses patient ratings of physician empathy. Objectives: We aimed to explore the relationship between patient-reported physician empathy and patient-reported outcomes of disease in the context of rheumatoid arthritis (RA) using the Hindi version of JSPPPE (Hi-JSPPPE). Methods: A cross-sectional study after Institute Ethics Committee approval in patients with RA presented to the rheumatology clinic in our tertiary care teaching hospital, at Jodhpur, India, catering to approximately 900+ patients with RA was conducted. After informed written consent, patients were administered a validated Hindi version of JSPPPE. Hi-JSPPPE is a 5-item measure and the items are answered on a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). Simultaneously, patients reported outcomes (PROs) namely Patient Health Questionnaire-9 (PHQ-9), Patient Global Assessment (PtGA), Rheumatoid Arthritis Impact of Disease (RAID), and Pittsburgh Sleep Quality Index (PSQI) were calculated. Correlations between Hi-JSPPPE scores and patient-reported outcomes and between individual Hi-JSPPPE items and RAID components were calculated using Spearman's correlation coefficient. Binary logistic regression was done using RAID as the dependent parameter and Hi-JSPPPE score as a predictor. A Receiver Operating Characteristic (ROC) curve was constructed to determine the optimal cut-off for Hi-JSPPPE score for defining RAID remission score in our population (3). Results: A total of 239 patients with RA were enrolled in the study, with a median age of 47 years (38-55), 191 (79.9%) were females and the median duration of RA was 5 years (2-5). The median patient global assessment was 3 (2-5) and median RAID scores were 2.69 (1.1-4.07). Depression was present in 111 (46.4%) and impaired sleep was present in 190 (79.5%) patients. Patients reported Hi-JSPPPE scores for 20 clinicians in the rheumatology clinic. Correlations between Hi-JSPPPE and PROs showed significant negative correlation with RAID (r = -0.235 p <0.001), and PHQ-9 (r = -0.025, p = 0.001). Correlations of each item of Hi-JSPPPE with individual components of RAID had significant negative correlations with almost all of them except sleep and coping (Table 1). Hi-JSPPPE had no significant correlations with PSQI, and PtGA. Binary logistic regression analysis showed that the Hi-JSPPPE score could predict the RAID score (cut off <2.32) {OR -0.220; 95% CI 0.69 - 0.93}. Hi-JSPPPE score of 29.5 had 99.1% sensitivity and 86.99% specificity to predict RAID score of 2.32 (AUC 0.596, 95% CI 0.525 - 0.668, P = 0.01) (Figure 1). Conclusion: Hi-JSPPPE has been found to correlate well with RAID as a composite score and as well as at individual item levels. Hi-JSPPPE score of 29.5 out of 35 had good sensitivity and specificity in predicting a RAID score of 2.32. To our knowledge, ours is the first study to conclusively show that physician empathy is key to achieving PRO targets in RA. Hence, interventions to improve clinician empathy may emerge as an important strategy in RA management. REFERENCES: [1] Derksen F, Bensing J, Lagro-Janssen A. Effectiveness of empathy in general practice: a systematic review. Br J Gen Pract J R Coll Gen Pract. 2013;63(606):e76-84. doi:10.3399/bjgp13X660814 [2] Georgopoulou S, Prothero L, D'Cruz DP. Physician-patient communication in rheumatology: a systematic review. Rheumatol Int. 2018 May;38(5):763-775. doi: 10.1007/s00296-018-4016-2. Epub 2018 Mar 26. PMID: 29582095; PMCID: PMC5910487. [3] S Kumar P, Kumar P H A, Garg MK, et al. AB0210 CAN RHEUMATOID ARTHRITIS IMPACT OF DISEASE (RAID) SCORE BE USED AS A PATIENT REPORTED OUTCOME BASED TARGET IN A TREAT-TO-TARGET APPROACH: A PROSPECTIVE STUDY FROM INDIA. Annals of the Rheumatic Diseases 2023;82:1289. Acknowledgements: Dr Jyoti Jain, Department of Internal Medicine and Thomas Jefferson University (TJU). Disclosure of Interests: None declared.

Background: In patients with rheumatoid arthritis (RA), obesity has been linked to poorer response to disease-modifying medications, increased disease activity, and decreased achievement of remission (1, 2). Weight loss has been associated with increased chances of remission (1). As of now, there are limited studies in the Indian population to explore the relationship between fat distribution, disease activity, and Patient Reported Outcomes (PROs). Objectives: To study the relationship between body mass index (BMI) and whole-body dual-energy x-ray absorptiometry (DEXA) parameters including fat-mass, lean mass, fat mass index, lean mass index and fat mass percentage with disease activity (DAS28) and PROs [Indian Health Assessment Questionnaire for disability, PROMIS fatigue score, Pittsburgh Sleep Quality Index, Patient Health Questionnaire 9 for depression and Rheumatoid Arthritis Impact of Disease (RAID) score]. Methods: In this cross-sectional study we recruited patients with RA at our rheumatology clinic from March 2022 to September 2023, in Jodhpur, India. Demographic, clinical, anthropometric, and treatment details of the patients were collected after informed written consent. Whole body DEXA was done using a DEXA scanner (Hologic Corp, model no - Horizon A S/N 303237M) (Image 1), and PROs were measured using relevant tools. Bivariate correlation analysis of BMI, fat mass, lean mass, fat mass index, lean mass index, and fat mass percentage with DAS28CRP and PROs was done. Binary logistic regression was done to see if BMI and fat distribution indices could predict disease activity and PROs. Results: Of the 144 patients enrolled in the study, the mean age was 46.41±13.23 years and 75.4% were females. Mean BMI was 23.7±5.0 kg/m2, 16.44% were overweight, 23.97% were pre-obese and 13.01% were obese. Whole-body DEXA was done for 102 patients. The median fat mass, lean mass, fat mass index, lean mass index, and fat percentage in the study population were 22.83±11.10 kg, 33.04±10.70 kg, 9.60±4.90 kg/m2, 13.90±3.20 kg/m2 and 39.80±9.60 % respectively. There was no significant correlation between BMI and DAS28 or PROs. A significant positive correlation was obtained between whole body fat mass and DAS-CRP (r = 0.198, p = 0.046) (Table 1), whole body fat percent and depression (PHQ9 depression score) (r = 0.187, p = 0.046), whole body fat mass and RAID composite score (r = 0.204, p = 0.04) and negative correlation was noted between lean mass and PROMIS Fatigue T score (r = -0.212, p = 0.033). None of the DEXA indices evaluated could reliably predict DAS28 and PROs using binary logistic regression models. Conclusion: Obesity is prevalent in RA patients (13.01%). While BMI was not related to disease activity, whole body fat mass correlated with disease activity and RAID composite score. Lean mass was inversely related to fatigue. Our study highlights the relationship of body fat composition with disease activity and patient-reported outcomes suggesting that interventions aimed at optimizing fat distribution might have a role in achieving treatment targets and better patient-reported outcomes in RA. REFERENCES: [1] Moroni L, Farina N, Dagna L. Obesity and its role in the management of rheumatoid and psoriatic arthritis. Clin Rheumatol. 2020 Apr;39(4):1039–47. [2] Son KM, Kang SH, Seo YI, Kim HA. Association of body composition with disease activity and disability in rheumatoid arthritis. Korean J Intern Med. 2021 Jan;36(1):214–22. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background Sleep disorders are prevalent in rheumatoid arthritis (RA). Sleep is closely related to disease activity, depression, stress, fatigue and pain [1]. Community prevalence of sleep disorders in India varies from 6.2% to 36.3% [2,3]. Studies assessing sleep quality in the Indian population with RA are limited. Objectives To assess the prevalence of impaired sleep quality using Pittsburgh Sleep Quality Index (PSQI) and determine factors predicting impaired sleep quality in patients with RA. Methods A cross-sectional study was conducted in patients with RA presenting to our rheumatology clinic after informed consent and Ethics Committee approval from January 2021. Sleep quality was assessed by PSQI, depression by Patient Health Questionnaire (PHQ-9) and Quality of life by Indian Health Assessment Questionnaire (IHAQ). Disease activity was assessed using Disease Activity Index (DAS28 CRP) and Clinical Disease Activity Index (CDAI). Serum samples for interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were collected and stored at -800 C. Relationship of fatigue was examined with age, serum TNF-α, IL-1, IL-6, CDAI, DAS28 CRP and patient global assessment (PtGA) using Spearman correlation coefficient. Linear regression analysis was performed to determine the predictors of impaired sleep quality in patients with RA. Results One hundred and fifty-four patients were enrolled, 133 were females (86.3%). Median pain VAS score was 6[2]. Mean DAS was 4.35 ± 1.31, mean CDAI: 19.75 ± 7.91 and median IHAQ was 9.5[8]. The prevalence of depression (PHQ-9 >10) was 5.8% (n = 9) with a median PHQ-9 of 2[3]. One patient was on tofacitinib, 20 were on methotrexate monotherapy and others were on combination of conventional DMARDs.The prevalence of impaired sleep (PSQI >5) was 8.4% (n = 13) with a median PSQI of 2[2]. PSQI had significant correlation with PHQ-9 (r = 0.471, p<0.0001), IHAQ (r = 0.288, p<0.0001), DAS28 (r = 0.197, p = 0.015) and CDAI (r = 0.235 p = 0.003). Age, pain VAS, serum TNF-α, IL-1 and IL-6 had no correlation with PSQI. Among individual components of DAS, PtGA (r = 0.296 p <0.0001) alone correlated with PSQI. PHQ-9, IHAQ and PtGA were significant predictors of impaired sleep quality (Table 1). Conclusion Compared to other studies within India, our patients had very low prevalence of impaired sleep quality. Sleep quality significantly influences disease activity likely by affecting PtGA. Risk factors for poor sleep quality are presence of depression, poor quality of life and patient global assessment of disease activity. Hence a holistic management of RA must involve addressing these risk factors. References [1] McBeth J, Dixon WG, Moore SM, Hellman B, James B, Kyle SD, et al. Sleep Disturbance and Quality of Life in Rheumatoid Arthritis: Prospective mHealth Study. J Med Internet Res. 2022 Apr 22;24(4):e32825.[2] Ramaswamy G, Premarajan KC, Kar SS, Narayan SK, Thekkur P. Prevalence and determinants of sleep disorders in a community in rural southern India. Natl Med J India. 2020 May 1;33:132.[3] Panda S, Taly AB, Sinha S, Gururaj G, Girish N, Nagaraja D. Sleep-related disorders among a healthy population in South India. Neurol India. 2012 Jan 1;60(1):68. Acknowledgements None. Disclosure of Interests None Declared.Table 1Predictors of impaired sleep qualityPredictorsβ (95% CI)P valuePtGA0.176(0.023 - 0.412)0.004Depression (PHQ-9)0.282 (0.101 - 0.342)<0.0001IHAQ0.230 (0.025 -.129)0.004