Rheumatoid arthritis - clinical aspects: 134. Predictors of Joint Damage in South Africans with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA. Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value <0.05 was considered significant. Results: The mean (SD) age was 56 (9.8) years, disease duration 17.5 (8.5) years, educational level 7.5 (3.5) years and DMARD lag was 9 (8.8) years. Female to male ratio was 10:1. The mean (SD) DAS28 was 4.9 (1.5) and total RAAD score was 28.3 (12.8). The mean (SD) BMI was 27.2 kg/m2 (6.2) and 93% of patients were rheumatoid factor (RF) positive. More than 90% of patients received between 2 to 3 DMARDs. Significant univariate predictors of a poor RAAD score were increasing age (p = 0.001), lower education level (p = 0.019), longer disease duration (p < 0.001), longer DMARD lag (p = 0.014), lower BMI (p = 0.025), high RF titre (p < 0.001) and high ESR (p = 0.008). The multivariate regression analysis showed that the only independent significant predictors of a higher mean RAAD score were older age at disease onset (p = 0.04), disease duration (p < 0.001) and RF titre (p < 0.001). There was also a negative association between BMI and the mean total RAAD score (p = 0.049). Conclusions: Patients with longstanding established RA have more severe irreversible joint damage as measured by the clinical RAAD score, contrary to other studies in Africa. This is largely reflected by a delay in the initiation of early effective treatment. Independent of disease duration, older age at disease onset and a higher RF titre are strongly associated with more joint damage. The inverse association between BMI and articular damage in RA has been observed in several studies using radiographic damage scores. The mechanisms underlying this paradoxical association are still widely unknown but adipokines have recently been suggested to play a role. Disclosure statement: C.I. has received a research grant from the Connective Tissue Diseases Research Fund, University of the Witwatersrand. All other authors have declared no conflicts of interes

Investigation of concrete strenght and development length effects on bond strenght by using hinged beam test

YÖK Tez No: 461064Bilindiği gibi, betonarme varlığını betonla donatı arasındaki aderansa borçludur. Beton-donatı aderansı konusunda birçok çalışma yapılmış olmasına rağmen, aderans olayının karmaşık olması sebebiyle konu tam olarak aydınlatılamamıştır. Bu sebeple, bu tez çalışmasında, farklı donatı çapları, kenetlenme boyları ve çimento dozajı kullanarak üretilen betonlarla donatı arasındaki aderans mafsallı kiriş deneyi yardımıyla eğilme altında deneysel olarak incelenmiştir. Deneysel çalışma, sabit 300 dozajla üretilen, farklı donatı çapı ve kenetlenme boylarının (100 mm, 150 mm ve 200 mm) kullanıldığı ve 250, 300, 400 ve 500 dozajlarla üretilen, farklı donatı çapı ve sabit 100 mm kenetlenme boyunun kullanıldığı iki seri halinde gerçekleştirilmiştir. Deneyler toplam 18 mafsallı kiriş üzerinde gerçekleştirilmiştir. Deney sonuçları, kenetlenme boyunun, beton dayanımının ve donatı çapının aderans dayanımını önemli derecede etkilediğini ortaya koymuştur. Artan kenetlenme boyu ve beton dayanımını için ulaşılan maksimum gerilmeler artarken sıyrılmalar azalmış, donatı çapı arttıkça ise sıyrılmalar artarken gerilme değerleri azalmıştır. Aynı çap ve kenetlenme boyu için dört farklı dozajla üretilen dayanımları değişken betonlarda, ?10, ?12 ve ?14 için ulaşılan maksimum yük değerleri sırasıyla %5-34, %13-29, %8-26 arasında artışlar olduğunu ortaya koymuştur.As it is known, reinforced concrete owes its existence to the bond strength between concrete and steelrebar. Although many studies have been carried out on bond strength, the subject has not been fully clarified as bond strength phenomenon is complicated. Therefore, in this thesis, the bond strength between rebar and concrete produced by using different rebar diameters, development lengths and cement dosages have been experimentally observed in bending with the help of hinged beam test. The experimental work was carried out in two series using different reinforcement diameters and development lengths (100 mm, 150 mm, 200 mm) with constant 300 dosage and different rebar diameters and a constant 100 mm development length with 250, 300, 400 and 500 dosages. Experiments were carried out on a total of 18 hinged beams. The results of the experiment showed that development length, concrete strength and reinforcement diameter significantly affect the bond strength. While the maximum stress increased for extending development length and concrete strength, slips decreased, as the reinforcement diameter expanded stress values decreased while the slip increased. The maximum load rates achieved for ?10, ?12 and ?14 in variable concretes produced with four different dosages on different concrete strengths for the same diameter and development length increase respectively between %5-34, %13-29, and % 8-26

CARD8 p.C10X polymorphism is associated with inflammatory activity in early rheumatoid arthritis

Objectives CARD8 and NLRP3 are constituents of the inflammasome which regulates interleukin 1 beta production. The influence of polymorphisms in CARD8 and NLRP3 on rheumatoid arthritis (RA) susceptibility and severity were evaluated. Methods CARD8 p.C10X and NLRP3 p.Q705K genotypes were assessed in andgt;500 controls and patients with early RA from northern Sweden. The patients were monitored regularly over a 2-year period. The 28-joint disease activity score (DAS28) and its separate components were compared across genotypes. Results Patients with one or more variant alleles in CARD8 (CARD8-X) had increased DAS28, tender joint count and erythrocyte sedimentation rate during the 2-year follow-up period despite receiving disease-modifying antirheumatic drugs to a greater extent. CARD8-X was significantly over-represented among patients who received anti-tumour necrosis factor therapy during the first 2 years. CARD8 and NLRP3 genotypes did not influence radiological joint damage and were not associated with an increased susceptibility. Conclusions Carriage of CARD8-X is associated with a worse disease course in early RA.Original Publication:Alf Kastbom, Martin Johansson, Deepti Verma, Peter Söderkvist and Solbritt Rantapaa-Dahlqvist, CARD8 p.C10X polymorphism is associated with inflammatory activity in early rheumatoid arthritis, 2010, ANNALS OF THE RHEUMATIC DISEASES, (69), 4, 723-726.http://dx.doi.org/10.1136/ard.2008.106989Copyright: BMJ Publishing Grouphttp://group.bmj.com

Treatment with tumor necrosis factor inhibitors and the risk of acute coronary syndromes in early rheumatoid arthritis

Objective Rheumatoid arthritis (RA) is associated with an increased risk of ischemic heart disease, in both early and established RA. Data on the risk of ischemic heart disease in relation to therapy with tumor necrosis factor (TNF) antagonists (anti-TNF) are conflicting in patients with established RA and essentially lacking in those with early RA. In established RA, the risk of myocardial infarction has been linked to the response to anti-TNF therapies. The aim of this study was to determine the risk of acute coronary syndromes (ACS) in patients with early RA in relation to treatment with, and response to, anti-TNF. Methods. A cohort consisting of patients in whom RA was diagnosed between 1999 and 2007 was identified from the Swedish Rheumatology Register (n = 6,000), from which information on disease activity and pharmacologic treatments was extracted. In a cohort study, the risk of first occurrence of an ACS was compared between patients treated with anti-TNF and those without exposure to anti-TNF, using hazard ratios (HRs). In a nested case-control study, the relationship between response to anti-TNF according to the European League Against Rheumatism (EULAR) response criteria and the risk of ACS was investigated. Results. In the cohort study, treatment with antiTNF was not related to any statistically significant alteration in the risk of ACS (HR 0.80, 95% confidence interval [95% CI] 0.52-1.24). In the nested case-control study, a good or moderate EULAR treatment response at 3 months and at 6 months was not associated with a risk of ACS (odds ratio [OR] 1.7, 95% CI 0.5-5.1 and OR 1.5, 95% CI 0.3-6.9, respectively), when adjusted for disease activity before treatment start. Conclusion. In this study of patients treated with anti-TNF within the first years of RA, neither treatment with, nor response to, anti-TNF therapy could be linked to any statistically significant decrease in the risk of ACS

No Increased Occurrence of Ischemic Heart Disease Prior to the Onset of Rheumatoid Arthritis Results From Two Swedish Population-Based Rheumatoid Arthritis Cohorts

Objective. To investigate the relative importance of shared etiologies for rheumatoid arthritis (RA) and ischemic heart disease (IHD) in terms of the well-known increased risk of HID in patients with RA, by assessing the occurrence of IHD up until the time of the onset of the first symptoms of RA. Methods. We assessed the prevalence of a history of IHD, myocardial infarction (MI), and angina pectoris before the onset of RA symptoms in 2 large population-based case-control studies. Patients with newly diagnosed RA according to the criteria of the American College of Rheumatology were included as cases. We used data from the Swedish Early Arthritis Register study and the Swedish Epidemiologic Investigation of Rheumatoid Arthritis case-control study and from general population controls. Information on IHD, MI, and angina pectoris was obtained from the nationwide Hospital Discharge Register and from self reports. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) to compare the prevalence of a history of IHD/Mi/angina pectoris among patients with RA with that among population controls. Results. We could not detect any increased occurrence of IHD, MI, or angina pectoris before the onset of symptoms of RA, regardless of whether data on IHD were obtained from the Hospital Discharge Register or were self reported. As detected in the Hospital Discharge Register, the OR for IHD overall was 1.0 (95% CI 0.9-1.1), the OR for MI was 1.0 (95% CI 0.9-1.1), and the OR for angina pectoris was 1.0 (95% CI 0.9-1.2). Conclusion. Shared risk factors or susceptibilities for RA and IHD are likely to contribute less than RA-related factors to the increased occurrence of IHD in patients with manifest RA. Nonetheless, the existence of shared factors associated with longer latency until the occurrence of IHD cannot be excluded

Anti-citrullinated protein antibody specificities and pulmonary fibrosis in relation to genetic loci in early rheumatoid arthritis

Objectives Pulmonary manifestations in RA are common comorbidities, but the underlying mechanisms are largely unknown. The added value of a multiplex of ACPA and genetic risk markers was evaluated for the development of pulmonary fibrosis (PF) in an inception cohort. Methods A total of 1184 patients with early RA were consecutively included and followed prospectively from the index date until death or 31 December 2016. The presence of 21 ACPA fine specificities was analysed using a custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden). Three SNPs, previously found related to PF were evaluated, rs2609255 (FAM13A), rs111521887 (TOLLIP) and rs35705950 (MUC5B). ACPA and genetic data were available for 841 RA patients, of whom 50 developed radiologically defined PF. Results In unadjusted analyses, 11 ACPA specificities were associated with PF development. In multiple variable analyses, six ACPA specificities were associated with increased risk of PF: vimentin (Vim)60-75, fibrinogen (Fib)beta 62-78 (72), Fib alpha 621-635, Bla26, collagen (C)II359-369 and F4-CIT-R (P &lt; 0.01 to P &lt; 0.05). The number of ACPA specificities was also related to PF development (P &lt; 0.05 crude and adjusted models). In multiple variable models respectively adjusted for each of the SNPs, the number of ACPA specificities (P &lt; 0.05 in all models), anti-Vim60-75 (P &lt; 0.05, in all models), anti-Fib beta 62-78 (72) (P &lt; 0.001 to P &lt; 0.05), anti-CII359-369 (P &lt; 0.05 in all models) and anti-F4-CIT-R AQ4 (P &lt; 0.01 to P &lt; 0.05), anti-Fib alpha 621-635 (P &lt; 0.05 in one) and anti-Bla26 (P &lt; 0.05 in two) were significantly associated with PF development. Conclusion The development of PF in an inception cohort of RA patients was associated with both presence of certain ACPA and the number of ACPA specificities and risk genes