Definition Of Flare Research Articles

Defining acute flares in knee osteoarthritis: a systematic review

ObjectiveTo identify and critically synthesise definitions of acute flares in knee osteoarthritis (OA) reported in the medical literature.DesignSystematic review and narrative synthesis. We searched Medline, EMBASE, Web of science and...

Prostate-specific antigen flare induced by 223RaCl2 in patients with metastatic castration-resistant prostate cancer.

Prostate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer, but its impact during radium-223 dichloride (223RaCl2) therapy is still unclear. This radioisotope has shown to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC). We sought to evaluate the impact of PSA flare on survival and its relation with metabolic parameters on 18F-labeled sodium fluoride PET/CT. We conducted a retrospective study of 168 patients with mCRPC (median age 69; median PSA 29.7) receiving 223RaCl2. Overall survival (OS) and progression-free survival (PFS), estimated by the Kaplan-Meier method and compared using a log-rank test, were evaluated for patient groups corresponding to different definitions of PSA flare. Metabolic 18F-fluoride PET/CT data were analyzed as well. Immediate PSA decline was observed in 49 patients (29.2%), whereas no PSA response was observed in 59 patients (35.1%). PSA flare (defined as rise after the first cycle followed by decrease below the baseline) was observed in 20 patients (11.9%) and PSA flare followed by a decrease from peak but not below baseline was observed in 40 (23.8%). The first flare subgroup had a median PFS and OS of 20.8 and 23.9months, respectively. These outcomes were not significantly different from patients with immediate PSA decrease, but were significantly better than in patients with persistent PSA elevation (3.1months for PFS and 11.5months for OS, p<0.001). Moreover, the PSA flare group showed an alkaline phosphatase (ALP) decrease significantly greater than non-responders (p=0.003). Metabolic 18F-fluoride PET/CT data were available in 35 patients at baseline and during 233RaCl2 therapy. The tumor burden reduction, expressed by ΔTLF10 and ΔFTV10, was more evident within PSA flare group below baseline than non-responders (p=0.005 and 0.001, respectively). This report suggests that a flare does not necessarily indicate lack of response to 223RaCl2 therapy.

How is symptom flare defined in musculoskeletal conditions: A systematic review.

To systematically review the definitions for "flare" in musculoskeletal conditions, the derivation processes, and validation of definitions for the 12 most burdensome musculoskeletal conditions. A literature search was conducted in MEDLINE, EMBASE, CINAHL, AMED, PsycInfo and Lilacs to identify studies that investigated derivation or validation of a flare definition, which we considered as a phrase or group of domains. Reports of derivation of flare definitions were identified for 9/12 musculoskeletal conditions. Validation of flare definitions was initiated for 4/12. For each condition, different derivation and validation methods have been used, with variable levels of consumer involvement, and in some cases different groups have worked on the process in parallel. Although some flare definitions began simply as "symptom worsening" or "change in treatment", most evolved into multidimensional definitions that include: pain, impact on function, joint symptoms, and emotional elements. Frequently initial attempts to create phrase to define the term flare evolved into consensus on the breadth of domains involved. Validation has compared flare definitions/domains against measures of disease activity, clinicians' diagnosis, response to drug therapy, or a combination. This review suggests that greater characterisation and definition of flares in musculoskeletal conditions are linked to the inclusion of multiple perspectives, multifaceted domains and compound comparators for their validation. Further work is required to optimise and test the derived definitions for most musculoskeletal conditions. As some elements are disease-specific, flare definitions cannot be extrapolated to other conditions. Research regarding flare in back pain (most burdensome disease) is limited.

Down-titration of biologics for the treatment of rheumatoid arthritis: a systematic literature review

Biologic therapies have improved the management of rheumatoid arthritis (RA) and the treat-to-target approach has resulted in many patients achieving remission. In the current treatment landscape, clinicians have begun considering dose reduction/tapering for their patients. Rheumatology guidelines in Asia, Europe, and the United States include down-titration of biologics but admit that the level of evidence is moderate. We conducted a systematic literature review to assess the published studies that evaluate down-titration of biologics in RA. The published literature was searched for studies that down-titrated the following biologics: abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Eligible studies included randomized controlled trials (RCTs), non-RCTs, observational, and pharmacoeconomic studies. The outcomes of interest were (1) efficacy and health-related quality of life, (2) disease flares, and (3) impact on cost. Eleven full-text publications were identified; only three were RCTs. Study results suggest that dosing down may be an option in many patients who have achieved remission or low disease activity. However, some patients are likely to experience a disease flare. Across the studies, the definition of disease flare and the down-titration criteria were inconsistent, making it difficult to conclude which patients may be appropriate and when to attempt down-titration. Studies have evaluated the practice of dosing down biologic therapy in patients with RA; however, a relatively small number of RCTs have been published. Although down-titration may be an option for some patients in LDA or remission, additional RCTs are needed to provide guidance on this practice.

Defining Flare in Osteoarthritis of the Hip and Knee: A Systematic Literature Review - OMERACT Virtual Special Interest Group.

Beyond the exacerbation of pain in describing a flare in osteoarthritis (OA), patients and health professionals add other elements that deserve to be fully elucidated, such as effusion, swelling, and mobility limitation. To define and conceptualize the construct flare in OA, the objective was to identify the key variables, or symptoms, that worsen, and to clarify how these variables are described in the literature by patients and clinicians. A systematic review of the literature was conducted in Medline and PsychINFO. In brief, the search terms used were "osteoarthritis," "knee," "hip," and "flare." Specific characteristics of included studies were identified, including the type of study design, type of flare assessed, how the flare developed, and what definition of flare was used, including whether the definition was based on qualitative or quantitative analysis. Pain was the major factor in the definition of flare within these studies. Four components of flare were identified: pain, other factors, composite criteria, and global assessment. While the majority of studies reported flare as an increase in pain using standardized outcome measures, only 1 study reported the antecedents and consequences of a pain flare using qualitative methods. The use of flare as an outcome or inclusion criterion in rheumatology trials is a common occurrence; however, this review highlights the wide variation in the definitions of OA flare currently in use and the emphasis on the measurement of pain. This variation in definition does not allow for direct comparison between trials and limits interpretation of evidence.

Prostate-Specific Antigen Flare Phenomenon Induced by Abiraterone Acetate in Chemotherapy-Naive Patients With Metastatic Castration-Resistant Prostate Cancer

BackgroundProstate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer treated with luteinizing hormone-releasing hormone agonist and chemotherapy. However, its incidence and the significance for the clinical outcomes of patients treated with abiraterone acetate (AA) are uncertain. Patients and MethodsA multicenter retrospective analysis of chemotherapy-naive patients treated with AA for metastatic castration-resistant prostate cancer (mCRPC) was conducted. The baseline characteristics, treatment history of mCRPC, and serum PSA kinetics during AA treatment were collected. The log-rank test was applied to compare progression-free survival (PFS) between patient groups with a PSA flare according to the different definitions and immediate PSA declines. ResultsThe data from 83 patients were analyzed. An immediate PSA decline of any amount was observed in 59 patients (71.1%). According to the various definitions of PSA flare, its incidence ranged from 6.0% to 10.8%. Although the median interval to the peak PSA level was 0.95 month, regardless of the PSA flare definition, the interval to the PSA nadir showed a wide range of 2.8 to 7.6 months. In PSA flare subgroup, the median PFS in patients with any PSA decline to less than the baseline and > 30% decline from the baseline was 12.4 months. The PFS duration of PSA flare patients did not significantly differ from that of patients with an immediate PSA decline of any amount and immediate > 30% decline without PSA flare. ConclusionThe PSA flare phenomenon is not rare event during AA treatment. A PSA decline during AA treatment, with or without a PSA flare, was associated with favorable clinical outcomes. Thus, AA should not be withdrawn early in patients with mCRPC in whom an initial, isolated PSA increase has been observed.

Effects of flare definitions on the statistics of derived flare distributions

The statistical examination of solar flares is crucial to revealing their global characteristics and behaviour. Such examinations can tackle large-scale science questions or give context to detailed single-event studies. However, they are often performed using standard but basic flare detection algorithms relying on arbitrary thresholds. This arbitrariness may lead to important scientific conclusions being drawn from results caused by subjective choices in algorithms rather than the true nature of the Sun. In this paper, we explore the effect of the arbitrary thresholds used in the GOES (Geostationary Operational Environmental Satellite) event list and LYRA (Large Yield RAdiometer) Flare Finder algorithms. We find that there is a small but significant relationship between the power law exponent of the GOES flare peak flux frequency distribution and the flare start thresholds of the algorithms. We also find that the power law exponents of these distributions are not stable, but appear to steepen with increasing peak flux. This implies that the observed flare size distribution may not be a power law at all. We show that depending on the true value of the exponent of the flare size distribution, this deviation from a power law may be due to flares missed by the flare detection algorithms. However, it is not possible determine the true exponent from GOES/XRS observations. Additionally we find that the PROBA2/LYRA flare size distributions are artificially steep and clearly non-power law. We show that this is consistent with an insufficient degradation correction. This means that PROBA2/LYRA should not be used for flare statistics or energetics unless degradation is adequately accounted for. However, it can be used to study variations over shorter timescales and for space weather monitoring.

A Single or Short Course of Palliative Radiotherapy Increases the Risk of Pain Flare

Objectives: To evaluate the incidence of pain flare after palliative radiation for painful osseous metastases, and whether a single or short course of radiotherapy increases the risk of pain flare using a physician-based assessment. Methods: A series of 55 consecutive patients who underwent palliative radiotherapy were included in this analysis. Their treatments were as follows: 8 Gy, single fraction (n = 5), 20 Gy, 5 fractions (n = 11), 30 Gy, 10 fractions (n = 39). Pain flare was defined as a 2-point increase in the present pain intensity (PPI) with no decrease in analgesic score or a 25% increase in the analgesic score with no decrease in PPI for at least 2 consecutive days. The assessment was performed by a radiation oncologist. Results: Using the definition of pain flare, 8 out of 34 (24%) patients experienced a pain flare with a median duration of 3 days (range: 2 to 6 days). The median onset of pain flare was the day after the start of radiotherapy (day 2; range, day 1 to 3). Two of the 5 (40%) patients and 4 of the 11 (36%) patients who received total doses of 8 Gy and 20 Gy, respectively, experienced a pain flare.In contrast, 2 of the 39 (5%) patients who received a total dose of 30 Gy experienced a pain flare. Conclusions: Pain flare is common after palliative radiotherapy for bone metastases.Single fraction or short course radiotherapy may be associated with a higher risk of pain flare.

Evaluation of the Disease Activity Score in Twenty-Eight Joints-Based Flare Definitions in Rheumatoid Arthritis: Data From a Three-Year Clinical Trial.

ObjectiveTo assess the flare rate using published criteria (Disease Activity Score in 28 joints [DAS28‐2] increase between visits of >1.2 or >0.6 if current DAS28 ≥3.2) in patients receiving constant treatment, and to compare published flare criteria to criteria used by study investigators after biologic treatment discontinuation in the ACT‐RAY study.MethodsPatients with rheumatoid arthritis (n = 553) were randomized to add tocilizumab to ongoing methotrexate, or switch to tocilizumab plus placebo. If DAS28 ≤3.2 occurred at week 24, treatment remained constant until week 52; here we assessed the DAS28‐2 flare rate. Between weeks 52 and 104, patients in sustained remission (DAS28 <2.6 at 2 consecutive visits 12 weeks apart) discontinued tocilizumab and were assessed every 4 weeks. Per protocol, flare was defined as a worsening of disease activity that required treatment beyond the permitted therapy based on investigator opinions (investigator flare) and was compared with the DAS28‐2 definition.ResultsAfter tocilizumab discontinuation, DAS28‐2 was sensitive (88–100%), but not specific (57–65%), for detecting investigator flare. Under constant treatment, DAS28‐2 criteria were met in 136 cases per 100 patient‐years despite stable disease activity. Sustained flares were infrequent. Other DAS28‐based criteria led to similar conclusions.ConclusionDAS28‐based flare occurred more often than investigator‐defined flares after biologic agent discontinuation. More stringent criteria may be more appropriate for clinical practice.

Characterizing Pain Flares From the Perspective of Individuals With Symptomatic Knee Osteoarthritis.

Although pain in knee osteoarthritis (OA) commonly affects activity engagement, the daily pain experience has not been fully characterized. Specifically, the nature and impact of pain flares is not well understood. This study characterized pain flares as defined by participants with knee OA. Pain flare occurrence and experience were measured over 7 days. This was a multiple methods study; qualitative methods were dominant. Data were collected during the baseline portion of a randomized controlled trial. Participants met criteria for knee OA and had moderate to severe pain. They completed questionnaires and a 7-day home monitoring period that captured momentary symptom reports simultaneously with physical activity via accelerometry (n = 45). Participants also provided individual definitions of pain flare that were used throughout the home monitoring period to indicate whether a pain flare occurred. Pain flares were described most often by quality (often sharp), followed by timing (seconds, minutes) and by antecedents and consequences. When asked if their definition of a flare agreed with a supplied definition, 49% of the sample reported only "somewhat," "a little," or "not at all." Using individual definitions, 78% experienced at least 1 daily pain flare over the home monitoring period; 24% had a flare on more than 50% of the monitored days. Pain flares were common, fleeting, and often experienced in the context of activity engagement. Participants' views on what constitutes a pain flare differ from commonly accepted definitions. Pain flares are an understudied aspect of the knee OA pain experience and require further characterization.

Validation of Treatment Escalation as a Definition of Atopic Eczema Flares

BackgroundAtopic eczema (AE) is a chronic disease with flares and remissions. Long-term control of AE flares has been identified as a core outcome domain for AE trials. However, it is unclear how flares should be defined and measured.ObjectiveTo validate two concepts of AE flares based on daily reports of topical medication use: (i) escalation of treatment and (ii) days of topical anti-inflammatory medication use (topical corticosteroids and/or calcineurin inhibitors).MethodsData from two published AE studies (studies A (n=336) and B (n=60)) were analysed separately. Validity and feasibility of flare definitions were assessed using daily global bother (scale 0 to 10) as the reference standard. Intra-class correlations were reported for continuous variables, and odds ratios and area under the receiver operator characteristic (ROC) curve for binary outcome measures.ResultsGood agreement was found between both AE flare definitions and change in global bother: area under the ROC curve for treatment escalation of 0.70 and 0.73 in studies A and B respectively, and area under the ROC curve of 0.69 for topical anti-inflammatory medication use (Study A only). Significant positive relationships were found between validated severity scales (POEM, SASSAD, TIS) and the duration of AE flares occurring in the previous week – POEM and SASSAD rose by half a point for each unit increase in number of days in flare. Smaller increases were observed on the TIS scale. Completeness of daily diaries was 95% for Study A and 60% for Study B over 16 weeks).ConclusionBoth definitions were good proxy indicators of AE flares. We found no evidence that ‘escalation of treatment’ was a better measure of AE flares than ‘use of topical anti-inflammatory medications’. Capturing disease flares in AE trials through daily recording of medication use is feasible and appears to be a good indicator of long-term control.Trial registrationCurrent Controlled Trials ISRCTN71423189 (Study A).

Outcome Measures for Gout Clinical Trials: a Summary of Progress

Gout is the most common form of inflammatory arthritis. With the development of new agents for the treatment of gout in the last decade, the lack of validated outcome measures for clinical trials in gout has become apparent. Gout has been a topic of discussion at Outcomes in Rheumatology Clinical Trials (OMERACT) meetings since 2002. This work has included identification of core domains for outcome measures for both acute and chronic gout studies. More recently, OMERACT have endorsed a number of these domains and measurement instruments for these domains. The domains appear to be largely relevant to patients with gout but additional issues have been identified, including the absence of an endorsed disease-specific measure of health-related quality of life. Concurrently, a preliminary definition of flare has been developed and leading from this, early versions of composite measures of disease activity and response criteria. With the ability for excellent serum urate control, remission should be possible and preliminary remission criteria have been proposed. Flare definition, response criteria and remission criteria require further validation. The role of serum urate as a biomarker for chronic gout studies is promising, but further work is required to show that serum urate is a biomarker of relevant clinical outcomes.

Flare in spondyloarthritis: Thresholds of disease activity variations

There is no definition of flare in spondyloarthritis (SpA). The aim of this study was to evaluate thresholds of disease activity variations using validated composite indexes. MethodsSpA patients (ASAS criteria) prospectively followed with at least two visits, were evaluated. Patients and physician answered at each visit the question: “do you consider your SpA/patient in a state of flare?”. Variations of BASDAI and ASDAS between visits were assessed and associated to the change of perception of a flare (yes/no). ROC curves were built to assess thresholds of variation in BASDAI and ASDAS associated with the change flare between visits. ResultsThe patients were issued from a prospective series of 250 SpA. Ninety-nine cases with at least 2 visits were analysed. They were: 67% men, mean age 45±12 years; disease duration: 16±10 years; 84% HLA-B27 positive; purely axial SpA: 81%; PASS at baseline: 56%; mean CRP: 8.6±13.5mg/l. Mean BASDAI and ASDAS-CRP at baseline were 4.3±2.2 and 2.5±1.1, respectively. The kappa coefficient of agreement between patient and physician for considering a flare was 0.68. The main results of the ROC curves are: a variation ≥2.1 units in BASDAI (sensitivity 59%, specificity 83%), 0.8 units in ASDAS-ESR (sen 56%, spe 91%) or 1.3 units in ASDAS-CRP (sen 47%, spe 100%) is associated to a flare. ConclusionWe propose thresholds of variations of BASDAI, ASDAS-ESR, and ASDAS-CRP associated to (and that may define) a flare, as considered by the patient and the physician.

Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B

BackgroundUnique immunological changes occur during pregnancy; the impact of which, on virological and biochemical markers of hepatitis B infection is not well established. Rapid changes in the immunological profile post...

Rémission et poussée dans la spondyloarthrite

Remission and flare are important concepts in the evolution and evaluation of spondyloarthritis. Currently, they have no consensual definition, and should take into account the phenotypic presentation of the disease as well as extra-rheumatologic features. Remission represents the therapeutic target, currently assessed mainly by disease activity evaluation of the rheumatologic involvement. Flare is an important component of follow up and therapeutic adaptation. The definition of flare and the tools for its assessment represent a matter of investigation in spondyloarthritis.

The French-Canadian validation of a disease-specific, patient-reported outcome measure for lupus.

The objective of this paper is to perform the cross-cultural validation of the French version of the LupusPRO, a disease-targeted patient-reported outcome measure, among systemic lupus erythematosus (SLE) patients in Canada. The French version of the LupusPRO and the MOS SF-36 were administered; demographic, clinical and serological characteristics were obtained. Disease activity (SELENA-SLEDAI and the Lupus Foundation of America definition of flare) and damage (SLICC/ACR SDI) were assessed. Physician disease activity and damage assessments were ascertained using visual analog scales. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent and discriminant validity (against corresponding domains of the SF-36), criterion validity (against disease activity, damage or health status) and known group validity were tested. A total of 99 French-Canadian SLE patients participated (97% women, mean (SD) age 45.2 (14.5) years). The median (IQR) SELENA-SLEDAI and SDI were 3.5 (6.0) and 1.0 (2.0), respectively. The ICR of the LupusPRO domains ranged from 0.81 to 0.93 (except for lupus symptoms, procreation and coping), while TRT ranged from 0.72 to 0.95. Convergent and discriminant validity, criterion validity and known group validity against disease activity, damage and health status measures were observed. Confirmatory factor analysis showed a good fit. The LupusPRO has fair psychometric properties among French-Canadian patients with SLE.

SP0139 A Tool to Identify Past or Present Rheumatoid Arthritis Flare from Both Patient and Physician Perspective

Rheumatoid arthritis (RA) patients with unstable and fluctuating disease activity have been shown to be at risk of structural damage progression. Despite considerable efforts dedicated to the assessment of RA...

THU0037 Validation of A Disease-Specific Patient-Reported Outcome Measure for Arabic Patients with Systemic Lupus Erythematosus

BackgroundIn comparison to the common chronic diseases, SLE has poorer outcomes with negative impact on the patient's life. Therefore, it became mandatory not only to recognize disease activity core set...

SP0138 Rheumatoid Arthritis Flare is More than a High Joint Count: Patient Perspectives on Flare

In rheumatoid arthritis, even with good inflammatory control, there are often episodes of increased inflammation (flare), which may prompt change in medication. However, there is no international definition of flare...

SAT0097 Assessing Significant Flares in Rheumatoid Arthritis: Validity of the Omeract Preliminary Flare Questionnaire (PFQ) in the Canadian Early Arthritis Cohort

BackgroundRheumatoid arthritis (RA) flares are common, poorly defined, and understudied. A new tool is needed that can precisely and reliably measure significant RA flares that may signal need for evaluation...