Work, family and social environment in patients with Fibromyalgia in Spain: an epidemiological study: EPIFFAC study.

BACKGROUND: Fibromyalgia (FM) is a condition characterized by widespread pain, estimated to affect 2.4% of the Spanish population. Nowadays, there are no consistent epidemiological studies on the actual impact of the disease on work and family of these patients in a representative manner; therefore, the purpose of the study is to analyze the impact on family, employment and social environment in a representative sample of patients with FM attending Primary Public Care Centers in Spain. METHODS: We carried out an epidemiological study, with a probability sampling procedure, stratified, relative to the municipality size and the number of health centres, seeking territorial representation. The survey was conducted using a self-administered structured questionnaire. RESULTS: A sample of 325 patients with FM was studied in 35 Primary Health Care Centers (PHCCs). The sample is composed of 96.6% of women, 51.9 (8) years of mean (standard deviation- sd) age. Ninety-three percent of the patients have worked throughout their life. Mean (sd) age onset of symptoms was 37 (11) years and diagnosis of FM was established 6.6 (8) years later. Family Environment: Fifty-nine percent of patients have difficulties with their partner. Forty-four percent of the patients report to be fairly or totally dependent on a family member in household chores. The household income decreased a mean (sd) of 708 (504) Euros/month in 65% of the patients. In 81% of the patients, there was an increase in extra expenses related to the disease with a mean (sd) of 230 (192) Euros/month. Working environment: At the moment of the study, 45% of the patients had work activity (34% were working and 11% were at sick leave), 13% were unemployed seeking job and 42% were not in the labor force. Twenty-three percent of patients had some degree of permanent work disability pension. Social Environment: The degree of satisfaction with health care professionals was low and twenty-six percent of the patients were members of specific patients associations. CONCLUSIONS: This study finds that people with FM who visit PHCCs of Spain experience a high impact on families and employment with heavy loss of ability to work.

Tackling missing radiographic progression data: multiple imputation technique compared with inverse probability weights and complete case analysis.

OBJECTIVE: To describe the results of different statistical ways of addressing radiographic outcome affected by missing data--multiple imputation technique, inverse probability weights and complete case analysis--using data from an observational study. METHODS: A random sample of 96 RA patients was selected for a follow-up study in which radiographs of hands and feet were scored. Radiographic progression was tested by comparing the change in the total Sharp-van der Heijde radiographic score (TSS) and the joint erosion score (JES) from baseline to the end of the second year of follow-up. MI technique, inverse probability weights in weighted estimating equation (WEE) and CC analysis were used to fit a negative binomial regression. RESULTS: Major predictors of radiographic progression were JES and joint space narrowing (JSN) at baseline, together with baseline disease activity measured by DAS28 for TSS and MTX use for JES. Results from CC analysis show larger coefficients and s.e.s compared with MI and weighted techniques. The results from the WEE model were quite in line with those of MI. CONCLUSION: If it seems plausible that CC or MI analysis may be valid, then MI should be preferred because of its greater efficiency. CC analysis resulted in inefficient estimates or, translated into non-statistical terminology, could guide us into inaccurate results and unwise conclusions. The methods discussed here will contribute to the use of alternative approaches for tackling missing data in observational studies.

Rapid reduction in tenosynovitis of the wrist and fingers evaluated by MRI in patients with rheumatoid arthritis after treatment with etanercept.

OBJECTIVE: To assess the efficacy of etanercept in reducing tenosynovitis evaluated by MRI of the hand (h-MRI) in patients with active rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drug (DMARD) after 6 weeks of treatment. METHODS: 31 patients with active RA defined by a disease activity score (DAS28) >3.2 and synovitis in the hands were randomised into two groups: 19 patients received 50 mg weekly subcutaneous etanercept added to previous DMARD treatment and 12 patients continued with previous DMARD therapy. Clinical evaluation, blood tests, functional capacity evaluation and h-MRI were performed at the start of the investigation and at week 6. Tenosynovitis was evaluated on T1-weighted sequences with fat suppression after gadolinium as the presence of a peritendinous signal enhancement on axial images using a new method including wrist and finger tendons. The reliability, sensitivity to change and responsiveness of this method were also evaluated. RESULTS: Scores for tenosynovitis showed a significant reduction in the etanercept group compared with placebo (p=0.01) after 6 weeks of treatment. Adding MRI joint synovitis to tenosynovitis scores gave an even higher significant reduction in the etanercept group (p=0.007). A positive and statistically significant correlation between tenosynovitis and DAS28, erythrocyte sedimentation rate and C-reactive protein was found, but not with functional capacity. Responsiveness for tenosynovitis was small but was higher when joint synovitis scores were added. CONCLUSION: Addition of etanercept significantly reduced MRI tenosynovitis of the wrist and fingers in patients with active RA refractory to DMARD treatment. The method of scoring tenosynovitis showed good reliability and moderate responsiveness.

[Risk factors of new fractures after vertebroplasty]. / Factores predictivos de nueva fractura tras vertebroplastia.

PURPOSE: To evaluate the risk factors of new fractures after vertebroplasty (VP). PATIENTS AND METHOD: Prospective, non-randomized study including patients with acute osteoporotic fractures treated with VP. Baseline visit included clinical and densitometric data. At 30, 90 and 180 days, changes in clinical data and side effects (cement leakage and new fractures) were recorded. To establish the predictive factors of a new fracture, differences between the group of patients with new fractures (R1) and those without fractures (R0) were evaluated. RESULTS: Vertebroplasty was performed in 43 patients (82 vertebrae). Cement leakage into a disc appeared in 11 cases (11,5%) and 12 new fractures occurred in 9 patients. No statistical differences were detected between groups R1 and R0 in the following variables: sex, age, vitamin D levels, T-score, kyphosis angle, primary/secondary osteoporosis, preexisting fractures, number of treated vertebrae and amount of cement injected. A positive, statistical significant correlation, was established between cement leakage into a disk and incidence of adjacent new fractures (p<0.001). CONCLUSIONS: Cement leakage into a disc increases the risk of adjacent new fractures after vertebroplasty.

[Expectations, preferences and satisfaction of patients with rheumatoid arthritis receiving infliximab treatment]. / Expectativas, preferencias y satisfacción de los pacientes con artritis reumatoide en tratamiento con infliximab.

BACKGROUND AND OBJECTIVE: Our goal was to assess expectations, preferences and treatment satisfaction in patients suffering from rheumatoid arthritis (RA) treated with infliximab and their relationship with health related quality of life in real clinical practice. PATIENTS AND METHOD: 198 patients with AR participated in the study who started medication with infliximab at the beginning of the survey. Evaluation of expectations, preferences, satisfaction, health related quality of life, clinic evolution of patients and safety were made 2, 6, and 14 weeks after, coinciding with infliximab transfusions. RESULTS: More than 85% of the patients preferred to be treated in the hospital. They valued positively to be in contact with other patients, nurses and doctors in order to speak about their illness. Between 70% and 80% of the patients were satisfied with the infliximab treatment. After 2 weeks patients had reduced tender joint count by 70% and swollen joint count by 75%. At the end of the 14th week, 56.6% of the patients matched criteria ACR20, 31.5% ACR50 and 11.3% ACR70. 33.8% of patients had adverse events. The results in the EuroQol-5D indicated that patients improved their punctuations getting closer to those of the general population. Functional capacity of 50% of the patients improved significantly after the first 2 weeks of treatment and after 14 weeks this percentage reached the 70%. CONCLUSIONS: The results demonstrate that patients preferred to be treated in the hospital rather than in their houses. Also, patients reported a high level of satisfaction with infliximab.

Prevalence and factors associated with fatigue in female patients with systemic lupus erythematosus. / Prevalencia y factores asociados a fatiga en pacientes del sexo femenino con lupus eritematoso sistémico.

OBJECTIVE: To determine the prevalence of fatigue in our cohort as well as the factors to which it is associated, its relationship with demographic variables, vitamin D levels, treatment, systemic lupus erythematosus (SLE) symptoms and disease activity. METHODS: A cross-sectional study was carried out including 102 consecutive female patients with SLE (American College of Rheumatology 1997 criteria) who attended the Parc de Salut Mar between January 2012 and May 2014. Variables collected were: sociodemographic data, vitamin D supplementation, fatigue VAS, pharmacological treatment, main serological markers of SLE, and plasma levels of 25(OH)-vitD. The association between fatigue and the different variables was evaluated by the Spearman's Rho correlation coefficient for the continuous variables, the Mann-Whitney U test for the categorical and the Kruskal-Wallis test for the seasons of the year. RESULTS: The fatigue variable was evaluated through a fatigue VAS with a mean score of 52.84 (range 0-100), a median of 59 and a standard deviation of 29.86. A statistically significant relationship was found between fatigue and age, MHAQ, SLICC, summer and photosensitivity. As for the relationship between fatigue and vitamin D insufficiency (defined as 25-(OH)-vitD≤30 levels), the sample was divided into patients receiving vitamin D supplements (n=60) and patients without supplements (n=40), finding a significant relationship in that last group. CONCLUSIONS: A statistically significant association was found between the presence of fatigue and age, MHAQ, SLICC, photosensitivity, fibromyalgia and summer, and with vitamin D insufficiency in the group of patients without supplements (n=40).

Recommendations for the use of parenteral methotrexate in rheumatic diseases. / Recomendaciones sobre el uso de metrotexato parenteral en enfermedades reumáticas.

OBJECTIVE: To develop recommendations for the use of parenteral methotrexate (MTX) in rheumatic diseases, mainly rheumatoid arthritis, based on best evidence and experience. METHODS: A group of 21 experts on parenteral MTX use was selected. The coordinator formulated 13 questions about parenteral MTX (indications, efficacy, safety and cost-effectiveness). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (involving Medline, EMBASE and the Cochrane Library). Three different reviewers selected the articles. Evidence tables were created. Abstracts from the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) were evaluated. Based on this evidence, the coordinator proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Center for Evidence-Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). RESULTS: Most of the evidence involved rheumatoid arthritis. A total of 13 preliminary recommendations on the use of parenteral MTX were proposed; 11 of them were accepted. Two of the 13 were not voted and are commented on in the main text. CONCLUSIONS: The manuscript aims to solve frequent questions and help in decision-making strategies when treating patients with parenteral MTX.

Memoria de trabajo y velocidad de procesamiento evaluado mediante WISC-IV como claves en la evaluación del TDAH / Work memory and processing speed evaluated through WISC-IV as keys in the evaluation of ADHD

Los procesos cognitivos medidos mediante la prueba WISC-IV que con más frecuencia se han relacionado con el TDAH son la memoria de trabajo y la velocidad de procesamiento. Sin embargo, existe controversia sobre la existencia de un perfil cognitivo para el TDAH según su presentación sea inatenta o combinada. El primer objetivo fue corroborar si existen para nuestra muestra correlaciones entre el perfil cognitivo obtenido a través del WISC-IV. El segundo, discernir entre las diferentes presentaciones clínicas. Para ello se seleccionó un grupo control compuesto por 31 sujetos y otro clínico compuesto por 95 sujetos diagnosticados de TDAH. En comparación con el grupo control, el grupo clínico presentó resultados significativamente más bajos en los índices coeficiente intelectual total, memoria de trabajo y velocidad de procesamiento. Por otra parte, el grupo clínico presentó puntuaciones en el índice de capacidad general significativamente superior a las del índice de competencia cognitiva

The cognitive processes that are measured by the scale WISC-IV, which has most often been related to ADHD, Working Memory and Processing Speed. However, there is some controversy concerning the existence of a cognitive profile for ADHD that is related to whether its presentation is of the inattentive type or the combined type. The primary aim of this study was to corroborate whether there are correlations between the cognitive profile obtained through WISC-IV for our sample. The secondary aim of this study was to determine whether that profile allows to discern between the different clinical presentations by using a control group composed of 31 subjects and a clinical group consisting of 95 subjects diagnosed with ADHD. Compared to the control group, the clinical group presented significantly lower results in Intelligence Quotient, Working Memory Index and Processing speed Index. Finally, the clinical group presented scores for the General Capacity Index that were significantly higher than for the Cognitive Competency Index

Regulation of CYP19 gene expression in primary human osteoblasts: effects of vitamin D and other treatments.

OBJECTIVE: Extragonadal estrogen biosynthesis is relevant for the regulation of bone metabolism. The aims of this paper were: (i) to examine CYP19 (aromatase) gene expression in primary cultures of osteoblasts under several hormone and cytokine treatments and (ii) to study the promoter usage of CYP19 in these cells. METHODS: Primary cultures of osteoblasts were obtained from healthy donors. The effects of vitamin D and other factors on CYP19 expression were analysed by semiquantitative RT-PCR. Furthermore, CYP19 alternative promoter usage under the different treatments was characterized by RT-PCR. RESULTS: CYP19 transcripts were detected in cultured human osteoblasts in serum-free conditions. Vitamin D, dexamethasone, 17beta-estradiol and testosterone increased transcript levels of CYP19, whereas interleukin-1beta or tumor necrosis factor alpha decreased them. Aromatase mRNA produced under treatment with vitamin D was transcribed from promoters I.4 and I.3, while stimulation with dexamethasone or dexamethasone plus vitamin D also involved promoter I.2. Testosterone activated promoters I.2 and I.4. CONCLUSIONS: Our results suggested that vitamin D, testosterone, estrogens and glucocorticoids regulate CYP19 gene expression in human primary osteoblasts and the main promoter used appears to be promoter I.4. Promoters pII and I.3 seem to be related to basal transcription and may mediate estrogen stimulation, while promoter I.2 seems to play a role in the effect of glucocorticoids. These findings indicate that vitamin D and several hormones regulate local estrogen synthesis in human osteoblasts mainly through usage of promoters I.4 and I.3.

[Paget's disease of bone: study of 314 patients]. / Enfermedad ósea de Paget: estudio de 314 pacientes.

BACKGROUND: To describe the clinical and laboratory features of Paget's disease of bone at the time of diagnosis. PATIENTS AND METHOD: This multicenter and retrospective study included 314 patients. Diagnosis was performed by means of characteristic radiological findings and typical bone scintigraphy. The variables analyzed included: epidemiological variables, cause of diagnosis, bone involvement, disease extension (Coutris index), complications, alkaline phosphate (AP) levels and disease activity (Renier index). RESULTS: There were 159 (50.5%) males and the mean age was 64.9 years (SD 12.6). Diagnosis was casual in 228 (72.6%) patients. Polyostotic involvement was detected in 201 (63.9%) patients. More common locations were pelvis, skull and lumbar spine. Sacrum was more frequently involved in men than in women (p < 0.05), whereas skull involvement was more common in women (p < 0.05). The number of bones involved was 3.1 SD 3 and the percentage of skeletal involvement was 8.7 % (SD 6.5). One hundred ninety eigth (63%) patients had complications. The disease was active in 242 (77%) patients with a mean AP value of 377 IU/L (SD 493); the activity of the disease measured by the Renier index was 34 (SD 46); the activity was greater in the skull and the humerus. CONCLUSIONS: Paget's disease of bone is usually asymptomatic. Polyostotic involvement and activity are common at the time of diagnosis. Knowledge of the extension and activity by means of a mathematical model may aid to make therapeutical decisions.

Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system.

Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear, and its genetic factors have not yet been identified. With the aim of elucidating FM genetic susceptibility factors, we selected 313 FM cases having low comorbidities, and we genotyped them on the Illumina 1 million duo array. Genotypic data from 220 control women (Illumina 610k array) was obtained for genome-wide association scan (GWAS) analysis. Copy number variants in FM susceptibility were analyzed by array comparative genomic hybridization (aCGH) experiments on pooled samples using the Agilent 2×400K platform. No single nucleotide polymorphism (SNP) reached GWAS association threshold, but 21 of the most associated SNPs were chosen for replication in 952 cases and 644 controls. Four of the SNPs selected for replication showed a nominal association in the joint analysis, and rs11127292 (MYT1L) was found to be associated to FM with low comorbidities (P=4.28×10(-5), odds ratio [95% confidence interval]=0.58 [0.44-0.75]). aCGH detected 5 differentially hybridized regions. They were followed up, and an intronic deletion in NRXN3 was demonstrated to be associated to female cases of FM with low levels of comorbidities (P=.021, odds ratio [95% confidence interval]=1.46 [1.05-2.04]). Both GWAS and aCGH results point to a role for the central nervous system in FM genetic susceptibility. If the proposed FM candidate genes were further validated in replication studies, this would highlight a neurocognitive involvement in agreement with latest reports.

Screening for the presence of FMR1 premutation alleles in women with fibromyalgia.

Fibromyalgia is a chronic condition characterized by widespread pain, fatigue, non-restorative sleep and cognitive difficulties that affects 2-4% of the general population. Recently a possible relationship between the FMR1 premutation and fibromyalgia has been pointed out. In attempt to gather more data we screened for the FMR1 CGG expansion 700 DNA samples from unrelated fibromyalgia patients. This data might be useful for evaluating the incorporation of this test in rheumatologic procedures for women with fibromyalgia. The observed frequency of FMR1 premutation carriers (3 of 700, 0.4%) is not significantly different from the estimated rate in the general female population (1/250-1/400) (P=0.539, P=0.716). Clinical examination of the FMR1 premutation carriers identified revealed that all of them had important neurological symptoms with regard to muscular symptoms, neurocognitive alterations and neurovegetative impairments. With regard to other clinical aspects of the disease the cases apparently did not differ from the average fibromyalgia patients. On the basis of our results an FMR1 screening among fibromyalgia female patients would not be recommended. However it would be worthwhile to further evaluate the different clinical presentations that fibromyalgia patients might present based on their FMR1 premutation carrier status.

Cluster analysis of clinical data identifies fibromyalgia subgroups.

INTRODUCTION: Fibromyalgia (FM) is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. MATERIAL AND METHODS: 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. RESULTS: VARIABLES CLUSTERED INTO THREE INDEPENDENT DIMENSIONS: "symptomatology", "comorbidities" and "clinical scales". Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1), high symptomatology and comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster 3), showing differences in measures of disease severity. CONCLUSIONS: We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment.

Recomendaciones sobre el uso de metrotexato parenteral en enfermedades reumáticas / Recommendations for the use of parenteral methotrexate in rheumatic diseases

Objetivos. Desarrollar recomendaciones sobre el uso de metrotexato (MTX) parenteral en pacientes con enfermedades reumáticas, fundamentalmente en la artritis reumatoide, basadas en la mejor evidencia y experiencia. Métodos. Se seleccionó un grupo de 21 expertos reumatólogos en el manejo de MTX. El coordinador generó 13 preguntas sobre el uso de MTX parenteral (perfiles de indicación, eficacia, seguridad, costo-eficacia y biodisponibilidad) para ser contestadas mediante una revisión sistemática de la literatura. Con base en las preguntas se definieron los criterios de inclusión y exclusión, y las estrategias de búsqueda (en Medline, EMBASE y la Cochrane Library). Tres revisores seleccionaron los artículos resultantes de la búsqueda. Se generaron tablas de evidencia. Paralelamente se evaluaron abstracts de congresos de la European League Against Rheumatism (EULAR) y del American College of Rheumatology (ACR). Con toda esta evidencia el coordinador generó 13 recomendaciones preliminares que se evaluaron, discutieron y votaron en una reunión del grupo nominal con los expertos. Para cada recomendación se estableció el nivel de evidencia y grado de recomendación, y el grado de acuerdo mediante un Delphi. Se definió acuerdo si al menos el 80% de los participantes contestaron sí a la recomendación (sí o no). Resultados. La mayoría de la evidencia proviene de la artritis reumatoide. De las 13 recomendaciones preliminares se aceptaron 11 recomendaciones sobre el uso de MTX parenteral en reumatología. Dos no se llegaron a votar y se decidió no incluirlas, pero se comentan en el texto final. Conclusiones. Este documento pretende resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones con el uso de MTX parenteral

Objective. To develop recommendations for the use of parenteral methotrexate (MTX) in rheumatic diseases, mainly rheumatoid arthritis, based on best evidence and experience. Methods. A group of 21 experts on parenteral MTX use was selected. The coordinator formulated 13 questions about parenteral MTX (indications, efficacy, safety and cost-effectiveness). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (involving Medline, EMBASE and the Cochrane Library). Three different reviewers selected the articles. Evidence tables were created. Abstracts from the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) were evaluated. Based on this evidence, the coordinator proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Center for Evidence-Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). Results. Most of the evidence involved rheumatoid arthritis. A total of 13 preliminary recommendations on the use of parenteral MTX were proposed; 11 of them were accepted. Two of the 13 were not voted and are commented on in the main text. Conclusions. The manuscript aims to solve frequent questions and help in decision-making strategies when treating patients with parenteral MTX

Effectiveness of a clinical practice intervention in early rheumatoid arthritis.

OBJECTIVE: To compare the outcome of early rheumatoid arthritis (RA) patients in a country where early clinics were established versus the outcome of patients in nonprotocolized clinics. METHODS: We compared 2 multicenter cohorts: an RA cohort derived from an early arthritis registry set in 36 reference hospitals in which a specific intervention was established (Evaluation of a Model for Arthritis Care in Spain [SERAP]), and a historical control cohort of patients with early RA attending 34 rheumatology departments (Prognosis in Rheumatoid Arthritis [PROAR] cohort). Effectiveness was tested by comparing the change in the Disease Activity Score in 28 joints (DAS28), the change in the Health Assessment Questionnaire (HAQ), and the change in the Sharp/van der Heijde radiologic score using marginal structural models. RESULTS: A total of 161 early RA patients were recruited in the PROAR cohort and 447 in the SERAP cohort. Being a SERAP patient was inversely correlated with activity, resulting in a decrease of -0.24 (95% confidence interval [95% CI] -0.39, -0.08) units in the population average of the DAS28 after adjustment was made. Moreover, intervention may be seen as a protective factor of radiologic damage, with a decrease of -0.05 (95% CI -0.09, -0.01) units in the logarithm of the total Sharp/van der Heijde score. On the other hand, a decrease in functional impairment was detected, but intervention was not statistically associated with HAQ changes. CONCLUSION: Preventing major radiographic progression in a 2-year term inside structured and organized special programs for the management of disease, such as early arthritis clinics, are effective compared to nonprotocolized referrals, treatment, and followup.

Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life.

BACKGROUND: The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users. METHODS: Information on medicinal cannabis use was recorded on a specific questionnaire as well as perceived benefits of cannabis on a range of symptoms using standard 100-mm visual analogue scales (VAS). Cannabis users and non-users completed the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI) and the Short Form 36 Health Survey (SF-36). RESULTS: Twenty-eight FM patients who were cannabis users and 28 non-users were included in the study. Demographics and clinical variables were similar in both groups. Cannabis users referred different duration of drug consumption; the route of administration was smoking (54%), oral (46%) and combined (43%). The amount and frequency of cannabis use were also different among patients. After 2 hours of cannabis use, VAS scores showed a statistically significant (p<0.001) reduction of pain and stiffness, enhancement of relaxation, and an increase in somnolence and feeling of well being. The mental health component summary score of the SF-36 was significantly higher (p<0.05) in cannabis users than in non-users. No significant differences were found in the other SF-36 domains, in the FIQ and the PSQI. CONCLUSIONS: The use of cannabis was associated with beneficial effects on some FM symptoms. Further studies on the usefulness of cannabinoids in FM patients as well as cannabinoid system involvement in the pathophysiology of this condition are warranted.

[Characteristics of early arthritis units that may be associated with better referral efficiency: survey of SERAP units]. / Características de una unidad de artritis precoz que mejoran la eficiencia de la derivación: encuesta a las unidades SERAP.

OBJECTIVE: To identify characteristics of early arthritis units, that may be associated with better referral eficiency. METHODS: A national survey of the 36 early arthritis units (EAU) in Spanish Rheumatology Units in 2004 (SERAP project). Survey collected information about general practitioners (GP) educational program to improve knowledge and practical skills of early arthritis, networking and feed-back system and referral efficiency. EAU were classified in two groups according to 25 and 50% of inappropriate referral process, respectively. RESULTS: Thirty four of the 36 (94%) EAU, answered the survey. GP were trained in only 1 medical meeting in the primary care clinic, with one or more rheumatologists responsible of GP education. Fourteen of the 34 EAU (42.4%) regularly interacted with GP and only 20 (39.4%) contacted the GP who were responsible for the wrong referral process. Median lag time for referral to the Rheumatology out-patient clinic, was 73 days (15-365 days). The percentage of wrongly referred patients was between 0 and 80% (38% ± 21). Only 10 EAU (27.8%) referred patients appropriately according to the most strict criteria (25% of inappropriate referral) and 27 EAU (75%), according to 50% of inappropriate referral criteria. CONCLUSIONS: Only two aspects of the EAU implementation strategy were associated with better referral efficiency: 1) interaction with the GP responsible of the inappropriate referral process and 2) a lower median lag time for referral to the Rheumatology out-patient clinic.

[Descriptive study of the use of DMARD in patients with rheumatoid arthritis or persistent arthritis who start drug treatment in Spain (FIRST)]. / Estudio descriptivo de la utilización de los FAMES en los pacientes con artritis reumatoide o artritis persistente que inician tratamiento farmacológico en España. (ESTUDIO FIRST).

INTRODUCTION: Rheumatoid arthritis is clinically very heterogeneous and variable in its progression, and no one treatment works the same for all patients, as this will depend on the clinical course and specific situations. OBJECTIVE: To describe the treatment with DMARDs established for the first time in patients with rheumatoid arthritis (RA) or persistent arthritis (PA) in routine clinical practice in Spain. MATERIAL AND METHODS: Epidemiological, cross-sectional, uncontrolled, multicenter study in 15 regions of Spain during a period of five months (July to November 2006). We included patients of both genders, aged 18 years and diagnosed with RA according to ACR criteria or PA defined as any arthritis (oligoarthritis or polyarthritis) lasting ≥12 weeks, which would be given DMARD to treat their disease. RESULTS: 1079 patients were recruited, 915 analyzed (33% ♂/♀ 67%) meeting all the criteria required to be evaluated in the study. Mean age of patients was 54.6 (SD=15.4) years. The mean time from onset of symptoms until the 1st visit with the rheumatologist was 6.3 (11.3) months and the time from the 1st visit with the rheumatologist and the start of treatment was 4 (13.5) months. Of the patients tested, 96.7% was treated with at least one DMARD, 62.1% were given NSAIDs, corticosteroids to 59.2% and 3.8% biological therapy. In patients who received DMARDs, 90.3% received treatment with a single DMARD, 9.5% with 2 DMARDs and 0.2% with three DMARDs. In polytherapy, the DMARDs that are most often administered together were MTX + hydroxychloroquine (4.8%), MTX + leflunomide (2.0%) and MTX + sulfasalazine (1.5%). The most frequently used DMARD in monotherapy was MTX (81.3%), followed by leflunomide (4.1%) and hydroxychloroquine (3.2%). In 89.6%, the treatment of first choice was adequate according to the SER. CONCLUSION: The most common pattern of initial treatment of RA is MTX monotherapy. Treatment of RA by rheumatologists has been homogenized in recent years.

Recomendaciones para el uso de metotrexato en artritis reumatoide establecida: monoterapia y combinación con otros fármacos modificadores de la enfermedad sintéticos o biológicos / Recommendations for the use of methotrexate in established rheumatoid arthritis: monotherapy and combination with other synthetic or biological DMARDs

El metotrexato, utilizado a dosis bajas semanales, es actualmente el tratamiento de referencia en la artritis reumatoide. No se conoce con exactitud el mecanismo de acción en esta enfermedad, pero se han descrito diversas acciones antiproliferativas, antiinflamatorias e inmunorreguladoras que pueden contribuir a su efecto terapéutico. Diversos ensayos clínicos demostraron en la década de los ochenta del siglo pasado su eficacia clínica, así como su efecto enlentecedor del daño anatómico. En los últimos años se ha visto además que llegar a dosis más altas de las inicialmente utilizadas, entre 25 y 30 mg/semanales, puede maximizar sus efectos. En pacientes resistentes, el metotrexato también puede ser útil en terapia combinada con otros fármacos modificadores de la enfermedad, sintéticos o biológicos. Habitualmente, el metotrexato es bien tolerado, pero puede tener efectos adversos a diversos niveles (hematológico, digestivo, hepático, neurológico o pulmonar), alguno de los cuales pueden ser graves, por lo que requiere una cuidadosa monitorización clínica y analítica (AU)

The aim of this document is to describe the optimal use of: a) methotrexate (MTX) monotherapy in established RA in readministration after a previous effective cycle, and b) MTX combination with synthetic and biological DMARD. Clinical questions were proposed and a systematic literature search was conducted. Recommendations were developed and then discussed and validated in a working session with fifteen experts. After an effective cycle, MTX will be restarted with the same dose and route of administration than previously, following an intensive strategy if the dose were insufficient or the patient had poor prognostic factors. When sustained remission, MTX may be reduced gradually, with a close monitoring of the patient. Before starting a combination therapy with other synthetic or biologic DMARD, full doses of MTX should be reached and the use of the parenteral route evaluated. In established RA, when starting the combination of MTX with a biological DMARD, the same dose and route of administration of MTX than previously used should be maintained. In patients in remission for at least 6 months and in combination therapy with a biological, it is recommended to reduce the dose of the biological agent or increase its administration period before reducing the dose of MTX, unless side effects due to MTX. This document pretends to solve some frequent clinical questions on the use of MTX in monotherapy and/or in combination therapy with other synthetic or biological DMAR (AU)

[Pharmacoeconomic analysis of Metoject(®) in the treatment of rheumatoid arthritis in Spain]. / Análisis farmacoeconómico de Metoject(®) en el tratamiento de la artritis reumatoide en España.

OBJECTIVES: The aim of this study was to compare the clinical and economic consequences of using subcutaneous methotrexate (Metoject(®)) with respect to oral methotrexate in the management of rheumatoid arthritis (RA) in Spain. METHODS: A cost-effectiveness analysis was performed to compare early treatment of RA using a Markov model. The model allowed us to estimate long term efficacy of RA treatment based on data from the literature and expert opinion, and to combine this data with costs of managing RA in Spain. The perspective of the study was from the National Health System point of view, using a time horizon of 5 years and patient lifetime. All costs were expressed in 2009 euros and a 3% discount rate was applied. RESULTS: The cost (only pharmacologic costs) per quality-adjusted life year (QALY) gained with Metoject(®) went from 25,173 to 35,807€ at 5 years and from 19,056 to 25,351€ for patient lifetime. When direct costs in RA treatment were considered, it was observed that cost-effectiveness at 5 years went from 29,682 to 42,175€/QALY gained, and for patient lifetime from 22,514 to 29,848€/ QALY gained. CONCLUSIONS: Additional costs of Metoject(®) with respect to oral methotrexate would be offset by their improved effectiveness, expressed in QALY, showing that Metoject(®) could be a cost-effective treatment option for RA in the Spanish Health System assuming a spanish threshold.