José Andrés Román Ivorra

Most calcium pyrophosphate crystals appear as non-birefringent

OBJECTIVE To determine the proportion of calcium pyrophosphate dihydrate (CPPD) crystals that appear as non-birefringent when observed under the polarised light microscope. METHODS Two observers examined independently 10 synovial fluid samples obtained during an episode of arthritis attributable to CPPD crystals. Ten synovial fluid samples from patients with acute gout were used as a reference. The examination was performed after placing a fluid sample in a Niebauer haemocytometric chamber; a crystal count was done first under ordinary light, then in the area corresponding to a 0.1 ml, under polarised light RESULTS The percentages of birefringence appreciated for CPPD were 18% (confidence intervals (CI) 12, 24) for observer 1, and 17% (CI 10, 24) for observer 2 (difference NS). The percentages of birefringence for monosodium urate were 127% (CI 103, 151) for observer 1 and 107% (CI 100, 114) for observer 2 (difference NS). Percentages above 100% indicate that crystals missed under ordinary light became apparent under polarised light. CONCLUSION Only about one fifth of all CPPD crystals identified by bright field microscopy show birefringence when the same synovial fluid sample is observed under polarised light. If a search for CPPD crystals is conducted under polarised light, the majority of the crystals will be missed. Ordinary light allows a better rate of CPPD crystal detection but observation under polarised light of crystals showing birefringence is required for definitive CPPD crystal identification.

Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice

Objective To evaluate the safety and efficacy of tocilizumab in clinical practice in patients with rheumatoid arthritis (RA) with inadequate responses (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour necrosis factor α inhibitors (TNFis). Methods Patients—categorised as TNFi-naive, TNFi-previous (washout) or TNFi-recent (no washout) —received open-label tocilizumab (8 mg/kg) every 4 weeks ± DMARDs for 24 weeks. Adverse events (AEs) and treatment discontinuations were monitored. Efficacy end points included American College of Rheumatology (ACR) responses, 28-joint disease activity score (DAS28) and European League Against Rheumatism responses. Results Overall, 1681 (976 TNF-naive, 298 TNFi-previous and 407 TNFi-recent) patients were treated; 5.1% discontinued treatment because of AEs. The AE rate was numerically higher in TNFi-recent (652.6/100 patient-years (PY)) and TNFi-previous (653.6/100PY) than in TNFi-naive (551.1/100PY) patients. Serious AE rates were 18.0/100PY, 28.0/100PY and 18.6/100PY; serious infection rates were 6.0/100PY, 6.8/100PY and 4.2/100PY, respectively. At week 4, 36.5% of patients achieved ACR20 response and 14.9% DAS28 remission (<2.6); at week 24, 66.9%, 46.6%, 26.4% and 56.8% achieved ACR20/ACR50/ACR70 responses and DAS28 remission, respectively. Overall, 61.6% (TNFi-naive), 48.5% (TNFi-previous) and 50.4% (TNFi-recent) patients achieved DAS28 remission. Conclusions In patients with RA who were DMARD-IR/TNFi-IR, tocilizumab ± DMARDs provided rapid and sustained efficacy without unexpected safety concerns.

Spanish Rheumatology Society and Hospital Pharmacy Society Consensus on recommendations for biologics optimization in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis

Objective. The aim of this study was to establish guidelines for the optimization of biologic therapies for health professionals involved in the management of patients with RA, AS and PsA. Methods. Recommendations were established via consensus by a panel of experts in rheumatology and hospital pharmacy, based on analysis of available scientific evidence obtained from four systematic reviews and on the clinical experience of panellists. The Delphi method was used to evaluate these recommendations, both between panellists and among a wider group of rheumatologists. Results. Previous concepts concerning better management of RA, AS and PsA were reviewed and, more specifically, guidelines for the optimization of biologic therapies used to treat these diseases were formulated. Recommendations were made with the aim of establishing a plan for when and how to taper biologic treatment in patients with these diseases. Conclusion. The recommendations established herein aim not only to provide advice on how to improve the risk:benefit ratio and efficiency of such treatments, but also to reduce variability in daily clinical practice in the use of biologic therapies for rheumatic diseases.

Efficacy of Raynaud's phenomenon and digital ulcer pharmacological treatment in systemic sclerosis patients: a systematic literature review

Abstract To evaluate the efficacy of current treatments for the Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc), a systematic literature search was performed using Medline, EMBASE, and Cochrane Central Register of Controlled Trials (from 1961 to October 2011). We included meta-analyses, systematic reviews, clinical trials, and high-quality cohort studies published in English or Spanish. Patient populations had to include adults diagnosed with limited cutaneous or diffuse SSc who had associated RP and/or digital ulcers under pharmacological treatment. Efficacy of treatments was evaluated based on: number of RP episodes, RP severity, episode-free time, ulcer improvement/healing, and appearance of new ulcers. We used the Jadad scale of methodological quality to evaluate the quality of randomized clinical trials, and the 2009 Oxford Centre for Evidence-Based Medicine classification for other studies. Of a total of 1617 studies identified, only 27 fulfilled inclusion criteria. Drugs received the following grade recommendations: Grade A for nifedipine, nicardipine, quinapril, IV iloprost, bosentan, tadalafil, and MQx-503; Grade B for beraprost, cicaprost, DMSO, cyclofenil, and atorvastatin; and Grade C for misoprostol, prazosin, OPC-2826, enalapril, sildenafil, antioxidant, and stanazolol. Calcium channel blockers, prostanoids, tadalafil, and bosentan received the highest recommendation level for their effectiveness. However, most systematic reviews reviewed just a handful of studies with small sample sizes and short follow-ups. Our review shows that the existing evidence on the efficacy of RP treatment in SSc patients is inconclusive which calls for further research, especially in the form of prospective studies of high quality with long-term follow-ups.

Bosentan in clinical practice for treating digital and other ischemic ulcers in Spanish patients with systemic sclerosis: IBER-DU cohort study.

Objective. To describe treatment outcomes and safety experience with bosentan in patients with systemic sclerosis (SSc) and digital ulcers (DU), in a clinical setting in Spain. Methods. This was a multicenter, noninterventional retrospective cohort study. Data were collected retrospectively from patients with DU, with or without pulmonary arterial hypertension (PAH), who were initiating bosentan therapy in 2003 (n = 26) or 2004 (n = 41) and followed until May 2005. Data were obtained from centers prescribing bosentan. Relevant measures included number of DU, occurrence of new DU, overall DU clinical status (improved, stabilized, worsened), and bosentan-associated adverse events. Results. Sixty-seven patients with SSc and DU or other ulcers were included. PAH was also present in 12 patients (18%). At the start of bosentan treatment, the median number of DU per patient was 3.0. The median change in number of DU was −3.6 and −5.0 at 12 and 24 months, respectively. Sixty-eight percent of the patients did not develop any new DU at 12 months. DU clinical status was reported at 12 months for 22 patients: 18 patients (81.8%) improved and 4 (18.2%) stabilized. The median treatment duration was 13.0 months. The main adverse event was increase of aminotransferase, observed in 5 patients (7%), leading to discontinuation of treatment in 3 patients (4.4%). Conclusion. Previously reported results of bosentan efficacy in DU management are reproducible in clinical practice. This efficacy is maintained in the longterm followup. Bosentan treatment was well tolerated and adverse events were comparable with those observed in previous reports.

El uso de abatacept en artritis reumatoide: revisión de la evidencia y recomendaciones

OBJECTIVE To review the clinical evidence on abatacept and to formulate recommendations in order to clear up points related to its use in rheumatology. METHOD An expert panel of rheumatologists objectively summarized the evidence on the mechanism of action, practicalities, effectiveness and safety of abatacept, and formulated recommendations following a literature review. The level of evidence and degree of recommendation was established. RESULTS The document presents 21 statements focused on evidence or recommendations on abatacept (14 evidence summaries and 9 recommendations). The level of evidence was 2b or higher according to the Oxford Centre for Evidence-Based Medicine scale on 14 occasions. The degree of the recommendation was A in two recommendations, C in one, and D in the rest. It was considered important to make recommendations on aspects with lower levels of evidence. CONCLUSIONS This is a practical document to supplement the summary of product characteristics.

¿Como son los pacientes con artritis reumatoide de reciente comienzo en Espana? Descripcion de la cohorte PROAR

OBJECTIVE To identify factors present in recent onset arthritis that may help to predict rheumatoid arthritis (RA), and to describe a cohort of recent onset RA. PATIENTS AND METHOD A 5 year prospective cohort of patients with early oligo and polyarthritis (< 1 year of evolution) from 34 rheumatology units, was studied. Sociodemographic, clinical features and RA risk factors were recorded. Rheumatoid factor (RF), anti-CCP determinations and radiographs of hands and feet were analyzed too. After three years, a diagnosis of certainty and the variables that determined the evolution to RA, were evaluated. RESULTS One hundred and seventy one patients were included; 161 (94.2%) fulfilled RA diagnostic criteria; most of them (157; 97.5%) in the first visit. Factors associated with RA diagnosis were: positive RF, anti-CCP and DAS-28; 65% of the patients had radiological erosions in the first visit. CONCLUSIONS Positive RF, anti-CCP and the disease activity are predictive factors of RA. Radiological damage exists very early in most of patients, thats why it is more important to treat the disease aggressively instead than achieving an RA diagnosis of certainty.

Estado actual de los hospitales de día donde se administran los tratamientos de reumatología en la Comunidad Valenciana

OBJECTIVE To evaluate and characterize the current status of the Rheumatology Day Hospital Care units in the Autonomous Community of Valencia. MATERIAL AND METHOD A structured brainstorming meeting was organized with 12 rheumatologists and a nurse and, after that, a questionnaire was sent to 20 rheumatologists to know more about the centers. RESULTS Variability was found in the services that the day care units have for their own operation and for patient care. Rheumatologists place more importance on having some services that are not present in all centers at the moment: specialized nursing, quick drug delivery from the pharmacy and administration supervision by a rheumatologist. The following deficiencies were identified: sharing the workspaces with other specialties, drug delivery delays from the pharmacy, few resources (few spaces, few locations and little time for drug administration), lack of specialized nursing, lack of some services for patients (i.e. hot-line telephone service or patient education), few clinical sessions and lack of some procedures. CONCLUSIONS It is necessary to establish measures that lead to the resolution of deficiencies and improve the services offered to patients.

Estándares de calidad en una Unidad de Hospitalización de Día reumatológica. Propuesta del Grupo de Trabajo de Hospitales de Día de la Sociedad Española de Reumatología

BACKGROUND In recent years, the Rheumatology Day-Care Hospital Units (DHU have undergone extensive development. However, the quality standards are poorly documented and mainly limited to structure items rather than including broad and specific areas of this specialty. OBJECTIVE To develop specific quality standards for Rheumatology DHU. METHODS After a systematic review of the literature and related documents, a working group (WG) involving 8 DHU-experienced rheumatologists developed an initial proposal of the quality standards, under the supervision of an expert methodologist. A second round was held by the WG group to review the initial proposal and to consider further suggestions. Once the content was agreed upon by consensus, a final report was prepared. RESULTS 17 structure standards, 25 process standards and 10 results standards were defined, with special emphasis on specific aspects of the Rheumatology DHU. The proposal includes: 1) essential standards to 2) excellent standards, 3) a Rheumatology DHU services portfolio and 4) performance criteria. CONCLUSIONS The proposed quality standards are the basis for developing the indicators and other management tools for Rheumatology DHU, thereby ensuring a patient-oriented practice based on both the evidence and the experience.

Quality-of-care standards for early arthritis clinics

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