title: European multicentre pilot survey to assess vitamin D status in rheumatoid arthritis patients and early development of a new Patient Reported Outcome questionnaire (D-PRO).
abstract: OBJECTIVE
  To collect data on vitamin D (25(OH)D) serum levels in a large number of rheumatoid arthritis (RA) patients from different European countries, to investigate their relation with disease activity, disability, quality of life, and possibly to construct a new Patient Reported Outcome (PRO) questionnaire in order to self-estimate if they are at risk for vitamin D insufficiency/deficiency-related clinical implications (D-PRO).
  
  
  METHODS
  This was a European League Against Rheumatism (EULAR) supported cross-sectional study (project No CLI064) which involved 625 RA patients (mean age 55±11years, mean disease duration 11±9years), 276 age and sex matched healthy subjects, and rheumatologists working in academic institutions or hospital centres, as well as PARE organizations (patient representatives) from 13 European countries. Serum samples for 25(OH)D level measurement were collected during winter time and analyzed in a central laboratory using chemiluminescence immunoassay (DiaSorin). Patient past medical history was recorded. RA patients were provided with three questionnaires: the Rheumatoid Arthritis Impact Diseases score (RAID), the Health Assessment Questionnaire (HAQ), and the new D-PRO questionnaire at the time of 25(OH)D serum sampling. D-PRO questionnaire consisted of three domains, Symptom Risk Score (SRS), Habitus Risk Score (HRS) and Global Risk Score (SRS+HRS=GRS), constructed with items possibly related to vitamin D deficiency. D-PRO was correlated with both clinical and PRO scores. DAS28-CRP was also evaluated. Statistical analysis was performed by non parametric tests.
  
  
  RESULTS
  Mean serum concentration of 25(OH)D in RA patients (17.62±9.76ng/ml) was found significantly lower if compared to the levels obtained in matched controls (18.95±9.45ng/ml) (p=0.01), with statistically significant differences among several European countries. Negative correlations were found between 25(OH)D serum levels and DAS28-CRP (p<0.001), RAID (p=0.05) and HAQ (p=0.04) scores in the RA patients group. Negative correlations were also found in the cohort of enrolled RA patients between 25(OH)D serum concentrations and SRS (p=0.04), HRS (p=0.02) and GRS (p=0.02) domains of the D-PRO questionnaire.
  
  
  CONCLUSIONS
  This first multicentre European survey add new evidences that vitamin D insufficiency/deficiency is frequent in RA patients with statistically significant differences among several countries. Vitamin D serum concentrations seem to correlate negatively and significantly with the D-PRO Global Risk Score, clinimetric indexes for quality of life, disease activity and disability in present cohort of RA European patients.
authors.affiliation: Clinical Centre, Medical Faculty, University of Nis, Bul Zorana Djindjica 81 Nis, Serbia. Electronic address: vojinovic.jelena@gmail.com.
authors.forename: Jelena
authors.initials: J
authors.lastname: Vojinovic
authors.affiliation: Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia and Dpt. of Clinical and Experimental Science, University of Brescia, Italy. Electronic address: tincani@med.unibs.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Tincani
authors.affiliation: Research Laboratory and Academic Division of Rheumatology, Department of Internal Medicine, University of Genova, IRCCS San Martino-Clinical, Viale Benedetto VX/6, 16132 Genova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sulli
authors.affiliation: Research Laboratory and Academic Division of Rheumatology, Department of Internal Medicine, University of Genova, IRCCS San Martino-Clinical, Viale Benedetto VX/6, 16132 Genova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Soldano
authors.affiliation: Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia and Dpt. of Clinical and Experimental Science, University of Brescia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Andreoli
authors.affiliation: Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia and Dpt. of Clinical and Experimental Science, University of Brescia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Dall'Ara
authors.affiliation: Spitalul Sf. Maria, Clinica Medicina Interna Reumatologie, Bulevard Ion Mihalache 37-39, sector 1, Bucarest, Romania. Electronic address: ruxandraionescu1@gmail.com.
authors.forename: Ruxandra
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authors.lastname: Ionescu
authors.affiliation: Institute of Rheumatology, Resavska 69, Belgrade, Serbia. Electronic address: simicpasalickatarina@gmail.com.
authors.forename: Katarina Simic
authors.initials: KS
authors.lastname: Pasalic
authors.affiliation: Division of Rheumatology, Paula Stradina Clinical Hospital, Pilsonu 13, Nr. 26, corpuss 10, LV-1001 Riga, Latvia. Electronic address: ine@no.lv.
authors.forename: Inete
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authors.lastname: Balcune
authors.affiliation: Hospital Universitario de Canarias, Servicio de Reumatología, Planta 5, Ofra s/n La Cuesta, 38320 Santa Cruz de Tenerife, Spain. Electronic address: iferrazamaro@hotmail.com.
authors.forename: Ivan
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authors.lastname: Ferraz-Amaro
authors.affiliation: Rheumatology Institute, Military Medical Institute, Ul. Szaserów 128, 04-141 Warszawa, Poland. Electronic address: m.tlustochowicz@gmail.com.
authors.forename: Małgorzata
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authors.lastname: Tlustochowicz
authors.affiliation: Clinic of Rheumatology, Orthopedics Traumatology and Plastic Surgery, Vilnius University, Santariskiu Str. 2, LT-08406 Vilnius, Lithuania.
authors.forename: Irena
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authors.lastname: Butrimiene
authors.affiliation: Clinic of Rheumatology, Orthopedics Traumatology and Plastic Surgery, Vilnius University, Santariskiu Str. 2, LT-08406 Vilnius, Lithuania. Electronic address: epunceviciene@gmail.com.
authors.forename: Egle
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authors.lastname: Punceviciene
authors.affiliation: Scientific Research Institute of Rheumatology "V.A.Nasonova", Kashirskoye shosse 34A, 115522 Moscow, Russia. Electronic address: epid@irramn.ru.
authors.forename: Natalia
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authors.lastname: Toroptsova
authors.affiliation: Department of Rheumatology, Sisters of Mercy Clinical Hospital Centre University, Physical and Rehabilitation Medicine Vinogradska 29, 10000 Zagreb, Croatia. Electronic address: simeon.grazio@zg.t-com.hr.
authors.forename: Simeon
authors.initials: S
authors.lastname: Grazio
authors.affiliation: Department for Clinical Immunology and Rheumatology, Clinical Hospital Dubrava, School of Medicine, University of Zagreb, Croatia. Electronic address: jmorovic@kbd.hr.
authors.forename: Jadranka
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authors.lastname: Morovic-Vergles
authors.affiliation: National Institute of Rheumatic Diseases, Nábrezie I. Krasku 4, 921 01 Piestany, Slovakia. Electronic address: pavol.masaryk@nurch.sk.
authors.forename: Pavol
authors.initials: P
authors.lastname: Masaryk
authors.affiliation: Department of Rheumatology, Tallinn Central Hospital, Pärnu mnt 104, 11312 Tallinn, Estonia. Electronic address: katii.otse@itk.ee.
authors.forename: Kati
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authors.lastname: Otsa
authors.affiliation: Rheumatology Department, São João Hospital Center, Faculty of Medicine, University of Porto, Rua Dr Plácido da Costa, 4200-450 Porto, Portugal. Electronic address: mbernardes09@gmail.com.
authors.forename: Miguel
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authors.lastname: Bernardes
authors.affiliation: UMHAT "St. Iv. Rilski" Clinic of Rheumatology, Medical University Sofia, Urvich str, fl 1, 1612 Sofia, Bulgaria. Electronic address: vladimira.boyadzhieva@gmail.com.
authors.forename: Vladimira
authors.initials: V
authors.lastname: Boyadzhieva
authors.affiliation: Department of Rheumatology, Università Politecnica delle Marche, Ancona, Italy. Electronic address: fausto.salaffi@gmail.com.
authors.forename: Fausto
authors.initials: F
authors.lastname: Salaffi
authors.affiliation: Research Laboratory and Academic Division of Rheumatology, Department of Internal Medicine, University of Genova, IRCCS San Martino-Clinical, Viale Benedetto VX/6, 16132 Genova, Italy. Electronic address: mcutolo@unige.it.
authors.forename: Maurizio
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mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000175:diagnosis*; D003430:Cross-Sectional Studies; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071066:Patient Reported Outcome Measures; D011788:Quality of Life; D011795:Surveys and Questionnaires; D014807:Vitamin D / Q000378:metabolism / Q000627:therapeutic use*; D014808:Vitamin D Deficiency / Q000209:etiology*
chemical_list: D014807:Vitamin D
keywords: DAS28; Disability; Disease activity; HAQ; Patient Reported Outcome questionnaire; Quality of life; RAID; Rheumatoid arthritis; Vitamin D