physician global assessment sle10 marca 2023
physician global assessment sle

The PISCOS results will allow for increased homogeneity and reliability of PGA ratings in routine clinical practice, definitions of remission and low disease activity, and future SLE trials. , Friebus-Kardash J van Vollenhoven R Notorious to increase IOP and cause severe PAIN and headache; Diagnostics: - History - Tonometry examinations - measures IOP QUESTION A client states that the physician has told her that her intraocular was 14. The interRR was assessed in seven studies [4, 10, 11, 36, 65, 68, 94], showing values ranging from 0.67 [68] to 0.96 [94]. , Bouter LM 12. and later incorporated into the SLE Responder Index used in the belimumab clinical trials, 13 et al. The Systemic Lupus Activity Measure-revised, the Mexican Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and a modified SLEDAI-2K are adequate instruments to measure disease activity in systemic lupus erythematosus. , Matos A Cloud, mobility, security, and more. The interrater reliability (interRR) of the PGA is the ability to provide consistent scores in a stable population between two or more physicians who evaluate the disease activity of the same patient. Bookshelf Thanou A, Chakravarty E, James JA, Merrill JT. , Piette EW SLE is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. They participate in physiologic and inflammatory cascades and have become a major focus of research, yielding novel therapies for immune-mediated inflammatory diseases (IMID). Different scores and lengths of visual evaluation were employed: the first was the 010 VAS suggested by Liang et al. The Physician Global Assessment (PGA) has been shown to be a valid, responsive, and feasible instrument to capture disease activity in systemic lupus erythematosus (SLE), but its low reliability further supports the need for a standardisation of its scoring. et al. The pooled correlation coefficient (95% CI) is given both for the fixed effects model and the random effects model. A validation study of the SRI for juvenile SLE [60] showed that exclusion of the BILAG or PGA from the SRI did not change the accuracy of the SRI in detecting improvement. The intrarater reliability (intraRR) is the ability to provide consistent scores in a stable population by the same assessor over time. Liang MH The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). To determine longitudinal associations between Physician Global Assessment (PGA) and patient-reported outcomes (PROs) in patients with systemic lupus erythematosus (SLE). Discrimination refers to whether the score (PGA-VAS) differentiates between situations of interest [18]: discrimination of the PGA measures the ability of the PGA-VAS to report a consistent score where no change in disease activity has occurred (reliability) and to detect a change when a change in disease activity has occurred (sensitivity to change or responsiveness). et al. Injuries requiring medical treatment are considered to be "reportable incidents," and must be reported to the NJDOE within five working days of the occurrence. Mina R , Merrill JT. , Maxwell LJ In the absence of a well-recognized gold standard for disease activity, criterion validity of the PGA is established when it correlates with a measure that the author of the study defined a priori as the gold standard. MD globals may vary based on their age, gender, practice setting and experience (number of patients seen per year and years in practice). A PGA 2 correlated with a risk of pregnancy loss (29% vs 8%, P=0.005) [49]. PGA is a simple instrument and the result is easily understood. , Francis S Construct validity is shown by the good correlation observed with the SLEDAI, BILAG, SLAM, LAI and ECLAM [10, 23, 24, 26, 28, 29, 35, 54, 68, 76, 84, 99]. The aim of this systematic literature review is to describe and analyse the psychometric properties of the PGA. , Hennis A. Jesus D Patient global assessment (PGA) is one of the most widely used PROs in RA practice and research and is included in several composite scores such as the 28-joint Disease Activity Score (DAS28). PGA is a valid, responsive and feasible instrument, though its reliability was impacted by the scale adopted, suggesting the major need for standardization of its scoring. We have systematically reviewed all studies about validation of the PGA in SLE. et al. Brunner HI Can Lupus Patients Take the Driver's Seat in Their Disease Monitoring. Forbess LJ The literature search identified 93 articles, and 12 additional articles were retrieved from the reference list of those publications. Liang et al. The Physician's Global Assessment (PhGA) is a number without unit. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. All articles published through 1 July 2019 in PubMed were screened, with no limitation on year of publication, language or patients age. The site is secure. This property is reported across all articles selected through this systematic review [24, 913, 21103]. Background/Purpose: The Physician Global Assessment (PGA) is a frequently-used outcome measure in Systemic Lupus Erythematosus (SLE). , Roberts WN Diet and Systemic Lupus Erythematosus (SLE): From Supplementation to Intervention. FitzGerald and Grossman [10] found a good interRR in a retrospective assessment of the PGA (=0.79). , Hochberg M. Wallace DJ A Comprehensive Digest of Research Publications From Cedars-Sinai Investigators. Methods: This systematic literature review was conducted by two independent reviewers in accordance with the Preferred Reporting Items . , Klein-Gitelman MS sharing sensitive information, make sure youre on a federal . A high variability in scales was found, causing a wide range of reliability (intraclass correlation coefficient 0.670.98). Moreover, a difference between the interRR of the PGA assessed by an untrained physician (0.50.63) and a trained investigator (0.790.81) was found, suggesting the need for PGA scoring training or standardization [36]. , Bertsias G , Carpenter AB Responsiveness. , Wallace DJ The measurements were in the form of a scale from 0 to 3 in 54 studies [2, 3, 9, 10, 12, 13, 21, 2469, 103], a 010 scale in 12 studies [4, 60, 7079], a 0100 scale in 9 studies [27, 40, 78, 8085], a 07 Likert scale [11, 78, 80], a 02 scale [53], a 04 scale [86] and a 05 scale [87]. All articles published through 1 July 2019 in PubMed were screened, with no limitation on year of publication, language or patients' age. Thank you for submitting a comment on this article. SLE3. Deconstruction of the safety of estrogen in lupus erythematosus national assessment-systemic lupus erythematosus disease activity index flare index. Stojan G The patients were diagnosed as having the following disorders: scleroderma (n = 27), dermatomyositis (n = 11), systemic lupus erythematosus (SLE) (n = 22), MCTD (n = 8), and RP without evidence of underlying CTD (n = 38). , Larson MG , Ogale S Wells GA Improving patient pathways for systemic lupus erythematosus: a multistakeholder pathway optimisation study. SLE or at an SLE site, but only if the injury requires treatment by a licensed medical doctor. Devilliers H physician global assessment Recently Published Documents. Supervise the development of junior medical affairs staff . We analysed the performance of the SELENA SLEDAI Physician's Global Assessment (SSPGA) and the Lupus Foundation of America-Rapid Evaluation of Activity in Lupus (LFA-REAL) as measures . , Hearth-Holmes M. Khan A All clinical diagnoses were verified by review of the patients' inpatient and outpatient files at the time of capillaroscopy. When expanded it provides a list of search options that will switch the search inputs to match the current selection. , Garabajiu M et al. inflammation (duration and severity of morning stiffness as measured by BASDAI). , Lerman RH Assessing disease activity in rheumatic diseases such as systemic lupus erythematosus (SLE) is vital for effective treatment. , Perez-Gutthann S et al. The aim of this systematic literature review is to describe and analyse the psychometric properties of the PGA. , Devilliers H It estimates how similar a given patients scores were at the two visits. , Rodrigues M Definition: At least a 20%, 40%, 50%, or 70% improvement and an absolute improvement of at least 1 unit on a scale of 1-10 in at least three of the following criteria: patient global assessment; pain; function (BASFI); and. No data were found regarding the feasibility of the PGA. et al. , Bonithon-Kopp C , Kalunian K Ensure second line of defense Derivatives RWA reviews are performed consistently and . The index assesses separately eight organ-based systems. , Block JA Parodis I Each study was examined in order to extract psychometric property data on the PGA according to the OMERACT Filter methodology version 2.1 [18]. (PGA) scoring of disease activity in systemic lupus erythematosus (SLE). , Urowitz MB , Andreoli L The aim of this systematic literature review is to describe and analyse the psychometric properties of the PGA. Content validity pertains to the degree to which the instrument measures all facets of a construct of interest [20]: this property is satisfied if the PGA is considered able to measure all aspects of disease activity in SLE in a comprehensive way. et al. , Mohan C. Jolly M The judgment of whether a patient with SLE has active disease is a central question both in routine patient management and in clinical research [4]. , Saad-Magalhes C watch for seizures after the procedure. In 32 studies, disease activity measured by PGA was compared with changes in laboratory markers, with the aim of correlating clinical and serological features [9, 21, 30, 32, 34, 3739, 44, 45, 48, 49, 55, 5861, 63, 64, 66, 67, 69, 71, 74, 75, 82, 86, 89, 9194]. HHS Vulnerability Disclosure, Help Some may be a consequence of therapy and others may be . , Clowse M. Moorthy LN Construct validity. No study has evaluated the feasibility of the PGA in SLE to date. European League Against Rheumatism. Mahler M The aim of this systematic review is to describe and analyse the measurement properties of the PGA, including the validity, reliability, responsiveness and feasibility. In 1988, Liang et al. , Ravelli A Enocsson H Please check for further notifications by email. Thousand Oaks. The aim of this systematic literature review is to describe and analyse the . Over the years, PGA-IGA scales were modified for the purpose of clinical settings and thus present a diversity in the number of response options (4 to 10 points), the response options label and the . AU - Kasitanon, Nuntana. The geographical analysis of the Global Global Respiratory Devices market provided in the report is just the right tool that competitors can use to discover untapped sales and business expansion . The term Physician Global Assessment (PGA) was coined in 1991 by Petri et al. disease activity). A good responsiveness for PGA was shown in eight studies. Int J Environ Res Public Health. Rheumatology (Oxford). , Fang H doi: 10.1136/rmdopen-2022-002395. Background: Physician Global Assessment (PGA) is a visual analogue score (VAS) that reflects the clinician's judgment of overall Systemic Lupus Erythematosus (SLE) disease activity. et al. [84] expressed the sensitivity in PGA scoring with the standardized response mean (SRM), demonstrating a very large effect size (ES=2.23) [110]. et al. et al. The OMERACT defines an instrument as an outcome measure if it passes the three pillars of evidence: truth (that refers to validity), discrimination (that includes reliability and responsiveness) and feasibility. , Siega-Riz AM Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of multifactorial origin that can affect any organ or organ system, resulting in a broad spectrum of clinical manifestations ranging from dermatological involvement to multi-organ failure with episodes of relapses and remissions. All versions are validated and used by lupus researchers for clinical and research purposes. , Glassman DS Objective Physician's global assessment (PGA) of disease activity is a major determinant of therapeutic decision making. A PGA >1 was predictive of polymorphic light cutaneous eruption (P=0.02) [59] and correlated negatively with LLDAS attainment [37]. In the last 30years, more than a dozen scores have been derived to assess disease activity in SLE, but not all of these have proven to be valid and reliable tools. Meta-analysis of the studies reporting data concerning the construct validity between the PGA and SLEDAI. Beaton DE Medical-Surgical Nursing Clinical Lab (NUR1211L) U.S. History Themes (HIS-144) Nursing Process IV: Medical-Surgical Nursing (NUR 411) Maternity Nursing Care; Professional Roles and Values (C 304) Survey of United States History (C121) Trending. (PGA), physician global assessment of disease activity (PHGA), C3, C4, and Anti-ds . et al. SELENA SLEDAI4. . Criterion validity. , Jolly M. Ribi C [8] suggested that the PGA should account for objective examination, laboratory results and what patients report. The assessment of PGA responsiveness was performed in 10 studies [4, 23, 50, 58, 7779, 81, 83, 84] using different methods [110]. Oxford University Press is a department of the University of Oxford. More frequently, responsiveness was assessed by correlating changes in the PGA with changes in other scores [23, 50, 58, 77, 78, 81, 83], finding a significant correlation with variations in the SLEDAI (r=0.390.66) [23, 77, 78], SLAM (0.61) [77], LAI (0.56) [77], patient global assessment (0.37) [77], SRI-50 (0.48) [78] and ESR (P<0.0001) [58], but not with C3, C4, circulating immunocomplexes and prednisone dose [77]. The PGA was developed on a 0 to 3 scale as part of the Lupus Activity Index. Nevertheless, despite the fact that the PGA was considered the reference in 39 studies involving other indices, it was used as the sole instrument in only 2 of them. The PGA is intended to encapsulate the physician's judgement of overall disease activity.Consensus on whether the PGA should be performed prior to, or after the receipt of laboratory values is lacking. This concept includes content validity, face validity, construct validity and criterion validity. The content can vary and relates either to global health (e . , Kalunian K The Physician Global Assessment (PGA) is an important tool for assessing disease activity in lupus. Strength. Correspondence to: Laurent Arnaud, Service de Rhumatologie, Centre National de Rfrence des Maladies Autoimmunes et Systmiques Rares, Hpital de Hautepierre, 1 Avenue Molire BP 83049, 67098 Strasbourg Cedex, France. , Suriano A Lead Medical Director heading up the global collaboration with Pfizer for Enbrel trials. Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of PGA . A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines [17], searching for articles reporting on the use of PGA in SLE. This study assesses the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional use of separate VAS scales for musculoskeletal (PhysMSK) and dermatologic (PhysSk) manifestations in patients with psoriatic arthritis (PsA). The last EULAR/ACR recommendations recommended use of the PGA in the routine monitoring of SLE [16]. The official NJDOE Incident Reporting Form, as well as a guide to completing Nehring J Accessibility , Petri M. Isenberg DA [8] and adopted in childhood SLE; the most common tool (the 03 VAS) was developed [68] to capture the concept of flare and is measured on a 3cm VAS in the SRI [3] and a 10cm VAS in the SFI [10, 104], but other scores (02, 04, 05, 07) [11, 53, 78, 80, 86, 87] and lengths (8cm, 15cm) [10, 8284] have also been used. Comparison of the validity and sensitivity to change of 5 activity indices in systemic lupus erythematosus. Montreal, Canada Area. Data regarding divergent validity are lacking for the PGA. Conclusion: , Engleman EG The PGA is a well accepted and commonly used scale for evaluating treatment response in clinical trials both in adults and children. Thus the development of a comprehensive index for assessing disease activity still represents one of the most important challenges in SLE [7]. The Physician Global Assessment International Standardisation COnsensus in Systemic Lupus Erythematosus (PISCOS) study aimed to obtain an evidence-based and expert-based consensus standardisation of the Physician Global Assessment (PGA) scoring of disease activity in systemic lupus erythematosus (SLE). A new tool -- the Lupus Activity Scoring Tool (LAST) - has been proposed to join the ranks of current disease activity indices. , Guzmn RM HRQoL: Health-related Quality of Life; ICAM: intercellular adhesion molecule; VCAM: vascular cell adhesion molecule; MCP-1: monocyte chemoattractant protein-1; NC: non-calcified; suPAR: soluble urokinase plasminogen activator receptor; LFA-REAL: Lupus Foundation of America Rapid Evaluation of Activity in Lupus; CES-D: Centers for Epidemiological StudiesDepression scale; SLAQ: Systemic Lupus Erythematosus Activity Questionnaire; NA: not acquired; NS: not significant. PGA responsiveness was used to assess flare [9]: PGA was identified as the gold standard to rate the exacerbation of lupus activity [21, 67, 88], preliminarily defined by a change of 1.0 on a 03 VAS since the last visit. In a post-hoc analysis of phase 3 belimumab trials, improvements and no worsening in the PGA were greater among SRI responders vs SRI non-responders (P<0.001) [52]. [35], the PGA correlated, although moderately, with the need for treatment change (r=0.46, P<0.01). . , Lin M Construct validity was recognized in 21 studies [2, 10, 11, 23, 24, 2629, 35, 47, 52, 54, 65, 68, 76, 84, 88, 92, 99, 101]. et al. , Genovese M , Mazur M. Fatemi A The PGA also showed good predictive validity, as it correlated significantly with measures of future outcomes, such as quality of life or laboratory exams, but no study has currently evaluated its correlation with measures of damage. , Rairie JE The Senior Lead will be responsible for: Managing end to end production, governance and controls of Derivatives Standardized and Advanced RWA, and SLE Actuals. et al. OBJECTIVE The Physician Global Assessment (PGA) is a visual analogue score that reflects the clinician's judgement of overall SLE disease activity. An official website of the United States government. Elevation of erythrocyte sedimentation rate is associated with disease activity and damage accrual, The systemic lupus activity measure-revised, the Mexican systemic lupus erythematosus disease activity index (SLEDAI), and a modified SLEDAI-2K are adequate instruments to measure disease activity in systemic lupus erythematosus, Small changes in outpatients lupus activity are better detected by clinical instruments than by laboratory tests, Development and initial validation of the systemic lupus erythematosus disease activity index 2000 responder index 50, Sensitivity to change of 3 systemic lupus erythematosus disease activity indices: international validation, Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index 50: sensitivity to response at 6 and 12 months, Validation of the functional assessment of chronic illness therapy-fatigue scale in patients with moderately to severely active systemic lupus erythematosus, participating in a clinical trial, Psychological distress and changes in the activity of systemic lupus erythematosus, The rating scale preference measure as an evaluative measure in systemic lupus erythematosus, Comparison of the validity and sensitivity to change of 5 activity indices in systemic lupus erythematosus, Treatment of systemic lupus erythematosus with dehydroepiandrosterone: 50 patients treated up to 12 months, Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus, Epratuzumab for patients with moderate to severe flaring SLE: health-related quality of life outcomes and corticosteroid use in the randomized controlled ALLEVIATE trials and extension study SL0006, Measuring systemic lupus erythematosus activity during pregnancy: validation of the lupus activity index in pregnancy scale, Autoantibodies against albumin in patients with systemic lupus erythematosus, Association of depression with socioeconomic status, anticardiolipin antibodies, and organ damage in patients with systemic lupus erythematosus: results from the KORNET registry, Placebo-controlled randomized clinical trial of fish oils impact on fatigue, quality of life, and disease activity in systemic lupus erythematosus, Serum free light chains, interferon-alpha, and interleukins in systemic lupus erythematosus, Vitamin D levels in Chinese patients with systemic lupus erythematosus: relationship with disease activity, vascular risk factors and atherosclerosis, Systemic lupus erythematosus disease activity index 2000 responder index-50: a reliable index for measuring improvement in disease activity, Testosterone patches in the management of patients with mild/moderate systemic lupus erythematosus, Turkish LupusPRO: cross-cultural validation study for lupus, Cross-cultural validation of a disease-specific patient-reported outcome measure for lupus in Philippines, Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial, Sensitivity and specificity of plasma and urine complement split products as indicators of lupus disease activity, The TNF locus is altered in monocytes from patients with systemic lupus erythematosus, Effect of pregnancy on disease flares in patients with systemic lupus erythematosus, Frequency of lupus flare in pregnancy: the Hopkins Lupus Pregnancy Center experience, Morbidity of systemic lupus erythematosus: role of race and socioeconomic status, Classification and definition of major flares in SLE clinical trials, Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study, COSMIN guideline for systematic reviews of patient-reported outcome measures, Validity and reliability in social science research, Understanding the minimum clinically important difference: a review of concepts and methods, Statistical significant change versus relevant or important change in (quasi) experimental design: some conceptual and methodological problems in estimating magnitude of intervention-related change in health services research, Minimum important difference between patients with rheumatoid arthritis: the patients perspective, Responsiveness and sensitivity to change of SLE disease activity measures, The Author(s) 2020. , Weisman MH. Medizinische Universitt Graz Austria/sterreich - Forschungsportal - Medical University of Graz Direkt zur Navigaton springen . Manzi S et al. Criterion validity was assessed exploring the PGA correlation with quality of life measurements, biomarker levels and treatment changes in 28 studies, while no study has evaluated correlation with damage. Quimby KR , Schirmbeck LA The search strategy for SSc-related publications identified 75 citations . Search for other works by this author on: Rheumatology Unit, AOU University Clinic and University of Cagliari, Department of Medical Sciences and Public Health, Cagliari, Italy, Centre Hospitalier Universitaire de Dijon, Hpital Franois-Mitterrand, service de mdecine interne et maladies systmiques (mdecine interne, 2) et Centre dInvestigation Clinique, Service de rhumatologie, Hpitaux Universitaires de Strasbourg, Universit de Strasbourg, Centre National de Rfrence des Maladies Systmiques et Autoimmunes Rares Est Sud-Ouest (RESO). The literature search identified 91 studies. BICLA responders had fewer lupus-related serious . et al. Supporting the face validity property, PGA was defined the gold standard in 11 studies [2, 10, 11, 21, 23, 49, 67, 76, 78, 84, 88] and in 32 it was used as the reference to which other activity scores were compared, such as the SLEDAI [4, 10, 13, 25, 27, 28, 31, 33, 35, 36, 41, 46, 47, 50, 51, 53, 62, 65, 68, 72, 73, 76, 81, 9699], BILAG [4, 27, 35, 36, 46, 65, 72, 73, 81, 98], SLAM [4, 72, 76, 99], LAI [68, 88], patient global assessment [81, 83, 84] and ECLAM [35]. Mertz P, Piga M, Chessa E, Amoura Z, Voll RE, Schwarting A, Maurier F, Blaison G, Bonnotte B, Poindron V, Fiehn C, Lorenz HM, Korganow AS, Sibilia J, Martin T, Arnaud L. RMD Open. PGA is an important tool for assessing disease activity, response to treatment (it is a component . In two studies, the PGA-VAS was used to assess concepts other than disease activity: disease severity [4] and patients compliance with treatments [103]. [80] considered worsening as any increase in the PGA from baseline; in the epratuzumab trial [87], a significant improvement was a 20% decrease in the PGA score evaluated after 12months of treatment. , Sayedbonakdar Z AU - Kandane-Rathnayake, Rangi. , Leung HW Five studies have demonstrated good ICC values for reliability (all >0.60 and ranging up to 0.97). , Lau CS The .gov means its official. , Kraag GR , Petri MA 2022 Sep 20;19(19):11895. doi: 10.3390/ijerph191911895. Compared with nonresponders, BICLA responders had greater improvements in global and organ-specific disease activity (Physician's Global Assessment, SLE Disease Activity Index 2000, Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity, and joint counts; all nominal P < 0.001). Kandane-Rathnayake R, Louthrenoo W, Hoi A, Luo SF, Wu YJ, Chen YH, Cho J, Lateef A, Hamijoyo L, Navarra SV, Zamora L, Sockalingam S, An Y, Li Z, Katsumata Y, Harigai M, Hao Y, Zhang Z, Kikuchi J, Takeuchi T, Basnayake BMDB, Chan M, Ng KPL, Tugnet N, Kumar S, Oon S, Goldblatt F, O'Neill S, Gibson KA, Ohkubo N, Tanaka Y, Bae SC, Lau CS, Nikpour M, Golder V, Morand EF; Asia-Pacific Lupus Collaboration. , Buyon J , Urowitz MB. , Brunetta P The Physician Global Assessment (PGA) is a visual analogue score that reflects the clinician's judgement of overall SLE disease activity. BICLA is a validated composite global measure of SLE disease activity including SLEDAI-2K, CLASI-A, OCS dosage reduction, and patient-reported outcomes. , McGuire JL. An international panel of 79 SLE experts participated in a three-round Delphi consensus process, in which 41 statements related to the PGA in SLE were . , Nguyen SC A difference between the interRR of the PGA assessed by an untrained physician (ICC=0.50.63) or a trained investigator (ICC=0.790.81) was found [36]. Oxford Textbook of. doi:10.1136/ rmdopen-2017-000578 Prepublication history and , Chan KL The Physician's Global Assessment (PGA) is a pragmatic disease activity measure, using a 100 mm visual analogue scale (VAS) for physicians to quantify the patient's overall disease . Disclosure statement: L.A. is a consultant for Alexion, Amgen, AstraZeneca, GlaxoSmithKline, Janssen-Cilag, LFB, Eli Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai and UCB.

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