Hospital General Universitario Of Elda
Hospital General Universitario Of Elda
Garcia-Donas J.,HM Hospitales Centro Integral Oncologico HM Clara Campal |
Font A.,Hospital Universitari Germans Trias i Pujol |
Perez-Valderrama B.,Hospitales Universitarios Virgen del Rocio |
Virizuela J.A.,Hospital Universitario Virgen Of Macarena |
And 16 more authors.
The Lancet Oncology | Year: 2017
Background Maintenance therapy improves outcomes in various tumour types, but cumulative toxic effects limit the choice of drugs. We investigated whether maintenance therapy with vinflunine would delay disease progression in patients with advanced urothelial carcinoma who had achieved disease control with first-line chemotherapy. Methods We did a randomised, controlled, open-label, phase 2 trial in 21 Spanish hospitals. Eligible patients had locally advanced, surgically unresectable, or metastatic transitional-cell carcinoma of the urothelial tract, adequate organ function, and disease control after four to six cycles of cisplatin and gemcitabine (carboplatin allowed after cycle four). Patients were randomly assigned (1:1) to receive vinflunine or best supportive care until disease progression. We initially used block randomisation with a block size of six. Four lists were created for the two stratification factors of starting dose of vinflunine and presence of liver metastases. After a protocol amendment, number of cisplatin and gemcitabine cycles was added as a stratification factor, and eight lists were created, still with a block size of six. Finally, we changed to a minimisation procedure to reduce the risk of imbalance between groups. Vinflunine was given every 21 days as a 20 min intravenous infusion at 320 mg/m2 or at 280 mg/m2 in patients with an Eastern Cooperative Oncology Group performance status score of 1, age 75 years or older, previous pelvic radiotherapy, or creatinine clearance lower than 60 mL/min. The primary endpoint was median progression-free survival longer than 5·3 months in the vinflunine group, assessed by modified intention to treat. Comparison of progression-free survival between treatment groups was a secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01529411. Findings Between April 12, 2012, and Jan 29, 2015, we enrolled 88 patients, of whom 45 were assigned to receive vinflunine and 43 to receive best supportive care. One patient from the vinflunine group was lost to follow-up immediately after randomisation and was excluded from the analyses. One patient in the best supportive care group became ineligible for the study and did not receive treatment due to a delay in enrolment, but was included in the intention-to-treat efficacy analysis. After a median follow-up of 15·6 months (IQR 8·5–26·0), 29 (66%) of 44 patients in the vinflunine group had disease progression and 24 (55%) had died, compared with 36 (84%) of 43 patients with disease progression and 32 (74%) deaths in the best supportive care group. Median progression-free survival was 6·5 months (95% CI 2·0–11·1) in the vinflunine group and 4·2 months (2·1–6·3) in the best supportive care group (hazard ratio 0·59, 95% CI 0·37–0·96, p=0·031). The most common grade 3 or 4 adverse events were neutropenia (eight [18%] of 44 in the vinflunine group vs none of 42 in the best supportive care group), asthenia or fatigue (seven [16%] vs one [2%]), and constipation (six [14%] vs none). 18 serious adverse events were reported in the vinflunine group and 14 in the best supportive care group. One patient in the vinflunine group died from pneumonia that was deemed to be treatment related. Interpretation In patients with disease control after first-line chemotherapy, progression-free survival exceeded the acceptable threshold with vinflunine maintenance therapy. Moreover, progression-free survival was longer with vinflunine maintenance therapy than with best supportive care. Vinflunine maintenance had an acceptable safety profile. Further studies of the role of vinflunine are warranted. Funding Pierre-Fabre Médicament. © 2017 Elsevier Ltd
PubMed | Institute Salud Musculoesqueletica inMusc, Hospital General Universitario Of Alicante and Hospital General Universitario Of Elda
Type: Journal Article | Journal: Rheumatology international | Year: 2016
To describe the variability in rheumatology visits and referrals to other medical specialties of patients with spondyloarthritis (SpA) and to explore factors that may influence such variability.Nation-wide cross-sectional study performed in 2009-2010. Randomly selected records of patients with a diagnosis of SpA and at least one visit to a rheumatology unit within the previous 2years were audited. The rates of rheumatology visits and of referrals to other medical specialties were estimated-total and between centres-in the study period. Multilevel regression was used to analyse factors associated with variability and to adjust for clinical and patient characteristics.1168 patients records (45 centres) were reviewed, mainly ankylosing spondylitis (55.2%) and psoriatic arthritis (22.2%). The patients had incurred in 5908 visits to rheumatology clinics (rate 254 per 100 patient-years), 4307 visits to other medical specialties (19.6% were referrals from rheumatology), and 775 visits to specialised nurse clinics. An adjusted variability in frequenting rheumatology clinics of 15.7% between centres was observed. This was partially explained by the number of faculties and trainees. The adjusted intercentre variability for referrals to other specialties was 12.3%, and it was associated with urban settings, number of procedures, and existence of SpA dedicated clinics; the probability of a patient with SpA of being referred to other specialist may increase up to 25% depending on the treating centre.Frequenting rheumatology clinics and referrals to other specialists significantly varies between centres, after adjustment by patient characteristics.
PubMed | Taichung Veterans General Hospital, Diakonhjemmet Hospital, University of the Basque Country, China Medical University at Taichung and 19 more.
Type: | Journal: Arthritis & rheumatology (Hoboken, N.J.) | Year: 2016
To examine the performance of ultrasound for the diagnosis of gout using presence of monosodium urate (MSU) crystals as the gold standard.We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multi-center observational cross-sectional study of consecutive subjects with at least one swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with MSU crystal confirmation. Rheumatologists or radiologists, blinded to the results of the MSU crystal analysis, performed ultrasound on one or more clinically affected joints. Ultrasound findings of interest were: double contour sign (DCS), tophus, and snowstorm appearance. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive ultrasound results among subjects with gout.Ultrasound was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV and NPV for the presence of any one of the features were 76.9%, 84.3%, 83.3% and 78.1% respectively. Sensitivity was higher among subjects with disease 2 years duration and among subjects with subcutaneous nodules on exam (suspected tophus). Associations with a positive ultrasound finding included suspected clinical tophus (odds ratio 4.77; 95% CI 2.23-10.21), any abnormal plain film radiograph (4.68; 2.68-8.17) and serum urate (1.31; 1.06-1.62).Ultrasound features of MSU crystal deposition had high specificity and high positive predictive value but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi. This article is protected by copyright. All rights reserved.
PubMed | Hospital Universitario Ciudad Of Jaen, Hospital Of Donostia, Hospital Santa Maria del Rosell, Hospital Universitario Of Canarias and 10 more.
Type: Journal Article | Journal: European journal of haematology | Year: 2016
Therapeutic approaches against multiple myeloma (MM) have largely changed during the past decade. Hematopoietic stem cell transplantation (HSCT) and licensing of immunomodulators and proteasome inhibitors have resulted in better response and increased overall survival rates compared to previous conventional therapies. To assess the impact that these new strategies have had on outcome of patients with symptomatic MM in Spain, we conducted an epidemiological retrospective analysis of 338 newly diagnosed patients with stage II-III MM who started first-line treatment over a 2-yr period (2003-2005) by collecting data from their medical records. Most patients had been diagnosed with secretory MM (94.4%), 41.7% stage II and 58.3% stage III. The presence of bone lesions (72.2%), as well as anemia (79.8%) and elevated beta2-microglobulin levels (62.3%), was a common finding; in contrast, hypercalcemia and elevated serum creatinine were less frequent (25% each). First-line treatment had consisted of either conventional chemotherapy (62%) or induction treatment plus autologous HSCT (38%), as per standard clinical practice. HSCT not only resulted in greater objective response rates (93% vs. 50%), but also contributed to a significant increase in 3-yr survival (85% vs. 49.7%; 95% CI, range 77-91 vs. 41-58; P < 0.001). Overall, 55% of patients presented treatment-related adverse events, mainly hematological. Toxicity rates were higher among patients treated with alkylating-based regimens and in those undergoing transplantation. In conclusion, data analysis shows an adequate balance between increased response rates and safety that supports the use of up-front high-dose HSCT therapy in younger patients. Most importantly, this study provides further confirmation that the introduction of HSCT has significantly prolonged survival of patients with MM.
PubMed | University Utrecht, University of Genoa, Diakonhjemmet Hospital, Paris-Sorbonne University and 8 more.
Type: Journal Article | Journal: Arthritis research & therapy | Year: 2016
The aim of this project was to analyze and compare the educational experience in rheumatology specialty training programs across European countries, with a focus on self-reported ability.An electronic survey was designed to assess the training experience in terms of self-reported ability, existence of formal education, number of patients managed and assessments performed during rheumatology training in 21 core competences including managing specific diseases, generic competences and procedures. The target population consisted of rheumatology trainees and recently certified rheumatologists across Europe. The relationship between the country of training and the self-reported ability or training methods for each competence was analyzed through linear or logistic regression, as appropriate.In total 1079 questionnaires from 41 countries were gathered. Self-reported ability was high for most competences, range 7.5-9.4 (0-10 scale) for clinical competences, 5.8-9.0 for technical procedures and 7.8-8.9 for generic competences. Competences with lower self-reported ability included managing patients with vasculitis, identifying crystals and performing an ultrasound. Between 53 and 91% of the trainees received formal education and between 7 and 61% of the trainees reported limited practical experience (managing 10 patients) in each competence. Evaluation of each competence was reported by 29-60% of the respondents. In adjusted multivariable analysis, the country of training was associated with significant differences in self-reported ability for all individual competences.Even though self-reported ability is generally high, there are significant differences amongst European countries, including differences in the learning structure and assessment of competences. This suggests that educational outcomes may also differ. Efforts to promote European harmonization in rheumatology training should be encouraged and supported.
Sivera F.,Hospital General Universitario Of Elda |
Andres M.,Hospital General Universitario Of Alicante |
Falzon L.,Columbia University |
Van Der Heijde D.M.F.M.,Leiden University |
Carmona L.,Camilo José Cela University
Journal of Rheumatology | Year: 2014
Objective. To analyze the diagnostic utility of clinical, laboratory, and imaging items for gout. Methods. A systematic literature search was performed in MEDLINE, EMBASE, and The Cochrane Library; and a manual search of abstracts from the 2010/2011 meetings of the American College of Rheumatology (ACR) and the European League Against Rheumatism, as well as the reference lists of retrieved papers. Studies were included if they evaluated the diagnostic utility of clinical, laboratory, or imaging features or criteria for the diagnosis or classification of gout in adult patients. Two independent reviewers selected papers, extracted the data, and assessed the risk of bias. Results. Nineteen studies were included in the review; 4 used the identification of monosodium urate (MSU) crystals as the reference standard (RS) and the rest used expert opinion or the ACR preliminary criteria. Most features were evaluated in a single study. Evidence for diagnostic utility, using MSU crystals as RS, of over 50 individual clinical, laboratory, and radiographic features was retrieved. Most items showed a positive likelihood ratio (LR+) < 3, except for the following: response of arthritis to colchicine (LR+ 4.3); presence of tophi on physical examination (LR+ 15.6-30.9); identification of the double-contour sign in ultrasound (US) (LR+ 13.6); and detection of urate deposits by dual-energy computed tomography (DECT) (LR+ 9.5). Conclusion. Individual clinical features show low diagnostic utility, with the exception of tophi and response to colchicine. Some US and DECT findings show better performance than most clinical features. The Journal of Rheumatology Copyright © 2014. All rights reserved.
PubMed | University Utrecht, Leiden University, University of Zürich, Karolinska University Hospital and 6 more.
Type: Journal Article | Journal: RMD open | Year: 2016
To understand the educational needs and preferences of young clinicians and physician researchers in the field of rheumatology in Europe.An international online survey was performed as a joint venture of ESCET and EMEUNET. The survey assessed the acceptance of and the access to the current European League Against Rheumatism (EULAR) educational portfolio, as well as the unmet educational needs and learning preferences among individuals below the age of 40years working in rheumatology in Europe.Among 568 European clinicians and physician researchers, 65% indicated that the existing EULAR educational portfolio adequately covers their educational needs. Within the EULAR portfolio, the online course on rheumatic diseases and the postgraduate course were the most appreciated. Participants were very much in favour of new educational courses on imaging techniques, and 63% of participants indicated a particular interest in musculoskeletal ultrasound. A strong interest in refresher (60%) and general review (55%) courses was observed. Lack of funding was considered the major obstacle to participating in existing EULAR programmes. Finally, participants showed diverse preferences regarding learning modalities with common interests in live courses and conferences.EULARs training opportunities are well appreciated among young clinicians and physician researchers in rheumatology. The results from this survey will help to develop EULARs future educational portfolio.
Pascual E.,University Miguel Hernández |
Addadi L.,Weizmann Institute of Science |
Andres M.,University Miguel Hernández |
Sivera F.,Hospital General Universitario Of Elda
Nature Reviews Rheumatology | Year: 2015
The mechanisms and sites of monosodium urate monohydrate (MSU) crystal deposition in gout have received little attention from the scientific community to date. Formalin fixation of tissues leads to the dissolution of MSU crystals, resulting in their absence from routinely processed pathological samples and hence neglect. However, modern imaging techniques - especially ultrasonography but also conventional CT and dual-energy CT - reveal that MSU crystals form at the cartilage surface as well as inside tendons and ligaments, often at insertion sites. Tophi comprise round white formations of different sizes surrounded by inflammatory tissue. Studies of fibres recovered from gouty synovial fluid indicate that these fibres are likely to be a primary site of crystal formation by templated nucleation, with crystals deposited parallel to the fibres forming transverse bands. In tophi, two areas can be distinguished: one where crystals are formed on cellular tissues and another consisting predominantly of crystals, where secondary nucleation seems to take place; this organization could explain how tophi can grow rapidly. From these observations based on a crystallographic approach, it seems that initial templated nucleation on structural fibres - probably collagen - followed at some sites by secondary nucleation could explain MSU crystal deposition in gout. © 2015 Macmillan Publishers Limited.
Sivera F.,Hospital General Universitario Of Elda |
Andres M.,Hospital General Universitario Of Alicante |
Pascual E.,Hospital General Universitario Of Alicante |
Pascual E.,University Miguel Hernández
Current Opinion in Rheumatology | Year: 2016
Purpose of review Calcium pyrophosphate (CPP) crystal disease is a common rheumatologic disorder that has received limited attention from the scientific community. This review is aimed at summarizing current evidence for managing CPP disease (CPPD), focusing on recently reported advances. Recent findings New data from case series indicate that interleukin-1b inhibitors can help patients with refractory forms of CPPD. Methotrexate, formerly a promising agent, failed to demonstrate benefits in a recent trial, but still merits consideration for some patients. No significant advances on crystal dissolution have been achieved to date. Proper characterization of the CPP crystal disease picture is needed, ruling out the possible coexistence of another persistent arthritis unrelated to the CPP deposition. Summary Advances on CPP crystal dissolution and establishing definitions of the clinical spectrum of CPPD remain the main challenges for CPP crystal disease management. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved..
PubMed | Hospital General Universitario Of Alicante, Hospital General Universitario Of Elda and University Miguel Hernández
Type: Journal Article | Journal: Therapeutic advances in chronic disease | Year: 2016
Gout is one of the most common inflammatory arthritides. The disease is due to the deposition of monosodium urate crystals. These deposits are reversible with proper treatment, suggesting that gout is a curable disease. The main aim in gout is to lower serum uric acid levels to a pre-established target; there are different urate-lowering drugs (xanthine oxidase inhibitors, uricosurics and uricases) through which this can be achieved. Proper treatment of gout also involves correct management of acute flares and their prevention. To ensure treatment adherence it is necessary to explain to the patient what the objectives are.