Nuclear pyruvate dehydrogenase complex regulates histone acetylation and transcriptional regulation in the ethylene response.

Ethylene plays its essential roles in plant development, growth, and defense responses by controlling the transcriptional reprograming, in which EIN2-C-directed regulation of histone acetylation is the first key step for chromatin to perceive ethylene signaling. But how the nuclear acetyl coenzyme A (acetyl CoA) is produced to ensure the ethylene-mediated histone acetylation is unknown. Here we report that ethylene triggers the accumulation of the pyruvate dehydrogenase complex (PDC) in the nucleus to synthesize nuclear acetyl CoA to regulate ethylene response. PDC is identified as an EIN2-C nuclear partner, and ethylene triggers its nuclear accumulation. Mutations in PDC lead to an ethylene hyposensitivity that results from the reduction of histone acetylation and transcription activation. Enzymatically active nuclear PDC synthesizes nuclear acetyl CoA for EIN2-C-directed histone acetylation and transcription regulation. These findings uncover a mechanism by which PDC-EIN2 converges the mitochondrial enzyme-mediated nuclear acetyl CoA synthesis with epigenetic and transcriptional regulation for plant hormone response.

Nuclear Pyruvate Dehydrogenase Complex Regulates Histone Acetylation and Transcriptional Regulation in the Ethylene Response.

Ethylene plays its essential roles in plant development, growth, and defense responses by controlling the transcriptional reprograming, in which EIN2-C-directed regulation of histone acetylation is the first key-step for chromatin to perceive ethylene signaling. But how the nuclear acetyl coenzyme A (acetyl CoA) is produced to ensure the ethylene-mediated histone acetylation is unknown. Here we report that ethylene triggers the accumulation of the pyruvate dehydrogenase complex (PDC) in the nucleus to synthesize nuclear acetyl CoA to regulate ethylene response. PDC is identified as an EIN2-C nuclear partner, and ethylene triggers its nuclear accumulation. Mutations in PDC lead to an ethylene-hyposensitivity that results from the reduction of histone acetylation and transcription activation. Enzymatically active nuclear PDC synthesize nuclear acetyl CoA for EIN2-C-directed histone acetylation and transcription regulation. These findings uncover a mechanism by which PDC-EIN2 converges the mitochondrial enzyme mediated nuclear acetyl CoA synthesis with epigenetic and transcriptional regulation for plant hormone response.

Bibliometric Analysis on Supercritical CO2 Power Cycles for Concentrating Solar Power Applications.

In recent years, supercritical CO2 power cycles have received a large amount of interest due to their exceptional theoretical conversion efficiency above 50%, which is leading a revolution in power cycle research. Furthermore, this high efficiency can be achieved at a moderate temperature level, thus suiting concentrating solar power (CSP) applications, which are seen as a core business within supercritical technologies. In this context, numerous studies have been published, creating the need for a thorough analysis to identify research areas of interest and the main researchers in the field. In this work, a bibliometric analysis of supercritical CO2 for CSP applications was undertaken considering all indexed publications within the Web of Science between 1990 and 2020. The main researchers and areas of interest were identified through network mapping and text mining techniques, thus providing the reader with an unbiased overview of sCO2 research activities. The results of the review were compared with the most recent research projects and programs on sCO2 for CSP applications. It was found that popular research areas in this topic are related to optimization and thermodynamics analysis, which reflects the significance of power cycle configuration and working conditions. Growing interest in medium temperature applications and the design of sCO2 heat exchangers was also identified through density visualization maps and confirmed by a review of research projects.

Do population-level risk prediction models that use routinely collected health data reliably predict individual risks?

The objective of this study was to assess the reliability of individual risk predictions based on routinely collected data considering the heterogeneity between clinical sites in data and populations. Cardiovascular disease (CVD) risk prediction with QRISK3 was used as exemplar. The study included 3.6 million patients in 392 sites from the Clinical Practice Research Datalink. Cox models with QRISK3 predictors and a frailty (random effect) term for each site were used to incorporate unmeasured site variability. There was considerable variation in data recording between general practices (missingness of body mass index ranged from 18.7% to 60.1%). Incidence rates varied considerably between practices (from 0.4 to 1.3 CVD events per 100 patient-years). Individual CVD risk predictions with the random effect model were inconsistent with the QRISK3 predictions. For patients with QRISK3 predicted risk of 10%, the 95% range of predicted risks were between 7.2% and 13.7% with the random effects model. Random variability only explained a small part of this. The random effects model was equivalent to QRISK3 for discrimination and calibration. Risk prediction models based on routinely collected health data perform well for populations but with great uncertainty for individuals. Clinicians and patients need to understand this uncertainty.

Antibiotic prescribing for common infections in UK general practice: variability and drivers.

OBJECTIVES: To examine variations across general practices and factors associated with antibiotic prescribing for common infections in UK primary care to identify potential targets for improvement and optimization of prescribing. METHODS: Oral antibiotic prescribing for common infections was analysed using anonymized UK primary care electronic health records between 2000 and 2015 using the Clinical Practice Research Datalink (CPRD). The rate of prescribing for each condition was observed over time and mean change points were compared with national guideline updates. Any correlation between the rate of prescribing for each infectious condition was estimated within a practice. Predictors of prescribing were estimated using logistic regression in a matched patient cohort (1:1 by age, sex and calendar time). RESULTS: Over 8 million patient records were examined in 587 UK general practices. Practices varied considerably in their propensity to prescribe antibiotics and this variance increased over time. Change points in prescribing did not reflect updates to national guidelines. Prescribing levels within practices were not consistent for different infectious conditions. A history of antibiotic use significantly increased the risk of receiving a subsequent antibiotic (by 22%-48% for patients with three or more antibiotic prescriptions in the past 12 months), as did higher BMI, history of smoking and flu vaccinations. Other drivers for receiving an antibiotic varied considerably for each condition. CONCLUSIONS: Large variability in antibiotic prescribing between practices and within practices was observed. Prescribing guidelines alone do not positively influence a change in prescribing, suggesting more targeted interventions are required to optimize antibiotic prescribing in the UK.

Relationship between prescribing of antibiotics and other medicines in primary care: a cross-sectional study.

BACKGROUND: High levels of antibiotic prescribing are a major concern as they drive antimicrobial resistance. It is currently unknown whether practices that prescribe higher levels of antibiotics also prescribe more medicines in general. AIM: To evaluate the relationship between antibiotic and general prescribing levels in primary care. DESIGN AND SETTING: Cross-sectional study in 2014-2015 of 6517 general practices in England using NHS digital practice prescribing data (NHS-DPPD) for the main study, and of 587 general practices in the UK using the Clinical Practice Research Datalink for a replication study. METHOD: Linear regression to assess determinants of antibiotic prescribing. RESULTS: NHS-DPPD practices prescribed an average of 576.1 antibiotics per 1000 patients per year (329.9 at the 5th percentile and 808.7 at the 95th percentile). The levels of prescribing of antibiotics and other medicines were strongly correlated. Practices with high levels of prescribing of other medicines (a rate of 27 159.8 at the 95th percentile) prescribed 80% more antibiotics than low-prescribing practices (rate of 8815.9 at the 5th percentile). After adjustment, NHS-DPPD practices with high prescribing of other medicines gave 60% more antibiotic prescriptions than low-prescribing practices (corresponding to higher prescribing of 276.3 antibiotics per 1000 patients per year). Prescribing of non-opioid painkillers and benzodiazepines were also strong indicators of the level of antibiotic prescribing. General prescribing levels were a much stronger driver for antibiotic prescribing than other risk factors, such as deprivation. CONCLUSION: The propensity of GPs to prescribe medications generally is an important driver for antibiotic prescribing. Interventions that aim to optimise antibiotic prescribing will need to target general prescribing behaviours, in addition to specifically targeting antibiotics.

Antibiotic prescribing patterns in general medical practices in England: Does area matter?

Antimicrobial resistance is an important public health concern. As most antibiotics are prescribed in primary care, understanding prescribing patterns in General Medical (GP) practices is vital. The aim of this study was a spatial pattern analysis of antibiotic prescribing rates in GP practices in England and to examine the association of potential clusters with area level socio-economic deprivation. The pattern analysis identified a number of hot and cold spots of antibiotic prescribing, with hot spots predominantly in the North of England. Spatial regression showed that patient catchments of hot spot practices were significantly more deprived than patient catchments of cold spot practices, especially in the domains of income, employment, education and health. This study suggests the presence of area level drivers resulting in clusters of high and low prescribing. Consequently, area level strategies may be needed for antimicrobial stewardship rather than national level strategies.

Coccigodinia relacionada con uso de anillo vaginal anticonceptivo / Coccydynia related to the use of a contraceptive vaginal ring

La coccigodinia es un síndrome que se presenta con frecuencia en las consultas de Reumatología en forma de dolor en punta terminal del coxis, empeorando habitualmente al sentarse. Aunque la causa más frecuente es la postraumática local, existen diversas causas de dolor en el coxis. Presentamos un caso inhabitual en el que la coccigodinia comenzó poco después de instaurar un sistema de anticoncepción por anillo vaginal y remitió completamente al retirar este sistema (AU)

Coccydynia is a syndrome that rheumatologists encounter frequently in the form of tailbone pain, which is usually worse when sitting. Although the most common origin is trauma, there are several other possible causes of pain in the coccyx. We present an unusual case in which coccydynia developed shortly after the insertion of a contraceptive vaginal ring and remitted completely upon removal of this system (AU)

Coccydynia related to the use of a contraceptive vaginal ring. / Coccigodinia relacionada con uso de anillo vaginal anticonceptivo.

Coccydynia is a syndrome that rheumatologists encounter frequently in the form of tailbone pain, which is usually worse when sitting. Although the most common origin is trauma, there are several other possible causes of pain in the coccyx. We present an unusual case in which coccydynia developed shortly after the insertion of a contraceptive vaginal ring and remitted completely upon removal of this system.

Integrating virtual reality with activity management for the treatment of fibromyalgia: acceptability and preliminary efficacy.

OBJECTIVES: Cognitive-behavioral therapies (CBT) for fibromyalgia syndrome (FMS) are important interventions in the management of this condition. Empirical evidence reports that although the results are promising, further research is needed to respond more appropriately to these patients. This study focuses on exploring the use of Virtual Reality (VR) as an adjunct to the activity management component. The aim of this study is to present the results of a small-sized randomized controlled trial to test the preliminary efficacy and acceptability of this component. MATERIALS AND METHODS: The final sample was composed of 61 women diagnosed with FMS according to the American College of Rheumatology. The sample was randomly allocated to 2 conditions: VR treatment and treatment as usual. RESULTS: Participants in the VR condition achieved significant improvements in the primary outcome: disability measured with the FIQ. The improvement was also significant in secondary outcomes, such as perceived quality of life and some of the coping strategies included in the Chronic Pain Coping Inventory: task persistence and exercise. There were no differences in other secondary outcome measures like pain intensity and interference and depression. Participants reported high satisfaction with the VR component. DISCUSSION: The effects were related to the psychological aspects targeted in the treatment. The component was well accepted by FMS patients referred from a public hospital. These findings show that the VR component could be useful in the CBT treatment of FMS and encourage us to continue exploring the use of integrating VR with CBT interventions for the treatment of FMS.

Improved prediction of knee osteoarthritis progression by genetic polymorphisms: the Arthrotest Study.

OBJECTIVE: The aim of this study was to develop a genetic prognostic tool to predict radiographic progression towards severe disease in primary knee OA (KOA) patients. METHODS: This investigation was a cross-sectional, retrospective, multicentric association study in 595 Spanish KOA patients. Caucasian patients aged ≥40 years at the time of diagnosis of primary KOA of Kellgren-Lawrence grade 2 or 3 were included. Patients who progressed to Kellgren-Lawrence score 4 or who were referred for total knee replacement within 8 years after diagnosis were classified as progressors to severe disease. Clinical variables of the initial stages of the disease (gender, BMI, age at diagnosis, OA in the contralateral knee, and OA in other joints) were registered as potential predictors. Single nucleotide polymorphisms and clinical variables with an association of P < 0.05 were included in the multivariate analysis using forward logistic regression. RESULTS: A total of 23 single nucleotide polymorphisms and the time of primary KOA diagnosis were significantly associated with KOA severe progression in the exploratory cohort (n = 220; P < 0.05). The predictive accuracy of the clinical variables was limited: area under the curve (AUC) = 0.66. When genetic variables were added to the clinical model (full model), the prediction of KOA progression was significantly improved (AUC = 0.82). Combining only genetic variables (rs2073508, rs10845493, rs2206593, rs10519263, rs874692, rs7342880, rs780094 and rs12009), a predictive model with good accuracy was also obtained (AUC = 0.78). The predictive ability for KOA progression of the full model was confirmed on the replication cohort (two-sample Z-test; n = 62; P = 0.190). CONCLUSION: An accurate prognostic tool to predict primary KOA progression has been developed based on genetic and clinical information from OA patients.

Virtual reality in the treatment of fibromyalgia: a pilot study.

The aim of this article is to present preliminary data on the effectiveness of virtual reality (VR) as an adjunct to cognitive behavioral therapy (CBT) in the treatment of fibromyalgia (FM). The sample comprised six women diagnosed with FM according to the American College of Rheumatology guidelines (1990). The treatment program consisted of 10 sessions of group CBT with the support of an adaptive virtual environment containing a specific content for developing relaxation and mindfulness skills. Patients were assessed at pretreatment, post-treatment, and at a 6-month follow-up for the following outcome variables: functional status related to pain, depression, a negative and positive affect, and coping skills. The results showed the long-term benefits of significantly reduced pain and depression and an increased positive affect and use of healthy coping strategies. This is the first study showing a preliminary utility of VR in treating FM.

Development and validation of a new disease activity index as a numerical sum of four variables in patients with early arthritis.

OBJECTIVE: To describe the development and validation of a disease activity index in early arthritis that can be easily applied in daily practice and clinical research. METHODS: The Hospital Universitario La Princesa Index (HUPI) was developed after analysis of data from an early arthritis cohort (202 patients with 756 visits). It is the sum of 4 variables (graded 0-3): tender joint count, swollen joint count, patient global assessment, and acute-phase reactants (erythrocyte sedimentation rate [ESR] and/or C-reactive protein [CRP] level, depending on availability at the moment of evaluation). The score for each variable was based on its quartile distribution in the cohort. The HUPI was validated using the following properties: feasibility, internal consistency (Cronbach's alpha), convergent validity (Pearson's r coefficients with other activity measures), criterion validity (area under the receiver operating characteristic curve [AUC ROC] to detect minimal disease activity [MDA]), and sensitivity to change (AUC ROC) to detect change with the physician's and patient's assessment of disease activity. RESULTS: Internal consistency is reasonable (α = 0.63). The HUPI correlates well with activity measures such as the Disease Activity Score in 28 joints (DAS28; r = 0.89) and the Simplified Disease Activity Index (SDAI; r = 0.70), and correlates slightly worse with the functional index of the Health Assessment Questionnaire (r = 0.69). It discriminates MDA correctly (AUC 0.95), and its sensitivity to change is slightly superior (AUC 0.902) to that of the DAS28-ESR (AUC 0.864), the DAS28-CRP (AUC 0.889), and the SDAI (AUC 0.791). CONCLUSION: The HUPI has face validity, is easy to calculate, is sensitive, and is a valid composite index for the assessment of disease activity in patients with early arthritis, both in clinical research and in routine care.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA study.

INTRODUCTION: Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. METHODS: The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. RESULTS: At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. CONCLUSIONS: Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

Remission and rheumatoid arthritis: data on patients receiving usual care in twenty-four countries.

OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >or=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study.

INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. RESULTS: Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries. CONCLUSION: In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.

Value of Disease Activity Score 28 (DAS28) and DAS28-3 compared to American College of Rheumatology-defined remission in rheumatoid arthritis.

OBJECTIVE: To assess the criteria for remission based on Disease Activity Score 28 (DAS28) and DAS28-3 (excluding patients' evaluation of disease activity) compared to American College of Rheumatology (ACR) preliminary criteria in established rheumatoid arthritis (RA), and to examine the value of each ACR criterion individually. METHODS: The EMECAR study was designed to assess the burden of comorbidity and inflammatory activity for RA in Spain. A random sample of 788 patients with RA from 34 Spanish centers was selected. Remission was defined by preliminary ACR criteria applied specifically and the clinical activity assessed by the DAS28 and the DAS28-3. A receiver operating characteristics curve analysis was performed to identify cutoff values with the highest usefulness in defining remission on both DAS indices. RESULTS: Thirty-two patients (4.1%) were in ACR-defined remission, 62 (7.9%) if fatigue was excluded from the criteria. The frequency of any single criterion that patients in remission fulfilled: no fatigue and joint pain by anamnesis in 31 patients (96.9%); morning stiffness < 15 min in 26 (81.3%); no swelling in joints in 21 (65.6%); normal erythrocyte sedimentation rate (ESR) in 29 (90.6%); and no joint tenderness in 21 (65.6%) patients. The positive predictive value for remission of each criterion: normal ESR 6.5%; morning stiffness < 15 min 8.4%; no fatigue 8.7%; no joint tenderness 13%; no swelling in joints 15.8%; and no joint pain by anamnesis 27.7%. The DAS28 cutoff values with higher discriminatory power for remission were 3.14 (sensitivity 87%; specificity 67%) when all the ACR criteria were used, and 2.81 (sensitivity 84%; specificity 81%) when fatigue was omitted. The equivalent cutoffs for the DAS28-3 were 3.52 (sensitivity 84%; specificity 66%) and 2.95 (sensitivity 82%; specificity 83%), respectively. CONCLUSION: DAS28 and DAS28-3 are good tools to define remission in established RA. No joint pain by anamnesis is the criterion with the highest value in defining remission, while normal ESR, an absence of morning stiffness, and fatigue are the least effective.

Hand bone segmentation in radioabsorptiometry images for computerised bone mass assessment.

From hand radiographs, the measurement of the bone density of hand bones is automatically performed, using units relative to an aluminium wedge, in order to know the absorption of the ray light intensity respect to a known substance. By means of a point distribution model, the variation modes of a statistical model of the phalanx are determined, and the boundaries of such bones localised, aiming to obtain their average grey level. The goal is to obtain an accurate and reliable computerised radiographic X-ray absorptiometry system for automatic bone mass assessment that can be easily applied to the population. The developed system has been tested and compared to other known methods with a high level of correlation.

Increased risk of tuberculosis in patients with rheumatoid arthritis.

OBJECTIVE: To quantify the risk of tuberculosis (TB) in an unselected sample of patients with rheumatoid arthritis (RA) compared to the risk in the general population. METHODS: The incidence of TB in the general population of Spain was obtained from the National Network of Epidemiological Surveillance reports. The incidence of TB was ascertained from a cohort of 788 patients with RA selected randomly from the registries of 34 participating centers throughout Spain. A patient was considered a TB case only if information about disease symptoms, microorganism identification, and TB treatment were confirmed in the clinical records. The relative risk of TB in RA was calculated by dividing the standardized mean incidence of TB from 1990 to 2000 in the RA cohort by the mean incidence of TB in Spain during the same years. RESULTS: The mean incidence of TB in the general population of Spain from 1990 to 2000 was 23 cases per 100,000. Seven cases of TB were identified in the RA cohort, yielding a mean annual incidence (1990-2000) of 134/100,000 patients. The incidence risk ratio of pulmonary TB in patients with RA compared to the general population is 3.68 (95% CI 2.36-5.92). CONCLUSION: We found a 4-fold increased risk of TB infection in patients diagnosed with RA. These results might help to interpret the magnitude of the problem attributable to the introduction of new therapies in RA.

Patterns of disease modifying antirheumatic drug use in a Spanish cohort of patients with rheumatoid arthritis.

OBJECTIVE: To determine the adequacy of disease modifying antirheumatic drug (DMARD) prescription to disease activity in patients with rheumatoid arthritis (RA) and to assess whether the reasons for DMARD discontinuation agree with published evidence. METHODS: Cross-sectional analysis of the baseline year of a RA cohort (n = 788) randomly selected from the clinical registries of 34 centers. Data about current and previous DMARD use was collected from medical records and confirmed by the patient. Disease activity score (DAS), Health Assessment Questionnaire (HAQ) and Larsen scores, and other clinical data were obtained during the study visit. RESULTS: At baseline visit, 607 patients (77%) were receiving one or more DMARD. Mean DAS, HAQ, and Larsen scores (+/- SD) were: 3.40 +/- 1.22, 1.6 +/- 0.4, and 54.68 +/- 26.37, respectively. Methotrexate (MTX) was the most frequently prescribed DMARD and parenteral gold salts (GS) showed the highest rate of discontinuation. MTX was used as single therapy in a significantly higher proportion (64.3%) than other DMARD (< 50%) and treatment discontinuation due to inefficacy was significantly less frequent (25.5%) than with other DMARD (> 40%). However, the DAS28 was significantly worse in the group treated with MTX in single therapy than in the group treated with GS alone (4.13 vs 3.43; p = 0.032). CONCLUSION: Despite the high use of DMARD among Spanish patients with RA, a significant number of them still have poor control of the disease. In addition, our data show a different perception of ineffectiveness depending on the DMARD used. A non-systematic use of objective quantitative tools for assessment of RA activity and some non-evidence based decisions on the management of DMARD may account for these findings.