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Background:Tofacitinib (TOFA) is an oral, small molecule drug used for rheumatoid arthritis (RA) treatment and is prescribed alone or with methotrexate (MTX). Tofa can be used as an alternative to biologic disease modifying antirheumatic drugs (bDMARDs) including tumor necrosis factor inhibitors (TNFi).Objectives:We aimed to evaluate the discontinuation rate of this drug, with and without concurrent MTX in comparison with TNFi, in patients with RA in the Ontario Best Practices Research Initiative (OBRI).Methods:RA patients enrolled in the OBRI initiating their TOFA or TNFi (adalimumab, certolizumab, etancercept, golimumab, and infliximab) within 30 days prior to or any time after enrolment between 1stJune 2014 (TOFA approval date in Canada) and 31stDec 2018 were included. Time to discontinuation (due to any reason) were assessed using Kaplan-Meier survival (adjusted for propensity score using inverse probability of treatment weight) to compare patients with and without MTX use at initiation of TOFA or TNFi.Results:A total of 565 patients initiated TOFA (n=208) or TNFi (n=357). Of those, 106 (51%) and 222 (62%) were treated with MTX in the TOFA and TNFi group, respectively and mean (SD) disease duration were 13.1 (9.4) and 9.5 (9.4) years. In the TOFA group, 86% were female and mean (SD) age at treatment initation was 60.4 (10.6) years. In the TNFi group 82% were female and mean age (SD) at treatment initation was 57.0 (12.6) years. The TOFA group was more likely to have prior biologic use (61.5%) compared with the TNFi group (31%). At treatment initiation, the mean (SD) clinical disease activcity index was 24.8 (12.1) in the TOFA group and 21.8 (12.0) in the TNFi group.Over a mean of 17.3 month follow-up, discontinuation was reported in 75 (36%) and 103 (29%) of all TOFA and TNFi patients, respectively. After adjusting for propensity score, patients treated with TNFi and MTX remained on treatment longer than those treated without MTX (Logrank p=0.002) while there was no significant difference in TOFA discontinuation in patients with and without MTX (Logrank p=0.31).Conclusion:In this real world data study, we found that TOFA retention is similar in patients with and without MTX, while patients treated with TNFi and MTX remained on treatment longer than those treated without MTX. Merging data with other RA registries in Canada is proposed to increase study power and to provide more robust results.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Angela Cesta: None declared, Xiuying Li: None declared, Edward Keystone Grant/research support from: AbbVie; Amgen; Gilead Sciences, Inc; Lilly Pharmaceuticals; Merck; Pfizer Pharmaceuticals; PuraPharm; Sanofi, Consultant of: AbbVie; Amgen; AstraZeneca Pharma; Bristol-Myers Squibb Company; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen, Inc; Lilly Pharmaceuticals; Merck; Myriad Autoimmune; Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis., Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd, Janssen, Inc; Merck; Pfizer Pharmaceuticals; Sanofi-Genzyme; UCB, Claire Bombardier Grant/research support from: Dr Bombardier reports sources of funding for Ontario Best Practice Research Initiative Research grants from Abbvie, Janssen, Amgen, Medexus, Merck, Pfizer, and Novartis outside of the submitted work. Consulting Agreements: Abbvie, Covance, Janssen, Merck, Pfizer, Sanofi and Novartis outside of the submitted work. Advisory Board Membership: Hospira, Sandoz, Merck, Pfizer and Novartis outside of the submitted work.

Background:Treat-to-target recommendations for rheumatoid arthritis (RA) dictate that remission or low disease activity should be aimed. Although numerous composite indices are available, the clinical disease activity index (CDAI) is commonly used in routine clinical care due to its simplicity and non-reliance on acute phase reactants.Objectives:The purpose of this analysis was to evaluate the CDAI properties both cross-sectionally and longitudinally in a cohort of RA patients followed in Canadian routine care.Methods:RA patients enrolled in the Ontario Best Practices Research Initiative (OBRI), with available follow-up for ≥6 months and data on CDAI, disease activity score based on 28 joints (DAS28), health assessment questionnaire (HAQ), and ACR/EULAR Boolean remission were included. For both the CDAI score and its change from baseline to 6 months, construct validity was assessed with principal component analysis, internal consistency with the Cronbach’s alpha coefficient (α), correlational validity with the Spearman’s rho coefficient, agreement in disease state classification with percent concordant pairs and the kappa statistic. Stratified analysis by presence of CDAI low disease activity (LDA) or remission was performed.Results:1,582 patients met the inclusion criteria. Principal component analysis showed that CDAI could be reduced to a single component when CDAI is >10 with SJC28 accounting for most variance in score and patient global assessment (PtGA) the least; whereas, when CDAI is ≤10, two distinct components were identified, the first comprising PtGA and physician global assessment (PhGA) and the second SJC28 and TJC28. In terms of internal consistency, high levels were observed for both CDAI at baseline (α=0.83) and its change from baseline to 6 months (α=0.81); however, the consistency between CDAI components was very low when CDAI is ≤10 (α=0.23).Overall, a strong positive correlation was observed between CDAI and DAS28 (rho=0.86) and their changes (rho=0.87) while its correlation with HAQ was weak. When stratifying by CDAI levels, the correlation of CDAI with DAS28 was moderate when CDAI is ≤10 and very weak when CDAI is ≤2.8. Similarly, agreement in the classification of LDA between CDAI and DAS28 or HAQ was fair to moderate, and agreement in classification of remission was poor to fair.Conclusion:CDAI and DAS28 correlate well when disease activity is moderate or high and poorly in LDA or remission. PtGA had a stronger influence on CDAI at LDA or remission state compared to moderate or high disease state. Thus, careful interpretation of PtGA is necessary particularly in patients who are identified as CDAI non-remitters.Disclosure of Interests:Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant of: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion,Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, LillyPharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Mohammad Movahedi Consultant of: Allergan, Angela Cesta: None declared, Claire Bombardier Grant/research support from: Dr Bombardier reports sources of funding for Ontario Best Practice Research Initiative Research grants from Abbvie, Janssen, Amgen, Medexus, Merck, Pfizer, and Novartis outside of the submitted work. Consulting Agreements: Abbvie, Covance, Janssen, Merck, Pfizer, Sanofi and Novartis outside of the submitted work. Advisory Board Membership: Hospira, Sandoz, Merck, Pfizer and Novartis outside of the submitted work., John Sampalis: None declared, Emmanouil Rampakakis: None declared

Background:Description of disease activity status in patients with rheumatoid arthritis (RA) at fixed points in time modelled as continuous (e.g. number of swollen joints counts), dichotomous variable (e.g. remission or low disease status using composite measures) do not reflect the patient’s disease course in chronic and relapsing RA.Objectives:We proposed to describe the longitudinal disease activity trajectories for patients with early and established RA over two years’ follow-up in routine clinical care.Methods:RA patients enrolled in the Ontario Best Practices Research Initiative (OBRI) with available DAS28-ESR over two years of follow-up were included. Using a latent growth curve modelling (LCGM), subgroups of patients following distinct pattern of DAS28-ESR change over time were identified. Fit statistics and model selection was based on Bayesian information criterion (BIC).Results:A total of 1273 patients were included, 454 (36%) with early RA and 819 (64%) with established RA. At baseline, patients with early RA were significantly younger (57.3 vs. 59.1 years) and with higher DAS28-ESR (4.6 vs. 4.3), and were less likely to have an erosion (25.0% vs. 59.7%), to be RF-positive (70.3% vs. 76.8%), and to use biologic DMARDs (7.0% vs. 29.2%).In patients with early RA (Figure 1A), three subgroups of patients were identified by LCGM with a better fit (BIC: -3070.84). Almost 88% patients with moderate disease activity reached remission (group 1: 48.4%) or low disease status (group 2: 39.3%) after two years, while 12% of patients with high disease profile remained in a moderate state (group 3).Figure 1.Observed and fitted trajectories from the latent growth curve analysis in patients with early and established RA.In patients with established RA (Figure 1B), seven subgroup of patients were identified by LCGM with a better fit (BIC: -5378.13). After two years’ follow-up, 37.5% of patients in remission or low disease state at baseline remained or reached to remission (group 1 and 2, respectively). Two groups of patients with high disease activity at baseline had an improvment after two years (17.3% reached remission and 9.3% reached moderate state; group 5 and 7, respectively). 16.5% of patients with high disease activity at baseline remained in high disease status after two years (group 4 and 6). 19.4% of patients with moderate activity at baseline remained in a moderate state after two years (group 3).Conclusion:Disease course is different between early and established RA. While 70% of early RA patients with moderate or high disease profiles reached remission, only 17% of established patients with high disease activity achieved remission after two years of follow-up. These findings suggest the potential effects of receiving early treatment and health care. The impact of sociodemographic, clinical and medication profile on disease course will be examined as future work for this study.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Angela Cesta: None declared, Xiuying Li: None declared, Claire Bombardier Grant/research support from: Dr Bombardier reports sources of funding for Ontario Best Practice Research Initiative Research grants from Abbvie, Janssen, Amgen, Medexus, Merck, Pfizer, and Novartis outside of the submitted work. Consulting Agreements: Abbvie, Covance, Janssen, Merck, Pfizer, Sanofi and Novartis outside of the submitted work. Advisory Board Membership: Hospira, Sandoz, Merck, Pfizer and Novartis outside of the submitted work.

Objective(s)This study evaluated the interaction of anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) in predicting sustained clinical response in an observational registry of patients with rheumatoid arthritis (RA) followed in routine practice.MethodsPatients with RA enrolled in the Ontario Best Practices Research Initiative registry, with ≥1 swollen joint, autoantibody information and ≥1 follow-up assessment were included. Sustained clinical remission was defined as Clinical Disease Activity Index (CDAI) ≤2.8 in at least two sequential visits separated by 3–12 months. Time to sustained remission was assessed using cumulative incidence curves and multivariate cox regression.ResultsAmong 3251 patients in the registry, 970 were included, of whom 262 (27%) were ACPAneg/RFneg, 60 (6.2%) ACPApos /RFneg, 117 (12.1%) ACPAneg/RFpos and 531 (54.7%) ACPApos /RFpos at baseline. Significant between group differences were observed in age (p=0.02), CDAI (p=0.03), tender joint count (p=0.02) and Health Assessment Questionnaire (p=0.002), with ACPApos patients being youngest with lowest disease activity and disability. No difference in biologic use was found between groups (20.2% of patients).Over a mean follow-up of 3 years, sustained remission was achieved by 43.5% of ACPApos/RFpos patients, 43.3% of ACPApos /RFneg patients, 31.6 % of ACPAneg/RFpos patients and 32.4% of ACPAneg/RFneg patients (p=0.01). Significant differences were observed in CDAI improvement based on ACPA and RF status where ACPApos/RFpos had a shorter time to achieving sustained remission (HR 1.30; 95% CI 1.01 to 1.67) and experienced significantly higher improvements compared with ACPAneg/RFneg patients.Conclusion(s)Combined ACPA and RF positivity were associated with improved and faster response to antirheumatic medications in patients with RA.

Background Collection of Anti-Rheumatic Medication (ARM) information from both patients and rheumatologists is considered a strength for Rheumatoid Arthritis (RA) registries and cohorts. However, it is important to assess the agreement between these two data sources. Objectives We aimed to examine the agreement of ARM use, their administration routes, and start and stop dates between self-reports and rheumatologist reports in the Ontario Best Practices Research Initiative (OBRI). Methods Adult Patients enrolled in the OBRI who consented to both patient interviews and rheumatologist evaluations were included. Patients in the OBRI are interviewed every six months, while rheumatologist assessments are conducted as per routine care. For this analysis, we included patients who enrolled in OBRI on or after Sep 1 st 2010 and compared ARM use reports where rheumatologist visits and interviews occurred within 60 days of each other. ARM included conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) and biologic DMARDs (bDMARDs). Cohens’ Kappa statistics of agreement between the two data sources were calculated. Kappa values 0.61–0.80 were considered to represent good and 0.81–1.00 as very good agreement. To examine factors associated with agreement, a multivariate backward stepwise logistic regression was used to model the odds of agreement for ARM use. The agreement and absolute time gap (days) for starts and stops dates between self-reports and rheumatologist reports were also assessed and presented by median and interquartile range (IQR) in a subset analysis. Results 2154 patients (78.7% female) were included with a mean (SD) age at OBRI enrolment of 57.8 (12.6) year. Mean (SD) disease parameters were: disease duration: 8.4 years (9.9); DAS28: 4.2 (1.6); physician global: 4.0 (2.5); and health assessment questionnaire (HAQ) disability Index: 1.1 (0.8). For csDMARDs use, the prevalence was 74.2% based on self-reports and 76.6% based on rheumatologist reports. The prevalence of bDMARDs use was approximately 20.0% based on both reports. Overall agreement for ARM use between self-reports and rheumatologist reports was good. In the regression model, increased HAQ-pain index (OR: 0.66; 95% CI: 0.60–0.73) and physician global (OR: 0.95; 95% CI: 0.92–0.98) were significantly associated with the lower agreement. By contrast, post-secondary education (OR: 1.20; 95% CI: 1.02–1.40), and seeing an academic rheumatologist (OR: 1.47; 95% CI: 1.25–1.73) were significantly associated with the higher agreement between two data sources. There was a good and very good agreement for reported administration route of bDMARDs and csDMARDs, respectively. The median absolute time gap (IQR) of start dates and stop dates for ARM use reported by two data sources was 7 days 1–27 and 19 days, 5–48 respectively. Conclusions The results of this analysis suggest that ARM reports from the two data sources have strong agreement in the OBRI. This agreement is even better for patients who have post-secondary education and are being treated by an academic rheumatologist. Disclosure of Interest M. Movahedi Employee of: OBRI, A. Cesta Employee of: OBRI, X. Li Employee of: OBRI, C. Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Bristol Myers Squibb, Celgene, Hospira, Janssen, Pfizer, Roche, and UCB, Consultant for: Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

Background Glucocorticoids (GC) are widely used to treat rheumatoid arthritis (RA), however they are known to have risks associated with them. It has been shown that GCs increase the risk of diabetes mellitus (DM). A few studies have investigated the long-term effects of GC use on outcomes in DM, but not in RA specifically. As people with RA already have increased risk of cardiovascular (CV) disease, the additional burden of DM and GCs may be important. If the effect of GCs was dependent on DM we would say there is effect modification and this can be on the additive scale, corresponding to variation in the absolute treatment effect, e.g. the risk difference (RD), across DM status, or the multiplicative scale, corresponding to variation in the relative treatment effect e.g. the rate ratio (RR).1 Objectives To examine in patients with RA 1) whether all-cause and CV mortality rates differ by GC and DM status, and 2) whether DM modifies the relationship between GC and all-cause and CV mortality on multiplicative and additive scales. Methods Patients with RA and linkage to mortality data were identified from the Clinical Practice Research Datalink (n=9085), a database of primary care electronic medical records in the UK. RR and RD for ever GC use were calculated by DM status. Cox proportional hazards (PH) regression models were fitted with an interaction term for DM and use of GC to assess multiplicative interaction. Additive interaction was measured with the Relative Excess Risk due to Interaction (RERI)2 where a value different from zero indicates a difference in the absolute effect of treatment. Results Those with DM and ever treated with GCs had a 3-fold increased all-cause mortality RR (95% CI: 2.27, 4.09) whilst those without DM had a slightly higher RR (3.46 (95% CI: 2.95, 4.07)). However those with DM had a higher RD: 36.46 deaths per 1000 patient years (pyrs) (95% CI: 27.5, 45.41) compared to those without DM: RD 22.83 deaths per 1000 pyrs (95% CI: 19.83, 25.82) because of higher baseline mortality rates. A similar pattern was seen for CV mortality. The adjusted Cox PH model for all-cause mortality showed no evidence of multiplicative interaction, but there was significant additive interaction (RERI 0.86 (95% CI: 0.18, 1.54)). For CV mortality there was no interaction on either scale. Conclusions Methodologically, this study showed assessing interaction on the additive and multiplicative scales can lead to different conclusions and should be considered carefully. In this study significant interaction was seen on additive scale but not on the multiplicative scale due to higher baseline rates in patients with DM. Clinically, this study provides some evidence that long-term GC therapy may be particularly harmful in patients with RA and DM. References [1] VanderWeele TJ, Knol MJ. A tutorial on interaction. Epidemiologic Methods2014;3(1):33–72. [2] Li R, Chambless L. Test for additive interaction in proportional hazards models. Annals of epidemiology2007Mar;17(3):227–236. Disclosure of Interest None declared

Background Access to care and management of Rheumatoid Arthritis (RA) patients may differ based on residential area which, in turn, can affect the real-world effectiveness of anti-rheumatic medications. Objectives We aimed to describe differences in the profile of patients initiating their first biologic disease modifying antirheumatic drug (bDMARD) based on their residence in urban vs. rural areas. Methods RA patients enrolled in the OBRI initiating their first bDMARD within 30 days prior to or anytime following enrolment were included in the analysis. Patients excluded if they had less than 2 years of follow-up and less than 2 visits during this period of time. Patients characteristics included sociodemographics (age, gender, race, education level, marital status, smoking status, annual household income, health insurance coverage), disease duration, disease severity parameters (Disease Activity Score (DAS), Clinical Disease Activity Index (CDAI), Swollen and Tender Joints (SJC28, TJC28), Physician Global Assessment (PhGA), Patient Global Assessment (PGA), Health Assessment Questionnaire – Disability Index (HAQ-DI), presence of erosion), bDMARD type, and concomitant anti-rheumatic medications including conventional synthetic disease modifying antirheumatic drug (csDMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), and oral steroids. Results A total of 629 RA patients were included of whom 522 (83%) resided in urban areas and 107 (17%) in rural areas. Other than marital status (urban vs. rural: 64.6% vs. 82.2% married; p Conclusions Important differences may exist in the profiles of RA patients initiating their first bDMARD, and residing in rural versus urban areas. The implications on treatment outcomes should be assessed. Disclosure of Interest R. Joshi Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, M. Movahedi Employee of: OBRI, E. Rampakakis Employee of: JSS Medical Research, C. Thorne Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, A. Cesta Employee of: OBRI, J. Sampalis: None declared, C. Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant for: Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

Background Positive anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) are included among the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA). Previous studies have shown that autoantibodies are positive predictors of response in RA patients treated with some biologics whereas other studies suggest worse prognosis if positive for ACPA and RF. Objectives The purpose of this study was to evaluate the interaction of RF and ACPA in predicting sustained clinical response in a large observational registry of RA patients followed in routine practice. Methods RA patients enrolled in the Ontario Best Practices Research Initiative (OBRI) registry, with active disease (≥1 swollen joint), available autoantibody information, and at least 1 follow-up assessment were included in the analysis. Sustained clinical remission was defined as CDAI ≤2.8 in at least 2 sequential visits separated by at least 3 and maximum of 12 months. Time to sustained remission was assessed by plotting cumulative incidence curves and multivariate cox regression. Results A total of 970 (30%) out of 3251 patients in the registry were included, of whom 262 (27%) were anti-CCPneg/RFneg, 60 (6.2%) anti-CCPpos/RFneg, 117 (12.1%) anti-CCPneg/RFpos, and 531 (54.7%) anti-CCPpos/RFpos. At baseline, significant differences were observed between groups in age (p=0.02), CDAI (p=0.03), tender joint count (p=0.02), and HAQ-DI (p=0.002), with anti-CCPpos/RFpos and anti-CCPpos/RFnegpatients being youngest and having the lowest disease activity and disability. No differences were observed in terms of biologic use (20.2% of patients). Sustained remission was 10% more likely if anti-CCPpos, and was achieved by 43.5% of anti-CCPpos/RFpospatients, 43.3% of anti-CCPpos/RFnegpatients, 31.6% of anti-CCPneg/RFpospatients and 32.4% of anti-CCPneg/RFnegpatients (p=0.01). Significant differences were observed in the time to achieving sustained clinical response from enrolment in the OBRI based on anti-CCP status (p Multivariate cox regression adjusting for baseline CDAI score, age and sex also showed differences between groups; statistically significance in anti-CCPpos/RFpos vs. anti-CCPneg/RFnegpatients (HR [95% CI]: 1.30 [1.01–1.67]; p=0.04). Conclusions These results suggest that anti-CCP but not RF positivity may be associated with a higher chance of remission, possibly due to an improved treatment response. Disclosure of Interest J. Pope Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, M. Movahedi Employee of: OBRI, E. Rampakakis Employee of: JSS Medical Research, A. Cesta Employee of: OBRI, J. Sampalis: None declared, C. Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant for: Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

Background: Patients with rheumatoid arthritis (RA) may discontinue their biologic disease modifying antirheumatic drug (bDMARDs) due to non-response, loss of response or adverse events. However, time to discontinuation may be related to mechanism of action. Objectives: We aimed to compare drug survival of tumor necrosis factor inhibitors (TNFi) versus non-TNFi in patients initiating bDMARD treatment in a Canadian (Ontario) observational cohort. Methods: Patients enrolled in the Ontario Best Practice Research Initiative (OBRI) who started bDMARD therapy within 30 days before or any time after OBRI enrolment were included in the primary analysis. Patients were followed from bDMARD start until discontinuation/switching, death, lost to follow-up, or last visit, whichever came first. Time to discontinuation/switching of bDMARD due to (i) any reason, (ii) non-response or loss of response, and (iii) adverse events (AEs), were assessed using Kaplan-Meier survival analysis for TNFi versus non-TNFi users. Results: Among the 943 patients included in the primary analysis, 187 (19.8%) received non-TNFi and 756 (80.2%) TNFi. Mean (SD) age and disease duration were 56.4 (12.7) years and 9.6 (9.8) years, respectively, and the majority were females (79.1%) and biologic naive (84.4%). TNFi included Etanercept, Adalimumab, Certolizumab, Golimumab, and Infliximab; and non-TNFi inlcuded Abatacept, Rituximab, Tocilizumab, and Tofacitinib. Over a mean (SD) follow-up of 2.4 (2.0) years, bDMARD discontinuation/switching was reported for 37.6% of patients, with significant difference in time to discontinuation between TNFi and non-TNFi users (Logrank p=0.01). However, there was no significant difference due to non-response or loss of response (Logrank p=0.67) between the two groups. At 2 years, more patients remained on TNFi (71.0%) compared to non-TNFi (57.0%). At 5 years, 51.0% and 44.0% of patients still remained on TNFi and non-TNFi, respectively. Conclusions: The overall retention rate for biologics was comparable to finding in European registries. We found that patients stay on TNFi longer compared to non-TNFi. However, no significant difference was found between the two groups, for discontinuation or switching of bDMARDs due to non-response or loss of response. Further analyses are required to adjust for the effect of potential confounders (e.g. age, sex, disease activity, and other treatment regimens) on biologic discontinuation. Reference [1]Alejandro Souto Jose Ramon Maneiro Juan J. Gomez-Reino. Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases. Rheumatology2016March 1;55(3):523–534. Disclosure of Interest: M. Movahedi Employee of: OBRI, S. Couta Employee of: OBRI, A. Cesta Employee of: OBRI, C. Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, & UCB, Consultant for: Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

Objective.We sought to determine if initial high disease activity or changes in disease activity contribute to persistent depression in early rheumatoid arthritis (ERA). We also determined if disease activity and depression is modified by sex.Methods.Depression was ascertained by self-report among patients enrolled in the Ontario Best Practices Research Initiative. The association between baseline disease activity, measured by the Clinical Disease Activity Index (CDAI), and persistent depression was evaluated with multivariate regression models, and effect modification by sex was tested. A general estimating equation assessed the association between change in CDAI over time and risk of depression.Results.The sample of 469 ERA subjects was predominantly female (73%). At baseline, the prevalence of depression was 26%, and 23% reported persistent depression. After adjusting for potential confounders, higher baseline CDAI was associated with both baseline and persistent depression (OR 1.03, 95% CI 1.01–1.05). Female sex was an effect modifier of this relationship (OR 1.04, 95% CI 1.01–1.06). Maintaining a moderate or high CDAI score over 2 years also increased the risk of future depression.Conclusion.Depression in ERA is common and initial high disease activity is associated with the probability of depression and its persistence. This risk seems particularly modified in women with active disease and represents an area for targeted focus and screening. Future studies in ERA are needed to determine if intervening during the “window of opportunity” to control disease activity has the potential to mitigate the development and maintenance of adverse mental health outcomes, including depression.

Background Despite the availability of safe and effective treatments and the establishment of treatment guidelines, real-world effectiveness remains suboptimal largely due to low patient adherence with prescribed treatment. Objectives The purpose of this study was to systematically evaluate sociodemographic, health insurance, and disease-related factors associated with patient reported decision for discontinuation of anti-rheumatic medications (ARM) in a large observational cohort of RA patients followed in Canadian routine clinical care. Methods RA patients enrolled in the Ontario Best Practices Research Initiative (OBRI) clinical registry and had at least two years of follow-up were included in the analysis. Treatment discontinuation due to patient reported decision was defined as ARM discontinuation. Independent predictors of ARM discontinuation were evaluated with multivariate cox-regression using both time-fixed and time-dependent variables. Factors considered included patient sociodemographics (age, gender, race, education status, annual income, smoking history), health insurance information (private vs. non-private, % coverage), disease parameters (RA duration, presence of erosion, RF positivity, DAS28, physician global, HAQ-DI, number of comorbidities), types of medications used, and physician characteristics (gender, academic position, urban vs. rural, distance from patient9s residence). Results A total of 1,762 patients were included in the analysis with a mean (SD) age of 57.4 (13.0) years and disease duration of 8.5 (9.3) at the time of enrolment to the registry (baseline). The majorities of patients were female (77.7%), had post-secondary education (55.3%), and had private insurance (67.2%). In terms of disease severity, 54.5% had prior erosion, 69.5% were RF positive, and mean (SD) DAS28 was 4.5 (1.5). In a multivariate analysis, married status (HR, 0.73; 95% CI 0.56–0.96), RF positivity (HR, 0.73; 95% CI 0.56–0.96), and higher number of comorbidities (HR, 0.92; 95% CI 0.85–0.99) were identified as significant predictors of ARM continuation while higher physician global score (HR, 1.10; 95% CI 1.04–1.15), NSAID use (HR, 1.75; 95% CI 1.29–2.38), and polypharmacy (HR, 1.23; 95% CI 1.07–1.40) were associated with ARM discontinuation due to patient reported decision. Conclusions In this systematic approach a variety of factors encompassing sociodemographics, disease, and medication characteristics, were identified as significant independent predictors of ARM discontinuation due to patient reported decision. These results should be taken into consideration when developing patient adherence support programs and in the choice of treatment regimens. Disclosure of Interest V. Ahluwalia Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Bristol Myers Squibb, Celgene, Hospira, Janssen, Pfizer, Roche, Sanofi, & UCB, M. Movahedi Employee of: OBRI/JSS, E. Rampakakis Employee of: JSS Medical Research, A. Cesta Employee of: OBRI, X. Li Employee of: OBRI, S. Couto Employee of: OBRI, J. Sampalis Employee of: Head of JSS, C. Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Bristol Myers Squibb, Celgene, Hospira, Janssen, Pfizer, Roche, Sanofi, & UCB

Objectives To investigate the associations between smoking status, smoking cessation and hospitalisations for cardiovascular events (CVE) and respiratory tract infections (RTI) in an inception cohort of patients with rheumatoid arthritis (RA). Methods The study was set within UK primary care electronic health records (the Clinical Practice Research Datalink) linked to hospital inpatient data (Hospital Episode Statistics). Patients with RA were followed from diagnosis to hospitalisation with a record of CVE or RTI, leaving their general practice, death, or 10 January 2012, whichever was earliest. Smoking status (never, current, former) was defined using primary care data and could vary over time. Survival analysis was performed using Cox regression (first event) and conditional risk set models (multiple RTIs). Results 5677 patients were included in the cohort: 68% female, median age 61 years. The age-adjusted and sex-adjusted risks of hospitalisation for CVE or RTI were more than twice as high in current vs never smokers (CVE HR (95% CI) 2.19 (1.44 to 3.31); RTI 2.18 (1.71 to 2.78)). The risks for both outcomes were significantly higher in current compared with former smokers (CVE 1.51 (1.04 to 2.19), RTI 1.29 (1.04 to 1.61)). For each additional year of smoking cessation, the risk of first CVE and RTI hospitalisation fell significantly, approximately 25% and 15% respectively in the adjusted models. Conclusions Patients with RA who smoke have an increased risk of hospitalisation with CVE or RTI compared with never and former smokers. The risk decreases for each additional year of smoking cessation. Patients with RA who smoke should be advised to stop smoking.

In active rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX), guidelines support adding or switching to another conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) and/or a biologic DMARD (bDMARD). The purpose of this analysis was to describe treatment practices in routine care and to evaluate determinants of regimen selection after MTX discontinuation.Biologic-naïve patients in the Ontario Best Practice Research Initiatives registry discontinuing MTX due to primary/secondary failure, adverse events, or patient/physician decision were included.Of 313 patients discontinuing MTX, 102 (32.6%) were on MTX monotherapy, 156 (49.8%) on double, and 55 (17.6%) on multiple csDMARDs. Patients on MTX monotherapy were older than patients on double or multiple csDMARDs (p=0.013), less likely to have joint erosions (p=0.009) and had lower patient global assessment (p=0.046) at MTX discontinuation. Post-MTX discontinuation, 169 (54.0%) transitioned to, or added new DMARD(s) (new csDMARD(s): 139 [44.4%]; bDMARD: 30 [9.6%]), and 144 (46.0%) opted for no new DMARD treatment. Patients on MTX monotherapy transitioning monotherapy, whereas patients on combination csDMARDs switched more to new csDMARDs and bDMARD combination therapy. Early RA (adjOR [95%CI]: 3.07 [1.40-6.72]) and treatment with multiple csDMARDs vs. MTX monotherapy (4.15 [1.35-12.8]) at MTX discontinuation were significant predictors of transitioning to or adding new csDMARD(s)/bDMARD treatment versus opting for no new DMARD treatment.Differences in subsequent treatment patterns exist between patients discontinuing MTX when used as monotherapy versus in combination with other csDMARDs where the former are more likely to use a subsequent monotherapy treatment.

Previous studies of glucocorticoid (GC) therapy and mortality have had inconsistent results and have not considered possible perimortal bias—a type of protopathic bias where illness in the latter stages of life influences GC exposure, and might affect the observed relationship between GC use and death. This study aimed to investigate all-cause and cause-specific mortality in association with GC therapy in patients with rheumatoid arthritis (RA), and explore possible perimortal bias. A retrospective cohort study using the primary care electronic medical records. Oral GC exposure was identified from prescriptions. Mortality data were obtained from the UK Office for National Statistics. Multivariable Cox proportional hazards regression models assessed the association between GC use models and death. Several methods to explore perimortal bias were examined. The cohort included 16,762 patients. For ever GC use there was an adjusted hazard ratio for all-cause mortality of 1.97 (95 % CI 1.81–2.15). Current GC dose of below 5 mg per day (prednisolone equivalent dose) was not associated with an increased risk of death, but a dose–response association was seen for higher dose categories. The association between ever GC use and all-cause mortality was partly explained by perimortal bias. GC therapy was associated with an increased risk of mortality for all specific causes considered, albeit to a lesser extent for cardiovascular causes. GC use was associated with an increased risk of death in RA, at least partially explained by perimortal bias. Importantly, GC doses below 5 mg were not associated with an increased risk of death. Electronic supplementary material The online version of this article (doi:10.1007/s10654-016-0167-1) contains supplementary material, which is available to authorized users.

An interferometer-based technique has been used to determine the change in the refractive index induced by a Q-switched Nd–YAG laser (λ=532 nm and pulse duration 6 ns) on an aluminum target under atmospheric air pressure. The average density changes in front of the target irradiated by two laser pulse energy were observed for different focusing conditions. An Abel inversion technique is also presented for calculating three-dimensional density distributions in cylindrical coordinates.

Breast cancer (BC) is the most prevalent cancer in Iranian women and the fifth most common cause of cancer-related death in Iran. Among predicting factors and preventive measures for BC, the parity and breastfeeding (BF) are controversial issues. We therefore conducted this case–control study to find out the relation of parity and BF to incidence and risk of BC. A structured questionnaire that covered demographic criteria and BC risk factors was completed for case (376 cases) and control (425 subjects) groups, both matched in terms of demographic variants, reproductive issues, and socioeconomic status. Odds ratio (OR) and 95% confidence intervals (CI) were computed as measures of association from the logistic models. All p values reported are two-sided. Parity significantly reduces the risk of BC (p

Payesh2010; 9: 83-89Accepted for publication: 1 March 2009[EPub a head of print-3 November 2009] Objective(s): This study was conducted for external evaluation of one intervention that has been carried out by traffic police. In this study the efficacy of provisional driver licensing on reducing traffic injuries and the intensity of injuries (fatal or non-fatal) was investigated.Methods: Data on traffic accidents and injuries from one year before till two years after the implementation of provisional driver licensing were obtained from traffic police data base. After data cleaning and stratification traffic injuries and mortalities, the implementation of graduate driver licensing compared in those in early years of their driving experience.Results: Drivers under 23 years of age consisted 22.8% of total road traffic injuries (RTIs) in the year prior to the implementation of graduate driver licensing. This proportion reduced to 15.5% and 16.1% in the first and second year after implementation, respectively, among holders of provisional B1 type driver license (P

BACKGROUND: For more than three decades, the main health indicators of the rural population of Iran have been gathered using a 'vital horoscope'. In this study, we use information derived from the vital horoscope to assess trends over time and geographic patterns of inequality in these health indicators. METHODS: Nine main health indicators were derived from official annual reports of the Ministry of Health & Medical Education from 1993 to 2005. Having plotted their temporal variations, we modelled their patterns and predicted their values for 2006 and 2007 using linear regression and fractional polynomial regression models. In order to illustrate spatial variations, we normalized the provincial indicators and mapped their geographical variations in two time bands: 1996-2000 and 2001-05. RESULTS: Neonatal mortality rate (NMR), infant mortality rate (IMR) and under-5 mortality rate (U5MR) had a decreasing trend between 1993 and 2005. However, the slop for NMR (beta = -0.26) was much smaller than the slopes for IMR (beta = -1.16) and U5MR (beta = -1.60), thus the rate of decline for NMR was less. The percentage of births attended by unskilled personnel declined from 27.2 to 7.5%, and the maternal mortality rate (MMR) declined from 47 to 34 deaths per 100 000 live births. At a provincial level, the heterogeneity in some indicators decreased (e.g. unskilled attendance at birth, IMR and total fertility rate), while we found no substantial changes in others. CONCLUSION: Our findings indicate a remarkable improvement in most of the health indicators in rural areas. On the other hand, there is still considerable inequality among the rural population at a provincial level.

Nazari A1, Noroozi H2, Movahedi M3, Khaksarian M1 1. Instructor, Department of Physiology, Faculty of Medicine, Lorestan University of Medical Sciences 2. Assistant Professor, Department of Mycology, Faculty of Medicine, Iran University of Medical Sciences 3. Assistant Professor, Department of Genetic Epidemiology, Faculty of Medicine, Lorestan University of Medical Sciences Abstract Background: Aflatoxin M1 is a hydroxylated form of aflatoxin B1 which is produced by Aspergillus flavus. This toxin is produced when cows or other ruminants eat foods contaminated with these mycotoxins and then excrete them in the milk. The toxin is a potent liver and kidney carcinogenetic agent. Materials and methods: Forty two raw cows milk samples from local sources of milk collection and forty samples of commercial pasteurized market milk from Khorramabad, Lorestan, Iran were collected in summer and winter season of 2005. Twenty-one cow milk samples and 20 pasteurized milk samples in each season were analyzed for the presence of aflatoxin M1 (AFM1) by HPLC immunoaffinity columns. Results: Four of 21 raw milk samples in summer showed AFM1 levels between 0.017-0.046 ng/ml and all samples (100%) in winter showed the presence of AFM1 levels between 0.003-0.041ng/ ml. AFM1 was detected in 55% of market pasteurized cow milk samples ranging from 0.017 to 0.533 ng/ml in summer and 100% ranging from 0.005-0.0054 ng/ml in winter.,Only one of all milk samples of pasteurized milk in summer had toxin level (0.533 ng/ml) more than the maximum permissive limit (0.5 ng/ml). No significant difference was observed among mean contamination level of raw and pasteurized cow milk in two seasons. Key words: Aflatoxin M1, raw milk, pasteurized milk, Khoramabad, HPLC

Nazari H1, Saki M2, Sohrabi P3, Tarrahi MJ4, Movahedi M5, Badrizadeh A6, Baqeri Kh7 1. Assistant Professor, Department of Psychiatry, Faculty of Medicine, Lorestan University of Medical Sciences 2. Instructor, Department of Psychiatry, Faculty of Nursing and Midwifery, Lorestan University of Medical Sciences 3. General Practitioner, Neurology and Psychoiatry Hospital, Khorramabad 4. Instructor, Department of Epidemiology and Statistics, Faculty of Medicine, Lorestan University of Medical Sciences 5. Assistant Professor, Department of Epidemiology, Faculty of Medicine, Lorestan University of Medical Sciences 6. B.Sc of Nursing, Staff Member of Research and Technology Office, Lorestan University of Medical Sciences 7. B.Sc of Nursing, Psychology hospital Abstract Background: Major depressive disorder (MDD) is one of the most common mental disorders all over the world. An effective treatment preserves an acceptable level of function in the affected patients. Different drugs are used in the treatment of MDD, and each of them has specific therapeutic and adverse effects. Recently, SSRI drugs are used in the treatment of this disorder, and yet there is not enough study about them. Thus, we decided to compare the effectiveness and adverse effects of Nortriptyline with that of Citalopram in MDD. Materials and methods: In this double-blinded clinical trial, 80 MMD (DSM-IV-TR) patients, who that not any other mental, substance and organic disorders were selected. Samples were randomly assigned into two groups which were treated with Nortriptyline or Citalopram. Efficacy and adverse effects were evaluated at 2, 4, 6, 8 and 12 weeks after the treatment. Data were analyzed by SPSS software. Results: Efficacy was similar in two groups, and no significant differences between the two groups were observed in the mean scores. The comparison of adverse effects between the two groups showed a significant difference in the hypersomnia, dry mouth, anorexia and nausea. There was not a significant difference between the two groups in the sexual dysfunction, insomnia headache, tremor, vertigo, obesity, diarrhea, vomiting and abdominal pain. Conclusion: Tricycles and SSRI drugs have an equal efficacy in the treatment of MDD. But they have different adverse effect profiles, thus they must be administrated with an attention to their adverse effects.

Objective To investigate the association between smoking status and smoking cessation with mortality in patients with rheumatoid arthritis (RA). Methods An incident cohort of patients with RA was identified using the Clinical Practice Research Datalink, a database of UK primary care electronic medical records. Time‐varying smoking status, years of cessation, and amount smoked were determined from patients' medical records. The date and underlying cause of death were identified by linkage with Office for National Statistics records. The associations between smoking status and smoking cessation with all‐cause and cause‐specific mortality (circulatory disease, all cancers, lung cancer, respiratory disease, and respiratory infection) were investigated using adjusted Cox (all‐cause mortality) and Fine‐Gray (cause‐specific mortality) regression. Results The cohort comprised 5,677 patients (median age 61.4 years, 68% women), with 40% as never smokers, 34% former smokers, and 26% current smokers at baseline. Compared to never smoking, current smoking was associated with an increased risk of all‐cause mortality (hazard ratio 1.98 [95% confidence interval (95% CI) 1.56, 2.53]), and mortality due to circulatory disease (subdistribution hazard ratio [SHR] 1.96 [95% CI 1.33, 2.90]) and lung cancer (SHR 23.2 [95% CI 5.15, 105]). Each year of smoking cessation was associated with a decreased risk of all‐cause mortality (former heavy smokers SHR 0.85 [95% CI 0.77, 0.94], former light smokers SHR 0.90 [95% CI 0.84, 0.97]). Conclusion Current smoking is associated with an increased risk of all‐cause, cardiovascular, and lung cancer mortality in patients with RA. Each year of cessation is associated with a reduced risk of all‐cause mortality. This information may prove helpful in smoking cessation programs for patients with RA.

Objective To quantify the risk of incident diabetes mellitus (DM) associated with the dosage, duration, and timing of glucocorticoid (GC) use in patients with rheumatoid arthritis (RA). Methods We undertook a cohort study using 2 databases: a UK primary care database (the Clinical Practice Research Datalink [CPRD]) including 21,962 RA patients (1992–2009) and the US National Data Bank for Rheumatic Diseases (NDB) including 12,657 RA patients (1998–2013). Information on the dosage and timing of GC use was extracted. DM in the CPRD was defined using Read codes, at least 2 prescriptions for oral antidiabetic medication, or abnormal blood test results. DM in the NDB was defined through patient self-reports. Data were analyzed using time-dependent Cox models and a novel weighted cumulative dose (WCD) model that accounts for dosage, duration, and timing of treatment. Results The hazard ratio (HR) was 1.30 (95% confidence interval [95% CI] 1.17–1.45) and 1.61 (95% CI 1.37–1.89) in current GC users compared to nonusers in the CPRD and the NDB, respectively. A range of conventional statistical models consistently confirmed increases in risk with the GC dosage and duration. The WCD model showed that recent GC use contributed the most to the current risk of DM, while doses taken >6 months previously did not influence current risk. In the CPRD, 5 mg of prednisolone equivalent dose for the last 1, 3, and 6 months was significantly associated with HRs of 1.20, 1.43, and 1.48, respectively, compared to nonusers. Conclusion GC use is a clinically important and quantifiable risk factor for DM. Risk is influenced by the dosage and treatment duration, although only for GC use within the last 6 months.

Purpose In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS). Patients and Methods Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2 × 2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months. Results During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41× (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m2 increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03). Conclusion Obesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.

Background: Colorectal cancer is the fourth most common cancer, in terms of incidence throughout the world. There are some differences for risk factors involved in the incidence of tumor in different anatomical subsites of large bowel. However, most investigations have not studied the association between dietary factors and colorectal cancer subsites. Thus the current ecological study investigates the potential association between dietary factors and occurrence of cancer in different subsites of large bowel. Materials and methods: Data on colorectal cancer incidence and dietary factors was obtained by the subsites of colorectal cancer for the 32 countries were estimated between the years 1988 and 1992. The association between alcohol, dietary factors and cancer in different subsites of large bowel was then analyzed by using linear regression. Findings: Multivariate analysis showed a significant association between red meat consumption and proximal colon cancer incidence (p=0.02). In contrast, there was a significant association between alcohol consumption and distal colon cancer in men (p=0.03) and rectal cancer in both men and women (p=0.01 and p=0.04 respectively). Conclusion: Investigation on the incidence of cancer in anatomical subsites of large bowel separately might help us to identify etiological factors and preventive ways of this cancer.

Ce papier concerne l’analyse de l’impact de l’exportation sur la productivité et l’innovation dans les entreprises. L’apport de ce travail réside principalement dans 1) la décomposition de l’effet global de l’exportation sur les performances de l’entreprise en un effet d’apprentissage, un effet d’auto-sélection et un effet de spécialisation, 2) la prise en compte simultanée de la persistance de l’exportation et de son intensité. L’objectif de ce papier est d’évaluer l’impact respectif des trois effets de l’exportation sur la performance des entreprises. Ces effets sont testés dans le cadre d’un modèle récursif à partir d’indicateurs synthétiques de l’output et de l’input d’innovation issus de l’analyse des correspondances multiple (ACM). Cette estimation est réalisée a partir des données d’un échantillon représentatif de 90 PMI de la région Basse-Normandie (France) provenant de l’enquête conduite en 2009-10 dans le cadre du projet IDEIS. English abstract: This paper presents an analysis of the impact of exporting on productivity and innovation in SMEs. The contribution of this work lies mainly in 1) the decomposition of the overall effect of the export on the firm performance into a learning effect, a self-selection effect and a specialization effect; and 2) the simultaneous consideration of the both persistence and intensity of export. The primary aim of this paper is to evaluate the respective impact of these three export effects on firm performance. These effects are tested in a recursive model from synthetic indicators of innovation using multiple correspondence analysis (MCA). For this end, we use the data from a representative random sample formed by 90 SMEs of regional of Normandy (France), obtained from the survey conducted in the IDEIS project.

Background Guidelines support the use of combination conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs), switching csDMARDs and/or use of biologic DMARDs (bDMARDs) treatment in active rheumatoid arthritis (RA) after use of methotrexate (MTX). Objectives The purpose of this study was to determine treatment practices after use of MTX in patients with RA who were on either monotherapy or combination csDMARDs in a large observational cohort (OBRI) in order to determine contemporary practice where use of bDMARDs from government coverage is restricted to active RA (+RF and/or +ACPA) or erosions, SJC≥5 with MTX failure, combination failure (triple csDMARDs: MTX + hydroxychloroquine + sulfasalazine) or use of leflunomide. Methods Patients enrolled in OBRI with documented MTX failure defined as discontinuation due to side effect, primary/secondary failure, or patient/physician decision. Demographics and disease parameters at MTX failure were compared between monotherapy failures, double therapy (Rx) failures, and triple Rx failures. Results A total of 313 patients with MTX failure were included with a mean (SD) age of 58.8 (13.2) years and disease duration of 6.7 (8.2) years. Of these, 102 (32.6%) were on MTX monotherapy, 156 (49.8%) were double (MTX +1 csDMARD) Rx, and 55 (17.6%) were on triple or more (MTX + multiple csDMARDs)Rx, respectively, at the time of MTX failure. At the time of MTX failure disease duration was numerically higher in patients failing monotherapy and double Rx as compared to triple Rx (7.5 vs. 6.8 vs. 4.5 years, respectively; P=0.276) while patients failing triple Rx were more likely to have an erosion (43.1% vs. 37.2% vs. 61.8%; P=0.009) and had significantly higher patient global (3.5 vs. 3.9 vs. 4.8; P=0.046). When looking at patient transition to csDMARDs monotherapy, csDMARDs combination Rx or bDMARDs treatment, patients receiving monotherapy were more apt to have switches to other monotherapy (87% of patients), whereas those on combination Rx received more combination csDMARDs (78% and 74% of patients on MTX + 1 csDMARDs or MTX + multiple csDMARDs, respectively) and bDMARDs combination Rx (21% and 26%, respectively)(Figure 1). Conclusions There are inherent differences in the selection of subsequent treatment regimen between patients failing MTX monotherapy vs. MTX combination therapy. Overall, the results of the current analysis suggest the use of a sequential treatment intensification strategy in routine clinical practice in Ontario. Disclosure of Interest None declared

Background The Ontario Best Practices Research Initiative (OBRI) collects data on RA treatment in a real-world setting. Patients are enrolled and prospectively followed to assess among other things, response to biologic Disease-Modifyng Antirheumatic Drugs (bDMARDs) and conventional synthetic Disease-Modifying Antirheumatic Drug (csDMARD) therapy. Objectives The objective of this study was to look at a real-world population and determine if initial disease activity influences the durability of the first used biologic in RA treatment. Methods bDMARD-naive RA patients were included if they started a biologic at baseline or at any time after entry into OBRI. For initial DAS, we used the DAS28 value between 6 months before and 3 months after the start of the first biologic, whichever was closer to the date of biologic use. Patients were censored at date of first biologic, or at date of last follow-up after initiation, whichever occurred first. Analysis was performed for all years of follow up, and also censored at 1.5 years (for investigating initial DAS impact). Persistence was defined as the length of time the patients continued to receive the drug, irrespective of change in dose, route, or addition of any other csDMARD or steroids. If the drug was stopped for 5.10). Survival was compared using KM curves. Results 563 patients were included. At 1 year, the survival probability was 0.78. The median survival of biologic was 57.8 (95% Confidence Interval: 42.2) months and with a mean survival of 44.5 (SE: 1.5) months. Patients who were on biologic monotherapy, with no concomitant csDMARD use, has worse persistence of their initial biologic. Figure 1 shows the KM Plot of survival on biologic stratified by DAS28. Despite the initial trend towards better survival associated with lower initial DAS, this was not statistically significant. Similarly, type of insurance (public/private) did not impact biologic survival. As seen in other studies, the only factor to impact longer persistence on initial biologic was use of a csDMARD with the bDMARD. Conclusions Early/initial DAS28 score did not impact patients9 persistence on their initial bDMARD, nor did insurance type. This suggests that initial DAS28 score does not influence the durability of the first bDMARD in active RA. Combination of csDMARD and bDMArD was more durable than bDMARD monotherapy. Disclosure of Interest None declared

In the present study, we define synthetic and relevant indicators of organizational innovation and measure the link of these indicators with various types of technological innovations (product innovation, process innovation, and hybrid innovations). They are constructed from sixteen variables reflecting organizational innovation with the aid of multiple correspondence analysis (MCA) method. The variables are grouped in five categories corresponding to different aspects of organizational changes, such as training & qualification, knowledge management, production management, quality, and market transaction. We then use a regression to estimate the link between organizational innovation indicators and technological innovations (product, process and their interaction). The original database exploited is part of the IDEIS project and relates to a representative sample of 90 SMEs in Lower Normandy - France. Our estimated indicators interpret the Intensity of the implementation of the Organizational Changes (IOC) and the orientation of the Organizational Innovation Strategies adopted (OIS). We find a positive and significant link between IOC and technological innovation (product innovation, process innovation, and hybrid innovations), particularly so for product innovation. However, we find no clear link between the choice of the OIS and technological innovation.

BACKGROUND: Breast cancer is the most common cancer among women worldwide. Based on the latest Iranian national cancer department report, the total number of women registered with breast cancer was 6976 cases during 2007. Five year survival is one of the indicators used for evaluation of the quality for care to different types of malignancies including breast cancer. OBJECTIVES: The aim of this study was to estimate survival rate of breast cancer in 6147 Iranian patients at a national level in different geographic regions. MATERIALS AND METHODS: 6147 cases of breast cancer, which had telephone number and were diagnosed between 2001-2006, were called to obtain information about their life status. Survival estimates were calculated using the Kaplan-Meier method, and the survival probability was calculated for the overall cohort and in different categories of gender, age and pathologic type of tumor. Hazard ratios (HR) according to demographic and risk variables were calculated by Cox's proportional hazard model. RESULTS: The overall 5-year survival rate was 71.0%. The mean survival time was different between men and women, which was statistically significant. The number of men involved with breast cancer was 172 (2.8%) of all cases. The 5-year survival rate for patients in age group 41-50 years was significantly higher than other age groups (P = 0.001). The likelihood of death was higher in patients with 61 years old or more years rather than those below forty years old (HR = 1.31; 95% CI: 1.12-1.55). CONCLUSIONS: THE FINDINGS OF THIS STUDY MIGHT HELP IRANIAN HEALTH MANAGERS: 1) to be more conscious about geographical and regional determinants which will affect overall survival rate. 2) To carry preventive activities such as public education particularly in Iranian men. 3) To think about screening and early detection of breast cancer.

To determine risky behaviors leading to unintentional injuries among Tehrani high school students in 2009.This cross-sectional study was carried out berween October and December 2009. Out of 237,300 (185151 governmental, 52149 non governmental) Tehrani high school students in both genders, 727 subjects were selected by multistage randomized sampling. Among 20 education districts, 8 districts were selected and divided by stratified sampling into 3 areas: North, Center, and South. Data were collected by cluster random sampling in each district using the standard questionnaire of the Management Diseases Center of America, which had been validated in Iran. Subjects were healthy students aged 12-18 years. Risky behaviors including fall, burn, poisoning, and road traffic injuries were studied.The mean age of subjects was 16.8+/-1.2, range 12-18 years. Overall, 44% of boys and 38% of girls were exposed to risky behaviors leading to unintentional injuries. Significant differences were observed in driving without licence among boys and in governmental schools (p=0.000). Using a motorcycle was more prevalent in the south of Tehran (p=0.000). Significant differences were observed among boys related to poisoning substance exposure, driving without a licence, motorcycle driving, and non-helmet use during motorcycle driving (p=0.000).Approximately half of the boys and more than one-third of the girls were exposed to risky behaviors leading to unintentional injuries. Prevention of unintentional injuries caused by children's risky behaviors is crucial, particularly among boys and those from deprived areas.

This paper presents an analysis of the relationship between innovation, productivity and exports regarding the SMEs. The main research aim of this study consists in analyzing the hypothesis of firms’ conscious self-selection in the export markets. To measure innovation, we consider the dimensions of technological as well as non technological innovation, as defined by the Oslo Manual (2005). To achieve this, we use the database of SMEs obtained from the survey conducted in the project IDEIS. First, we highlight the existence of export as well as innovation apparent premium, i.e. the advantage of exporting (innovative) firms versus non-exporting (not innovative) ones in terms of productivity. In addition, we demonstrate the effectiveness of the export premium for firms carried out process and organization innovations with the enough exportation. Finally we show the firms’ conscious self-selection in export markets in endogenizing productivity through innovation.

The recent significant improvement in most health indicators in Iran has not been explored deeply particularly in comparison with other countries in Eastern Mediterranean Region (EMR). We aimed to explore the temporal variations of five main indicators in Iran and compare their variations in EMR countries.Data on DPT vaccination and birth weight were obtained from EMR office reports, and total fertility rate, under 5 mortality rate (U5MR) and adult literacy rate (ALR) were obtained from WHO sources for the time period 1995-2005. Using linear regression, we modeled the temporal variations in Iran and other EMR countries classified by their human development index (HDI) levels.The estimated annual decline rate of U5MR in Iran as a middle HDI country was 2.5 per 1000 live birth which was much greater than the corresponding number in countries with medium HDI (1.85) and very close to countries with high HDI (2.67). The WHO data showed that Iran was very successful in increasing ALR.It seems that most health indicators in Iran have improved more rapidly compared with countries with low and medium HDI in EMR. The improvement rates were also very close to countries with high HDI in the region.

Background Oral glucocorticoids (GCs) are commonly used to treat rheumatoid arthritis (RA) with GC prescriptions often issued in primary care. Some general practitioners (GPs) may have a greater tendency to prescribe GCs, which could affect the likelihood of a patient receiving a GC prescription. Patient characteristics such as age and comorbidities may influence GC prescribing differently, depending on GC prescribing tendency. Objectives To a) determine whether GC prescribing tendency influences GC prescriptions for RA patients and b) whether baseline patient characteristics affect GC prescribing differently in patients seen by prescribers with high vs low GC prescribing tendencies. Methods Patients with incident RA during a defined follow up period were identified from the Clinical Practice Research Datalink, a large UK general practice database. The primary (i.e. most frequent) prescriber of all medications was determined for each patient. For each primary prescriber, the mean proportion of time their patients spent on GCs during follow up was calculated. The median of these values was used as a cut-off for “low” or “high” GC prescribers. Logistic regression was used to determine the effect of prescriber tendency on the likelihood of receiving a GC prescription during follow up and to test the interaction between prescriber tendency and a range of baseline patient characteristics, including patient demographics, comorbidities that are also indications for GC use and known steroid-related comorbidities. Results 16 536 patients with RA were identified and 3270 GPs were assigned as primary prescribers. The mean proportion of time their patients spent on GCs ranged from 0 to 100% (median 10.2%, IQR 0.1%– 24.4%), and GPs were categorised as ‘high’ prescribers if their patients spent a mean of ≥10.2% of follow-up on GCs. 6,372 (38.5%) patients were assigned a “low” GC prescriber and 10,164 (61.5%) were assigned a “high” GC prescriber. The odds of a patient receiving a GC prescription during follow up was 3.1x greater if they were seen by a “high” GC prescriber compared to a “low” GC prescriber (95%CI 2.88-3.29). The probability of receiving a GC prescription increased with age, but the effect differed significantly between the prescriber groups: OR 1.14 (95%CI 1.10, 1.18) per decade in the “low” GC prescriber group, OR 1.27 (95% CI 1.23-1.30) in the “high” GC prescriber group. Baseline comorbidities that influenced the probability of receiving a GC prescription and that were significantly different between GC prescriber groups were asthma (“low” OR 2.65 CI 2.29-3.06, “high” OR 1.76 CI 1.57-1.98) lower respiratory tract infection (“low” OR 1.75 CI 1.53-2.00, “high” OR 1.45 CI 1.31-1.61), hypertension (“low” OR 1.21 CI 1.03-1.42, “high” OR 1.30 CI 1.18-1.43), and inflammatory bowel disease (“low” OR 0.85 CI 0.46-1.56), “high” OR 1.92 CI 1.21-3.06). Conclusions Prescriber tendency towards high GC use was associated with an increased likelihood of RA patients receiving GCs. The effect of certain patient characteristics on GC prescription differed according to prescriber tendency. Disclosure of Interest None declared

Introduction The efficacy of provisional driver licensing and mandatory seat belt use legislations on reducing traffic injuries and the intensity of injuries was investigated. Methods Data on traffic crashes and injuries from 1 year before till 2 years after the implementation of provisional driver licensing and mandatory seat belt use legislations were obtained from traffic police. Data of traffic injuries and mortalities from 1 year before till 2 year after the implementation of graduate driver licensing compared in those in early years of their driving experience. To evaluate the efficiency of mandatory seat belt use legislation the intensity of traffic injuries were compared. Results Drivers under 23 years of age consisted 22.8% of total crashes in the prior to the implementation of graduate driver licensing. This proportion reduced to 15.5% and 16.1% in the first and second year after implementation, respectively, in holders of provisional B1 type driver license. This approximately 7% reduction in total accident was statistical significant (p Conclusion It is suggested that both interventions were efficient in reduction of intensity of traffic injuries and provisional driver licensing was efficient in reducing the crude number of traffic injuries.

Background Glucocorticoid (GC) therapy is used by more than one in two patients with Rheumatoid Arthritis (RA)[1][1]. GCs are effective [2][2] but have side effects including Diabetes Mellitus (DM) [3][3]. Objectives The aim of this retrospective cohort study was to quantify the risk of incident type II DM in patients with RA treated with oral GCs, and its relationship with dose. Methods Adult patients with RA were identified from a large UK primary care research database, the Clinical Practice Research Database (CPRD) using a validated algorithm during the study period 01/92-12/09. Patients with prevalent DM at the time of their first code for RA were excluded. GC exposure from first code for RA was considered using several models including a time-varying binary indicator of ever or current use, current daily dose, average daily dose and cumulative dose. Incident DM was defined as a READ code for type II DM, at least two oral anti-diabetic prescriptions or abnormal blood results (blood sugar, HbA1C or glucose tolerance test). Gender, age, BMI, smoking status, family history of DM, hypertension, prior cumulative dose of oral GC, current DMARDs and ever NSAID use were potential confounders. Multiple imputations were used to impute missing data for BMI and smoking status. Incidence rates for type II DM were calculated for different patterns of GC exposure. Crude and adjusted Hazard Ratios (HR) were estimated using Cox regression. Results 23,736 adult RA patients were included. 70% were female with a median age of 59 years (IQR 49-71). Median time at risk per patient was 5.39 years (Range: 0.003-18.0). 2,462 patients were diagnosed with type II DM during follow-up: incidence 14.0 events/1000 person years (pyrs) in unexposed patients and 21.9 events/1000pyrs in time following GC exposure. The crude HR was 1.53 (95%CI 1.41-1.66) in ever GC users compared with non-use. After adjusting for all covariates, the HR reduced to 1.38 (95%CI 1.27-1.51). This equates to one additional case of DM per year for every 185 patients currently receiving GCs. Each 5mg increase of current oral GC was associated with a 14% increased risk of DM (HR:1.14; 95%CI 1.11-1.17). Patients currently taking between 10-30mg/day had an adjusted HR of 1.95 (95%CI 1.62-2.34) compared to non-use, equating to one additional case of DM for every 67 patients treated. A 5mg increase in average daily dose was associated with a 32% increased risk (HR 1.32; 95%CI 1.26-1.39), suggesting prolonged exposure increased risk. Conclusions Oral GC therapy is a significant and clinically important risk factor for incident Type II DM in patients with RA. Screening for DM might be warranted in patients taking oral GC therapy. References 1. Caplan L, Wolfe F, Russell AS, Michaud K. Corticosteroid use in rheumatoid arthritis: prevalence, predictors, correlates, and outcomes. J Rheumatol. 2007;34(4):696-705. 2. Gotzsche PC, Johansen HK. Meta-analysis of short-term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. Bmj 1998;316(7134):811-8. 3. Hoes, J. N., M. C. van der Goes, et al. (2011). “Glucose tolerance, insulin sensitivity and β-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids.” Annals of the Rheumatic Diseases 70(11): 1887-1894. Disclosure of Interest None Declared [1]: #p-7 [2]: #p-8 [3]: #p-9

Objective Traffic crashes information presented by the I.R. of Iran9s significant information sources was compared with in-use models of the USA and different Asian countries. Methods Information on traffic crashes epidemiology was investigated and collected directly in the organisations by trained experts of the study using questionnaires verified in validity and reliability. Afterwards, information collecting and traffic injury surveillance systems of some countries were explored and after being compared with current information recording systems of the I.R. of Iran qualitatively, differences and probable weaknesses were clarified. Results Traffic Police collects five major parts of the mentioned model in the 113 and 114 Com from format. Emergency Medicine Management Center is responsible for providing some parts of the injury surveillance system9s information—which are some parts of the mentioned model—in the 115 EMS mission form format. In comparison with the American traffic records model, records of the I.R. of Iran9s traffic police are similar to the model in the crash and vehicle information components completely. They are also similar in all details of the roadway and driver information components except for the traffic volume and conviction history. In comparison with some Asian countries, in the core minimum data on any case of injury class, the diagnosis of injury-related disease in not based on ICD and AIS in the I.R. of Iran. Conclusions Traffic injury information gathering system needs utilising ICDs and AISs and—like other countries in the region—a unit format and language on traffic injuries records.

Introduction There is 65 deaths per day from road traffic injuries (RTIs). In Iran. Despite some interventions having been implemented, the impacts of these interventions on mortality and morbidity rates have not been evaluated. Objective To ascertain the pattern of RTIs in Iran for the years 2004–2007 and to compare the epidemiological trends of RTIs, before and 2 years after four road safety programs were put into place. Methods A 4-year database from two sources, the traffic police and medico-legal data were employed. The four interventions concurrently/simultaneously put into place in 2005 were as follows: enforcement of laws on the mandatory fastening of seat belts, enforcement of the laws on use of motorcycle helmets, enforcement of general traffic laws and mass media educational campaigns on national radio and television. Results There was a significant decrease in RTIs-related-death and morbidity rates in Iran, after the intervention programs (p Conclusion These findings demonstrate the role of traffic police interventions, initiated simultaneously on a national level, in RTI prevention. They do highlight the importance of the contribution made by law enforcement and mass education campaigns.

Background and Objective This study investigated the efficacy of mandatory seat belt use legislation on reducing traffic injuries and the intensity of road traffic injuries (RTIs). Materials and Methods Data on RTIs from 1 year before till 2 years after the implementation of mandatory seat belt use legislation were obtained from the police department. After data cleaning and stratification RTIs and moralities from 1 year before till 2 year after the implementation of mandatory seat belt use legislations was compared with those in year prior to the intervention. Results After the implementation of the mandatory seat belt use, traffic mortalities consisted of 13.3% of all RTIs in the year prior to the implementation, while this proportion decreased to 9.9% and 11.5% in the first and second years after the implementation, respectively. The trend of mortality reduction was not consistent for seat belt use, as we observed a slight increase in the proportion of moralities in the second year after the implementation of mandatory seat belt use, though they did not reach the levels for before implementation of those laws. Conclusion Our findings suggested that the mandatory of seat belt use was efficient in reduction of intensity of RTIs and it was also efficient in reducing the crude number of RTIs. However, in the second year after the implantation the efficiency of this intervention reduced.

"nBackground: A crucial part of a case-control study is the selection of a sample of controls that represent the base-popula­tion from which cases were drawn. Controls may be matched to cases by one or more potentially important confounding vari­ables, such as socioeconomic status. In the United Kingdom, one method for control selection has been based on the pa­tient list of the General Practice with whom the cases were registered, which we refer to as GP-matching. We aimed to ex­plore whether GP-matching adequately control for the potential confounding effect of socioeconomic status."nMethods: The Townsend index of deprivation was calculated for different two national census geography levels of Elec­toral ward/Postcode Sector and Enumeration District/Output area for the three study areas of Dundee, Leeds and York. Con­ditional logistic regression was used to estimate the association of cases with deprivation (based on the Townsend index) com­pared with that of matched controls for the two geographical scales. "nResults: At the largest geographical level (Electoral ward/Postcode Sector) there was no evidence of a difference in the dis­tribution of deprivation scores between cases and controls. However, analysis at the smallest level (Enumeration Dis­trict/Output area) showed that, despite GP matching, cases were more likely to live in deprived areas than matched controls."nConclusion: Using General Practice lists for the selection of controls for controlling the confounding effect of socioeco­nomic status might not be an appropriate method for case-control studies conducted in the United Kingdom.

Background Patients with rheumatoid arthritis (RA) have shared care between rheumatologists and general practitioners (GPs). Rheumatologists guide immunosuppressive therapy, whilst GPs rely on analgesia and glucocorticoid (GC) therapy to manage active disease. The objective of this study was to describe patterns of GC prescribing for patients with RA in primary care and to determine the influence of patient characteristics and prescriber. Methods Incident RA patients were identified within the Clinical Practice Research Datalink, a United Kingdom (UK) primary care research database. Descriptive statistics identified patterns of oral GC prescribing. Prescribers were categorised by their tendency to prescribe GCs (high/low). Logistic regression was used to identify baseline characteristics associated with GC prescriptions during follow-up and to examine whether baseline characteristics influenced prescribing differently in high versus low prescribers. Results A total of 7777 patients (47 %) received ≥1 GC prescription during follow-up. The average daily dose was 7.5 mg (IQR 5–15.3 mg). Of those who received GCs, >50 % were prescribed >10 mg/day and 20 % >30 mg/day. The median proportion of time spent on GCs was 26.3 % (IQR 3.8–70.0 %). Age and cardiovascular disease (CVD) were associated with increased likelihood of receiving GCs. High prescribers more commonly prescribed GC therapy in older patients and patients with hypertension. Conclusions Half of patients with incident RA received GCs in primary care. Average GC use was 7.5 mg for 25 % of the time, perhaps higher usage than rheumatologists and GPs might expect. GCs were prescribed more commonly in certain high-risk populations, including older patients and those with CVD.