Abatacept retention and clinical outcomes in Austrian patients with rheumatoid arthritis: real-world data from the 2-year ACTION study.

BACKGROUND: AbataCepT In rOutiNe clinical practice (ACTION; NCT02109666) was a 2-year international observational study of patients with moderate to severe rheumatoid arthritis. METHODS: Baseline characteristics, abatacept retention rates, and clinical outcomes were compared by treatment line in the Austrian cohort of ACTION. RESULTS: Of 100 patients enrolled in Austria, 98 (98.0%) were evaluable: 33/98 (33.7%) biologic naïve and 65/98 (66.3%) with ≥1 prior biologic failure. At baseline, biologic-naïve patients had shorter disease duration and lower concomitant corticosteroid use than biologic-failure patients. Overall crude abatacept retention rate was 60.5% and retention rate was higher in biologic-naïve (65.1%) versus biologic-failure (58.0%) patients. Good/moderate EULAR (European League Against Rheumatism) response rates were 85.7% in biologic-naïve and 100% in biologic-failure patients. CONCLUSIONS: In the Austrian cohort of ACTION, overall abatacept retention at 2 years was high, with higher retention rates in patients receiving abatacept as an earlier treatment line. Good/moderate EULAR response rate was higher in biologic-failure than in biologic-naïve patients.

Correction to: Predictors of abatacept retention over 2 years in patients with rheumatoid arthritis: results from the real-world ACTION study.

The article listed above was initially published with incorrect copyright information. Upon publication of this Correction, the copyright of this article changed to "The Author(s)". The original article has been corrected.

Predictors of abatacept retention over 2 years in patients with rheumatoid arthritis: results from the real-world ACTION study.

OBJECTIVES: Evaluate abatacept retention over 2 years in the AbataCepT In rOutiNe clinical practice (ACTION) study. METHOD: ACTION was an international, observational study of patients with moderate-to-severe rheumatoid arthritis (RA) who initiated intravenous abatacept. Crude abatacept retention rates over 2 years were estimated using Kaplan-Meier analyses in biologic-naive and -failure patients. Clinically relevant risk factors and significant prognostic factors for retention were evaluated using a Cox proportional hazards multivariable model. RESULTS: Overall, 2350/2364 enrolled patients were evaluable; 673 (28.6%) were biologic naive and 1677 (71.4%) had prior biologic failure (1 biologic, 728/1677 [43.4%]; ≥ 2 biologics, 949/1677 [56.6%]). Abatacept retention rate (95% confidence interval [CI]) at 2 years was 47.9% (45.7, 50.0): 54.5% (50.4, 58.3) for biologic-naive vs 45.2% (42.7, 47.7) for biologic-failure patients (log-rank P < 0.001). For patients with 1 and ≥ 2 prior biologic failures, respectively, retention rates (95% CI) were 50.2% (46.3, 53.9) vs 41.3% (38.0, 44.6; log-rank P < 0.001). Main reasons for discontinuation (biologic-naive vs biologic-failure, respectively) were lack of efficacy (61.4 vs 67.7%) and safety (21.3 vs 21.2%). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) double positivity versus negativity were predictive of higher retention in both biologic-naive (hazard ratio [HR] [95% CI] 0.71 [0.53, 0.96]; P = 0.019) and biologic-failure patients (HR [95% CI] 0.76 [0.62, 0.94]; P = 0.035). CONCLUSIONS: Abatacept initiation as earlier vs later line of therapy in RA may achieve higher 2-year retention rates. RF and anti-CCP seropositivity could predict increased abatacept retention, irrespective of treatment line. TRIAL REGISTRATION: NCT02109666.

Efficacy of tocilizumab monotherapy after response to combined tocilizumab and methotrexate in patients with rheumatoid arthritis: the randomised JUST-ACT study.

OBJECTIVES: The aim of the JUST-ACT study was to assess whether the add-on effect of tocilizumab (TCZ) to background methotrexate (MTX) observed in MTX-inadequate responders with active rheumatoid arthritis (RA), would be sustained when MTX is withdrawn. METHODS: A double-blind, parallel-group, phase 3 study in biologic-naïve RA patients with a disease activity score 28 (DAS28)>3.2 despite MTX which were treated with TCZ+MTX for an initial 16-week period. Patients who at week 16 achieved low disease activity (LDA) (DAS28≤3.2) were randomised to continue with TCZ+MTX or switch to TCZ + placebo (PBO) for an additional 12 weeks. The primary endpoint was the change in DAS28-ESR from the randomisation at week 16 to week 28. Non-inferiority was confirmed if the upper limit of the two-sided 95%CI for the treatment difference between TCZ+MTX and TCZ monotherapy groups was lower than the selected non-inferiority margin of 0.6. RESULTS: 261 patients completed the first 16 weeks of TCZ+MTX treatment and 165 were randomised (83 to TCZ+MTX and 82 to TCZ+PBO). For the primary endpoint, the adjusted treatment difference (95% CI) in mean change of DAS28-ESR was -0.06 (-0.40 to 0.27), and therefore the non-inferiority of switching to TCZ monotherapy versus continuing with TCZ+MTX was demonstrated. In both treatment groups, the percentage of patients in clinical remission from 16 to 28 weeks was similar as were the improvements in disease activity, functional disability and quality of life. CONCLUSIONS: In MTX non-responder patients achieving LDA with TCZ+MTX, switching to TCZ monotherapy is non-inferior to continuing the combination.

Lack of replication of interactions between polymorphisms in rheumatoid arthritis susceptibility: case-control study.

INTRODUCTION: Approximately 100 loci have been definitively associated with rheumatoid arthritis (RA) susceptibility. However, they explain only a fraction of RA heritability. Interactions between polymorphisms could explain part of the remaining heritability. Multiple interactions have been reported, but only the shared epitope (SE) × protein tyrosine phosphatase nonreceptor type 22 (PTPN22) interaction has been replicated convincingly. Two recent studies deserve attention because of their quality, including their replication in a second sample collection. In one of them, researchers identified interactions between PTPN22 and seven single-nucleotide polymorphisms (SNPs). The other showed interactions between the SE and the null genotype of glutathione S-transferase Mu 1 (GSTM1) in the anti-cyclic citrullinated peptide-positive (anti-CCP+) patients. In the present study, we aimed to replicate association with RA susceptibility of interactions described in these two high-quality studies. METHODS: A total of 1,744 patients with RA and 1,650 healthy controls of Spanish ancestry were studied. Polymorphisms were genotyped by single-base extension. SE genotypes of 736 patients were available from previous studies. Interaction analysis was done using multiple methods, including those originally reported and the most powerful methods described. RESULTS: Genotypes of one of the SNPs (rs4695888) failed quality control tests. The call rate for the other eight polymorphisms was 99.9%. The frequencies of the polymorphisms were similar in RA patients and controls, except for PTPN22 SNP. None of the interactions between PTPN22 SNPs and the six SNPs that met quality control tests was replicated as a significant interaction term--the originally reported finding--or with any of the other methods. Nor was the interaction between GSTM1 and the SE replicated as a departure from additivity in anti-CCP+ patients or with any of the other methods. CONCLUSIONS: None of the interactions tested were replicated in spite of sufficient power and assessment with different assays. These negative results indicate that whether interactions are significant contributors to RA susceptibility remains unknown and that strict standards need to be applied to claim that an interaction exists.

Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis.

INTRODUCTION: In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations. METHODS: The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients. RESULTS: None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis. CONCLUSION: Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes.

Quality-of-care standards for early arthritis clinics.

The diagnosis and treatment of early arthritis is associated with improved patient outcomes. One way to achieve this is by organising early arthritis clinics (EACs). The objective of this project was to develop standards of quality for EACs. The standards were developed using the two-round Delphi method. The questionnaire, developed using the best-available scientific evidence, includes potentially relevant items describing the dimensions of quality of care in the EAC. The questionnaire was completed by 26 experts (physicians responsible for the EACs in Spain and chiefs of the rheumatology service in Spanish hospitals). Two hundred and forty-four items (standards) describing the quality of the EAC were developed, grouped by the following dimensions: (1) patient referral to the EAC; (2) standards of structure for an EAC; (3) standards of process; (4) relation between primary care physicians and the EAC; (5) diagnosis and assessment of early arthritis; (6) patient treatment and follow-up in the EAC; (7) research and training in an EAC; and (8) quality of care perceived by the patient. An operational definition of early arthritis was also developed based on eight criteria. The standards developed can be used to measure/establish the requirements, resources, and processes that EACs have or should have to carry out their treatment, research, and educational activities. These standards may be useful to health professionals, patient associations, and health authorities.

Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial.

BACKGROUND: Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis. METHODS: Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5-5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372). RESULTS: The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: -0.23 (SD 0.56) mm; 2 g/day: -0.27 (SD 0.63) mm; placebo: -0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p<0.001 for 1 g/day and 0.10 (SE 0.04), 95% CI 0.02 to 0.19, p=0.018 for 2 g/day. Fewer radiological progressors were observed with strontium ranelate (p<0.001 and p=0.012 for 1 and 2 g/day). There were greater reductions in total WOMAC score (p=0.045), pain subscore (p=0.028), physical function subscore (p=0.099) and knee pain (p=0.065) with strontium ranelate 2 g/day. Strontium ranelate was well tolerated. CONCLUSIONS: Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.

Efficacy and safety of oral strontium ranelate for the treatment of knee osteoarthritis: rationale and design of randomised, double-blind, placebo-controlled trial.

OBJECTIVE: The osteoporosis drug strontium ranelate dissociates bone remodelling processes. It also inhibits subchondral bone resorption and stimulates cartilage matrix formation in vitro. Exploratory studies in the osteoporosis trials report that strontium ranelate reduces biomarkers of cartilage degradation, and attenuates the progression and clinical symptoms of spinal osteoarthritis, suggesting symptom- and structure-modifying activity in osteoarthritis. We describe the rationale and design of a randomised trial evaluating the efficacy and safety of strontium ranelate in knee osteoarthritis. RESEARCH DESIGN, METHODS, AND RESULTS: This double-blind, placebo-controlled trial (98 centres, 18 countries) includes ambulatory Caucasian men and women aged ≥50 years with primary knee osteoarthritis of the medial tibiofemoral compartment (Kellgren and Lawrence grade 2 or 3), joint space width (JSW) 2.5 to 5 mm, and knee pain on most days in the previous month (intensity ≥40 mm on a visual analogue scale). Patients are randomly allocated to three groups (strontium ranelate 1 or 2 g/day, or placebo). Follow-up is expected to last 3 years. The primary endpoint is radiographic change in JSW from baseline in each group versus placebo. The main clinical secondary endpoint is WOMAC score at the knee. Safety is assessed at every visit. It is estimated that 1600 patients are required to establish statistical significance with power >90% (0.2 mm ± 10% between-group difference in change in JSW over 3 years). Recruitment started in April 2006. The results are expected in spring 2012. CLINICAL TRIAL REGISTRATION: The trial is registered on www.controlled-trials.com (number ISRCTN41323372). CONCLUSIONS: This randomised, double blind, placebo-controlled study will establish the potential of strontium ranelate in improving structure and symptoms in patients with knee osteoarthritis.

[Differences in the management of early and established rheumatoid arthritis]. / Diferencias en el manejo de la artritis reumatoide precoz y establecida.

OBJECTIVE: To assess the differences in the clinical and therapeutic management of early and established rheumatoid arthritis (RA) in clinical practice. METHODS: Retrospective and multicentre study including 360 patients diagnosed with RA. During the 12 months prior to the study, onset, sociodemographic, clinical and therapeutic data were collected by clinical chart review. RESULTS: A total of 152 patients with early RA and 208 with established RA were studied. 97.5% had received disease-modifying anti-rheumatic drugs (DMARDs) and 43.6% a TNFa blocker between the diagnosis and the start of the study. Established RA patients used TNFa blockers more frequently than early RA patients (60,1% vs 21,1%, p<0,001). Methotrexate was the most commonly used drug (70.6%). A treatment change was seen in 79% of patients with early RA and 60.6% of those with established RA. A dose change was the most frequent modification and an inadequate response the most frequent reason. A 25.8% of treatments were stopped due to adverse events. The mean (SD) decrease on DAS28 score was 0.9 (1.5) on early RA and 0.2 (1.0) on established RA patients. A 35.8% of early RA patients showed a good EULAR response, while only 16.2% among established RA patients (p<0.001). Rheumatoid factor and radiological progression assessment were the most requested determinations in early RA (p<0.05). CONCLUSIONS: Spanish rheumatologists used biological drugs with a higher frequency in patients with more advanced disease, as recommended in the main clinical practice guidelines.

Diferencias en el manejo de la artritis reumatoide precoz y establecida / Differences in the management of early and established rheumatoid arthritis

Objetivo. Evaluar las diferencias en el manejo clínico y terapéutico de la artritis reumatoide (AR) precoz y establecida en la práctica clínica. Pacientes y método. Estudio retrospectivo y multicéntrico en el que se incluyó a 360 pacientes con diagnóstico de AR. Mediante la revisión de historias clínicas se recogieron variables sociodemográficas, clínicas y terapéuticas en los 12 meses previos al inicio del estudio. Resultados. Se estudió a 152 pacientes con AR precoz (ARp) y 208 con AR establecida (ARe). El 97,5% había recibido fármacos modificadores de enfermedad (FAME) y el 43,6% tratamiento anti-factor de necrosis tumoral (TNF) entre el diagnóstico y el inicio del estudio. Los anti-TNF fueron utilizados con mayor frecuencia en pacientes con ARe (el 60,1 frente al 21,1%; p<0,001). El metotrexato fue el fármaco más utilizado (70,6%). Se detectó cambio del tratamiento en un 79% de pacientes con ARp y en el 60,6% con ARe. El cambio de dosis fue la modificación más frecuente y una respuesta inadecuada el motivo más frecuente. El 25,8% de los tratamientos se suspendieron por reacciones adversas. La disminución media±desviación estándar del DAS28 fue 0,9±1,5 en ARp y 0,2±1,0 en ARe. El 35,8% de las ARp presentó buena respuesta EULAR, mientras sólo el 16,2% de las ARe (p<0,001). La determinación del factor reumatoide y la valoración de la progresión radiológica fueron más solicitadas en la ARp (p<0,05). Conclusiones. Los reumatólogos españoles utilizaron agentes biológicos con mayor frecuencia en los pacientes con enfermedad más evolucionada, ajustándose a las recomendaciones de las principales guías de práctica clínica (AU)

Objective. To assess the differences in the clinical and therapeutic management of early and established rheumatoid arthritis (RA) in clinical practice. Methods. Retrospective and multicentre study including 360 patients diagnosed with RA. During the 12 months prior to the study, onset, sociodemographic, clinical and therapeutic data were collected by clinical chart review. Results. A total of 152 patients with early RA and 208 with established RA were studied. 97.5% had received disease-modifying anti-rheumatic drugs (DMARDs) and 43.6% a TNFa blocker between the diagnosis and the start of the study. Established RA patients used TNFa blockers more frequently than early RA patients (60,1% vs 21,1%, p<0,001). Methotrexate was the most commonly used drug (70.6%). A treatment change was seen in 79% of patients with early RA and 60.6% of those with established RA. A dose change was the most frequent modification and an inadequate response the most frequent reason. A 25.8% of treatments were stopped due to adverse events. The mean (SD) decrease on DAS28 score was 0.9 (1.5) on early RA and 0.2 (1.0) on established RA patients. A 35.8% of early RA patients showed a good EULAR response, while only 16.2% among established RA patients (p<0.001). Rheumatoid factor and radiological progression assessment were the most requested determinations in early RA (p<0.05). Conclusions. Spanish rheumatologists used biological drugs with a higher frequency in patients with more advanced disease, as recommended in the main clinical practice guidelines (AU)

Rheumatoid arthritis does not share most of the newly identified systemic lupus erythematosus genetic factors.

OBJECTIVE: Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) share some genetic factors such as HLA, PTPN22, STAT4, and 6q23. The aim of this study was to determine whether 9 other SLE genetic factors are also implicated in RA susceptibility. METHODS: A characteristic single-nucleotide polymorphism (SNP) in each of 9 genetic factors, ITGAM (rs1143679), C8orf13-BLK (rs13277113), TYK2 (rs2304256), 1q25.1 (rs10798269), PXK (rs6445975), KIAA1542 (rs4963128), MECP2 (rs17435), BANK1 (rs17266594), and LY9 (rs509749), was studied in 1,635 patients with RA and 1,906 control subjects from Spain. The rs7574865 SNP in STAT4 was also included. Analyses were conducted globally and after stratification by sex and clinical features (anti-cyclic citrullinated peptide and rheumatoid factor, shared epitope, rheumatoid nodules, radiographic changes, sicca syndrome, and pneumonitis). RESULTS: No association was observed between RA and any of the 9 newly identified SLE genetic factors. A meta-analysis using previous data was consistent with these results. In addition, there were no significant differences between individuals with and those without each of the clinical features analyzed, except the frequency of the minor allele in the C8orf13-BLK locus that was decreased in patients with sicca syndrome (14.6% versus 22.4% in controls; P = 0.003). CONCLUSION: None of the 9 recently identified SLE risk factors showed association with RA. Therefore, common genetic factors affecting the pathogenesis of these 2 disorders seem to be limited, revealing that the genetic component contributes to the different expression of these diseases.

Lack of association with rheumatoid arthritis of selected polymorphisms in 4 candidate genes: CFH, CD209, eotaxin-3, and MHC2TA.

OBJECTIVE: To investigate associations with rheumatoid arthritis (RA) of single-nucleotide polymorphisms (SNP) in 4 candidate genes, complement factor H (CFH), CD209 or DC-SIGN, eotaxin-3, and the MHC class II Transactivator (MHC2TA) genes. These SNP have been reported as important for RA (eotaxin-3 and MHC2TA) or for other immune-mediated diseases (CFH and CD209). METHODS: Genotypes for the 7 selected SNP were obtained from 1587 patients with RA and 1570 controls of Spanish ancestry. Analyses were carried out after stratification for sex, erosions, rheumatoid factor, shared epitope, anti-cyclic citrullinated peptide antibodies, and the R620W PTPN22 SNP. RESULTS: None of the comparisons between patients with RA and controls or between the different strata of patients according to disease features was significant. CONCLUSION: None of the SNP in CFH and CD209 showed evidence of association with RA. We did not replicate the association of eotaxin-3 with RA described in Koreans, or that of the MHC2T SNP.

Oral sodium phosphates solution versus polyethylene glycol for colon cleansing prior to radiological assessment.

A clean bowel environment is essential prior to radiological assessment of the colon. The objectives were to determine patient compliance and acceptability, physician satisfaction, overall clinical effectiveness and tolerability with the use of oral sodium phosphates (Fosfosoda) and polyethylene glycol solutions as bowel cleansing agents in a relatively large cohort of Spanish patients requiring radiologic examination of the colon. This was an observational survey involving 592 patients (> or =18 years and approximately 60% women) who received Fosfosoda or polyethylene glycol solutions according to data sheet instructions. Parameters measured included mucosal cleansing (presence of solid residues), patient acceptability (including any adverse effects to treatment) and compliance with the treatment regimen, and physician-rated satisfaction with the procedure. The date from the study demonstrated that Fosfosoda and polyethylene glycol solutions were found to be equally well tolerated in this study, although patients receiving Fosfosoda found it easier to complete the treatment regimen. Fosfosoda was significantly superior to polyethylene glycol solutions with regards to mucosal cleansing with 52% achieving an 'excellent' result compared with only 36% of the polyethylene glycol group (relative risk:1.43; 95% confidence interval: 1.12-1.82). Physician-rated assessment of the bowel cleansing procedure also significantly favored Fosfosoda (p = 0.014). In conclusion, while Fosfosoda and polyethylene glycol solutions were equally well tolerated when given to patients prior to radiologic examination of the colon, Fosfosoda was shown to be significantly more effective in terms of bowel cleansing. Based upon the available evidence this could provide significant cost benefit for Fosfosoda.

Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-kappaB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility.

INTRODUCTION: Genome-wide association studies of rheumatoid arthritis (RA) have identified an association of the disease with a 6q23 region devoid of genes. TNFAIP3, an RA candidate gene, flanks this region, and polymorphisms in both the TNFAIP3 gene and the intergenic region are associated with systemic lupus erythematosus. We hypothesized that there is a similar association with RA, including polymorphisms in TNFAIP3 and the intergenic region. METHODS: To test this hypothesis, we selected tag-single nucleotide polymorphisms (SNPs) in both loci. They were analyzed in 1,651 patients with RA and 1,619 control individuals of Spanish ancestry. RESULTS: Weak evidence of association was found both in the 6q23 intergenic region and in the TNFAIP3 locus. The rs582757 SNP and a common haplotype in the TNFAIP3 locus exhibited association with RA. In the intergenic region, two SNPs were associated, namely rs609438 and rs13207033. The latter was only associated in patients with anti-citrullinated peptide antibodies. Overall, statistical association was best explained by the interdependent contribution of SNPs from the two loci TNFAIP3 and the 6q23 intergenic region. CONCLUSIONS: Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus.

Association of interferon regulatory factor 5 haplotypes, similar to that found in systemic lupus erythematosus, in a large subgroup of patients with rheumatoid arthritis.

OBJECTIVE: Previous studies have shown either a lack of effect of IRF5 polymorphisms or an association of the IRF5 gene in only a minor subset of rheumatoid arthritis (RA) patients in whom anti-citrullinated protein antibodies (ACPAs) are absent. The present study was undertaken to investigate the role of genetic variation in IRF5 in susceptibility to RA. METHODS: Nine IRF5 single-nucleotide polymorphisms (SNPs) were studied in 1,338 patients with RA and 1,342 control subjects in analyses of exploratory and replication sample collections, with stratification according to sex and by the presence or absence of ACPAs, rheumatoid factor, the shared epitope, the 620W PTPN22 allele, and erosions. A meta-analysis that included results from previous studies was also carried out. RESULTS: Our findings together with those from previous studies, in a total of 4,620 RA patients and 3,741 controls, showed a significant association of the rs2004640 IRF5 SNP in RA patients as a whole (odds ratio [OR] 0.88, 95% confidence interval [95% CI] 0.83-0.94; P = 6.5 x 10(-5) versus controls). This association was stronger in ACPA- patients, but was also present in ACPA+ patients (from 3 sample collections). Further analysis of our exploratory sample collection showed that only patients in the ACPA+ and SE- group lacked an association with IRF5 SNPs. All of the remaining RA patients (ACPA- or SE+) showed a strong association with IRF5 SNPs, which followed a complex pattern of opposing effects mediated by independent haplotypes. The susceptibility haplotype showed an OR of 1.8 (95% CI 1.4-2.3; P = 1.2 x 10(-6) versus controls), whereas the protective haplotype showed an OR of 0.76 (95% CI 0.6-0.98; P = 0.046 versus controls). CONCLUSION: IRF5 polymorphisms seem to influence RA susceptibility in a large subgroup of patients, following a pattern of association very similar to that described in patients with systemic lupus erythematosus.

Morphotypic and genotypic characterization of sequential Candida parapsilosis isolates from an outbreak in a pediatric intensive care unit.

Candidemia outbreaks that due to cross-infection are an emerging problem in hospitals. Typing of microorganisms is an essential tool for understanding the epidemiologic aspects of the infection. Techniques based on phenotypic characteristics are inexpensive and easy to perform but are limited by their lack of reproducibility. This study assessed the value of several phenotypic and genotypic techniques that are used in epidemiologic investigations of Candida parapsilosis in clinical practice and used a combination of these methods to analyze outbreak of C. parapsilosis candidemia. Random amplification of polymorphic DNA polymerase chain reaction with several primers was unsatisfactory because it lacked discriminatory power. By simplifying the reading of the morphotypes, we increased their reproducibility for each malt agar and 2,3,5-triphenyltetrazolium media (97% and 90%) and thus their suitability for its use. The combination of electrophoretic karyotype and the simplified morphotypes was rapid and practical to characterize the different clusters involved in the intensive care unit outbreak.

Temperamento e Caráter sob uma visão pós-reichiana

De acordo com Federico Navarro, temperamento é biológico. Cada um nasce com um temperamento que é a constelação neuroendócrina da pessoa. Já o caráter é sócio-cultural. Ele forma-se sobre o temperamento. Já o caráter, é uma defesa crônica do ego contra situações externas desconfortantes. Navarro utiliza terminologias diferentes de Baker e Lowen alegando que ambos não consideraram a estrutura de caráter de cobertura. A maioria das pessoas que encontramos são borderline, mas apresentam uma caracterialidade, ou seja, um traço de caráter de cobertura. Portanto, para se chegar a caracterialidade genuína é preciso interferir sobre a estrutura psicológica da pessoa. (AU)