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Background To assess mortality rate (MR) and standardized mortality rate (SMR) of rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients and to evaluate the role of radiographic patterns in mortality. Methods A longitudinal multicentric study was conducted in RA-ILD patients from 2005 to 2015 and followed-up until October 2018 in Madrid. Patients were included in the Neumologia-Reumatología y Enfermedades Autoinmunes Registry, from diagnosis of ILD. The main outcome was all-cause mortality. The radiographic pattern at baseline [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), or others] was the independent variable. Covariables included sociodemographic and clinical data. Survival techniques were used to estimate MR, expressed per 1000 persons-year with their 95% confidence intervals [CI]. Cox multiple regression model was run to examine the influence of radiographic patterns on survival. SMR [CI] was calculated comparing MR obtained with MR expected in the general population of Madrid by indirect age-gender standardization. Results 47 patients were included with a follow-up 242 patients-year. There were 16 (34%) deaths, and most frequent causes were acute ILD exacerbation and pneumonia. MR was 64.3 [39.4–104.9], and 50% of the patients died at 8.3 years from ILD diagnosis. After adjusting for confounders, (UIP compared to NSIP was associated with higher mortality risk. The overall SMR was 2.57 [1.4–4.17]. Women of 60–75 years of age were the group with the highest SMR. Conclusions RA-ILD is associated with an excess of mortality compared to general population. Our results support that UIP increases the risk of mortality in RA-ILD, regardless other factors.

ObjectivesTo describe patients with autoimmune inflammatory rheumatic diseases (AIRD) who had COVID-19 disease; to compare patients who required hospital admission with those who did not and assess risk factors for hospital admission related to COVID-19.MethodsAn observational longitudinal study was conducted during the pandemic peak of severe acute respiratory syndrome coronavirus 2 (1 March 2020 to 24 April). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid, Spain with a medical diagnosis of AIRD and with symptomatic COVID-19 were included. The main outcome was hospital admission related to COVID-19. The covariates were sociodemographic, clinical and treatments. We ran a multivariable logistic regression model to assess risk factors for the hospital admission.ResultsThe study population included 123 patients with AIRD and COVID-19. Of these, 54 patients required hospital admission related to COVID-19. The mean age on admission was 69.7 (15.7) years, and the median time from onset of symptoms to hospital admission was 5 (3–10) days. The median length of stay was 9 (6–14) days. A total of 12 patients died (22%) during admission. Compared with outpatients, the factors independently associated with hospital admission were older age (OR: 1.08; p=0.00) and autoimmune systemic condition (vs chronic inflammatory arthritis) (OR: 3.55; p=0.01). No statistically significant findings for exposure to disease-modifying antirheumatic drugs were found in the final model.ConclusionOur results suggest that age and having a systemic autoimmune condition increased the risk of hospital admission, whereas disease-modifying antirheumatic drugs were not associated with hospital admission.

Background This study aimed to assess the baseline characteristics and clinical outcomes of coronavirus disease 2019 (COVID-19) in pediatric patients with rheumatic and musculoskeletal diseases (RMD) and identify the risk factors associated with symptomatic or severe disease defined as hospital admission, intensive care admission or death. Methods An observational longitudinal study was conducted during the first year of the SARS-CoV-2 pandemic (March 2020–March 2021). All pediatric patients attended at the rheumatology outpatient clinics of six tertiary referral hospitals in Madrid, Spain, with a diagnosis of RMD and COVID-19 were included. Main outcomes were symptomatic disease and hospital admission. The covariates were sociodemographic and clinical characteristics and treatment regimens. We ran a multivariable logistic regression model to assess associated factors for outcomes. Results The study population included 77 pediatric patients. Mean age was 11.88 (4.04) years Of these, 30 patients (38.96%) were asymptomatic, 41 (53.25%) had a mild-moderate COVID-19 and 6 patients (7.79%) required hospital admission. The median length of hospital admission was 5 (2–20) days, one patient required intensive care and there were no deaths. Previous comorbidities increased the risk for symptomatic disease and hospital admission. Compared with outpatients, the factor independently associated with hospital admission was previous use of glucocorticoids (OR 3.51; p = 0.00). No statistically significant risk factors for symptomatic COVID-19 were found in the final model. Conclusion No differences in COVID-19 outcomes according to childhood-onset rheumatic disease types were found. Results suggest that associated comorbidities and treatment with glucocorticoids increase the risk of hospital admission.

We developed and independently validated a rheumatoid arthritis (RA) mortality prediction model using the machine learning method Random Survival Forests (RSF). Two independent cohorts from Madrid (Spain) were used: the Hospital Clínico San Carlos RA Cohort (HCSC-RAC; training; 1,461 patients), and the Hospital Universitario de La Princesa Early Arthritis Register Longitudinal study (PEARL; validation; 280 patients). Demographic and clinical-related variables collected during the first two years after disease diagnosis were used. 148 and 21 patients from HCSC-RAC and PEARL died during a median follow-up time of 4.3 and 5.0 years, respectively. Age at diagnosis, median erythrocyte sedimentation rate, and number of hospital admissions showed the higher predictive capacity. Prediction errors in the training and validation cohorts were 0.187 and 0.233, respectively. A survival tree identified five mortality risk groups using the predicted ensemble mortality. After 1 and 7 years of follow-up, time-dependent specificity and sensitivity in the validation cohort were 0.79–0.80 and 0.43–0.48, respectively, using the cut-off value dividing the two lower risk categories. Calibration curves showed overestimation of the mortality risk in the validation cohort. In conclusion, we were able to develop a clinical prediction model for RA mortality using RSF, providing evidence for further work on external validation.

Chronic pain is a complex experience that has now become a major public health issue. This has prompted many researchers to study attention, understanding it to be a crucial factor that allows altering the experience of pain, while attributing considerable importance to sustained attention. Accordingly, the main studies in this field stress the importance of emotion regulation processes and emotions on the perception of painful stimuli and attentional processes themselves. Nevertheless, only a handful of studies have been found that directly study the relationship between these variables. Within this context, this article sets out to analyse emotional regulation processes, emotional variables (depression and anxiety), the experience of pain, and age on the ability to maintain the vigilance response in a sample of patients with chronic pain. This involved selecting a sample of 49 patients with rheumatoid arthritis and examining their performance in an ad-hoc sustained attention test. With a view to complying with the study’s main purpose, the participants were also assessed through the use of the following self-report measures: the Beck Depression Inventory (BDI-I); the Hospital Anxiety and Depression Scale (HADS); the McGill Pain Questionnaire, and the Difficulties in Emotion Regulation Scale (DERS). Linear regression analyses revealed a significant impact of the aging process on the performance times in the attention task. Likewise, age and depression recorded a significant correlation with the mistakes made during the task. These results suggest that higher depression levels and an older age might be related to a worse adaptation to pain management techniques based on attention processes, such as mindfulness.

Individualized treatment of rheumatoid arthritis (RA) based on genetic/serologic factors is increasingly accepted. Moreover, patients are more actively involved in the management of their disease. However, personality has received little attention with respect to perception of the need and adherence to treatment. Our objective was to evaluate whether patient personality was associated with the acceptance or rejection of more aggressive early treatment. We performed a cross-sectional study in two hospitals with early arthritis clinics where sociodemographic, clinical, and therapeutic variables are systematically recorded. Patients completed Eysenck Personality Questionnaire, Multidimensional Health Locus of Control, Pain-Related Self-Statement Scale and Pain-Related Control Scale. Aggressive treatment was considered if patients received more than two DMARDs or biological agents during the first year of follow-up. Multivariate logistic regression analysis was performed to determine predictors of aggressive treatment. One hundred seventy-six RA patients were included (80 % women, disease begin median age 55 years). Treatment was considered aggressive in 57.9 % of the sample. Scores were high in extraversion in 50.8 % of patients, neuroticism in 29.5 % and psychoticism in 14.7 %. Neuroticism was the only factor associated with aggressive treatment, which was less probable (p = 0.04, OR = 0.40). Neuroticism also decreased the possibility of receiving a combination of biologics and DMARDs (p = 0.04, OR = 0.28). Patients with high scores on neuroticism are more worried, obsessive and hypochondriac, leading them to reject more aggressive therapy. It is important to educate about their disease so that they will accept more aggressive approaches in clear cases of poor outcome.

The study aims to analyze the association between the bone and cartilage/periarticular components of the radiographic joint damage and disability over the course of disease, in a cohort of rheumatoid arthritis (RA) patients from a day-to-day clinical practice. The secondary aim is to study the role of demographic and disease-related variables in this association. We performed a retrospective longitudinal study including 736 RA patients. Disability was assessed with the health assessment questionnaire (HAQ), and radiographic joint damage of hands and wrists with the Sharp van-der-Heijde score (total (SHS), erosion (ES), and narrowing/(sub)luxation (NSLS) components]. Generalized estimating equations models, adjusted by disease activity, demographic and disease-related variables, were used to test the relationship between SHS and medium-term (median value of the HAQs performed in the following year after each radiograph) and long-term (set of HAQ measures performed during follow-up, at least 1 year apart from the first x-ray) disability. Interaction terms between the SHS and demographic and disease-related variables were introduced in the models. To account for multiple testing, Bonferroni correction was applied. NSLS was independently associated with medium-term disability, even after Bonferroni correction. We observed significant and positive interactions between NSLS and age at x-ray, and with the ES. SHS showed no association with long-term disability. The cartilage/soft tissue component of the radiographic joint damage seems to exert a much more important role in medium-term disability than the erosive component. This association could be modulated by the age at the x-ray and by the magnitude of the erosive damage.

Objective The aim of this study was to assess the reliability and validity of the Spanish version of the Rosser classification system for disease states in patients with musculoskeletal disorders. Methods Our study was based on a questionnaire validation design. Patients were attended at an outpatient rheumatology clinic at Hospital Clinico San Carlos, Madrid, Spain. The Rosser classification system was completed by the physician from the research team (PMQ) and by the patient (HMQ). Criterion standards: The EuroQol-5D for the HMQ and the physician global estimate (DOCGL) for the PMQ. Internal consistency reliability was assessed using Cronbach α. Test-retest reliability and interobserver reliability were analyzed using the intraclass correlation coefficient. The criterion validity between HMQ and EuroQol-5D and between PMQ and DOCGL was assessed using the Spearman correlation coefficient. Results The full analysis was based on 4 samples of patients (104 to 266 patients), most of whom were middle-aged women. For HMQ, Cronbach α was 0.70. Test-retest reproducibility was 0.7. With respect to criterion validity, significant correlations in the expected direction were observed. For PMQ, Cronbach α was 0.70, indicating excellent intraobserver and interobserver reliability. With respect to criterion validity, strong correlations were observed between the PMQ and the DOCGL. Conclusions The Rosser classification system showed satisfactory reliability and suitable criterion validity for patients with musculoskeletal disorders. The instrument seems to be suitable for clinical decision making and research.

To assess the incidence and the risk of relapses in giant cell arteritis (GCA) patients treated with and without methotrexate (MTX) in clinical practice. Other associated factors were also investigated.An inception cohort of GCA was assembled in the out-patient clinic at Hospital Clínico San Carlos, including patients from the date of diagnosis (Jan-1991 until Sept-2013), and followed-up until lost of follow up or Sept-2014.relapse defined as recurrence of symptoms or signs of GCA with high ESR and the need to increase glucocorticoids at least 10mg over the previous dose. The independent variable was exposure to MTX over time. Covariables: Sociodemographic, clinical, and treatment. Incidence rates of relapses (IR) per 100 patient-year with their 95% confidence intervals [CI] were estimated using survival techniques. MTX influence on relapses was analysed by Cox models.168 patients were included (675 patient-year). 31% of patients had relapses (IR of 12 [9.6-14.9]), and the median number of relapses was 1[1-2]. 65% of the patients were on MTX, (mean dose: 10mg). In the bivariate analysis, the risk of relapses in patients with and without MTX did not achieve statistical signification (p=0.1). After adjusting in the multivariate analysis, exposure to MTX had 72% less risk of relapse compared to those without MTX (p0.05). Other variables included in the final model were: visual alterations and malaise at clinical presentation of GCA.The use of MTX seems to decrease the risk of recurrences. We also found other factors influencing on relapses.

Objective To assess European pediatric rheumatology providers’ current clinical practices and resources used in the transition from child-centered to adult-oriented care. Methods European pediatric rheumatologists were invited to complete a 17-item anonymized e-survey assessing current transition practices, transition policy awareness, and needs in advance of the publication of EULAR/PReS recommendations on transition. Results The response rate was 121/276 (44%), including responses from 115 centers in 22 European Union countries. Although 32/121 (26%) responded that their centers did not offer transition services, the majority (99%) agreed that a formalized process in transitioning patients to adult care is necessary. A minority (

Objective.To analyze sociodemographic and clinic-related factors associated with the use of orthopedic surgical procedures in rheumatoid arthritis (RA), focusing on the potential role of new biologic therapies.Methods.A retrospective medical record review was performed in a probability sample of 1272 patients with RA from 47 units distributed in 19 Spanish regions. Sociodemographic and clinical features, use of drugs, and arthritis-related joint surgeries were recorded following a standardized protocol.Results.A total of 94 patients (7.4%) underwent any orthopedic surgery during their disease course, with a total of 114 surgeries; 47 (41.2%) of these surgeries were total joint replacement (TJR). The median time to first orthopedic procedure was 7.9 years from the onset of RA symptoms, and the rate of orthopedic surgery (excluding TJR) was 4.5 procedures per 100 person-years from the beginning of RA, while the rate of TJR was 2.25 interventions per 100 person-years. A higher risk of undergoing an orthopedic surgical procedure was associated with taking nonsteroidal antiinflammatory drugs (NSAID) in the previous 2 years, female sex, longterm disease, and the presence of extraarticular complications. The risk factors for undergoing a TJR were being old, having a longterm disease, and taking biologic therapies.Conclusion.In the era of biologics, our national audit found a low percentage of patients who underwent orthopedic surgery, probably reflecting a thorough management of the RA. Sociodemographic factors, longterm RA, extraarticular complications, and NSAID were associated with orthopedic surgery.

The aims of this study were to describe the rate of leflunomide discontinuation in rheumatoid arthritis (RA) patients, in standard clinical practice, and to analyse which factors could influence this rate, paying particular attention to the concomitant treatment with other disease-modifying anti-rheumatic drugs (DMARDs).We selected RA patients, diagnosed according to the 1987 American College of Rheumatology (ACR) criteria, attending the rheumatology outpatient clinic of the San Carlos Clinical Hospital (Madrid, Spain), who had started treatment with leflunomide between 1 January 2006 and 1 January 2011. Clinical records were examined until withdrawal of the drug, loss of follow-up, or 1 October 2011. Kaplan-Meier curves were set to account for leflunomide withdrawal. Cox bivariate and multivariate regression models were conducted to examine risk factors for leflunomide discontinuation.The incident rate (IR) for leflunomide discontinuation, regardless of the cause, was 27 per 100 patient-years [95% confidence interval (CI) 22-31]. We observed, in both the bivariate and multivariate regression analysis, that those aged75 years at the start of the leflunomide treatment and undergoing concurrent treatment with methotrexate (MTX) and/or hydroxychloroquine (HC) had a significantly higher risk of leflunomide discontinuation.An older age at the start of the treatment with leflunomide, or concomitant treatment with MTX and/or HC, could be associated with a higher risk of leflunomide discontinuation, regardless of the cause. Therefore, when taking MTX or HC, patients receiving leflunomide should be closely monitored early to detect the occurrence of adverse reactions, and hence prevent their aggravation.

To evaluate a rheumatology outpatient consultation access system for new patients. New patients seen from April 2005 to April 2006 at our rheumatology clinic (n = 4,460) were included and classified according to their appointment type: ordinary appointments (OA) to be seen within 30 days, urgent appointments (UA) and work disability appointments (WDA) to be seen within 3 days. Age, sex, diagnosis, and health-related quality of life (HRQoL) as determined by the Rosser Index were recorded. Logistic regression models were run to identify factors that contribute to each type of appointment. OA was the method of access for 1,938 new patients, while 1,194 and 1,328 patients were seen through WDA and UA appointments, respectively. Younger male patients, and those with microcrystalline arthritis, sciatica, shoulder, back, or neck pain, were more likely to use the faster access systems (UA or WDA), whereas patients with a degenerative disease were mainly seen through OA (

Biological DMARDs are widely used in the treatment of rheumatoid arthritis (RA) but their relationship with adverse drug reaction (ADR) is important. RA is now known to increase in incidence and prevalence with age. Our objective was to assess the incidence of severe ADR in the long term, compare safety between the different bDMARDs and identify other possible risk factors for severe ADR in elderly RA patients.A 14-year retrospective longitudinal study was performed. RA patients followed in an out-patient clinic starting bDMARDs after the age of 65 were included.discontinuation due to a severe ADR related to bDMARDs (etanercept, infliximab, adalimumab, rituximab, golimumab, certolizumab, abatacept and tocilizumab). Covariables: sociodemographic, clinical and therapy. Incidence rates of discontinuation were estimated using survival techniques and comparison between bDMARDs discontinuation rates and other associated factors were run by Cox regression models.We analysed 286 courses of bDMARDs therapy in 146 elderly patients (604 patient-years). 78% were women, with a mean age at diagnosis of 66.5±7 years, and a median time to the start of the first bDMARDs of 6±4 years. The incidence of discontinuation due to severe ADR estimated was 10.2% patient-years, with a median survival of around 7 years. The most frequent cause was infections. Etanercept had the lowest risk of severe ADR compared to other bDMARDs.Our study reflects the 'real world' experience in elderly RA patients on bDMARDs, with non-selected patients for a 14-year follow-up.

To assess and compare the long-term drug survival (time to drug discontinuation) of biological agents (BA) in patients with rheumatoid arthritis (RA) in clinical practice. Factors associated with discontinuation of BAs were also investigated.We conducted an observational longitudinal study of RA patients taking BAs from 1999 to 2013. The primary endpoint was BA discontinuation due to: adverse drug reactions (ADRs), inefficacy, and other causes. Incidence rates of discontinuation (IRs) per 100 patient-years were estimated using survival techniques. Comparisons between BA discontinuation rates and other associated factors were made using Cox regression models.We included 851 courses of BA therapy (1869 patient-years). Adalimumab (33%) was the BA most frequently used, followed by etanercept (24.4%), infliximab, and rituximab. Treatment was suspended in 558 cases [IR 29.8, 95% confidence interval (CI) 27-32]. In the first year of therapy 68% continued on BAs, and after 10 years the retention rate did not exceed 10%. The IR due to inefficacy was 12.1 (95% CI 10.6-13.8) and the IR of ADRs was 13.6 (95% CI 12-15). The unadjusted IR was higher for rituximab than for tumour necrosis factor (TNF) antagonists. In multivariate analysis, infliximab was the BA with the highest risk of discontinuation, compared to adalimumab. Calendar period, taking subsequent courses of BAs, concomitant therapy, and specific comorbidities were also independent factors associated with discontinuation.After several years of BA treatment in clinical practice, the survival rate was low, mainly as a result of ADRs and inefficacy. We also found differences between the discontinuation rates of BAs and other clinical factors that modify their survival.

To analyze the resource utilization in rheumatoid arthritis (RA) patients and predictive factors in and patients treated with biological drugs and biologic-naïve.A cross-sectional study was performed in a sample including all regions and hospitals throughout the country. Sociodemographic data, disease activity parameters and treatment data were obtained. Resource utilization for two years of study was recorded and we made costs imputation. Correlation analyzes were performed on all RA patients and those treated with biological and biological naïve, to estimate the differences in resource utilization. Factors associated with increased resources utilization (costs) attending to treatment was analyzed by linear regression models.We included 1,095 RA patients, 26% male, mean age of 62±14 years. Mean of direct medical costs per patient was €24,291±€45,382. Excluding biological drugs, the average cost per patient was €3,742±€3,711. After adjustment, factors associated with direct medical costs for all RA patients were biologic drugs (P=.02) and disease activity (P=.004). In the biologic-naïve group, the predictor of direct medical costs was comorbidity (P.001). In the biologic treatment group predictors were follow-up length of the disease (P=.04), age (P=.02) and disease activity (P=.007).Our data show a remarkable economic impact of RA. It is important to identify and estimate the economic impact of the disease, compare data from other geographic samples and to develop improvement strategies to reduce these costs and increase the quality of care.

To assess the mortality rate (MR) and the mortality risk of a rheumatoid arthritis (RA) inception cohort, with and without biologic agents (BAs). Other factors associated to mortality were also investigated.Retrospective longitudinal study of RA patients, attending the rheumatology outpatient clinic of a tertiary Hospital (Madrid), collected over 5 years (2000-2004), and followed from the diagnosis of RA up to the patients' death, lost to follow-up or September 2013. The dependent variable was death and the independent variable was exposure to BAs. Covariables: sociodemographic, clinical and therapy variables. MR was expressed per 1,000 patient-years with the 95% confidence interval [CI]. BA influence on MR was analysed by multivariable Cox models. Clinical and therapy variables were used in a time-dependent manner. The results are expressed in hazard ratio (HR) and [CI].We included 576 patients and 711 courses of therapy. 19.6% were taking BA, 86% disease-modifying anti-rheumatic drugs (DMARDs) (70% on methotrexate - MTX), and 12% were untreated. There were 133 deaths during 4,981.64 patient-years at risk. The MR for BA was 12.6 [6-26], for DMARDs was 22.3 [18.4-27.1], and for those without treatment was 89.1 [61.9-128.2]. The adjusted HR for mortality in those exposed to BA versus those not exposed was 0.75 [0.32-1.71]). Other variables independently associated with mortality were: age, rheumatoid factor, hospital admissions, Health Assessment Questionnaire (HAQ), and MTX use (HR: 0.44 [0.29-0.66]).BAs and standard DMARDs are more effective in decreasing mortality compared to no therapy. Patients exposed to Bas were not associated with a significant increase or decrease in mortality when compared to patients with non-biological DMARDs. The use of MTX remains the only drug that has independently shown a beneficial effect on mortality.

The objective of this study is to identify risk factors for permanent work disability (PWD) related to musculoskeletal disorders (MSDs). This is a secondary data analysis of a randomized controlled intervention study in Temporary Work Disability (TWD) due to MSDs. The association of PWD (claim submission and status recognition) with baseline clinical, sociodemographic, work-related administrative and occupational factors was analyzed by Cox proportional hazards models. Of 3,311 patients with TWD, 47 submitted a PWD claim, of whom 32 achieved PWD status. The main alleged causes of the PWD were back pain, sciatica, and inflammatory diseases. The following factors were independently associated with an increased probability of PWD claim submission: age (odds ratio (OR) 5.1), being woman (OR 2.1), self-employment (OR 3.4), unemployment (OR 13.8), previous musculoskeletal surgery (OR 16), repeated TWD (OR 3.4), sitting (OR 2.8), and raising arms frequently (OR 3.1). Patients with inflammatory disease were more likely to file PWD claims (OR 10.4) while tendonitis was associated with lower probability (OR 0.3). The sociodemographic factors that better predicted PWD status recognition were age (OR 5.7), low educational level (OR 4.2), previous musculoskeletal surgery (OR 14.9), unemployment (OR 17.6), sitting (OR 2.6), and raising arms frequently (OR 2.7). Inflammatory diseases were the diagnoses associated with a higher rate of PWD status recognition (OR 6.1). Inflammatory diseases have a high chronic disability potential in active workers. Sociodemographic, work-related, occupational factors, and other clinical factors, some of which are modifiable, may explain the development of long-term work disability related to MSDs.

Objective To evaluate whether an early cognitive–behavioral treatment complementary to a rheumatologic care program, for patients with recent-onset temporary work disability caused by musculoskeletal disorders (MSDs) is effective. Methods Patients with an MSD-related temporary work disability episode from 3–8 weeks' duration who were in a rheumatologic care program were randomized into a control group (rheumatologic care program) or an intervention group (rheumatologic care program plus cognitive–behavioral treatment). Enrollment lasted 24 months and followup lasted 6–24 months. Efficacy variables included duration of temporary work disability episodes, total number of work days saved, relative efficacy, and relative rate to return to work. An economic evaluation was also performed. Results One hundred eighty-one patients were included (66 control and 115 intervention patients), generating 222 episodes of MSD-related temporary work disability. Episodes tended to be shorter in the intervention group than in the control group (mean 98 versus 127 days; P = 0.053), with a relative efficacy of 22.9%. There were no differences in duration of the first episode between groups (mean 105 versus 110 days; P = 0.79), but relapse episodes were significantly shorter in the intervention group (mean 63 days versus 197 days; P = 0.0002). Costs were also lower in the intervention group. To save 1 day of temporary work disability, $13.50 had to be invested in the program. Each dollar invested generated a benefit of $4.08. The program had a net benefit of $172,607. Conclusion Early cognitive–behavioral treatment complementary to a rheumatologic care program is cost-effective, adds >20% efficacy to the rheumatologic care program, and reduces the duration of relapses.

To describe and compare dosing optimisation in biological DMARDs (bDMARDs) and relapses after that, in a cohort of rheumatoid arthritis (RA) during clinical practice.Observational retrospective longitudinal study of RA patients taking bDMARDs from December 1999 to November 2013. Optimisation was defined as a 15% decrease in dose either reducing single dose or separating dose interval administration, for at least 4 times the recommended period between dosages. Relapse was defined as suspension or starting again with the recommended dose after optimisation. Incidence rates (IR) per 100 patient-years were estimated using survival techniques. Cox multivariate models were conducted to compare bDMARDs expressed in hazard ratios (HR) and confidence intervals [95%CI].443 patients and 752 different courses of bDMARDs treatments were included. We observed 146 optimisations with an IR of 8.1. The HR of optimisation in: a) adalimumab, etanercept and rituximab compared to infliximab was 1.56 [1.01-2.4], 1.5 [0.9-2.4] and 0.6 [0.3-1.4], respectively; b) adalimumab, etanercept compared to rituximab were 2.3 [1.2-4.5] and 2.2 [1.2-4.3]. There were no statistically significant differences between adalimumab and etanercept. Following optimisation, 36% relapsed (78% due to disease activity). The IR related to disease activity was 6.3, and was lower for adalimumab and etanercept compared to infliximab (HR: 0.42; [0.19-0.94]; HR: 0.34; [0.13-0.89], respectively). There were no statistically significant differences between etanercept and adalimumab. No patients on rituximab relapsed.Optimisation was similar between adalimumab and etanercept, and was lower for infliximab and rituximab. After optimisation, rituximab did not relapse, but infliximab did with the highest hazard.

Objectives To describe the mortality rate (MR) and standardized MR (SMR) of an incident cohort of rheumatoid arthritis (RA) patients followed up for 20 years, and to analyze the influence on morality risk of different demographic and clinical variables, including radiographic joint damage. Methods Retrospective longitudinal study that included 2271 RA patients attending the rheumatology outpatient clinic of the Hospital Clinico San Carlos (Madrid, Spain), enrolled from January 1994 to February 2013 and followed up from RA diagnosis to patients׳ death or September 2013. Disability and disease activity were measured as the averaged value of the Heath Assessment Questionnaire and the erythrocyte sedimentation rate, respectively, of the first 2 years after RA diagnosis. Radiographic joint damage of hands and wrists was assessed with the Sharp/van der Heijde score. Indirect SMRs with a 95% of confidence interval (95% CI) were calculated. Cox bivariate and multivariate regression models were performed to assess risk factors for death. Results A total of 431 patients died (19%) during the observation time (18,482 person-years), resulting in a MR of 23 subjects per 1000 patient-years [95% CI: 21–26]. SMR was 1.89 (1.72–2.08). In the multivariate analysis, men, older age at diagnosis, the presence of rheumatoid factor, higher number of hospital admissions, greater disease activity, and greater radiographic joint damage were independently associated with greater mortality risk. Conclusions RA patients have an excess mortality compared with the general population. Radiological joint damage and early disease activity are independent mortality risk factors. A tighter control at early stages may be necessary to reduce mortality.

Cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of anticancer agents; its overexpression was associated with resistance to docetaxel, a commonly used drug for second-line treatment of NSCLC. Several functional single nucleotide polymorphisms (SNPs) have been associated with CYP1B1 expression and activity. The objective of this study was to retrospectively evaluate the correlation of CYP1B1 SNPs with the outcome of NSCLC patients treated with docetaxel in second or third line.Associations between CYP1B1 4326CG and 4390AG polymorphisms with response, progression-free survival (PFS) and overall survival (OS) were estimated using Pearson χ(2) test, Kaplan-Meier curves and log-rank test; a multivariate analysis was performed using Cox proportional hazards modeling.A total of 65 advanced NSCLC patients were enrolled into the analysis. Median age was 66 years (range 46-81). Forty-nine patients were male; only five were never smokers. Performance status (PS) was 0 in 25 patients, 1 in 28 and 2 in 12. Histology was adenocarcinoma in 28 patients, squamous carcinoma in 22, other NSCLC in the remaining 15. At univariate analysis, stage and CYP1B1 4326CG SNPs are associated with PFS, while PS and CYP1B1 4326CG SNPs correlated with OS. In particular, patients with CYP1B1 4326-GG genotype had shorter PFS and OS than patients with other genotypes (PFS 1.80 vs. 2.70 months, p = 0.12; OS 3.63 vs. 9.83 months, p = 0.039). CYP1B1 4326CG SNPs were also associated with response rate. Multivariate analysis confirmed the independent prognostic/predictive role of CYP1B1 4326CG SNPs on OS (p = 0.042) with only a trend for PFS (p = 0.083).CYP1B1 4326CG polymorphism emerged as possible prognostic/predictive marker of activity and efficacy of docetaxel in NSCLC patients.

To evaluate the efficacy of a program for subacute physical disability due to musculoskeletal disorders (MSD) in the elderly. We carried out a randomized controlled evaluator-blinded intervention study in a health district (October 2005 to April 2008). Subjects older than 64, starting a subacute MSD episode of physical disability—defined as moderate disability or higher in the Rosser classification—and identified by general practitioners, were randomized into standard care or an early specific program. The program was carried out by rheumatologists following detailed proceedings. Efficacy was defined as the difference between groups in the duration of episodes—time from onset until an improvement larger than a point in the Rosser classification). Hazard ratios (HR) to recovery of the program over standard care were obtained from Cox regression analyses. One hundred and twenty-three patients were included, generating 244 episodes of subacute MSD. Mean duration of episodes was 5 months; 14.5 % of them were chronically disabled throughout follow-up. The program was associated with shorter duration of episodes compared with CG analyzing just the ended ones (p = 0.004). The HR to recovery between groups did not achieve statistical differences. Nevertheless, recovery rate at 12 months and HR from those with moderate physical disability at the inclusion period (Rosser disability level 4, n = 84) were superior in the IG (HR 1.9, p = 0.03; HR 1.93; p = 0.03 respectively). An early intervention program for subacute MSD-related disability in elderly has partial efficacy; the program benefited patients with moderate physical disability and after a year of follow-up.

Objective The aim of this study was to describe the incidence rate (IR) of adverse drug reactions (ADRs) in daily clinical practice, related to disease-modifying antirheumatic drugs (DMARDs) and biologic agents (BA) in rheumatoid arthritis (RA) patients, and to analyze factors causing discontinuation due to ADRs. Methods This was a prospective observational study (October 2010 to October 2011). RA patients who were attended in our hospital taking DMARDs or BA during the study period were included. ADRs were injuries related to these drugs and registered with a software system in routine visits. ADRs could be mild (lowering dosage), moderate (drug discontinuation), or severe (hospital admission). The IR of ADR per 100 patient-years was estimated using survival techniques. Cox regression models (HR; 95% confidence interval) were used to explore factors associated with discontinuation due to ADRs. Results In total, 1202 patients were analyzed, with 158 ADRs (IR = 15.2). Of all ADRs, 80.4% required drug discontinuation (IR = 12.2). Age, less disease and therapy duration, taking corticoids, and combined therapy versus monotherapy (HR = 3; 95% CI: 2.0–4.4) were the factors independently associated to discontinuation due to ADRs. We did not find statistical differences between the different monotherapy regimens. Regarding combinations, Methotrexate + BA had the lowest risk of discontinuation compared to the rest (HR = 0.24; 95% CI: 0.09–0.6). Conclusions We have estimated the incidence of ADRs related to DMARDs/BA in real-life conditions. We confirm the role of combined therapy in the development of discontinuations due to ADRs, except for BA + MTX, which did not show an increase of toxicity compared to monotherapy. This combination seems to be safer than others.

To estimate the incidence of musculoskeletal-related acute physical disability in the elderly (APDE).A primary care-based registry was established in Madrid's Health Area 7 from October 1, 2005 to September 31, 2006. We included all persons age ≥65 years, who were non-institutionalized and covered by the health cards assigned to the participating general practitioners (GPs). A case of APDE was defined as a moderate mobility alteration in the disability level within the Rosser's Classification System, in the last 3 months, related to a musculoskeletal cause. Incidence rates (IRs) were estimated per 10,000 person-years by direct standardization with a 95% confidence interval (95% CI).Eight primary care centers and 23 GPs participated in the registry, covering 8,546 elderly patients. In the inclusion year, the GPs identified 147 new APDE cases in 106 patients. The annual estimated incidence of APDE was 331 cases per 10,000 person-years (95% CI 280-389) and the IR of new patients with an APDE episode was 239 (95% CI 196-288); the IR was higher in women (344 cases; 95% CI 279.8-423.0) than in men (207 cases; 95% CI 127.0-338.2).The incidence estimate of acute physical disability related to musculoskeletal disorders in the elderly should help us to determine the magnitude of this health problem, as well as the first step to establishing a specific practice for the recovery of cases and for the prevention of loss of functioning, mobility, and independence.

a b s t r a c t Objective: Patients with rheumatoid arthritis (RA) complain that weather conditions aggravate their symptoms. We investigated the short-term effects of weather conditions on worsening of RA and deter- mined possible seasonal fluctuations. Methods: We conducted a case-crossover study in Madrid, Spain. Daily cases of RA flares were collected from the emergency room of a tertiary level hospital between 2004 and 2007. Results: 245 RA patients who visited the emergency room 306 times due to RA related complaints as the main diagnostic reason were included in the study. Patients from 50 to 65 years old were 16% more likely to present a flare with lower mean temperatures. Conclusions: Our results support the belief that weather influences rheumatic pain in middle aged patients.

To assess the diagnostic correlation between primary care physicians and rheumatologists in patients with temporary work disability (TWD) related to musculoskeletal diseases (MSD). All patients with TWD related to MSDs in three health districts of Madrid, Spain, were randomized into standard care by primary care physicians (PCP) or the intervention group by rheumatologists. According to the cause, every TWD episode was classified into 11 syndrome categories. To examine the concordance between the rheumatologist and the referring PCP for each diagnosis, we used Kappa statistic (k) and 95% confidence interval (CI). A total of 3,311 (62.8%) were analyzed, 49.8% women, with a mean age of 41 years ± 12 years, 93.3% were general workers. The agreement between PCP and rheumatologists in all the diagnoses was moderated (k = 0.62). The highest agreement was found in tendonitis (k = 0.81, 95% CI 0.78–0.84), and microcrystalline and undifferentiated arthritis (k = 0.72, 95% CI 0.68–0.77). Lowest agreements were found for peripheral osteoarthritis (k = 0. 48 95% CI 0.38–0.57), knee pain (k = 0.40, 95% CI 0.29–0.52), and muscular pain (k = 0.15, 95% CI 0.10–0.20) Although the global agreement on the musculoskeletal diagnosis between PCPs and rheumatologist in patients with TWD related to MSDs was reasonable, the correlation for peripheral osteoarthritis, knee pain, and muscular pain was low.

The aim of this study was to evaluate the involvement of human endogenous retrovirus K18 (HERV-K18) in osteoarthritis (OA), by genotyping the HERV-K18 env locus in OA patients and controls, and analysing HERV-K18 RNA expression and its association with OA risk and clinical variables.We recruited 558 patients with symptomatic OA and 600 controls. We performed the genotyping by TaqMan assays and the analysis of expression by quantitative real-time polymerase chain reaction (qRT-PCR). Scores on the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), the Lequesne index, and the Stanford Health Assessment Questionnaire (HAQ) were analysed with regard to the expression levels of HERV-K18.The 18.3 haplotype tended towards an association with OA risk and concordantly this haplotype was associated with a higher HERV-K18 expression (p = 0.05). We found statistically significant differences when we compared the scores on the WOMAC, the Lequesne index for knee and hip, and the HAQ between OA patients with higher expression [normalization ratio (NR)10] and OA patients without HERV-K18 expression (p = 0.0003, 0.0005, 0.002, and 0.05, respectively), and also when the comparison was made between OA patients with higher expression (NR10) and OA patients with low expression of HERV-K18 (NR = 1) for the WOMAC and the Lequesne index for knee and hip (p = 0.002, 0.013, and 0.006, respectively).We found an association between health status measurement systems and severity index for OA and the levels of expression of HERV-K18. These results suggest the possible involvement of HERV-K18 in the aetiopathogenesis of the disease.