I. Saulescu

Monitoring Drug and Antidrug Levels: A Rational Approach in Rheumatoid Arthritis Patients Treated with Biologic Agents Who Experience Inadequate Response While Being on a Stable Biologic Treatment

Clinical response in patients with rheumatoid arthritis (RA) treated with biologic agents can be influenced by their pharmacokinetics and immunogenicity. The present study evaluated the concordance between serum drug and antidrug levels as well as the clinical response in RA patients treated with biological agents who experience their first disease exacerbation while being on a stable biologic treatment. 154 RA patients treated with rituximab (RTX), infliximab (IFX), adalimumab (ADL), or etanercept (ETN) were included. DAS28, SDAI, and EULAR response were assessed at baseline and reevaluated at precise time intervals. At the time of their first sign of inadequate response, patients were tested for both serum drug level and antidrug antibodies level. At the next reevaluation, patients retreated with RTX that had detectable drug level had a better EULAR response (P = 0.038) with lower DAS28 and SDAI scores (P = 0.01 and P = 0.03). The same tendency was observed in patients treated with IFX and ETN regarding EULAR response (P = 0.002 and P = 0.023), DAS28 score (P = 0.002 and P = 0.003), and SDAI score (P = 0.001 and P = 0.026). Detectable biologic drug levels correlated with a better clinical response in patients experiencing their first RA inadequate response while being on a stable biologic treatment with RTX, IFX, and ETN.

How Useful is Anti-TNF Serum Level and Anti-drug Antibodies Detectionin Evaluating Patients with Spondyloarthritis?

Objective: The aim of this study was to assess whether infliximab and adalimumab drug serum levels and the detection of anti-drug antibodies can be of use in better observing disease activity in patients with spondyloarthritis, besides classical tools such as BASDAI, ASDAS and inflammatory markers. We proposed to evaluate the influence of ADA in non-responders and in drug-related adverse events. Methods: Over one year, we enrolled 115 patients with SpA, treated with infliximab or adalimumab. Patients who delayed prescribed drug administration were excluded from the study cohort. The population comprised 69 patients - 33 on IFX and 35 on ADA. NSAIDs administration was recommended “on demand”. Demographic, clinical (BASDAI, ASDAS) and laboratory (ESR, CRP) data was collected together with drug serum level and anti-drug antibodies using ELISA. The statistical analysis was performed using the SPSS software, version 20.0 with the aid of Student t-test, Spearman and Pearson tests. Results: Detectable IFX serum levels were identified in 60% of patients while 40% had undetectable drug titers. The IFX-negative had significantly higher disease activity scores: BASDAI (P=0.023), ASDAS-ESR (P<0.001) and ASDAS-CRP (P<0.001). Significant differences were found in the same subgroups regarding inflammatory markers, with higher ESR (P<0.001) and CRP (P=0.032) in patients with undetectable IFX levels. When measuring ADL serum levels, 82% had detectable drug concentrations, with lower BASDAI (P<0.001), ASDAS-ESR and ASDASCRP (P<0.001) and higher ESR and CRP at collection time when compared to ADL-negative patients. NSAID consumption correlated to undetectable levels of IFX and ADL as well as with anti-drug antibodies for both IFX and ADL positivity. All patients who experienced drug related adverse events on both IFX and ADL had positive anti-drug antibodies. Conclusion: Serum drug level measurement and anti-drug antibody detection can be used as a completion of a clinician’s tools in assessing disease activity, leading to an optimal patient management.

SAT0664 Is there an early ultrasonographic pattern in salivary glands in both primary and secondary sjogren syndrome

Background Sjogren Syndrome (SS) affects mainly exocrine glands. Ultrasonography (US) demonstrates specificity and sensibility in major salivary glands (SG) evaluation. Recent data confirm US might be used as primary evaluation technique for its ability to show structural alterations of parenchyma [1]. Objectives To assess the gray scale (GS) parenchymal inhomogeneity of major SG in patients with established primary and secondary SS and correlate with clinical and biological data. Methods Consecutive patients with SS were recruited and SG US was performed. Inhomogeneity of glandular parenchyma was quantified binary on each gland. ESSDAI and ESSPRI scores were calculated. Statistics was performed with SPSS. Results Twenty one (42.85% primary SS, 90.47% female) consecutive patients were included. Mean age was 53.66+/-12.99 years and disease duration 5.33+/-3.74 years. Antibody SSA/SSB presence was found in 85.7% (18/21). ESSDAI mean was 8.67+/-8.9 (0–29), ESSPRI 10.13+/-5.59 (0–20). There were no differences regarding ESSDAI and ESSPRI in the two groups (primary and secondary SS). Right parotid gland showed alterations in 71.4% patients (77% with primary SS, 66% with secondary SS). Frequently inhomogeneity was found in all major SG (33%, 22% left and right submandibular, 77%, 44.4% left and right parotid glands) in primary SS. Both submandibular glands were symmetrically involved (p<0.02). Duration of disease was negatively correlated to inhomogeneity of right parotid gland (p<0.02). Conclusions Inhomogeneity in major SG in GS US was found in the majority of patients with primary and secondary SS. The symmetrical involvement of submandibular glands was significant. The inhomogeneity appears in the early period of diagnosis. No major differences were found between two groups. References Damjanov N, Milic V, Nieto-González JC, Janta I, Naredo E. Multiobserver Reliability of Ultrasound Assessment of Salivary Glands in Patients with Established Primary Sjögren Syndrome. J Rheumatol. 2016 Oct;43(10):1858–1863. Disclosure of Interest None declared

AB1068 Ultrasound of salivary glands in sjogren's syndrome- which semi-quantitative scoring system is the best?

Background Sjogren Syndrome (SS) affects mainly exocrine glands. The latest diagnostic criteria designed for clinical studies are also used as guidance in clinical practice [1]. Ultrasonography (US) demonstrates specificity and sensibility in parotid and submandibular gland evaluation (SG). Parameters considered are echogenicity, homogeneity and margins regularity [1,2,3]. To standardize the assessment of B mode US of SG, different semi-quantitative scores were proposed. Objectives To apply and compare 9 US semi-quatitative scoring systems in B mode scanning of salivary glands in Sjogren Syndrome. Methods A research using keywords “salivary glands”, “ultrasonograpy”, “Sjogren Syndrome”, “semi-quantitative score” in Medline/Pubmed was performed. There was a selection of most relevant articles. There were not considered relevant publications with impact factor <1. We performed the examination on SG in B mode US and applied these scores (De Vita, Niemela, Hocevar, Salaffi, Yukinori, Cornec,Theander) to our patients (primary and secondary SS). Results Eighty four SG in patients diagnosed with primary and secondary (57.15%) SS were assessed. In the group of patients with SSA/SSB presence (85.7%), mean score was De Vita 1.78+/-1.21, Niemela 2.56+/-2.17, Hocevar and Wernicke 2.39+/-2.14, Salaffi 2.83+/-2.52, Yukinori 2.39+/-2.14, Milic 3.39+/-2.14, Cornec 1.78+/-1.215, Theander 1.28+/-0.752. Schirmer test and the need for using the artificial tears was correlated to SG alterations in scoring systems proposed by Niemela (r 0.465, p<0.05) and Salaffi ( r 0.496, p<0.02). All scoring systems were strongly correlated between them (r>0.8, p<0.01). Conclusions Inhomogeneity of parenchyma was considered in all scoring systems. Others considered relevant glandular dimension and margins regularity [2,3.4]. There was no difference between the scoring systems. Xeroftalmia valided through Schirmer test is correlated to SG parenchymal alterations. Our data is an update about semi-quantitative scoring systems in US of SG in SS. References Vitali C, Bombardieri S, Jonsson R et al. Classification criteria for Sjögrens Syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. AnnRheum Dis 2002;61:554–8. Makula E, Pokorny G, Palkό A.The place of magnetic resonance and ultrasonographic examinations of the parotid gland in the diagnosis and follow-up of primary Sjögrens syndrome. Rheumatology (Oxford). 2000;39(1):97–104. Niemelä RK, Takalo R, Hakala M. Ultrasonography of salivary glands in primary Sjogrens syndrome. A comparison with magnetic resonance imaging and magnetic resonance sialography of parotid glands. Rheumatology (Oxford). 2004 Jul;43(7):875–9. El Miedany YM, Ahmed I, El Gafaary M. Quantitative ultrasonography and magnetic resonance imaging of the parotid gland: can they replace the histopathologic studies in patients with Sjogrens syndrome? Joint Bone Spine.2004;71(1):29–38. Disclosure of Interest None declared

AB1158 Prevalence of comorbidities in psoriatic arthritis: a cross-sectional study

Background Psoriatic arthritis (PsA) is associated with important comorbidities: cardiovascular, gastro-intestinal, infectious, malignant, and psychiatric [1, 2]. However, they are less studied in PsA compared to other chronic inflammatory arthritis. Objectives The objective of this study was to calculate the prevalence of comorbidities and risk factors in a cohort of PsA patients. Methods This was an observational cross-sectional study, including consecutive, unselected adult patients, with a diagnosis of PsA according to their rheumatologist. Data collected: demographical, clinical (affected joints, current psoriasis, axial involvement, enthesitis, dactylitis), biological (acute phase reactants), and treatment related (nonsteroidal anti-inflammatory drugs, synthetic remissive drugs and biologics). Data on comorbidities and risk factors were collected according to the European League Against Rheumatism (EULAR) recommendations on reporting comorbidities in chronic inflammatory rheumatic diseases in daily practice [3]. Results In all, 129 PsA patients were included: 77 (59.7%) women, mean age ± standard deviation 53.5±11.8 years, disease duration 7±7.4 years; 53 (41.1%) had axial involvement, 33 (25.6%) dactylitis, 18 (14%) enthesitis, and 24 (18.6%) current moderate/severe psoriasis. Most of them had low or moderate disease activity and almost a quarter of them (32; 24.8%) were taking a biologic. The most prevalent comorbidities were: dyslipidaemia 103 patients (79.8%), hypertension 67 (51.9%), obesity 44 (34.1%), diabetes 21 (16.3%) and ischemic heart disease 15 (11.6%). Almost a third of patients (42, 32.6%) suffered a cardiovascular event after their PsA diagnosis, of which heart attack 2 patients, stroke 4, cardiac failure 4 and peripheral arterial disease one patient. Cardiovascular events correlated with smoking (r=0.893, p<0.001) and current moderate/severe psoriasis (r=0.218, p=0.013). Regarding infectious comorbidities: 11 patients (8.5%) had a history of tuberculosis after being diagnosed with PsA, 7 (5.4%) chronic viral hepatitis, of which 4 with B virus and 3 with C virus, and 5 patients (3.9%) developed severe infections. Five patients (3.9%) were diagnosed with neoplasia, but no correlation was identified with any of the clinical, biological or treatment related included variables. Only 11 patients (8.5%) were diagnosed with depression, but the prevalence is probably underestimated, since not all patients were screened to this end. Conclusions PsA is associated with a high prevalence of comorbidities, especially cardiovascular diseases. This should be taken into consideration in the therapeutic and the global management of PsA patients. References Husni ME, Mease PJ. Managing comorbid disease in patients with psoriatic arthritis. Curr Rheumatol Rep 2010;12(4):281–7. Ogdie A, Yu Y, Haynes K, et al. Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: apopulation-based cohort study. Ann Rheum Dis 2015;74(2):326–32. Baillet A, Gossec L, Carmona L, et al. Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative. Ann Rheum Dis 2016;75(6):965–73. Disclosure of Interest None declared

SAT0271 Is there a need to include serological pattern to predict damage in patients with antiphospholipid syndrome: diaps application

Background Antiphospholipid syndrome (APS) is an autoimmune disease defined as the presence of antiphospholipid antibodies (aPL), at least a clinical thrombotic event and is associated with an important risk of organ damage. The new index proposed, Damage Index in patients with Thrombotic Antiphospholipid Syndrome (DIAPS) may be an useful tool to estimate cumulative damage in patients with primary and secondary APS. It includes 38 clinical items expanded to show the complexity of clinical manifestations in APS patients. Objectives The aim of this study is to analyze the serological pattern as potential predictive factor for an increased DIAPS. Methods All consecutive patients known with APS according to the Sapporo and/or Sydney classification criteria were included in our monocentric cohort. Data on medical history, clinical manifestations, aPL profile and medication were collected. DIAPS score was used to measure damage in each patient. The relationship between aPL profile and DIAPS score was analysed. Results Seventy six patients with APS were included: 11 patients with primary APS, 65 patients with secondary APS. Their mean disease duration was 9.59±7.39years. The most frequent clinical manifestation from DIAPS was the peripheral vascular (deep vein thrombosis, intermittent claudication, tissue loss, vascular venous insufficiency) found in 61.8% of patients, followed by the neuropsychiatric manifestations (46.1%). The mean DIAPS score in our cohort was 4.25±3.51, not significantly different between patients with primary vs secondary APS (4.72 vs 4.16, p=0.629). Lupus anticoagulant (LA) was found in 25 patiens (32.9%), anti cardiolipin antibodies (aCL) in 49 patients (64.5%) and antibodies to β2-glycoprotein I (β2GPI) in 23 patients (30.3%). There were 36 patients known with a single positive aPL (47.4%), 27 patients (35.5%)with 2 positive aPL and only 2 patients with triple positivity. There were no significant differences regarding antibody profile between patients with primary and secondary APS. Higher values of DIAPS were seen in patients with β2GPI (p=0.042) and with positivity for 2 aPL (p=0.003). DIAPS value correlated to the presence of β 2GPI (p=0.042, R=0.233) and to positivity for two aPL (p=0.003, R=0.341). Conclusions Our study suggests that double positivity for aPL, especially the presence of β2GPI confers an increased value of DIAPS in patients with primary and secondary APS. References M-C Amigo et al. Development and initial validation of a damage index (DIAPS) in patients with thrombotic antiphospholipid syndrome (APS). Lupus (2015) 24, 927–934. LM Amezcua-Guerra. Improving definitions for an index of cumulative organ damage in patients with the antiphospholipid syndrome (DIAPS). Lupus (2016) 25, 671–672. Disclosure of Interest None declared

FRI0256 Significance of Cognitive Impairment in Systemic Sclerosis

Background There is an increased appreciation of the burden of cognitive impairment in people with autoimmune diseases (1). Recent studies have demonstrated that patients with systemic sclerosis (SSc) have a specific pattern of cognitive impairment: the dysexecutive syndrome (2). Objectives We evaluated the prevalence of cognitive impairment in SSc and assessed the association with the disease features and impact on daily living Methods Consecutive SSc from EUSTAR center 096 were examined. Montreal Cognitive Assessment (MoCA) was used to assess cognitive dysfunction and scores ≤26 were considered abnormal (3). SSc patients were assessed according tu MEDS evaluation sheets to determine organ involvement, autoantibody profile, disease activity (Valentine Activity Index) and disease severity (Medsger Severity Index). sHAQ (Scleroderma Health Assessment Questionnaire) has also been completed. Data were compared by difference tests according to the types of variables: t-test, Mann-Whitney or chi-square. To evaluate correlations between variables Pearson or Spearman correlations were used. Results A total of 70 SSc patients [36 (51.42%) limited SSc (lSSc) and 34 (48.57%) with diffuse SSc (dSSc), 60 female; mean age 54.5 (±11.62) years; mean disease duration 66 (±429.6) months] were included in the study. 47.14% of the patients had active disease, the mean Rodnan score was 7 (±4.17), the mean Medsger score was 5.5 (±2.89), 24.28% of the patients had lung involvement and 20% had pulmonary arterial hypertension. The mean HAQ was 1 (±0.59). Cognitive impairment was identified in 65.71% SSc patients; the mean MOCA score was 26 (±2.83). Cognitive impairment of SSc patients was related to older age (r=-0.378, p=0.001), rural provenience (r=-0.351,p=0.003), severity of the disease evaluated by the Medsger score (r=–0.262,p=0.029) and poor quality of life evaluated by sHAQ (r=-0.323,p=0.003).Correlations were also identified with musculoarticular involvement (r=-0.330,p=0.006), advanced capillaroscopy patttern (r=-0.331, p=0.006). The diiffuse SSc patients were more likely to have cognitive dysfunction (likehood ratio 0.012) as were those with SCL70 positive (0.0.18). No relationship was identified between cognitive impairment and lung, heart or renal involvement, the presence of digital ulcers, the use of corticosteoids or immunosuppression. Conclusions An increased prevalence of cognitive impairment was observed in SSc and associated with age, rural provenience, more severe disease, muscle involvement and poor quality of life. Further studies are needed to be compared with healthy controls and to assess the role of microvascular damage or that of other confounders. References T.N.Amaral et al. Prevalence and significance of cognitive impairment in systemic sclerosis Ann Rheum Dis 2015;74:605 Ylmaz N. et al Dysexecutive syndrome: a specific pattern of cognitive impairment in systemic sclerosis Cogn Behav Neurol. 2012 Jun;25(2):57–62. www.mocatest.org/normative-data/ Disclosure of Interest None declared

AB0457 How Much Different Is Juvenile Onset Systemic Lupus Erhytematosus? Data from A Romanian Cohort

Background Systemic Lupus Erhytematosus (SLE) is a multiorgan disease in which pattern of evolution is linked to activity and damage. When the disease starts at an early age, all the outcomes might be influenced by this. Objectives The main focus of this study is to describe the differences between juvenile and adult onset SLE in a Romanian cohort. Methods 101 SLE patients were evaluated between March 2015 and December 2015. Patients were diagnosed with SLE according to ACR classification criteria and splited in 2 groups, taking into account age at disease onset: before and after 18. All patients agree to participate in this study. Data about demographic, clinical or serological characteristics, activity (SLEDAI) or damage (SLICC damage index SDI), treatment were collected. Statistical analisys was performed with SPSS 20.0. Results Our cohort was made from 18 patients with juvenile onset SLE and 83 with adult onset SLE. Mean age at diagnosis was 14.05 versus 37.89. The juvenile onset SLE group had significant more autoimmune disease as family background, mainly SLE and rheumatoid arthritis (33.3% versus 12.04%, p 0.025), significant more severe organ involvement during the disease evolution: SLE related neurologic involvement 33.3% versus 12% (p 0.025) and renal involvement 50% versus 16.8% (p 0.023), more frequent anti dsDNA Ab positives 88.8% versus 60.24% (p 0.021). This more severe pattern of evolution is also reflected by immunosuppressant therapy, Cyclophosphamide being used in juvenile subgroup in 66% cases versus 35.3% in adults (p 0.014). Interesting, there were no differences between cumulative damage between groups, as measured by SDI (p 0.24), with the mention that in juvenile onset patients, SDI>1 was more frequent SLE related. This is in line with the fact that side effects of the corthicotherapie were identified more in adult onset SLE 61.44% versus 33.3% in juvenile onset (p 0.029). Conclusions Our data clearly show that juvenile onset SLE has more genetic background and it is more prone to a severe disease, renal and neurologic involvement being more frequent than in adult onset form. Severity seems to be related both to the activity, but also to fast damage accrual over time. Controlling the disease activity must be our goal, since cumulative irreversible damage is mainly SLE related for our patients. References Watson, L., Leone, V., Pilkington, C., et all, on behalf of the UK Juvenile-Onset Systemic Lupus Erythematosus Study Group, “Disease activity, severity, and damage in the UK juvenile-onset systemic lupus erythematosus cohort”. Arthritis & Rheumatism, 2012, 64: 2356–2365. doi: 10.1002/art.34410. Disclosure of Interest None declared

AB0756 Living with Osteoarthritis: Real Life Perception upon Pain and Function

Background Osteoarthritis (OA) is a prevalent condition for which treatments are based on analgesia and physical therapies. Despite that, most of the patients continue to have pain and limited function influencing there day by day life. Objectives Our objective was to evaluate pain perception in a cohort of participants, diagnosed with osteoarthritis. Methods 75 patients with osteoarthritis were enrolled in this study, conducted in Sf. Maria Hospital between 1 June and 30 December 2015. All patients signed an informed consent approved by local ethic committee. Data about demographics, joint involvement and treatment were collected. All patients completed a HAQ evaluation and a Visual Analogue Scale (VAS) for pain (0–10). We developed a questionnaire in order to capture patient perception about osteoarthritis symptoms and how this disease impact there life. They were asked about how pain interfere with usual activity (work, preparing meal, house kipping), with social activity (family interaction, friends) or how they perceived pain or efficacy of the treatment in the last month. They were also asked about there expectations related to this disease. Statistical analysis was made with SPSS. Results Mean age at evaluation was 63 with a female predominance (83%). 89.3% were taking NSAIDs and 73.3% acetaminophen. Functional status evaluated by HAQ showed that 24% patients had a score of 0, with 57% having a score of 1 and 19% a score of 2. VAS for pain was at least 5 for more than 80% of patients, despite treatment. Higher VAS was significant more frequent in female patients (p 0.001), in patients with family history of osteoarthritis (p 0.023) and in the one with sedentary life style (p 0.035). Most of the patients considered that pain interfere with daily activity, the impact being evaluated as moderate for 46.67% of patients and severe for 32%. Pain also had a negative impact on their social life, the percentage for moderate disturbance being of 38.67% and 18.67% for severe one. Only 11% of patients consider that the pain control is well managed. Despite these results, 40% of the patients do not expect that there quality of life will improve in the future. Conclusions Residual pain after treatment is present in most of the patients with osteoarthritis and these interfere significantly with daily living and quality of life. These patients enter in a vicious cycle related to worsening pain – low physical activity. Although this findings, there is a resumption of these patients in front of the disease. References Neogi T, The epidemiology and impact of pain in osteoarthritis, Osteoarthritis and cartilage, 2013, 21: 1145–1153. Disclosure of Interest None declared

AB0250 Wrist Ultrasound Better Correlates with Disease Activity Score (DAS28) in Rheumatoid Arthritis Patients Treated with Biologics

Objectives To assess which particular joint ultrasound (US) evaluation better correlate with disease activity based on DAS28 in rheumatoid arthritis (RA) patients treated with biologics. Methods Consecutive RA patients on stable biologic treatment for more than 6 months were evaluated. Clinical and US evaluation were performed by two independent assessors, the same day as all laboratory tests. The scanning technique and the settings of the machine (ESAOTE MY LAB70, 15 MHz linear probe) were the same for all the patients. Examinations were perform by a trained ultrasonografer who was blinded to all clinical evaluations. US of both hands (dorsal wrist, 2nd to 5th volar metacarpophalangeal and 2nd to 4th volar proximal interphalangeal) was done. Synovial hypertrophy and power Doppler (PD) signal were scored (grade 0–3). Synovial hypertrophy >2 plus power Doppler signal was classified as active synovitis. Based on DAS284v(ESR) patients were split in 2 groups: remission and non-remission. Results One hundred and six patients were evaluated. Most of them (84%) were females, mean age group 58.72 (11.49) years, mean disease duration 13.48 (7.4) years. Regarding the treatment, 87.7% had a DMARD associated to the biologic: 49.1% (52) patients were treated with rituximab, 27.35% (29) with etanercept,19.9% (19) with adalimumab, 9.33% (9) with infliximab. Mean DAS28 ESR was 3.14, with 36.8% of patients being on remission. We found a significant statistical difference (p=0.005) between active synovitis score in active disease patients (82.05% of them heaving active synovitis) versus 56.41% synovitis in remission patients. Statistical significance was also found regarding inflammation markers, PD joint number, PD total score, but not regarding Grey Scale (GS) number and total score (see table). When every joint was evaluated separately, statistically significance was found only between wrists and PD: right wrist (p=0.01) and left wrist (p=0.002), but not for GS (p=0.181 and 0.337). DAS 28 remission group (SD) DAS 28 non-remission group (SD) p Tender joint count 0.00 (0.00) 2.06 (2.54) <0.001 Swollen joint count 0.08 (0.35) 3.52 (4.13) <0.001 ESR 11.00 (6.43) 27.87 (21.30) <0.001 RF 28.12 (28.52) 74.83 (147) 0.016 ACPA 358.31 (677.46) 531.37 (829.91) 0.307 GS joint number 5.09 (3.23) 6.15 (2.59) 0.661 PD joint number 1.33 (1.49) 2.28 (1.65) 0.004 Total GS score 8.62 (4.71) 10.15 (5.30) 0.138 Total PD score 1.62 (1.75) 3.13 (2.41) 0.001 Active synovitis 56.41% 82.08% 0.005 Conclusions Active synovitis score, total PD joint number and total PD score correlates with DAS284vESR in rheumatoid arthritis patients treated with biologics. Both wrist US evaluation seems to be the most accurate in identifiing disease activity. Acknowledgements This paper is partially supported by the Sectoral Operational Program Human Resources Development, financed from the European Social Found POSDRU/159/1.5/S/137390. Disclosure of Interest None declared