Mabel Sánchez-Barrioluengo

Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis.

To date, anti-tumor necrosis factor alfa (anti-TNF-α) therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of hepatitis B virus infection, congestive heart failure, demyelinating neurologic disorders, hematologic disorders like aplastic anemia and pancytopenia, vasculitis, immunogenicity, and exacerbation or induction of psoriasis are class effects of all the anti-TNF drugs, and have been seen in patients with ankylosing spondylitis. However, etanercept is less likely to induce reactivation of tuberculosis than the other anti-TNF drugs and it has been suggested that etanercept might be less immunogenic, especially in ankylosing spondylitis. Acute uveitis, Crohn’s disease, and sarcoidosis are other adverse events that have been rarely associated with etanercept therapy in patients with ankylosing spondylitis.

The pursuit of academic excellence and business engagement: is it irreconcilable?

Universities currently need to satisfy the demands of different audiences. In light of the increasing policy emphasis on “third mission” activities, universities are attempting to incorporate these into their traditional missions of teaching and research. University strategies to accomplishing its traditional missions are well-honed and routinized, but the incorporation of the third mission is posing important strategic and managerial challenges for universities. This study explores the relationship between university–business collaborations and academic excellence in order to examine the extent to which academic institutions can balance these objectives. Based on data from the UK Research Assessment Exercise 2001 at the level of the university department, we find no systematic positive or negative relationship between scientific excellence and engagement with industry. Across the disciplinary fields reported in the 2001 Research Assessment Exercise (i.e. engineering, hard sciences, biomedicine, social sciences and the humanities) the relationship between academic excellence and engagement with business is largely contingent on the institutional context of the university department. This paper adds to the growing body of literature on university engagement with business by examining this activity for the social sciences and the humanities. Our findings have important implications for the strategic management of university departments and for higher education policy related to measuring the performance of higher education research institutions.

‘Turning the tables’: regions shaping university performance

This paper straddles the systems of innovation and the economic geography theories that conceptualize universities as engines of regional development and drivers of growth. However, these approaches overlook the heterogeneity of universities in the process of engagement, assuming their equal capacity to contribute to their region. In the view proposed here, not only does the university influence the surrounding region, but also regional characteristics shape university performance. The paper puts into perspective differences between university profiles in Spain based on their strategies and performance, and the scale and scope of the capabilities to contribute to their regions.

Clinical usefulness of serum level of adalimumab, in patients with rheumatoid arthritis.

Objectives To analyze the clinical relevance, in clinical practice, of adalimumab (ADA) serum levels (SL) and anti-ADA antibodies (anti-ADA-Abs). 2. To evaluate if there is correlation between SL of ADA and result of DAS28. 3. To determine the minimum appropriate SL of ADA to keep the patients in remission or in low clinical activity. Methods Serum levels of ADA and anti-ADA-Abs (ELISA kit. Promonitor®-ADA. Proteomika, Derio. Vizcaya. Spain) were analyzed in patients with rheumatoid arthritis (RA) receiving ADA >6 months. Cut-off level for serum Abs anti-ADA was >32 U/mL and for serum level of ADA <0.004 mg/L. Clinical characteristics, clinical activity index (DAS in 28 joints), using ESR, were recorded. All the patients were receiving DMARD (methotrexate, leflunomide or hydroxychloroquine). Serum samples were collected before injection of ADA (same day), and stored frozen until analysis. Patients were considered on clinical remission if they had at the same time of extraction, DAS28≤2,6, and low clinical activity if DAS28 between 2,7-3,2. The patients was distributed in tertiles groups from serum levels of ADA: <2,8 mg/L; 2,9-7,3 mg/L; >7,3 mg/L. ROC curvewas used to select optimus cut-off level of ADA to keep the patients on remission or low activity level of disease. Finally, correlation between DAS28 and SL of ADA was evaluated. Results We included 63 determinations from 56 patients with RA. 75% were women; mean age: 62 years. The average time of evolution of RA was 156±122 months, and for the treatment of ADA 32,26±18,31months. ADA was the first anti-TNF received in 80% of patients. The distribution of DMARDs: methotrexate: 65% (mean dose: 15 mg), leflunomide: 21% (18 mg) and hydroxychloroquine: 14% (200 mg). In 4 (7%) patients anti-ADA Abs was detected; all in the group of SL of ADA <2,8 mg/L. We obtained a negative relation between SL of ADA and DAS28 (r: -0.46. CI 95%: -0.66,-0.21). The cut-off of SL of ADA in ROC curves was, for DAS28≤2,6: 3,01 (AUC: 65,77%; sensitivity: 50% y specificity: 77,77%); for DAS28 2,7-3,2: 3,48 (AUC: 83,18%; sensitivity: 83,33% y specificity: 77,80%). Table show the relation of SL of ADA anti-ADA Abs and DAS28-ESR, according ADA tertiles. Conclusions The cut-off of ROC curve for serum level of ADA, to keep the patients in low activity of disease is 3,45 mg/L. 2. There is a negative correlation between the serum level of ADA and DAS28. 3. Serum level of ADA >7,3 mg/L does not increase the improvement of DAS28. In these patients, we can consider to decrease the ADA dose or its delay. 4. The prevalence of anti-ADA Abs in patients with RA treated with ADA and DMARD is 7%. Disclosure of Interest None Declared

Duración del tratamiento con etanercept y razones de discontinuación en una cohorte de pacientes con patología reumática

OBJECTIVE To evaluate the duration of etanercept (ETN) treatment and motives for discontinuation in our local cohort of patients with rheumatic pathology and compare them to the group with other biological treatments. PATIENTS AND METHODS Prospective observational cohort study. Disease diagnosis, start and end date and motive for discontinuation were recorded. Survival estimation was explored using Kaplan-Meier analysis with remaining patients censored at 1-year, 2-years and 5-years follow-up. RESULTS Ninety-two (45%) out of 205 patients started ETN treatment. Disease diagnoses recorded were: 48% rheumatoid arthritis, 33% ankylosing spondylitis, 11% psoriatic arthritis, 8% others (juvenile idiopathic arthritis, inflammatory bowel disease related spondylitis, SAPHO syndrome). 52% of patients are still on the drug. The motives for discontinuation were: inefficacy (65%), adverse events (33%) and lack of compliance (2%). Two patients discontinued ETN due to prolonged disease control. Adverse events were: infection (4 patients), post-injection skin reaction (3), uveitis (3), neoplasia (2) and others (3). Using a Kaplan-Meier analysis, at 1-year 64% (CI(95%) 54-74) of patients with ETN treatment had not experienced treatment failure, at 2-years, 59% (48-69) and at 5-years, 43% (30-52). With the rest of biologicals estimated survival was 61% (51-68), 47,5% (40-55) and 23% (10,5-32) respectively. Statistical analysis revealed significant differences (log-rank: P=.024; Breslow: P=.068; Tarone-Ware: P=.040). CONCLUSIONS In our cohort of patients treated with ETN the estimated survival was better than patients treated with other biological drugs at 1-year, 2-years and 5-years.

Análisis de los Mecanismos de Transferencia Tecnológica entre los Sectores Científico-tecnológico y Productivo de Argentina

El objetivo de este articulo es analizar el comportamiento de las estructuras de gestion que, en la Argentina, actuan como interfaz en la relacion entre los sectores cientifico-tecnologicos y los productivos. Estas estructuras son denominadas “Oficinas de Vinculacion Tecnologica y Transferencia”. En ese sentido, se presentan los resultados obtenidos a partir del analisis cuantitativo de los distintos mecanismos de gestion de la interaccion entre ambos sectores. A partir del procesamiento estadistico de informacion de base, se obtuvieron resultados que permitieron definir y categorizar distintas variables relacionadas con las caracteristicas de estas oficinas y de los sectores de la demanda. El analisis de la relacion entre estas variables, permitio obtener informacion de base a partir de la cual se realizan inferencias acerca del comportamiento general sobre la generacion y gestion de los mecanismos que regulan su relacion con los sectores cientifico-tecnologicos y los productivos en la Republica Argentina.

Motives for international cooperation on R&D and innovation: Empirical evidence from Argentinean and Spanish firms

This paper focuses on the strategic motives and firm characteristics that influence cooperation for R&D and innovation among Argentinean and Spanish firms. On the basis of a review of different theoretical perspectives we propose and apply a taxonomy of motives for inter-firm technological cooperation. We combined quantitative and qualitative methodologies, developing a database of 540 innovative firms and conducting a survey that obtained evidence from 104 of these firms, supplemented by information gathered from 19 in-depth interviews. Our results show that technological cooperation is not easy to achieve and determined by a complex interplay of intentions and practical opportunities. The lack of convergence in the motives for cooperation creates un-favourable conditions and affects negatively the initiation of the cooperation processes. These differences together with asymmetries in access to funding are important obstacles to cooperation with implications in the administration of national policy incentives and its regulation mechanisms.

Risk factors for osteoporosis from a rheumatology bone densitometry registry.

Background Osteoporosis (OP) affects 8% of Spanish women, reaching to 23% when they are over 65 years old1,2. The analysis of risk factors (RF) has high importance for the evaluation of patients with suspected OP. Objectives To evaluate risk factors pattern for OP through the combination of those factors which increment more noteworthy its risk in postmenopausal women. Methods We conducted a cross-sectional study with 3,049 postmenopausal women. They were sent for DXA at the lumbar spine (LS) to our Bone Densitometry of Rheumatology Unit, between 2010 and 2012. We include epidemiological characteristics (age, gender), RF for OP, location of fracture for adults, diseases and drugs that cause bone loss. We used an ordinal logistic regression to calculate Odds Ratios (ORs) and CI95% for RF combinations, adjusted by: BMI, tobacco, alcohol, hip fracture on her mother, diagnoses and treatment. Results In 42.9% of patients had osteopenia and in 25.6%, OP. Age average is 63.08±0.34 years old (median 62, rank 32-93). Descriptive statistics about RF show: 30.3% has BMI<25 or underweight (UW); 25% premature menopause (PM); and 31% previous fracture, among which osteoporotic one is the most common (19.8%). Between diseases that cause bone loss, 6.1% had any kind of chronic arthritis (rheumatoid arthritis, spondyloarthropathies or SLE) or collagenopathies (polymyalgia rheumatica, temporal arteritis, dermatomyositis), and 22.4% some other non-rheumatic disease. In women with 55 or less years old (23.3%), only the combination between UW and OP previous fracture is a pattern of risk; OR: 2.17 (1.01-4.67). In women between 56-65 years old (35.1%), UW, PM or osteoporotic previous fracture (OPfx) implies a risk increment between 51% and 96%. The combination of two of these RF raises the OP risk from two to three times: OR UW+PM: 3.12 (1.84-5.27); PM+OPfx: 2.74 (1.33-5.65); UW+OPfx: 2.30 (1.32-4.02). If a disease that cause bone lost is added, the baseline risk increase between 53% and 64%: OR 2.49 (1.31-4.76). In women over 65 years (35.8%), to be underweight and to have a non-rheumatic disease increase the risk in 91%. The OR for the combination of UW+PM+fracture non-osteoporotic was 2.93 (1.36-6.31), and between UW+PM+OPfx: 2.64 (1.41-4.95) Independently from the age, PM implies a risk from 1.52 when it combines with a non-osteoporotic previous fracture to 1.86, when it is combined with a UW. However, previous fracture plus a disease that cause bone loss raise the OP risk around 70%. To be UW joined other RF leads to the highest risks. Conclusions Analysis of RF for OP is useful to guide the disease risk. 2. Women underweight combined with other RF result in the highest OP risks. 3. The presence of two isolated RF increases the OP risk in 65% on average. 4. Three RF joined implies a risk average of 2.35, reaching 3.12 in women between 56-65 years old who are underweight and had premature menopause. References INE. INEBASE: Encuesta Nacional de Salud. Tablas nacionales, 2006. Instituto de Mayores y Servicios Sociales (IMSERSO). Informe 2008. Las personas mayores en España. Datos estadísticos estatales y por CC.AA. Disclosure of Interest None Declared

Comparative study of both versions of an immunoassay commercialized for therapeutic drug monitoring of adalimumab.

Background Adalimumab (ADA) is commonly used in rheumatic diseases. Some patients do not respond or present a loss of response in the time. Till now, the decision in these cases was based only on the clinical evolution of the patient. For two years it is commercialized in Spain an enzyme linked immunosorbent assay (ELISA) for quantification of the free serum concentration of ADA, and of antibodies anti-adalimumab (Ac anti-ADA). Recently the manufacturer (Promonitor, Proteomika S.L., distributed by Menarini Diagnóstics S.A.) has thrown a new version of this ELISA with significant changes for analytical workability of the test. Objectives To describe the results obtained of the comparative study between both versions of the ELISA commercialized for therapeutic drug monitoring of ADA. Methods We selected samples of patients with rheumatoid arthritis treated with ADA, with different concentrations of drug and Ac anti-drug that covered the whole analytical range of the assay. The samples were extracted just before the administration of ADA and remained frozen to -80ºC up to his later analysis for duplicate with both available versions of the ELISA. Different lots from reagent were in use in every shift of analysis. The test was realized t of Student of samples paired to compare ADA’s average concentrations between both analyses realized with the same version of the test. By means of the statistician kappa the conformity was evaluated between the results obtained with the same version. There has been calculated the Coefficient of Correlation of Conformity (CCC) and his interval of confidence to know if the measurements with both versions (V1 or previous and V2 or updated) of the test show conformity. Results Statistically significant differences are not observed in the comparison of averages for ADA’s concentrations between both measurements of 24 samples by the V1 (7,62±6,15 y 7,13±4,08 mg/L, p=0,59), not between both measurements of 20 samples with the V2 (6,94±4,37 y 7,20±4,57 mg/L, p=0,08) of the ELISA. On having categorized the measurements for ranges (from 0 to 3, from 3 to 7, from 7 to 12 and major of 12 mg/L), is observed a conformity moderated between ADA’s concentrations obtained with V1 (Kappa 0,55; 0,18-0,79) and a very good conformity between ADA’s concentrations obtained with V2 (Kappa 0,91; 0,65-1,00), with a major discrepancy for the highest concentrations, whereas below 7 mg/L the degree of association is major, for having a number of cases classified under different practically void range in the different analized samples. In the ELISA for the detection of Ac anti-ADA there was obtained a conformity of 100%, 4 patients Ac anti-ADA met positives in both versions evaluated (n = 40). Conclusions The V2 of the test provides higher results of ADA’s concentration that the V1. Nevertheless, a major precision is observed in the range of near concentrations at the level of clinical decision. The new version of the ELISA allows the complete automation, which simplifies very much the analysis, and reduces significantly the variability in the repetitions of the samples. Disclosure of Interest None Declared