Prevalence of ankylosing spondylitis in Spain: EPISER2016 Study.

Objective: The aim of this study was to estimate the prevalence of ankylosing spondylitis (AS) in Spain.Method: This is a cross-sectional, population-based study of people aged 20 years or older in Spain. Randomly selected individuals were contacted by telephone and rheumatic disease screening was performed. If the first screening was positive, medical records were then reviewed and/or a telephone questionnaire was conducted by a rheumatologist, followed by an appointment if necessary. Cases had to fulfil the modified New York (mNY) criteria.Results: In total, 4916 individuals were included, of whom 355 had a positive screening result for AS. Of these, 11 were classified as AS. An additional individual who reported a prior diagnosis of rheumatoid arthritis had a diagnosis of AS confirmed on review of the medical records. Estimated prevalence was 0.26% (95% CI 0.14-0.49).Conclusion: EPISER2016 is the first population-based study to estimate the prevalence of AS in Spain, which has been estimated as being similar to that in other European countries.

Erosive discovertebral lesion (Andersson lesion) as the first sign of disease in axial psoriatic arthritis.

OBJECTIVES: To present two cases of Andersson lesion (AL) as the form of onset of psoriatic arthritis (PsA), to review the form of onset of axial disease in PsA in our area, and to study the prevalence of AL in this series. PATIENTS AND METHODS: Two patients with psoriasis and recent-onset inflammatory back pain (IBP) with no known arthritis are presented. A final diagnosis of AL based on magnetic resonance imaging (MRI) findings was made. The medical records of 120 consecutive patients with axial PsA were reviewed and the most relevant features at disease onset analysed. RESULTS: Including the two cases presented, an AL prevalence of 5.7% was found in this series. The most common onset forms of axial PsA were: oligoarthritis (30%), IBP (21.7%), enthesitis (17.5%), polyarthritis (16%), gluteal pain (8.3%), dactylitis (3.3%), and distal interphalangeal (DIP) involvement (3.3%). Compared to women, men more frequently showed enthesitis (25% vs. 9%, p = 0.03) and IBP (31% vs. 10.7%, p = 0.007) as onset forms whereas a polyarticular onset was predominant in women (25% vs. 8%, p = 0.01). The polyarticular onset was predictive of radiological damage in the cervical column during follow-up [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.82-6.83, p = 0.01]. Enthesitis (23.6% vs. 8.3%, p = 0.02) and IBP (29.7% vs. 10.4%) were the predominant onset forms in patients with age at disease onset ≤ 40 years and polyarthritis (27% vs. 8.3%, p = 0.009) was predominant in those with disease onset > 40 years. CONCLUSIONS: AL is an uncommon finding in axial PsA and its appearance at disease onset is exceptional. MRI is a key tool in its early recognition.

Synovitis-acne-pustulosis-hyperostosis-osteitis syndrome and psoriatic arthritis exhibit a different immunogenetic profile.

BACKGROUND AND OBJECTIVES: Patients with psoriatic arthritis (PsA) as well as those with synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome share some common features, and in fact, for many authors the SAPHO concept fits well into the broader concept of PsA. However, some clinical features are unique to the SAPHO syndrome, and in the other hand, these patients do not show the known association between the HLA-B27 antigen and the spondyloarthropathies. To date, there are no studies comparing the immunogenetic profile of these two conditions, so the main objective of the present report was to analyse whether or not both entities may share the same genetic basis. PATIENTS AND METHODS: All patients with SAPHO syndrome (n=25) seen in a single university hospital from 1985 to 2005 were recruited and followed up in standardised manner in order to study their main characteristics and HLA profile. The HLA-Cw6, DR and B27 antigen distribution of these cases was compared to that of 50 patients with psoriasis vulgaris, 120 with PsA, and 170 healthy blood donors. PsA patients were classified in accordance with their predominant pattern observed in the last 5 years of disease evolution. Odds ratios (OR) values were calculated to measure the strength of the association between HLA antigens and disease, while the statistical significance of the association was assessed with a two-tailed Fisher's exact test. P<0.05 values were considered significant. RESULTS: No association was found between HLA-Cw6, B27, or DR antigens, and SAPHO syndrome. HLA-Cw6 was strongly associated with psoriasis, OR 12 (95% CI: 5.6-26, p<0.0001) and PsA, OR 10 (95% CI: 5.4-19.5, p<0.0001), however this antigen was equally distributed among the three articular categories of PsA. HLA-DR4 was found under-represented in PsA patients compared to controls, OR 0.4 (95% CI: 0.2-0.7, p=0.002). HLA-DR7 correlated well with psoriatic oligoarthritis, OR 9.6 (95% CI: 2.9-28, p<0.0001), HLA-DR8 was found associated with polyarthritis, OR 6.7 (95% CI: 2-25, p=0.002), while HLA-B27 was over-represented in psoriatic spondylitis, OR 10 (95% CI: 3.3-25, p<0.0001). CONCLUSIONS: Psoriasis/PsA and SAP-HO syndrome show a different immunogenetic background, however the genetic basis of SAPHO syndrome remains unknown.

Análisis de costes en una cohorte de enfermos con artritis reumatoide atendidos en área especializada de reumatología en España / Cost analysis in a cohort of rheumatoid arthritis patients managed in rheumatology units in Spain

Objetivo: Conocer los costes generados durante un año por pacientes con artritis reumatoide (AR) atendidos en unidades de reumatología de hospitales públicos españoles. Métodos: Estudio observacional, multicéntrico, longitudinal y prospectivo, de un año de duración, realizado en unidades de reumatología de hospitales públicos españoles seleccionados de forma probabilística. Los pacientes con AR se seleccionaron aleatoriamente en cada hospital. Se realizaron 4 visitas (basal y cada 4 meses). Se registró la utilización de recursos y costes mediante diarios y entrevistas estructuradas. Resultados: Se incluyó a 301 pacientes y completaron 190 (83% mujeres), con edad (media ± DE) de 59 ± 13 años y duración de la enfermedad de 10 ± 10 años. El coste mediano anual por paciente fue de 3.845 euros (318- 36.783). El coste global anual estimado para la AR atendida en unidades de reumatología de hospitales públicos españoles es de 590.110.000 euros. De los costes globales, el 74% correspondió a costes directos y el 26% a costes indirectos. El 81% del coste directo fue por gasto médico y, de éste, el 56%, por fármacos y el 11%, por hospitalización, el 21% correspondió a visitas médicas y el 12%, a pruebas de laboratorio y complementarias. El principal componente del coste indirecto fue la invalidez, que supuso el 66% del total. Conclusión: El coste directo de la AR fue sustancialmente mayor que el indirecto. El coste por medicamentos fue el principal componente del coste. El coste anual por paciente tuvo un rango muy amplio debido a la gran variabilidad en la utilización de recursos(AU)

Objective: To assess the annual costs of rheumatoid arthritis (RA) patients attended at rheumatology units in Spanish public hospitals. Methods: A longitudinal, prospective, multicenter, observational, 1-year study was performed in the rheumatology units of randomly selected Spanish public hospitals. Randomly selected RA patients were included. The patients made four visits (at baseline and every 4 months). Resource use and costs were collected from patient diaries and structured questionnaires. Results: A total of 301 patients were included and 190 (83% women) completed the study. The mean (± SD) age was 59 ± 13 years and the mean disease duration was 10 ± 10 years. The median annual cost per patient was 3,845 euros (318-36,783). The estimated total annual cost of the Spanish RA population managed in the rheumatology units of public hospitals was 590,110,000 euros. Of total costs, 74% were direct costs and 26% were indirect costs. Medical costs represented 81% of direct costs. The main components of medical costs were drugs (56%), medical visits (21%), complementary tests (12%), and hospitalizations (11%). Permanent work disability represented 66% of indirect costs. Conclusions: Direct costs were substantially higher than indirect costs. The main components of medical costs were drugs. There was high variability in resource use with a wide range of annual costs per patient(AU)

[Resource utilization in a cohort of rheumatoid arthritis patients attended in rheumatology units in Spain]. / Utilización de recursos en una cohorte de pacientes con artritis reumatoide atendidos en área especializada de reumatología en España.

OBJECTIVE: To determine resource use over a 1-year period in patients with rheumatoid arthritis (RA) attended in rheumatology units in hospitals within the Spanish public health system. PATIENTS AND METHODS: An observational, longitudinal, prospective, multicenter, 1-year study was performed in randomly selected rheumatology units in hospitals of the Spanish public health system. Patients with RA were randomly selected in each hospital. Four visits (at baseline and every 4 months) were conducted by a rheumatologist not routinely involved in the care of the patient. Demographic and disease-related variables were collected. Patient diaries and systematic interviews were used to gather data on resource use. RESULTS: A total of 301 patients were included and 190 (83% females) completed the study. The mean age was 59 ± 13 years and the mean disease duration was 10 ± 10 years. The resources most heavily used were medical. All of the patients made medical visits with a median of four visits to rheumatologists (1-13). Ninetynine percent of the patients took at least one drug. The most frequent drugs were paracetamol (41%), deflaza-cort (32%), and methotrexate (24%). Laboratory tests were performed in all patients, and x-rays were performed in 59%. Sixty-one patients (32%) were hospitalized; 75% of these patients were non-surgical. The most frequently used non-medical direct resources were meals and home visits by non-medical staff (39%). Thirtyone patients (16%) had some type of work disability. CONCLUSIONS: AR is associated with substantial utilization of medical and non-medical resources related to the disease and work disability.

[Cost analysis in a cohort of rheumatoid arthritis patients managed in rheumatology units in Spain]. / Análisis de costes en una cohorte de enfermos con artritis reumatoide atendidos en área especializada de reumatología en España.

OBJECTIVE: To assess the annual costs of rheumatoid arthritis (RA) patients attended at rheumatology units in Spanish public hospitals. METHODS: A longitudinal, prospective, multicenter, observational, 1-year study was performed in the rheumatology units of randomly selected Spanish public hospitals. Randomly selected RA patients were included. The patients made four visits (at baseline and every 4 months). Resource use and costs were collected from patient diaries and structured questionnaires. RESULTS: A total of 301 patients were included and 190 (83% women) completed the study. The mean (± SD) age was 59±13 years and the mean disease duration was 10±10 years. The median annual cost per patient was 3,845 euros (318-36,783). The estimated total annual cost of the Spanish RA population managed in the rheumatology units of public hospitals was 590,110,000 euros. Of total costs, 74% were direct costs and 26% were indirect costs. Medical costs represented 81% of direct costs. The main components of medical costs were drugs (56%), medical visits (21%), complementary tests (12%), and hospitalizations (11%). Permanent work disability represented 66% of indirect costs. CONCLUSIONS: Direct costs were substantially higher than indirect costs. The main components of medical costs were drugs. There was high variability in resource use with a wide range of annual costs per patient.

Impacto del consumo de AINE en la población general española. Resultados del estudio EPISER / Effect of non-steroidal antiinflammatory agents in the general population in Spain. Results of the EPISER study

Objetivo: Estimar la frecuencia del uso significativo de los antiinflamatorios no esteroides (AINE) en la población adulta en España, así como de episodios adversos gastrointestinales (GI) y su repercusión sociosanitaria. Diseño: Encuesta poblacional. Sujetos: Se seleccionaron 2.988 sujetos mediante muestreo polietápico estratificado, a partir del padrón de 20 municipios. Intervención: Diversos reumatólogos específicamente entrenados administraron una entrevista estructurada en la que, entre otras preguntas, se interrogaba sobre el consumo de analgésicos y AINE, al menos durante un mes del año precedente (consumo significativo) para el alivio de síntomas musculosqueléticos. A todos los que habían tomado AINE se les preguntó si habían padecido episodios adversos GI y si su aparición había afectado a su actividad laboral o había obligado al uso de recursos asistenciales. Resultados: La tasa de captación fue del 73 por ciento (205 errores censales confirmados, 390 no localizados y 213 rechazos).La prevalencia acumulada en un año del consumo de AINE, durante al menos un mes, se estima en un 20,6 por ciento (IC del 95 por ciento, 15,8-25,4). La frecuencia de episodios adversos GI entre los consumidores de AINE se estima en el 23,7 por ciento (IC del 95 por ciento, 12,0-35,5), siendo causa de consultas médicas en un 72,5 por ciento de las veces. En 3 episodios adversos GI fue necesaria la hospitalización y en 10 tuvo lugar una pérdida de días de trabajo. Conclusión: El consumo significativo de AINE para el alivio de síntomas musculosqueléticos en la población general española es elevado. Existe una alta frecuencia de efectos adversos GI por AINE que ocasionan importantes consecuencias sanitarias y económicas. Impacto del consumo de AINE en la población general española. Resultados del estudio EPISER (AU)

The prevalence of rheumatoid arthritis in the general population of Spain.

OBJECTIVE: To estimate the prevalence of rheumatoid arthritis (RA) in the adult Spanish population and to assess its distribution by basic sociodemographic characteristics. METHODS: Two thousand nine hundred and ninety-eight adults were selected randomly from the censuses of 20 municipalities. Trained rheumatologists administered a structured interview that included a screening questionnaire for RA. Subjects with a positive screening result were examined according to a standardized protocol. Cases were defined by the 1987 American College of Rheumatology (ACR) criteria adapted to epidemiological surveys. RESULTS: One hundred and eighty-six persons (8.5%) had a positive screening result for RA and 11 of these fulfilled the ACR criteria for RA. The estimated prevalence was 0.5% (95% confidence interval 0.25-0.85). The ratios of women to men and of urban to rural were both 4:1. Function and health perception of the cases were significantly impaired, even after controlling for age and sex. CONCLUSION: The prevalence of RA in Spain is comparable to that in other Mediterranean countries. RA may be less frequent in rural settings, a finding that merits further research. A significant proportion of RA cases in the community remain undiagnosed despite impaired functional status.

The burden of musculoskeletal diseases in the general population of Spain: results from a national survey.

OBJECTIVE: The objective of the EPISER study was to estimate the prevalence of rheumatoid arthritis (RA), low back pain, hand and knee osteoarthritis (OA), and fibromyalgia in the adult Spanish population, and to assess the impact of these diseases on function and quality of life, and use of health and social resources. METHODS: 2998 subjects aged 20 years or above were randomly selected by stratified multistage cluster sampling from the censuses of 20 municipalities. Trained rheumatologists carried out structured visits at which subjects were asked about rheumatic symptoms and sociodemographic characteristics, completed validated instruments for measuring function (HAQ) and quality of life (SF-12), and underwent a standardised physical examination. Cases were defined by previously validated criteria. RESULTS: The estimated prevalences with 95% confidence intervals were as follows: RA lifetime cumulative: 0.5% (0.3 to 0.9); low back pain: 14.8% (12.2 to 17.4); symptomatic knee OA: 10.2% (8.5 to 11.9); hand OA: 6.2% (5.9 to 6.5); fibromyalgia: 2.4% (1.5 to 3.2). Most conditions significantly impaired function and quality of life. CONCLUSIONS: The EPISER study has internal and external validity for application of the results to the adult Spanish population. The diseases studied affect a significant proportion of the population, with various degrees of impact on disability and quality of life resulting in a significant number of physician visits, work disability, and medication use.

Pharmacokinetic differences between sodium fluoride and sodium monofluorophosphate and comparative bone mass increasing activity of both compounds in the rat.

After the administration of an oral dose of 80 mumol/l of NaF (CAS 7681-49-4) to rats, the area under the curve of total plasma fluoride equals 10,200 mumol.min/l. After an oral dose of 80 mumol of monofluorophosphate (MFP/CAS 10,163-15-2), two forms of fluoride appear in plasma: protein-bound MFP and diffusible fluoride. The areas under the curve of total (protein-bound + diffusible) and diffusible fluoride equal 22,200 and 8,850 mumol.min/l, respectively. The activity of MFP for increasing the bone mass of the rat was assessed with NaF as the standard. The animals were treated chronically for 100 days since weaning with food ad libitum and 5 mmol/l NaF, 5 or 2.5 mmol/l MFP solutions as the water supply. The effect obtained with 2.5 mmol/l MFP was similar to that produced by 5 mmol/l NaF, indicating a potency ratio MFP is twice as active as NaF.

Bone mass increase and glucose tolerance in rats chronically treated with sodium fluoride.

Female rats were treated with fluoride for 100 days (between 21 and 121 days of age) replacing the water supply with a 5 mM NaF solution. Bone mass was assessed by destructive physical and chemical measurements on the whole skeleton, that gave an overall view not reported previously. Bone mass (dry, fat-free weight of the skeleton/100 g of body weight) increased 7% (P less than 0.001) with respect to control animals. This phenomenon was equally evident in the head, the axial and the appendicular skeleton. Fluoride treatment did not affect the ratio ashes/organic matrix. Treated animals showed a subtle disturbance of glucose tolerance as shown by glucose tolerance tests. The disturbance was manifest as high plasma and soft tissue levels of fluoride during the period of bone mass increase. Glucose tolerance was normalized when the maximum bone mass was achieved and plasma and soft tissue fluoride returned to control levels.

Inhibitory effect of fluoride on the secretion of insulin.

The oral administration of sodium fluoride (NaF) (40 mumol/100 body weight [bw]) to fasting rats produced an immediate fall in insulin levels and the consequent increase in glycemia. These phenomena were observed with plasma fluoride concentrations 5-15 microM. Glycemia and insulin returned to normal levels within 4-5 hours, together with the washing out of fluoride from plasma and soft tissues. The insulin secretion of isolated Langerhans islets, perifused with solutions containing 5, 10, or 20 microM fluoride, was found to be significantly inhibited as a function of fluoride levels, both with basal and stimulatory concentrations of glucose. One hour after the intake of 60 mg of NaF, fasting human volunteers showed increased fluoride (5-15 microM) together with a significant fall of plasma insulin levels.

Calcium metabolism of intact and thyroparathyroidectomized rats fed a bicarbonate enriched diet.

Rats fed a bicarbonate-enriched diet become alkalotic during their feeding period (ca. 10 h/day). Alkalosis produced a significant reduction in the plasmatic concentration of ionized calcium and increased parathyroid hormone secretion confirmed by concurrent hypophosphatemia and increased urinary excretion of cAMP. Three weeks of treatment produced, however, a significant reduction of bone Ca resorption. The increased endogenous fecal excretion of calcium counteracted the enhancement of true calcium absorption. No significant change in the skeletal calcium mass was observed. Thyroparathyroidectomized rats fed the alkaline diet reduced further their rate of bone Ca resorption and increased significantly their skeletal calcium mass.

The effect of alkalosis on the glucose-mediated insulin release by the rat.

Bicarbonate loaded (alkalotic) rats had reduced plasma phosphate and ionized Ca concentrations and increased urinary cAMP excretion, phosphate clearance and pancreatic tissue uptake of extracellular calcium, all known effects of increased parathyroid hormone (PTH) secretion. Total insulin secretion after glucose challenge was enhanced in these animals. The response of alkalotic thyroparathyroidectomized rats, on the other hand, suggested exhaustion or inhibition of insulin secretion. The hypothesis is advanced that PTH, enhancing the permeability to calcium of the beta-cell membrane, compensated the effect of decreased calcium concentration in the extracellular fluid caused by alkalosis. PTH appears instrumental for homeostatic adjustments of insulin secretion.

The effect of alkalosis on the glucose-mediated insulin release by the rat.

Bicarbonate loaded (alkalotic) rats had reduced plasma phosphate and ionized Ca concentrations and increased urinary cAMP excretion, phosphate clearance and pancreatic tissue uptake of extracellular calcium, all known effects of increased parathyroid hormone (PTH) secretion. Total insulin secretion after glucose challenge was enhanced in these animals. The response of alkalotic thyroparathyroidectomized rats, on the other hand, suggested exhaustion or inhibition of insulin secretion. The hypothesis is advanced that PTH, enhancing the permeability to calcium of the beta-cell membrane, compensated the effect of decreased calcium concentration in the extracellular fluid caused by alkalosis. PTH appears instrumental for homeostatic adjustments of insulin secretion.