Definition Of Flare Research Articles

Consensus on a Patient-Centered Definition of Atopic Dermatitis Flare

Flare is a term commonly used in atopic dermatitis (AD) care settings and clinical research, but little consensus exists on what it means. Meanwhile, flare management is an important unmet research and treatment need. Understanding how various therapies might comparatively improve AD flares as a measure of treatment effectiveness may facilitate shared decision-making and enable assessment of effectiveness within and outside clinical settings. To identify patient-reported attributes associated with an AD flare to develop a patient-centered, consensus-based working definition. This consensus survey study used a modified eDelphi method involving consensus-building focus groups and a survey conducted from January 10 through October 24, 2023. Focus groups were conducted virtually, and the online survey was advertised to National Eczema Association members. US adults aged 18 years or older with AD were recruited via convenience sampling. Lived experience of AD. The main outcome was consensus on which attributes of AD to include in a patient-centric definition of flare. Using a rating scale (range, 1-9), consensus for the modified eDelphi statement rating was defined as at least 70% of participants rating a statement as 7 to 9 (critical to a flare definition) and less than 15% rating it as 1 to 3 (not important). Twenty-six participants with AD who completed focus group activities (24 aged 18-44 years [92.3%] and 2 aged 45-64 years [7.7%]; 18 women [69.2%]) and 631 participants with AD (mean [SD] age, 45.5 [18.1] years; 533 women [84.5%]) who completed the survey were included in the analysis. Fifteen statements reached consensus from the focus groups, and of those, 12 reached consensus from survey participants. More than half (334 of 631 [52.9%]) of survey participants reported alignment with their health care practitioner on what a flare is, and most (478 of 616 [77.6%]) reported that a patient-centered definition would be useful when communicating with their health care practitioner about their condition. In this study, participants with AD reached consensus on what an AD flare means from the patient perspective. This understanding may improve research and care by addressing this key patient-centered aspect of evaluating treatment effectiveness.

Investigating gout flares: beyond a definition.

Gout flares are a paramount component of disease burden inflicted by gout onto the patient. Furthermore, they are included in the core domain set for long-term gout studies recognized by Outcome Measures in Rheumatology. Along with a validated classification criterion for gout, gout investigators have turned their efforts into defining and characterizing the gout flare. This brief review will summarize the efforts that have been done to define and characterize a gout flare in clinical studies. Recent findings include a validated definition of a gout flare that has been utilized in novel clinical studies, use of technology to monitor for gout flares and their effects on patient life, and qualitative analyses into the disease burden that a patient undergoes. Although guidelines for core outcome domains have been well established, there is question in methods of measuring and reporting gout flares in long-term trials. Furthermore, there is question as to the effectiveness of the agreed upon instruments' abilities to fully capture the disease burden experienced by patients with gout. A combination of outcome measurements including binary data (gout flare present or absent) along with a comprehensive measurement of disease burden over time would theoretically provide a more accurate description of the disease and serve as a basis for intervention development.

Measuring GPPGA, Pain, Symptom, and Quality of Life Index Scores in Untreated Generalized Pustular Psoriasis: Results from the Placebo Group of the Effisayil-2 Trial

Introduction & Objectives: Generalized pustular psoriasis (GPP) is a chronic inflammatory, and potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab is approved to treat GPP flares in adults. Effisayil 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous spesolimab in preventing GPP flares. Here, we report on the underlying disease burden of untreated GPP by longitudinally analyzing patients in the placebo group who did not experience a GPP flare.
 Materials & Methods: Eligible patients with a history of GPP were randomized (1:1:1:1) to receive one of three subcutaneous spesolimab regimens or placebo for 48 weeks. Patients were assessed for measures of chronic disease burden through the use of Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) Total Score, Pain Visual Analog Scale (VAS), and Psoriasis Symptom Scale (PSS) at baseline and at 4-week intervals during the trial, and Dermatology Quality of Life Index (DLQI) at baseline and weeks 4, 8, 12, 24, 36, and 48.
 Results: 16/31 placebo-treated patients experienced a GPP flare over the 48-week observational period of the trial, defined as an increase in GPPPGA score by ≥2 from baseline and the pustular component of GPPPGA ≥2. Of the remaining (“non-flaring”) 15 patients, 40% (6/15) had at least one GPPPGA Total Score value of 2 (skin not clear or almost clear); 4/6 reported such score at ≥4 visits. Pain scores ranged from 0 to 92.47, with 47% (7/15) and 20% (3/15) of patients having at least one “moderate” and “severe” VAS score over 48 weeks, respectively. Most of the 7 patients’ pain scores fluctuated with episodic peaks and valleys. 47% (7/15) and 13% (2/15) of patients had at least one “moderate” and “severe” PSS score, respectively. “Moderate” and “very large” effect on quality of life was reported, at least once, in 67% (10/15) and 40% (6/15) of patients, respectively.
 Conclusion: Acute flare was reported in more than 50% (16/31) of patients in the placebo group over 48 weeks. Despite not meeting the trial’s definition of GPP flare, most of the 15 “non-flaring” placebo-treated patients showed clear evidence of underlying GPP disease activity – nearly half did not have “clear” or “almost clear” skin and had moderate pain and symptoms; a small subset reported severe pain and symptoms. Majority of patients experienced a moderate to very large impact on quality of life over the 48 weeks. These findings suggest that untreated GPP negatively affects patients even in the absence of acute flare events.

Dose Tapering and Discontinuation of Biologic DMARDs in Axial Spondyloarthritis: A Narrative Review (2023 SPARTAN Annual Meeting Proceedings).

Limited data is available for tapering or discontinuation of biologic therapy in patients with axSpA who are in disease remission. The current review concentrates on published studies regarding dose tapering or withdrawal of biologics in axSpA. Recent evidence in light of randomized controlled trials suggests that tapering of b-DMARDs is a feasible strategy to maintain remission or low disease activity in axSpA patients. TNF inhibitors were the studied biologics in most of these trials. The disease flare rates were comparable to those maintained on standard dose in most of these studies, although with variable tapering strategies and follow-up. Additionally, the duration of disease in remission prior to tapering, studied primary outcome, and flare definitions were heterogeneous. Female sex, HLA-B*27 negativity, high physician global score, and high CRP were negative predictors of successful tapering, but not consistently reported in all the trials. Although designed to address efficacy, there were no safety concerns with b-DMARD tapering. Withdrawal or complete discontinuation of biologics met with increased risk of flares compared to standard dosing. Tapering of TNF inhibitors may be feasible in certain axSpA patients with an acceptable disease state; however, discontinuation is not currently recommended owing to increased risk of flare. Future studies with axSpA patients with longer remission duration prior to taper and different doses and types of b-DMARDs may provide more guidance.

Towards a patient-centred definition for atopic dermatitis flare: a qualitative study of adults with atopic dermatitis.

The term 'flare' is used across multiple diseases, including atopic dermatitis (AD), to describe increased disease activity. While several definitions of an AD flare have been proposed, no single definition of AD flare is widely accepted and it is unclear what the term 'AD flare' means from the patient perspective. To understand AD flares from the adult patient perspective and to explore how adults with AD define an AD flare. Participants were adults with AD recruited from the National Eczema Association Ambassadors programme, a volunteer patient-engagement programme. They participated in online focus groups to discuss how they describe AD flares from their perspective, how they define its start and stop, and how they relate to existing definitions of flare. Using a grounded theory approach, transcripts were analysed and coded using an iterative process to identify concepts to support a patient-centred conceptual framework of 'flare'. Six 90-min focus groups of 3-8 participants each were conducted with 29 US adults (≥ 18 years of age) with AD who had at least one self-reported AD flare in the past year. When participants were presented with examples of previously published definitions of AD flare, participants found them problematic and unrelatable. Specifically, they felt that flare is hard to quantify or put on a numerical scale, definitions cannot solely be about skin symptoms and clinical verbiage does not resonate with patients' lived experiences. Concepts identified by patients as important to a definition of flare were changes from patient's baseline/patient's normal, mental/emotional/social consequences, physical changes in skin, attention needed/all-consuming focus, itch-scratch-burn cycle and control/loss of control/quality of life. Figuring out the trigger that initiated a flare was an underlying concept of the experience of flare but was not considered a contributor to the definition. The results highlight the complexity and diversity of AD flare experiences from the adult patient perspective. Previously published definitions of AD flares did not resonate with patients, suggesting a need for a patient-centred flare definition to support care conversations and AD management.

Definition of rheumatoid arthritis flare based on SDAI and CDAI

ObjectiveTo develop and validate definitions for disease flares in rheumatoid arthritis (RA) based on the quantitative Simplified and Clinical Disease Activity Indices (SDAI, CDAI).MethodsWe analysed RA treatment courses from the...

Differences in risk factors for flare-ups in patients with lumbar radicular pain may depend on the definition of flare.

The objective was to determine whether specific physical activity (PA) or psychological stress factors are associated with different definitions of flare-ups (pain-defined flares [PDFs]: periods of increased pain lasting at least 2 h, when pain intensity is distinctly worse than it has been recently; and non-pain-defined flares [NPDFs]: obviously uncomfortable feelings, such as fatigue, loss of function, or emotional/psychosocial fluctuations, without major fluctuations in pain intensity based on 11-point scales) among people with lumbar radicular pain. This was a case-crossover study. Participants with acute or subacute lumbar radicular pain completed serial face-to-face or online assessments for 6 weeks at 3-day intervals to determine whether they experienced sciatica flare-ups (PDF/NPDF) after specific types of PA or psychological stresses. A total of 152 participants were enroled. There were 597 PDF and 323 NPDF case periods and 800 control periods. The odds of PDFs were increased by prolonged walking and standing, and the odds of NPDFs were increased by prolonged sitting, mental distress, and depressed mood. According to the multivariable analyses, prolonged sitting (OR: 3.0, 95% CI: 1.7-5.5), prolonged walking (OR: 6.2, 95% CI: 3.9-9.9), and prolonged standing (OR: 5.6, 95% CI: 3.3-9.5) were significantly associated with the odds of PDFs, and prolonged sitting (OR: 3.4, 95% CI: 1.8-6.2), mental distress (OR: 6.7, 95% CI: 2.5-17.5), and depressed mood (OR: 5.8, 95% CI: 2.6-12.8) associated with the odds of NPDFs. Prolonged sitting, walking, and standing triggered the occurrence of PDF. Prolonged sitting, mental distress, and depressed mood triggered the occurrence of NPDF.

Patient and Physician Perspectives of Systemic Lupus Erythematosus Flare: A Qualitative Study.

Systemic lupus erythematosus (SLE) flares are associated with increased damage and decreased health-related quality of life. We hypothesized that there is discordance between physicians' and patients' views of SLE flare. In this study, we aimed to explore patient and physician descriptions of SLE flares. We conducted a qualitative descriptive study using in-depth interviews with a purposeful sample of patients with SLE (who met 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria) and practicing rheumatologists. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. Forty-two patient participants with SLE, representing a range of SLE activity, completed interviews. The majority described flare symptoms as joint pain, fatigue, and skin issues lasting several days. Few included objective signs or laboratory measures, when available, as features of flare. We interviewed 13 rheumatologists from 10 academic and 3 community settings. The majority defined flare as increased or worsening SLE disease activity, with slightly more than half requiring objective findings. Around half of the rheumatologists included fatigue, pain, or other patient-reported symptoms. Patients and physicians described flare differently. Participants with SLE perceived flares as several days of fatigue, pain, and skin issues. Providers defined flares as periods of increased clinical SLE activity. Our findings suggest the current definition of flare may be insufficient to integrate both perceptions. Further study is needed to understand the pathophysiology of patient flares and the best way to incorporate patients' perspectives into clinical assessments.

Flares of Acute Graft-Versus-Host Disease: Mount Sinai Acute Gvhd International Consortium (MAGIC) Study

[Background] The current standard first-line treatment for acute graft-versus-host disease (GVHD), systemic high-dose steroids, induces clinical responses in a majority of patients. Flares of GVHD after initial improvement often occur during tapering or discontinuation of immunosuppression. There is no consensus regarding the definition of GVHD flare and little has been published regarding its natural history. [Methods] We retrospectively evaluated clinical data and blood samples from 968 allogeneic hematopoietic cell transplantation (HCT) recipients from 23 Mount Sinai Acute GVHD International Consortium (MAGIC) transplant centers who achieved complete response (CR) or very good partial response (VGPR) within 4 weeks of acute GVHD treatment between 2014 and 2021. VGPR was defined as the complete resolution of acute GVHD manifestations except residual stage 1 skin disease. Flares were defined as a recurrence of acute GVHD after achievement of CR/VGPR if (1) patients had an increased symptom severity of at least 1 organ stage; (2) received intensified treatment (increase in steroid dose ≥ 0.25 mg/kg or initiation of additional systemic immunosuppression); and (3) had no prior history of primary disease relapse or donor lymphocyte infusion preceding the flare. Serum samples obtained at the time of CR/VGPR and at the time of flares were analyzed for ST2 and REG3α concentrations that generated MAGIC algorithm probabilities (MAPs) resulting in previously validated Ann Arbor (AA) scores (1, 2, and 3). [Results] The median recipient age at HCT was 55 years (range: 0 to 79); 18.6% of patients had grades III-IV acute GVHD before CR/VGPR. The median maximum daily dose of corticosteroids before CR/VGPR was 1 mg/kg methylprednisolone equivalent (range, 0.1 to 3.2 mg/kg). Flares developed within 6 months following CR/VGPR in 210/968 (21.7%) patients with a median onset of 28 days (range: 2 to 448). Symptom severity at the onset of flare symptoms varied widely (grade I: 22%; grade II: 38%; grade III-IV: 41%) and the development of a flare was associated with a five-fold increase in NRM (hazard ratio [HR], 4.84 [95% CI, 3.19-7.36], P < 0.001) when considered as a time-dependent covariate in a multivariate regression model. The large majority of non-relapse deaths after flares (54/71, 76%) were due to acute GVHD or complications from its treatment. The AA scores at the time of first CR/VGPR successfully stratified patients for risk of six-month NRM (AA1: 5%, AA2: 11%, AA3: 34%, P < 0.001) (Figure A). Increasing AA score at CR/VGPR was also associated with significantly increased risk of GVHD flares (Figure B). Not only did the risk of flare increase with each rising AA score, but the number of patients with severe (grade III/IV) symptoms at flare onset also increased (AA1: 34%, AA2: 43%, AA3: 54%). We next generated a multivariate regression model of risk factors for the development of flares. High AA scores at the time of CR/VGPR (AA2: HR, 1.81 [95% CI, 1.32-2.48], P = 0.001; AA3: HR, 3.14 [95% CI, 1.98-4.98], P < 0.001), HCT from HLA mismatched unrelated donor (HR, 1.74 [95% CI, 1.00-3.02], P = 0.049), and interestingly, rapid achievement of CR/VGPR from the time of initial treatment (≤14 days) (HR, 1.84 [95% CI, 1.21-2.80], P = 0.004) were all identified as significant risk factors. Meanwhile, no other transplant, GVHD, or treatment characteristics associated with the development of flares including maximum GVHD severity, maximum steroid dose, and use of additional immunosuppressive agents other than steroids before CR/VGPR. AA scores measured at the onset of flare symptoms in 98 patients also predicted six-month NRM (AA1, 6%; AA2, 19%; AA3 42%, P = 0.01). [Conclusion] Despite advances in treatment, flares of GVHD symptoms following excellent (CR/VGPR) responses still occur in over one fifth of patients in current practice and are associated with a five-fold increase in six-month NRM. AA scores from serum biomarkers predict outcomes despite the absence of symptoms, suggesting that MAGIC biomarkers detect subclinical damage to GI crypts that can drive later recrudescence of clinical GVHD. Measurement of the MAP at the time of response to GVHD treatment may thus help to risk-stratify tapering strategies of immunosuppressive therapy.

The SLE-DAS provides an accurate and feasible flare tool in the clinical setting: a validation study.

To assess the criterion validity of the SLE disease activity score (SLE-DAS) flare tool and compare its performance in identifying flares against other instruments. Patients with SLE fulfilling SLE-DAS low disease activity at baseline were included from two academic lupus clinics. During follow-up, flares were identified by the senior attending clinician, applying the expert-consensus-based definition as gold-standard. The first clinical flare from flaring patients, and the first visit after baseline in patients without flares were analysed. In each no flare/flare visits, we assessed flares by SLE-DAS (score increase ≥1.72), classic-SELENA Flare Index (c-SELENA FI), revised-SELENA FI (r-SELENA FI), and SLEDAI-2K (score increase ≥4). We estimated the sensitivity, specificity, and Cohen's Kappa agreement of each flare tool against the gold-standard. A total of 442 patients were included and followed-up for 22.9 (14.2) months. Incidence of flares was 8.19/100 patient-years, with 69 patients experiencing flares. The SLE-DAS identified 96.6% of the expert-defined flares implying a treatment change and classified 28.0% of those as moderate/severe. Sensitivity and specificity for the gold-standard flare definition were: SLE-DAS 97.1% and 97.3%, c-SELENA FI 88.4% and 98.1%, r-SELENA FI 88.4% and 96.8%, SLEDAI-2K 56.5% and 99.2%, respectively. Kappa coefficients of these instruments were 0.902 (95% CI: 0.847, 0.957), 0.870 (95% CI: 0.805, 0.935), 0.832 (95% CI: 0.761, 0.903), and 0.663 (95% CI: 0.557, 0.769), respectively. The number of flare misclassifications was lowest with the SLE-DAS, and highest with the SLEDAI-2K. The SLE-DAS accurately identifies and categorizes flares as mild or moderate/severe. It is feasible and, thus, may help the physicians' treatment decisions in the clinical practice setting.

OA29 Flares following COVID-19 vaccination in patients with idiopathic inflammatory myopathies: combined analysis from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) studies

Abstract Background/Aims Flares following COVID-19 vaccination are an emerging concern among patients with rare rheumatic disease like idiopathic inflammatory myositis (IIMs), whereas data and understanding of this is rather limited. We aimed to study the prevalence, characteristics and determinants of IIM flares following COVID-19 vaccination. Methods CoVAD (COVID-19 Vaccination In Autoimmune Diseases) surveys are global patient self-reported e-surveys from 109 countries conducted in 2021 and 2022. Flares of IIM were defined by 4 definitions; a. patient self-reported, b. physician and immunosuppression (IS) denoted, c. sign directed (new erythematous rash, or worsening myositis or arthritis), d. MCID worsening of PROMISPF10a score between the patients who had taken both surveys. Descriptive statistics and multivariate regression were used to describe the predictors of flare. Cox-regression analysis was used to differentiate flares by IIM subtypes. Results Among the 1,278 IIM patients, aged 63 (50-71) years, 276 (21.5%) were dermatomyositis, 237 (18.5%) IBM, 899 (70.3%) were female and most were Caucasian (80.8%). Flares of IIM were seen in 123/1278 (9.6%), 163/1278 (12.7%), 112/1278 (8.7%), and 16/96 (19.6%) by definitions a-d respectively with median time to flare being 71.5 (10.7-235) days. Muscle weakness (69.1%), and fatigue (56.9%) were the most common symptoms of flare. The predictors of self-reported flare were: inactive/disease in remission prior to first dose of vaccine (OR = 4.3, 95%CI=2.4-7.6), and anxiety disorder (OR = 2.2, 95%CI=1.1-4.7). Rituximab use (OR = 0.3, 95%CI=0.1-0.7) and IBM (OR = 0.3, 95%CI=0.1-0.7) were protective. Physician defined flares were seen more often in females, mixed ethnicity, and those with asthma, ILD, and anxiety disorder (OR ranging 1.6-7.0, all p < 0.05). Notably, overlap myositis (OM) had higher HR for flare compared to polymyositis (HR = 2.3, 95%CI=1.2-4.4, p = 0.010). Conclusion Nearly one in ten individuals with IIM develop flares after vaccination, more so among women, those with overlap myositis, and inactive disease prior to vaccination. Formal definition of flares in IIM is needed. Disclosure L. Gupta: None. N. R: None. Z. Griger: None. V. Agarwal: None. P. Sen: None. M. Joshi: None. S. Saha: None. K. Jagtap: None. O. Distler: Honoraria; Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. E. Nikiphorou: Honoraria; Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, and Lilly. Grants/research support; Pfizer and Lilly. A. Tan: Honoraria; Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB. S. Shinjo: None. N. Ziade: Honoraria; Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre. M. Milchert: None. I. Parodis: Honoraria; Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG. M. Kuwana: None. A. Makol: None. J. Pauling: None. C. Wincup: None. J. Lilleker: Honoraria; Sanofi Genzyme, Roche, and Biogen. A. Nune: None. J. Day: Grants/research support; CSL Limited. H. Chinoy: Consultancies; Novartis, Eli Lilly, Orphazyme, Astra Zeneca. Honoraria; UCB, and Biogen. Grants/research support; Eli Lilly and UCB. V. Agarwal: None. R. Aggarwal: Consultancies; Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant.

Corrigendum to: International consensus definition of disease flare in hidradenitis suppurativa.

Using gene expression and proteomic studies, Toll-like receptor 2 has been found to play a role in epidermal hyperkeratosis and the development of congenital ichthyosis. Downstream signalling involving GATA-3 reveals potential novel drug targets for congenital ichthyosis. Further studies of ichthyosis subtypes will provide more precise strategies for targeted therapies.

Short- and long-term follow-up after fecal microbiota transplantation as treatment for recurrent Clostridioides difficile infection in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at an increased risk of developing Clostridioides difficile infection (CDI). Treatment of CDI in patients with IBD is challenging due to higher failure rates and concomitant IBD activity. We performed a multicentre cohort study in patients with IBD who received fecal microbiota transplantation (FMT) for recurrent CDI (rCDI), to further investigate factors that influence the clinical outcome and course of both rCDI and IBD. This is a multicentre cohort study conducted in five European FMT centres. Adult IBD patients treated with FMT for rCDI were studied. Cure was defined as clinical resolution of diarrhoea or diarrhoea with a negative C. difficile test. The definition of an IBD flare was record based. Long-term follow-up data were collected including new episodes of CDI, IBD flares, infections, hospital admissions, and death. In total, 113 IBD patients underwent FMT because of rCDI. Mean age of the patients was 48 years; 64% had ulcerative colitis. Concomitant rCDI was associated with an IBD flare in 54%, of whom 63% had received IBD remission-induction therapy prior to FMT. All FMT procedures were preceded by vancomycin treatment, 40% of patients received FMT via colonoscopy. CDI cure rate was 71%. Long-term follow-up data were available in 90 patients with a median follow-up of 784 days (402-1251). IBD activity decreased in 39% of patients who had active IBD at baseline, whereas an IBD flare occurred in only 5%. During follow-up of up to 2 years, 27% of the patients had infections, 39% were hospitalized, 5% underwent colectomy, and 10% died (median age of these latter patients: 72 years). FMT for rCDI in IBD patients is safe and effective, and IBD exacerbation after FMT is infrequent. Further studies should investigate the effects on IBD course following FMT.

Solar flare catalog based on SDO/AIA EUV images: Composition and correlation with GOES/XRS X-ray flare magnitudes

Supervised Machine Learning (ML) models for solar flare prediction rely on accurate labels for a given input data set, commonly obtained from the GOES/XRS X-ray flare catalog. With increasing interest in utilizing ultraviolet (UV) and extreme ultraviolet (EUV) image data as input to these models, we seek to understand if flaring activity can be defined and quantified using EUV data alone. This would allow us to move away from the GOES single pixel measurement definition of flares and use the same data we use for flare prediction for label creation. In this work, we present a Solar Dynamics Observatory (SDO) Atmospheric Imaging Assembly (AIA)-based flare catalog covering flare of GOES X-ray magnitudes C, M and X from 2010 to 2017. We use active region (AR) cutouts of full disk AIA images to match the corresponding SDO/Helioseismic and Magnetic Imager (HMI) SHARPS (Space weather HMI Active Region Patches) that have been extensively used in ML flare prediction studies, thus allowing for labeling of AR number as well as flare magnitude and timing. Flare start, peak, and end times are defined using a peak-finding algorithm on AIA time series data obtained by summing the intensity across the AIA cutouts. An extremely randomized trees (ERT) regression model is used to map SDO/AIA flare magnitudes to GOES X-ray magnitude, achieving a low-variance regression. We find an accurate overlap on 85% of M/X flares between our resulting AIA catalog and the GOES flare catalog. However, we also discover a number of large flares unrecorded or mislabeled in the GOES catalog.

43 Egyptian evidence-based consensus recommendations for diagnosis and targeted management of childhood-onset systemic lupus erythematosus. An initiative by the Egyptian College of Pediatric Rheumatology

Abstract Background Childhood-onset systemic lupus erythematosus (cSLE) is a rare prototype of a multi-systemic, inflammatory, heterogeneous and potentially life-threatening autoimmune condition with quite significant linked morbidity. To date, there are no Egyptian nationally agreed, evidence-based guidelines concerning the diagnosis and management of kDa in children and treatment is often based on clinical expertise. Consequently, treatment regimens vary broadly. This work was an initiative by the Egyptian College of Paediatric Rheumatology aiming at optimising the management approaches for children and young adults with cSLE. Objective To provide evidence-based consensus recommendations for diagnosis and management of cSLE Methods This study was carried out to achieve an Egyptian expert consensus on a management strategy for cSLE using Delphi technique. A multistep process strategy was adopted, which started by developing 18 key clinical questions by scientific committee according to the Patient/Population, Intervention, Comparison, Outcomes and Time (PICOT) approach. The core leadership team identified clinicians and researchers with expertise in pediatric rheumatology all over Egypt. An evidence-based, systematic, literature review was conducted to compile evidence for the cSLE management. Delphi process was implemented (3-rounds) to reach a consensus. Results Twenty-five expert panel participated in the 3 rounds with response rate 100%. A total of 24 recommendations, categorized into 14 domains (Targeted population, criteria for classification, definition of disease activity status, definition of flare up, lab tests, treatment targets, monitoring, treatment, recommendations for specific organ system, prognostic markers, refractory condition, vaccination and transition program. The Agreement with the recommendations (rank 7–9) ranged from 84.8–94.8%. The Consensus was reached (i.e. ≥75% of respondents strongly agreed or agreed) on all the clinical standards. Algorithm for management has also been developed. Conclusion This work provided an updated management approach for cSLE patients. This evidence-based informed consensus process is expected to support uniform, high quality standards of care for children with cSLE in Egypt The implication to policy, practice, research and advocacy: to provide updated recommendations for better management of cSLE.

Sun CubE OnE: A multi-wavelength synoptic solar micro satellite

The Sun cubE onE (SEE) is a 12U CubeSat mission proposed for a phase A/B study to the Italian Space Agency that will investigate Gamma and X-ray fluxes and ultraviolet (UV) solar emission to support studies in Sun-Earth interaction and Space Weather from LEO. More in detail, SEE’s primary goals are to measure the flares emission from soft-X to Gamma ray energy range and to monitor the solar activity in the Fraunhofer Mg II doublet at 280 nm, taking advantage of a full disk imager payload. The Gamma and X-ray fluxes will be studied with unprecedented temporal resolution and with a multi-wavelength approach thanks to the combined use of silicon photodiode and silicon photomultiplier (SiPM) -based detectors. The flare spectrum will be explored from the keV to the MeV range of energies by the same payload, and with a cadence up to 10 kHz and with single-photon detection capabilities to unveil the sources of the solar flares. The energy range covers the same bands used by GOES satellites, which are the standard bands for flare magnitude definition. At the same time SiPM detectors combined with scintillators allow to cover the non-thermal bremsstrahlung emission in the gamma energy range. Given its UV imaging capabilities, SEE will be a key space asset to support detailed studies on solar activity, especially in relation to ultraviolet radiation which strongly interacts with the upper layers of the Earth’s atmosphere, and in relation to space safety, included in the field of human space exploration. The main goal for the UV payload is to study the evolution of the solar UV emission in the Mg II band at two different time scales: yearly variations along the solar cycle and transient variations during flare events. The Mg II index is commonly used as a proxy of the solar activity in the Sun-as-a-star paradigm, in which solar irradiance variations in the UV correlate with the variations in stratospheric ozone concentrations and other physical parameters of the Earth high atmosphere. SEE data will be used together with space and ground-based observatories that provide Solar data (e.g. Solar Orbiter, IRIS, GONG, TSST), high energy particle fluxes (e.g. GOES, MAXI, CSES) and geomagnetic data in a multi-instrument/multi-wavelength/multi-messenger approach.

Development and Validation of a Juvenile Spondyloarthritis Disease Flare Measure: Ascertaining Flare in Patients With Inactive Disease.

Our objective was to develop and validate a composite disease flare definition for juvenile spondyloarthritis (SpA) that would closely approximate the clinical decision made to reinitiate or not reinitiate systemic therapy after therapy de-escalation. Retrospective chart reviews of children with SpA who underwent systemic therapy de-escalation of biologic or conventional disease-modifying antirheumatic drugs were used to develop and validate the flare outcome. Data on independent cohorts for development (1 center) and validation (4 centers) were collected from large tertiary health care systems. Core measure thresholds and candidate disease flare outcomes were assessed using sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs), and the receiver operating characteristic (ROC) area under the curve (AUC), with physician assessment of active disease plus re-initiation of standard dose of systemic therapy as the reference standard. Of the candidate definitions, clinically meaningful worsening in ≥3 of the following 5 core measures performed best: caregiver/patient assessment of well-being; physician assessment of disease activity; caregiver/patient assessment of pain, physical function, and active joint count. The ROC AUC was 0.91, PPV 87.5%, NPV 98.1%, sensitivity 82.4%, and specificity 98.7%. Cronbach's α was 0.81, signifying internal consistency, and factor analysis demonstrated that the outcome measured 1 construct. The Juvenile SpA Flare measure had face validity according to 21 surveyed pediatric rheumatologists. Juvenile SpA Flare had an ROC AUC of 0.85, a PPV of 92.3%, and an NPV of 96.8% in the validation cohort. There is initial support for the validity of the Juvenile SpA Flare measure as a tool to identify disease flare in juvenile SpA patients de-escalating therapy, and the measure is potentially applicable in clinical practice, observational studies, and therapeutic trials.

Defining and managing flares in axial spondyloarthritis.

Flares correspond to fluctuations in disease activity or symptoms. They should be avoided in chronic inflammatory diseases. In axial spondyloarthritis (axSpA), work is ongoing to better conceptualise and treat flares. This review highlights recent data on the definition and management of flares in axSpA. Many definitions of flares have been used in clinical trials, limiting the interpretation and comparison of studies. The expert group Assessment of SpondyloArthritis International Society (ASAS) developed a data-driven definition of flares/disease worsening: an increase in Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) of at least 0.9 points, for use in axSpA clinical trials. Flares are more challenging to define in clinical practice because of their multifaceted nature. Qualitative studies have shown that flares from the patient's perspective are related not only to disease activity, but also to fatigue, mood, sleep and general well-being. The management of axSpA relies on a treat-to-target (T2T) strategy and aims at reaching clinical remission while monitoring closely disease activity to prevent and shorten flares. The concept of flares has been clarified, and definitions have been developed for use in trials. The T2T approach aims at minimising flares in axSpA. The early recognition of flares and their severity may lead to better management.

Preliminary definition of cutaneous flare in dermatomyositis: A retrospective review

To the Editor: The Cutaneous Dermatomyositis Disease Activity and Severity Index (CDASI) is a reliable, validated outcome measure that correlates with quality of life and disease progression.1 Whereas a decrease in activity score correlates well with an improvement in skin disease, the CDASI activity (CDASI-A) score has not been used to quantitatively measure a significant increase in skin activity or a cutaneous flare.

Insights Into the Concept of Rheumatoid Arthritis Flare.

Identification of a pathological change in the course of systemic chronic immune-inflammatory diseases is key to delivering effective treatment strategies. In this context, one of the most compelling issues is the concept of flare. The multifaceted expression of disease activity in rheumatoid arthritis (RA) makes it challenging to provide an omni-comprehensive definition of flare, encompassing the pathology's different objective and subjective domains. Our incomplete understanding of the pathophysiological mechanisms underlying this process contributes to the partial comprehension of its potential clinical expression. This review focuses on the proposed pathophysiological processes underlying disease recrudescence in RA and the variable definitions adopted to capture flare in clinical practice through its objective, subjective, and temporal domains. Overall, what emerges is a complex landscape far from being unraveled.