Aspirin is associated with lower risks of severe covid-19 disease: a population-based study

IntroductionThe use of aspirin has been hypothesized to improve severe clinical outcomes in COVID-19 infection. The present study aims to evaluate the effect of both antecedent and inpatient aspirin use, individually and concomitant with other medications, on severe disease outcomes in COVID-19 positive patients treated with steroids/antiviral therapy.MethodsConsecutive patients who attended Hong Kong's public hospitals or outpatient clinics between 1st January and 8th December 2020 for COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) and received steroids/antiviral therapy were included. Propensity score matching (1:1) between aspirin users and non-users was performed. The primary endpoint was the composite outcome of the need for intubation and 30-day all-cause mortality.ResultsA total of 2664 RT-PCR positive and hospitalized COVID-19 patients receiving steroids/antiviral therapy were included (male= 50.7%, baseline age= 52.3 [35.2-64.6] years old). Over follow-up, 2.96% suffered from 30-day all-cause mortality. Univariable logistic regression showed that aspirin use was associated with lower odds of severe COVID-19 in the propensity score-matched cohort (odds ratio [OR]: 0.33, 95% confidence interval [CI]: [0.18, 0.6];P=0.0003). This association remained significant following adjustment for significant confounders (OR= 0.33, 95% CI= [0.18, 0.59], P= 0002).ConclusionAspirin use was associated with lower odds of severe outcomes in COVID-19.Conflict of InterestNone

AVASCULAR NECROSIS OF THE FEMORAL HEAD – NOT TO BE OVERLOOKED SEQUELA AFTER COVID 19 INFECTION

BackgroundCOVID 19 infection could lead to different sequelae in survivors, known as post-COVID or long COVID 19 syndromes. Some of them are thought to be due to the thrombophylic changes observed in COVID 19 infection, but some are thought to be caused by the administrated (especially high dose) corticosteroid treatment. Avascular necrosis of the femoral head (AVNFH) is a multifactorial disease which leads to compromised vascular supply, ischemia and finally necrosis of the femoral head. As corticosteroids usage and thrombophylic states are among the main known risk factors for the development AVNFH [1], it could be presumed that the frequency of this disease will increase with the COVID 19 pandemic. The exact corticosteroid dose needed for the development of AVNFH is not clear, but it has been stated that a higher daily dose and a larger total cumulative dose increase substantially the risk for the development of osteonecrosis [2].ObjectivesTo describe in detail the characteristics of AVNFH diagnosed in patients after COVID 19 infection.MethodsThe study was done in a tertiary university rheumatological clinic. Data was extracted from the records of patients who have been referred to the clinic because of hip pain between June and December 2022. Inclusion criteria were: - a new onset of uni-or bilateral hip pain that started after a documented COVID 19 infection;and an MRI scan of the hip joints showing osteonecrosis of one or both femoral heads. Exclusion criteria were the presence of hip pain prior to the COVID 19 infection, anamnesis of traumatic injuries of the hips or pelvis, personal history of hypercoagulable states.ResultsNine patients (4 women and 5 men) with an average age 59.1 years (range 38-72) were included in the study. Four patients had been diagnosed with bilateral and five – with unilateral AVNFH, thus 13 hip joints were analysed in total (8 left and 5 right sided). The mean time lap between the COVID 19 infection and the start of the hip pain was 26.2 weeks (range 10-48 weeks). All patients had limited and painful movement in their symptomatic hip(s), especially internal rotation and four of the patients had also elevated CRP levels (mean 11.7 mg/L). The stage of the AVNFH was evaluated according to the Ficat-Arlet classification (0-IV stage). In four hips the AVNFH was stage I, five hips were classified as stage II and the remaining four joints - as stage III. All symptomatic hip joints exhibited effusion/synovitis on both ultrasound examination and the corresponding MRI scan. It should be noted that the presence of hip effusion was found to be related with a worse prognosis in AVNFH [1]. In three patients the amount of the effusion required arthrocentesis and fluid aspiration. The analysis of the joint fluid was consistent with a degenerative disease (i.e., low WBC count with predominant lymphocytes and no crystals). All patients included in our study had received corticosteroids during their COVID19 infection, while 6 of the patients had also been hospitalized due to more severe disease. According to the patients' documentation, the mean cumulative dose of the received corticosteroids was 936.2 mg prednisolone equivalent per patient (range 187-2272 mg).ConclusionAVNFH must not be overlooked in a new onset hip pain after COVID 19 infection. Our results show that corticosteroids administrated during the infection and the presence of hip joint effusion on ultrasound are especially suggestive for the development of osteonecrosis, as they were registered in all of our patients. The presence of these two factors necessitates patient referral for an MRI scan of the hips, in order that AVNFH be detected timely.References[1]Petek D, Hannouche D, Suva D. Osteonecrosis of the femoral head: pathophysiology and current concepts of treatment. EFORT Open Rev. 2019 Mar 15;4(3):85-97.[2]Kerachian MA, Séguin C, Harvey EJ. Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action. J Steroid Biochem Mol Biol. 2009 Apr;114(3-5):121-8.Acknowledgements:NIL.Disclosur of InterestsPLAMEN TODOROV Speakers bureau: speaker at national level for AbbVie, Novartis and UCB, Lily Mekenyan: None declared, Anastas Batalov Speakers bureau: Speaker at national level for AbbVie, Novartis, Pfizer, Stada, Elly Lilly.

Risk factors affecting outcome of rhino-orbital-cerebral mucormycosis in COVID-19 patients

Background: Mucormycosis is a serious life-threatening fungal infection that recently made severe sudden and devastating surge during the second wave of the COVID-19 epidemic with a mortality rate of up to 50%. Although the causality link between COVID-19 and rhino-orbito-cerebral mucormycosis (ROCM) remains unclear, many factors including poor diabetes control, high doses of steroids, viral-induced lymphopenia, and cytokine storm have been attributed to ROCM in patients with COVID-19. Orienting to risk factors and early recognition of this potentially fatal opportunistic infection is the key to optimal management and improved outcomes. In these contexts, we conducted a prospective study for 33 patients admitted to our tertiary hospital to determine the risk factors for ROCM in patients with COVID-19 and the cumulative mortality rates. Result(s): This study found a statistically significant relation between the fate of death in COVID-MUCOR patients who had presented fever, ophthalmoplegia, facial skin necrosis, and visual loss with those who received dose of steroid to control their respiratory symptoms P < 0.001. Death from COVID-MUCOR was statistically significant related to the prolonged interval from the onset of the symptoms to start of treatment and intervention. Also, it was found that there was a significant decrease in duration between COVID-19 infection and the start of mucormycosis (days) with incidence of DKA on admission. Nineteen (57.6%) of the patients had uncontrolled diabetes mellitus (hemoglobin A1C (HbA1c) of > 7.0%). Conclusion(s): Mucormycosis epidemic was precipitated by a unique confluence of risk factors: diabetes mellitus, widespread use of steroids, and perhaps SARS-CoV-2 infection itself. Restricting steroid use in patients with severe COVID-19 requiring oxygen therapy, and screening for and optimally controlling hyperglycemia, can prevent COVID-MUCOR in a large majority.Copyright © 2023, The Author(s).

EFFICACY AND SAFETY OF ABBV-599 HIGH DOSE (ELSUBRUTINIB 60 MG AND UPADACITINIB 30 MG) AND UPADACITINIB MONOTHERAPY FOR THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS: A PHASE 2, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

BackgroundABBV-599 is a novel combination of elsubrutinib (ELS;a selective BTK inhibitor) and upadacitinib (UPA;a JAK inhibitor) that targets non-overlapping signaling pathways associated with systemic lupus erythematosus (SLE).ObjectivesTo report results from SLEek, a phase 2, randomized, placebo (PBO)-controlled, parallel-group, multicenter study evaluating efficacy and safety of ABBV-599 and UPA monotherapy in adults with moderately to severely active SLE (NCT03978520).MethodsPatients (pts) were randomized 1:1:1:1:1 to once daily (QD) ABBV-599 high dose (HD;ELS 60 mg + UPA 30 mg), ABBV-599 low dose (LD;ELS 60 mg + UPA 15 mg), ELS 60 mg, UPA 30 mg, or PBO. The primary endpoint was the proportion of patients at W24 achieving SLE Responder Index-4 (SRI-4) and steroid dose ≤ 10 mg QD;additional efficacy and safety endpoints through W48 are also reported. The pre-specified 2-sided alpha level was 0.1.Results341 patients were enrolled. After a planned interim analysis when 50% of pts reached W24, the ABBV-599LD and ELS 60 mg arms were discontinued for lack of efficacy (no safety concerns). Of 205 continuing pts (ABBV-599HD n = 68, UPA 30 mg n = 62, PBO n = 75), baseline characteristics were well balanced. The primary endpoint (proportion achieving SRI-4 and steroid dose ≤ 10 mg QD at W24 vs PBO) was met by ABBV-599HD and UPA 30 mg. Key secondary endpoints were also achieved at W48 in both groups (Table 1). Overall flares and time to first flare were substantially reduced in the ABBV-599HD and UPA 30 mg groups through W48 (Figure 1). Anti-double stranded DNA antibodies were significantly decreased with both treatments. TEAEs considered related to study drug were 42.6% ABBV-599HD, 32.3% UPA 30 mg, and 33.3% PBO. There were no malignancies or VTE. There were 3 non-fatal CV events (1 MI on PBO and 2 ruptured cerebral aneurysms [1 each on ABBV-599HD and UPA 30 mg]);all were assessed as unrelated to study drug by investigators. No new safety signals were observed beyond previously known data for UPA or ELS.ConclusionABBV-599HD (ELS 60 mg + UPA 30 mg) and UPA 30 mg demonstrated significant improvements in SLE disease activity and flares with acceptable safety through 48 weeks.Table 1.Key Endpoints at Week 48PBO (n = 75)ABBV-599HD (n = 68)UPA 30 mg (n = 62)SRI-4 and steroid dose ≤ 10 mg QD, n (%) [95% CI]a24 (32.0) [21.4, 42.6]33 (48.5) [36.7, 60.4]*27 (43.5) [31.2, 55.9]SRI-4, n (%) [95% CI]a24 (32.0) [21.4, 42.6]35 (51.5) [39.6, 63.3]*28 (45.2) [32.8, 57.5]+BICLA, n (%) [95% CI]a19 (25.3) [15.5, 35.2]33 (48.5) [36.7, 60.4]***33 (53.2) [40.8, 65.6]***LLDAS, n (%) [95% CI]a18 (24.0) [14.3, 33.7]27 (39.7) [28.1, 51.3]*31 (50.0) [37.6, 62.4]***Joint-Count 50 in patients with ≥ 6 affected joints at baseline, n/n (%) [95% CI]a26/59 (44.1) [31.4, 56.7]37/58 (63.8) [51.4, 76.2]*34/59 (57.6) [45.0, 70.2] +CLASI-50 in patients with baseline CLASI ≥ 10, n/n (%) [95% CI]a5/14 (35.7) [10.6, 60.8]6/12 (50.0) [21.7, 78.3]5/8 (62.5) [29.0, 96.0]*Change from baseline in steroid dose, mg, LS mean (SE)b−1.5 (0.5)−1.5 (0.5)−1.2 (0.5)SFI, events/patient-years (95% CI)c Overall flares2.8 (2.4, 3.3)1.5 (1.2, 1.9)***2.0 (1.6, 2.4)** Mild/moderate flares2.5 (2.1, 2.9)1.3 (1.0, 1.6)***1.9 (1.5, 2.3)* Severe flares0.3 (0.2, 0.5)0.2 (0.1, 0.3)0.2 (0.1, 0.3) +Time to first flare by SFI, days, median (Q1, Q3)c141 (57, NE)312 (114, NE)*311 (99, NE)**BILAG-based flare rate, estimated incidence ratec0.570.19*0.26Data are presented for the full analysis set.aMissing data imputed using NRI incorporating multiple imputation to handle missing data due to COVID 19.bMissing data imputed using MMRM.cObserved data w/o imputation.+P <.1;*P <.05;**P <.01, ***P <.001 vs PBO.ABBV-599HD, elsubrutinib 60 mg QD and UPA 30 mg QD;CLASI-50, ≥ 50% reduction in CLASI activity score;Joint-Count 50, ≥ 50% improvement in tender or swollen lupus joints;LLDAS, Lupus Low Disease Activity State;NE, not estimated;PBO, placebo;SFI, SELENA SLEDAI Flare Index;UPA, upadacitinib.AcknowledgementsAbbVie and the authors thank the patients who particip ted in the study and all study investigators for their contributions. Medical writing assistance, funded by AbbVie, was provided by Callie A S Corsa, PhD, of JB Ashtin.Disclosure of InterestsJoan T Merrill Consultant of: AbbVie, Alexion, Alumis, Amgen, Astra Zeneca, Aurinia, Bristol Myers Squibb, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Lilly, Merck, Pfizer, Provention, Remegen, Sanofi, UCB, and Zenas, Grant/research support from: Astra Zeneca, Bristol Myers Squibb, and GlaxoSmithKline, Yoshiya Tanaka Speakers bureau: AbbVie, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Gilead, Lilly, Mitsubishi-Tanabe, and Pfizer, Grant/research support from: AbbVie, Asahi-Kasei, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, and Takeda., David d'cruz Consultant of: GlaxoSmithKline, Lilly, and UCB., Karina Vila Consultant of: AbbVie, Daniel Siri Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Gilead, Hoffman Laroche, Jansen, Lilly, and Sanofi, Xiaofeng Zeng: None declared, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Ling Cheng Shareholder of: AbbVie, Employee of: AbbVie, Thierry Sornasse Shareholder of: AbbVie, Employee of: AbbVie, Thao Doan Shareholder of: AbbVie, Employee of: AbbVie, Denise Kruzikas Shareholder of: AbbVie, Employee of: AbbVie, Alan Friedman Shareholder of: AbbVie, Employee of: AbbVie.

CLINICAL CHARACTERISTICS OF PEDIATRIC PATIENTS WITH RHEUMATIC DISEASES UNDER TREATMENT WITH BIOLOGICAL THERAPY: INFORMATION FROM BIOBADAMEX

BackgroundThe advent of biologic treatment (bDMARD) in childhood rheumatic diseases (RD) has changed their evolution and prognosis. Evidence is robust for diseases such as juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE), but in other diseases we still have to learn which is the ideal therapy, time to discontinuation and the potential adverse events (AE) in short and long term.ObjectivesIdentify the clinical and treatment characteristics of pediatric patients with rheumatic diseases with bDMARD treatment and describe the development of AE.MethodsBIOBADAMEX is a prospective ongoing cohort of Mexican patients with RD using bDMARDs since 2016. We included all patients younger than 18 years of age registered in BIOBADAMEX. Descriptive statistics were used for the baseline characteristics and the Chi-square test to analyze the differences between the characteristics of the groups in relation to the development of AE.ResultsA total of 45 patients were included, 31 (69%) of them female, mean age of 13.3 (±3.6) years. (Table 1).The most frequent diagnosis was JIA 25 (56%), followed by SLE 9 (20%), uveitis 5 (11%), polymyositis/dermatomyositis and hidradenitis 2 (4%) respectively;systemic sclerosis and CINCA 1 patient (2%) respectively. The mean duration disease in years was 4.67 (±2.1). Nine patients (20%) used a biologic prior to the current;23 (51%) patients had comorbidities.The most frequent bDMARDs used was Adalimumab (ADA) in 17 (38%) patients followed by Rituximab in 15 (33%) and Tocilizumab in 10 (22%), Infliximab, Abatacept and Canakinumab were used in one patient respectively.When compared by groups, ADA and Tocilizumab were the most used bDMARDs in JIA, Rituximab the only one used in SLE and PM/DM, and ADA the only one for uveitis.15 patients discontinued biological treatment, 4 (27%) due to AE. 82% used an additional synthetic DMARD, being methotrexate the most used in 48% of patients. Steroids were used by 21 (47%) of the patients with a median dose of 10mg (IQR 5 - 25).Fifteen AEs were recorded: 7 (47%) were infections, 5 of these (71%) were COVID;allergies and neutropenia in 2 (13%) patients respectively. By disease infections were more frequent in patients with JIA and Uveitis;neutropenia only occurred in patients with JIA (p 0.95). 87% of the AEs were non-serious, 1 patient with JIA presented a severe AE and one patient with SLE a fatal AE associated with COVID (p 0.93), with no statistically significant difference between groups.ConclusionJIA is the most frequent indication to use bDMARD as worldwide reported. The AE in this analysis are similar to previous registries in terms of the prevalence of infections, in our group the most frequent infectious complication was COVID, being fatal in one patient related with rituximab in SLE. Our study did not find statistically significant differences in the development of AE between diseases;however, they will continue to be reported and the number of patients in the registry will increase.References[1] Sterba,Y.et al. Curr Rheumatol Rep 2016;18,45[2] Fuhlbrigge RC, et al. 2021;47(4):531-543.Table 1.Baseline CharacteristicsBaseline characteristics (n = 45)n%Female, n(%)3168.9Age, media (SD)13.3 (±3.6)Index Body Mass, media (SD)19.6 (±4.9)Dx n(%)n %- JIA25 55.6- SLE9 20- PM/DM2 4.4- Uveitis5 11.1- Hidradenitis2 4.4- Systemic sclerosis1 2.2- CINCA1 2.2Disease duration(years) media (IQR)4.67±2.1Current treatment n(%)n %- Infliximab1 2.2- Adalimumab17 37.8- Rituximab15 33.3- Abatacept1 2.2- Tocilizumab10 22.2- Canakinumab1 2.2Treatment duration (months) median (IQR)4.5 (0.56 – 36.9)Treatment suspension, n(%)15 (33.2)Months to suspension, median (IQR)0.66 (0.46 – 1)Discontinue cause, n(%)n %- Inefficacy1 6.6- Remission1 6.6- Side effects4 26.6- Others5 33.3- Unknown4 26.6Steroids use, n(%):21 46.7Steroids dose (mg), median (IQR)10 5 – 25DMARDs use n(%):37 82.2AE, n(%):15 33.3By disease:AE TypeInfectionAllergyNeutropeniaOtherChi2JIA31230.95SLE1101Uveitis3000Acknowledgements:NIL.Disclosure of InterestsSamara Mendieta: None declare , Alfonso Torres: None declared, Fedra Irazoque-Palazuelos: None declared, Sandra Sicsik: None declared, Iris Jazmin Colunga-Pedraza: None declared, Daniel Xavier Xibille Friedmann: None declared, Deshire Alpizar-Rodriguez Employee of: Scientific advisor in GSK-Mexico, VIJAYA RIVERA TERAN: None declared.

IS THERE HIGHER RISK OF FATIGUE, DEPRESSION, ANXIETY AND STRESS AFTER COVID-19 IN PATIENTS WITH IMMUNE-MEDIATED RHEUMATIC DISEASES? DATA FROM THE REUMACOV BRASIL COHORT

BackgroundSome individuals may have persistent symptoms after COVID-19, a new condition known as long COVID-19. However, these complaints can be misunderstood with disease activity in patients with immune-mediated rheumatic diseases (IMRD), especially fatigue and mental distress.ObjectivesTo evaluate fatigue, depression, anxiety, and stress in IMRD patients after 6 months of COVID-19, compared with IMRD patients without COVID-19.MethodsThe ReumaCoV Brasil is a longitudinal study designed to follow-up IMRD patients for 6 months after COVID-19 diagnosis (cases) compared with IMRD patients no COVID-19 (controls). Clinical data, such as age, sex, comorbidities, as well as disease activity measurements and current treatment regarding IMRD, and COVID-19 outcomes were evaluated in all patients. The FACIT questionnaire (Functional Assessment of Chronic Illness Therapy) and the DASS 21 (Depression, Anxiety and Stress Scale - 21 Items) were applied at 6 months after COVID in both groups.ResultsA total of 606 IMRD patients were included, of whom 322 (53.1%) cases and 284 (46.9%) controls. Most patients were female (85.3%) with mean age 46.1 (13.0) years old. Specific disease activity were similar between cases and controls. There was a significant difference between FACIT scores and 3 domains of DASS-21 comparing cases and controls (Figure 1). The factors associated with FACIT were female gender, diabetes, obesity, no comorbidities, COVID manifestations (skin, joint pain, asthenia, diarrhea, and dyspnea), and chronic oral corticosteroid use. DASS-21 Depression was associated with these same factors. Female gender, COVID manifestations as skin, joint pain, asthenia, cough, dyspnea, and chronic oral corticosteroid use were associated with DASS-21-Anxiety. DASS-21 Stress was associated with female gender, asthenia, diarrhea, dyspnea, cough, chronic oral corticosteroid use, and hospitalization. Table 1 shows the variables that remained in the models after the univariate logistic analysis. A weak correlation between disease activity and FACIT was observed in rheumatoid arthritis (p=0.010;r2 = 0.035) and ankylosing spondylitis patients (p=0.010;r2 = 0.129). No other correlations were observed between the scores results and disease activity (patient's global assessment - PGA), medications or specific IMRD.ConclusionFatigue and mental changes such as depression, anxiety, and stress, occurred more frequently in IMRD patients who had COVID-19 than in those who did not have COVID-19, especially in women, regardless of disease activity score. Fatigue was more related to female gender, diabetes, obesity, and current joint pain. Mental impairment was more associated with severity of COVID-19, including respiratory and non-respiratory symptoms.Figure 1.Comparison between cases and controls of FACIT and DASS-21 depression, anxiety, and stress scoresFACIT (Functional Assessment of Chronic Illness Therapy);DASS-21 (Depression, Anxiety and Stress Scale - 21 Items):Table 1.Final model using binary Logistic Regression analysis to evaluate the preditive factors associated with FACIT and DASS-21 scoresFACIT Score ≤ 37 x score > 37§DASS-21-DEPRESSION Score ≤ 6 (normal/mild) x score > 6 (moderate/severeDASS-21-ANXIETY Score ≤ 5 (normal/mild) x score > 5 (moderate/severe)DASS-21-STRESS Score ≤ 9 (normal/mild) x score > 9 (moderate/severeVariableP-valueOR (CI 95%)VariableP-valueOR (CI 95%)VariableP-valueOR (CI 95%)VariableP-valueOR (CI 95%)Female0.151.83 (1.12-2.98)No comorbidities0.0290.66 (0.46-0.95)Joint pain0.0022.44 (1.39-4.26)Female0.0122.31 (1.20-4.46)Diabetes0.0062.35 (1.28-4.32)Joint pain**0.0012.58 (1.57-4.22)Dyspnea0.0013.61 (2.11-6.19)Dyspnea0.0013.69 (2.09-6.51)Dyspneia0.0012.00 (1.23-3.26)Dyspnea0.0012.82 (1.79-4.44)Oral CE0.0141.55 (1.09-2.21)Joint pain0.0052.20 (1.41-3.43)Oral CE0.0481.41 (1.00-1.99)§Lower scores mean worse fatigue;CE: corticosteroid;OR: odds ratio;CI: confiance intervalAcknowledgementsReumaCoV Brasil researchers, Brazilian Rheumatology Society and National Council for Scientific and Technological Deve opment.Disclosure of InterestsNone Declared.

PREDICTION OF MORTALITY USING CLUSTERS BASED ON CLINICAL AND LAB PARAMETERS: DATA FROM 2072 PATIENTS FROM INSPIRE COHORT

BackgroundLupus is a heterogenous diseases which results in significant premature mortality. Most studies have evaluated risk factors for lupus mortality using regression models which considers the phenotype in isolation. Identifying clusters of patients on the other hand may help overcome the limitations of such analyses.ObjectivesThe objectives of this study were to describe the causes of mortality and to analyze survival across clusters based on clinical phenotype and autoantibodies in patients of the Indian SLE Inception cohort for Research (INSPIRE)MethodsOut of all patients, enrolled in the INSPIRE database till March 3st 2022, those who had <10% missing variables in the clustering variables were included in the study. The cause of mortality and duration between the recruitment into the cohort and mortality was calculated. Agglomerative unsupervised hierarchical cluster analysis was performed using 25 variables that define SLE phenotype in clinical practice. The number of clusters were fixed using the elbow and silhouette methods. Survival rates were examined using Cox proportional hazards models: unadjusted, adjusted for age at disease onset, socio-economic status, steroid pulse, CYC, MMF usage and cluster of the patients.ResultsIndian patients with lupus have significant early mortality and the majority of deaths occurs outside the hospital setting.Out of 2211 patients in the cohort, 2072 were included into the analysis. The median (IQR) age of the patients was 26 (20-33) years and 91.7% were females. There were 288 (13.1%) patients with juvenile onset lupus. The median (range) duration of follow up of the patients was 37 (6-42) months. There were 170 deaths, with only 77 deaths occurring in a health care setting. Death within 6 months of enrollment occured in in 80 (47.1%) patients. Majority (n=87) succumbed to disease activity, 23 to infections, 24 to coexisting disease activity and infection and 21 to other causes. Pneumonia was the leading cause of death (n=24). Pneumococcal infection led to death in 11 patients and SARS-COV2 infection in 7 patients. The hierarchical clustering resulted in 4 clusters and the characteristics of these clusters are represented in a heatmap (Figure-1A,B). The mean (95% confidence interval [95% CI] survival was 39.17 (38.45-39.90), 39.52 (38.71-40.34), 37.73 (36.77-38.70) and 35.80 (34.10-37.49) months (p<0.001) in clusters 1, 2, 3 and 4, respectively with an HR (95% CI) of 2.34 (1.56, 3.49) for cluster 4 with cluster 1 as reference(Figure 1C). The adjusted model showed an HR (95%CI) for cluster 4 of 2.22 (1.48, 3.22) with an HR(95%CI) of 1.78 (1.29, 2.45) for low socioeconomic status as opposed to a high socioeconomic status (Table 1).ConclusionIndian patients with lupus have significant early mortality and the majority of deaths occurs outside the hospital setting. Disease activity as determined by the traditional activity measures may not be sufficient to understand the true magnitude of organ involvement resulting in mortality. Clinically relevant clusters can help clinicians identify those at high risk for mortality with greater accuracy.Table 1.Univariate and multivariate Cox regression models predicting mortalityUnivariateMultivariateVariablesHazard ratio (95% Confidence interval)P valueHazard ratio (95% Confidence interval)P valueCluster1Reference-Reference-20.87 (0.57, 1.34)0.5320.89 (0.57, 1.38)0.59831.22 (0.81, 1.84)0.3371.15 (0.76, 1.73)0.51342.34 (1.56, 3.49)<0.0012.22(1.48, 3.22)<0.001Socioeconomic statusLower1.78 (1.29, 2.45)<0.001Pulse steroidYes1.6 (0.99, 2.58)0.051MMFYes0.71 (0.48, 1.05)0.083CYCYes1.42 (0.99, 2.02)0.052Proliferative LNYes0.99 (0.62, 1.56)0.952Date of birth age0.99 (0.98, 1.01)0.657CYC- cyclophosphamide, MMF- Mycophenolate mofetilFigure 1.A. Agglomerative clustering dendrogram depicting the formation of four clusters. B.Heatmap depicting distribution of variables used in clustering C. Kaplan-Meier curve showing the survival function across the 4 clusters[Figure omitted. See PDF]REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone eclared.

REAL WORLD EXPERIENCE OF MODERATE DISEASE ACTIVITY STATE (MDAS) RA PATIENTS OVER 4-YEAR FOLLOW-UP

BackgroundIn recent years despite improved therapies for RA, there is an increased awareness of persistent pain in people with RA. Before the pandemic we assessed a large group of patients with RA with comprehensive joint ultrasound (US) and for presence of fibromyalgia (FM) meeting 2010 ACR diagnostic criteria. When combinations of synovitis and/or FM were made we noted 4 groups of patients. As well as some with only FM, we also noted a group we believe had peripheral non-inflammatory pain, a new concept in RA. Here we investigate if these different groups change over time in our T2T routine care pathway.ObjectivesTo assess the progress and outcomes patients with RA with different well defined pain states during 4 years of follow up including the COVID19 pandemic.MethodsThe TITRATE-ULTRASOUND patient cohort categorised patients with RA into 4 groups depending on the presence or absence FM and the presence or absence of power doppler synovitis (PD, defined as positive PD signal in ≥2 joints in a 44 joint US). We identified 72 patients with active RA (DAS28 3.2 – 5.1) from this cohort with sufficient clinical data during the study period and collected the following data on each follow up encounter: visit type, treatment changes and disease activity measures. In the COVID19 pandemic follow up visits were largely virtual without the ability to collect physician assessed disease activity scores. Progress assessment was performed as to whether the patient had improved, no change or worse with a numerical value of +1, 0 and -1 at each visit to calculate a score tracking patient progress during the pandemic. Statistical analysis was performed using 1-way ANOVA to assess for difference between the 4 groups.Results72 patients with were assigned into the following categories: FM-PD-, 12 (peripheral pain group);FM-PD+,18;FM+PD-, 29;FM+PD+, 13. Table 1 shows baseline characteristics of the 4 groups and reveals no significant difference by ANOVA between the 4 groups in total visits, face to face visits, telephone visits, tender joint count, treatment escalations, steroid prescriptions, csDMARD prescriptions, and progress score. Biologic prescriptions did vary significantly between the groups (p = 0.009).Table 1.FM-PD- (n=12)FM-PD+ (n=18)FM+PD- (n=29)FM+PD+ (n=13)ANOVA p-valueFemale (n, %)10 (83%)13 (72%)24 (83%)13 (92%)CCP+ve (n, %)4 (33%)12 (67%)14 (48%)6 (46%)Disease duration (years) (mean, SEM)11.04 (2.676)16.19 (2.889)12.29 (1.709)16.23 (3.340)On csDMARD (n, %)11 (92%)15 (83%)24 (83%)10 (77%)On bDMARD (n, %)4 (33%)5 (28%)7 (24%)8 (61.5%)Baseline DAS28 (mean, SEM)4.412 (0.1641)4.344 (0.1177)4.192 (0.08910)4.366 (0.1461)Total visits (mean, SEM)11.67 (2.647)10.50 (2.031)8.724 (1.039)8.308 (1.407)0.533F2F visits (mean, SEM)7.909 (2.164)7.944 (1.924)5.793 (1.033)5.769 (1.311)0.5959Telephone visits (mean, SEM)4.417 (1.474)2.556 (0.3154)2.931 (0.3327)2.538 (0.6162)0.2268Tender joint count (mean, SEM)3.604 (1.101)3.506 (0.6177)5.376 (0.6899)4.603 (1.246)0.3179Treatment escalations (mean, SEM)2.917 (1.062)3.722 (1.028)2.000 (0.5526)1.615 (0.6257)0.2671Steroid prescriptions (mean, SEM)1.833 (0.7160)1.611 (0.5310)1.000 (0.3908)0.7692 (0.5329)0.503csDMARD prescriptions (mean, SEM)0.7500 (0.3046)0.7778 (0.2070)0.5185 (0.1634)0.3636 (0.2787)0.5789Biologic prescriptions (mean, SEM)0.3333 (0.2247)1.778 (0.6291)0.3793 (0.1257)0.3077 (0.2371)0.009Progress score (mean, SEM)-1.167 (1.461)0.6111 (0.3889)-0.1379 (0.2366)0.4615 (0.6265)0.2579ConclusionOver the follow-up period we show the management of RA patients without active power doppler synovitis or fibromyalgia did not differ significantly from other categories of patients. Similar numbers of visits, treatment escalations, csDMARDs and corticosteroid prescriptions were observed. This illustrates how it can be difficult to define the specific causes of disease activity without access to US. Despite similar management strategies, FM-PD- patients tended towards worse progress scores, suggesting a potential unmet need in such patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of In erestsMark Gibson: None declared, Nadia Ladha Hassan: None declared, L Bruce Kirkham Speakers bureau: Abbvie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB, Grant/research support from: Eli Lilly.

TIME MANAGEMENT AND RISK FACTORS IN LIFE-THREATENING ANCA-VASCULITIS

BackgroundAccuracy of diagnosis and prompt therapeutic intervention are the mainstay in patients with ANCA-associated vasculitis(AAV) suffering from life-threatening complications [1].However, there is no definition of therapeutic window in vital AAV, nor its impact on patient outcome regarding length of hospital stay, intensive care unit(ICU) admission or survival.ObjectivesThe aim of the study is to analyze the process of care from the perspective of time management in vital organ involvement AAV patients and to identify potential risk factors for ICU admission.MethodsA retrospective multicenter study identified AAV patients with life-threatening organ involvement, defined as alveolar hemorrhage, rapidly progressive renal failure, myocarditis and cerebral granuloma. Demographic data was collected. Key time frames were recorded, namely the interval from acute symptom onset to hospital presentation, days until imaging(plain X-ray, cardiac ultrasound, CT-scan), time to therapeutic intervention with corticosteroids or biologic/non-biologic immunosuppression(cyclophosphamide or rituximab) and to renal replacement therapy(RRT) or plasmapheresis. Time to ICU admission, hospital length-of-stay, Birmingham Vasculitis Activity Score(BVAS) were also noted. Statistical analysis was performed using SPSS and Chi-square and Pearson correlation tests were applied.Results66 patients with AAV were enrolled, out of which 17 fulfilled inclusion criteria. Mean age in the study group was 58.6±11.1 years old,10 patients(58.8%) were females and 7 (41.2%) males.11(64.7%) patients were c-ANCA positive, while 6 (35.3%) had p-ANCA and all were diagnosed with AAV prior to life-threatening event. Two patients had COVID-19 triggered AAV.In the study group, the most frequent critical organ suffering was rapidly progressive renal failure(12), followed by alveolar hemorrhages(10), 2 cerebral granulomas and one acute myocarditis. Three patients(17.6%) had more than one vital manifestation. Ten patients(58.8%) had more than three additional non-organ-threatening manifestations. Mean interval from AAV diagnosis to emergency admission was 30.1± 61.1 days, median 3 and from severe episode onset to hospitalization 1.65±0.18 days, median 1. There was only one death in the study group. Three patients were admitted in the ICU in 0.59±1.5 days following hospital presentation and required either RRT or plasma exchange within 2.66 days. Imaging examination was performed unanimously the day upon hospital admission. All patients received corticosteroids in the first 5.95±14.3 days, while immunosuppression was given to 13(76.5%) patients within 11.5±15.5 days from hospitalization.12 patients(70.5%) suffered from associated infections. Mean BVAS(13.6±6.76) correlated to ICU admission(p 0.013, r 0.58).Patients in ICU revealed higher BVAS(22±9.53) versus non-ICU(11.8±4.76).Hospital length of stay was 14.7±10.7 days(median 14) and showed no relationship to the type of severe organ involvement. The need for ICU caring was dominant in males(p 0.05) and confirmed in patients with proteinuria(p 0.012) and at least two major organ damage.ConclusionThis study shows that severity risk factors for potential ICU admission for life-threatening AAV appear to be male gender, proteinuria and the number of affected organs.Moreover, BVAS should be considered a useful tool to predict patients' risk for intensive care management since a higher score indicates a more aggressive disease.However, time to investigational or therapeutic intervention did not correlate to patient outcome in AAV.References[1]Geetha, D., Seo, P. (2011). Life-Threatening Presentations of ANCA-Associated Vasculitis. In: Khamashta, M., Ramos-Casals, M. (eds) Autoimmune Diseases. Springer, London. https://doi.org/10.1007/978-0-85729-358-9_8Acknowledgements:NIL.Disclosure of InterestsNone Declared.

SARS-CoV-2 Infection in Venezuelan Pediatric Patients-A Single Center Prospective Observational Study.

Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analyzed by flow cytometry, and IFNγ, IL-6, and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month to 18 years. The majority, 52.8%, had mild disease, and 30.6% of the patients were diagnosed with MIS-C. The main symptoms reported were fever, cough, and diarrhea. A correlation was found between IL-10 and IL-6 concentrations and age group, lymphocyte subpopulations and nutritional status and steroid use, and IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.

Epidemiological and clinical features of the first cohort of patients diagnosed with COVID-19 in Bahrain

Background: This study investigates the clinical characteristics of the first confirmed cases of Coronavirus disease-2019 (COVID-19) in Bahrain. Methods: This is a retrospective, cross-sectional study including the first 247 confirmed cases in Bahrain. Demographic, clinical, and laboratory data were extracted from electronic medical records. Results: Mean Standard Deviation (SD) age of patients was 44.15 (16.5) years. More males were affected by the disease (61%;151/274). Mean (SD) of the duration between confirmation and discharge was 9.8 (5.1) days. Of 247 patients, 4 deaths were reported (1.6%);17.5% (24/137) showed a temperature of >37- on admission, with 4% (6/148) yielding an oxygen saturation of 94% or less. Leukopenia was reported in 36.8% of patients (63/171). One quarter of patients (25.5%) received oseltamivir, 24.7% received hydroxychloroquine sulfate (24.7%), and 1.2% received steroids. Conclusion: In this study, the authors have captured the epidemiological and clinical profiles of the first cases of COVID-19 pertaining to the first wave of the pandemic in Bahrain. The early strict measures may have contributed to the lower incidence as well as lower morbidity and mortality of COVID-19 infection in Bahrain. Major gaps in our knowledge of the clinical spectrum of COVID-19 and its prognosis, outcomes, and associated risk factors indicate the need for further research.

Best practices for pediatricians in diagnosing and treating asthma

Additionally, they can treat atopic comorbidities such as atopic dermatitis, chronic urticaria, nasal polyps, eosinophilic esophagitis, and hypereosinophilic syndrome, resulting in improved quality of life for our patients. Parents should be made aware of its updated black box warning for possible effects on mental health and behavior changes,3 including but not limited to suicidal ideation. FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair);advises restricting use for allergic rhinitis.

Relationship of clinical symptoms, comorbidities and treatment options along with disease outcomes in individuals tested for COVID-19 in Pakistan: a national survey

Background: This web-based survey is done to collect and assess data from people tested for COVID-19 with PCR in Pakistan. Methods: This 3-month study is a cross-sectional online survey, conducted by Pakistan Islamic Medical Association (PIMA), Health Research Advisory Board (HealthRAB) and National Institute of Health (NIH). Data collection was done using Google Forms. People who were tested for COVID-19 using Polymerase Chain Reaction (PCR) were included in the study. The sample size of the study was 1,537. SPSS version 22 was used for data analysis. Results: Majority of the respondents belonged to the age group 20 - 39 years. The most common symptoms found were fever 633 (41%), cough 534 (34%), generalized body aches 432 (28%) and sore throat 392 (25%). The mean COVID-19 mental health score was 3.59 (SD: 5.808, range: 0-18). Treatment with antibiotics and painkillers had a strong correlation (p-value < 0.05) with the disease outcomes. The disease outcomes had moderate correlation (p-value < 0.05) with anti-allergy, steroids, plasma and oxygen therapy, and weak correlation (p-value < 0.05) with Antiviral and Antimalarial therapy. Out of the total respondents, 561 (36.1%) were cured from COVID-19, 14 (0.9%) were expired during/after hospitalization, 15 (1%) were still infected and 962 (62%) were not infected. Conclusion: Pakistani population has a better cure rate than some of its neighboring countries. However, further research in this area is required to draw a definite conclusion.

Etiology of Pancreatitis in Patients at a Tertiary Care Center

Objective: To compare etiological frequencies in patients of acute pancreatitis presenting to our setup with international data. Study Design: Cross-sectional study Place and Duration of Study: Department of Gastroenterology, Pakistan Emirates Military Hospital and Combined Military Hospital, Rawalpindi Pakistan, from Aug 2020 to Jan 2022. Methodology: Patients over 12 years suffering from pancreatitis were recruited using a convenience sampling technique based upon predefined criteria for diagnosis of pancreatitis on a questionnaire. Relevant basic lab tests, including chemistries and imaging, including Ultrasound abdomen and CECT abdomen, were analyzed to establish aetiology. Data were continuously uploaded into an electronic data sheet. International Consensus Diagnostic Criteria (ICDC) algorithms were applied to diagnose autoimmune pancreatitis. Results: Out of 120 patients, 74(61.7%) were males, and 46(38.3%) were females. Biliary pancreatitis was the most common aetiology 50(41.7%), followed in descending order by idiopathic 36(30%), drug-induced pancreatitis (DIP) 9(7.5%), Post ERCP Pancreatitis (PEP) 8(6.7%), tumours 5(4%), Autoimmune pancreatitis (AIP), Hypertriglyceridemia and alcohol-induced pancreatitis each 2(1.7%). Conclusion: Biliary pancreatitis has the highest frequency, followed by idiopathic and drug-induced pancreatitis.

Factors Associated with Outcome in Patients Managed for Invasive Fungal Infections at the Infectious Diseases Department of a Tertiary Care Hospital

Objective: To look for the factors associated with outcomes in patients managed for invasive fungal infections at the Infectious Diseases Department of a Tertiary Care Hospital Study Design: Comparative cross-sectional study Place and Duration of Study: Department of Infectious Diseases, Pak Emirates Military Hospital, Rawalpindi Pakistan,from Apr 2021 to Sep 2022. Methodology: A total of 90 patients with a different types of invasive fungal infections diagnosed by consultant infectious diseases were recruited. First, they were given standard treatment for fungal infection;they were diagnosed as per guidelines. Then, they were followed up for one month to look for an outcome. Results: Out of 90 patients with invasive fungal infections included in the study, 62(68.8%) had a good outcome, while 28(31.2%) had a poor outcome. The mean age of the patients recruited in our study was 39.54±6.27 years. Of all the participants, 65(72.2%) patients were male, while 25(27.8%) were female. Statistical analysis revealed that poorly controlled diabetes, COVID-19 infection and HIV positive were statistically significantly associated with poor outcomes in our study participants (p-value<0.05). Conclusion: The Considerable number of patients with invasive fungal infections had a poor outcome in our study. The presence of poorly controlled diabetes, COVID-19 infection and being HIV positive were the factors associated with poor outcomes in our study participants.

Practical Guide to Glucocorticoid Induced Hyperglycaemia and Diabetes.

Glucocorticoids, also known as steroids, are a class of anti-inflammatory drugs utilised widely in clinical practice for a variety of conditions. They are associated with a range of side effects including abnormalities of glucose metabolism. Multiple guidelines have been published to illustrate best management of glucocorticoid-induced hyperglycaemia and diabetes in a variety of settings. This article discusses current best clinical practice including diagnosis, investigations and ongoing management of glucocorticoid-induced dysglycaemia in both in- and outpatient settings.

COVID-19 in a Cystic Fibrosis Patient.

Based on experience with other viral respiratory illnesses, patients with cystic fibrosis were believed to have worse prognosis when infected with COVID-19. We report a case of a 14-year-old female with cystic fibrosis who developed COVID-19 with short-term evolution and made a good recovery with no known major long-term sequelae.

Rhino-Orbito-Cerebral Mucormycosis During the Second Wave of Covid-19: The Indian Scenario.

Mucormycosis is a life threatening, opportunistic infection often seen in individuals with a weak immune system. With an upsurge of cases of Covid-19, a drastic increase in cases of Rhino-Orbito-Cerebral Mucormycosis is being witnessed at present. This article has been written with the purpose of understanding the factors responsible for it and the challenges it brings along for the Indian health-care system at present. Possible solutions for dealing with these problems have also been included in the manuscript. Google, PubMed and ENT Cochrane databases were searched without a time limit using key words like "Mucormycosis", "Rhino-cerebral-mucormycosis" in conjunction with "COVID-19" and "SARS CoV-2". We found 34 articles to be relevant and hence included them to write this review. Rhino-Orbito-Cerebral Mucormycosis is being seen due to coming together of the three entities-the agent, host and environment that constitute the epidemiological triad for this disease in India. Responsible factors are uncontrolled diabetes mellitus, overzealous use of steroids and antibiotics and other environment related issues. The solutions for these problems lie in spreading awareness about prevention of these practices along with early diagnosis and treatment of mucormycosis. To deal effectively with this situation, particularly when there is an existing overload on otolaryngologists and the rest of the health-care system, a multipronged and multilevel collaborative approach is the need of the hour. With effective Standard Operating Procedures and guidelines promoting a multidisciplinary approach for early diagnosis and treatment, we can surely overcome this situation.

New onset diabetes mellitus in post-COVID-19 patients.

Background: Diabetes, is known to have a bilateral relationship with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Precise mechanism of diabetes onset in COVID-19 patients remains unclear. Aim: To analyse the incidence of new onset diabetes (NODM) among COVID-19 patients, as well as the effect of body mass index (BMI), family history, and steroid use on the incidence of the disease. Methods: Adult, not known diabetic patients, tested positive with Rapid Antigen Test or RT-PCR admitted to a tertiary care hospital and research institute were included in the present prospective observational study. The patients who developed NODM and NOPD (New Onset Pre-diabetes) during the three months follow-up and the risk factors associated were assessed. Patients with HbA1c >6.4% were diagnosed with NODM. An HbA1c of 5.7% to 6.4% was used to characterize NOPD. Results: Out of 273 previously not known diabetic COVID-19 infected individuals, a total of 100 were studied for three months after consent. Mean age of the patients 48.31 ± 19.07 years with male predominance (67%). Among these, 58% were non-diabetics and 42% were pre-diabetics. 6 (10.3%) of the 58 non-diabetics developed NOPD, and 8 (13.8%) developed NODM. 6 (14.2%) of the 42 pre-diabetics became non-diabetic, and 16.6% (7) developed NODM. Family history of DM (P < 0.001), severity at admission (P < 0.006), diabetic ketoacidosis (P < 0.0275), and persistent symptoms were associated significantly with NODM. Those with NODM had significantly greater BMI, O2 duration, steroid duration, FBS, and PPBS (P < 0.001 for all). Nearly 67% of the patients who developed NOPD had shortness of breath as the common symptom at time of admission (P = 0.0165). Conclusion: The incidence of NODM was strongly influenced by positive family history of DM, higher BMI, steroid dosage, and its duration. Hence, patients with COVID-19 need to be under surveillance for blood glucose screening.

Football, dementia, . . . and other stories

The increased risk of dementia didn't apply to goalkeepers, which is compatible with the hypothesis that repeated head impacts sustained when heading the ball are part of the cause (Lancet doi:10.1016/S2468-2667(23)00027-0). Mental illness and septic shock A nationwide study of 200 000 adults admitted to intensive care units in French hospitals with septic shock reveals that those with severe mental illness (schizophrenia, bipolar disorder, or major depressive disorder) have substantially lower case fatality, assessed at 30, 90, and 365 days after admission, than controls matched for age, sex, and social deprivation. For vascular dementia, the most consistent precursors were an abnormal electrocardiogram, cardiac dysrhythmias, cerebrovascular disease, non-epithelial skin cancer, depression, and hearing loss (Ann Neurol doi:10.1002/ana.26584).