Rendimiento del ASAS Health Index en pacientes con Espondiloartritis de la vida real / Performance of ASAS Health Index in real life spondyloarthritis patients

Introducción: El cuestionario "Assessment of Spondyloarthritis International Society Health Index" (ASAS-HI) fue desarrollado para medir de manera global la funcionalidad y el estado de salud en pacientes con espondiloartritis (EspA). Se han propuesto puntos de corte para determinar diferentes estados de salud que fueron poco evaluados en pacientes de la vida real. Objetivos: Describir el estado de salud medido por ASAS-HI en pacientes argentinos con EspA axial (EspAax) y periférica (EspAp) en la práctica diaria y evaluar los factores asociados al pobre estado de salud. Materiales y métodos: Estudio de corte transversal, analítico y multicéntrico. Se incluyeron consecutivamente pacientes con EspAax y EspAp según criterios ASAS, de 15 centros argentinos. Análisis estadístico: Se realizó estadística descriptiva, análisis bivariado y multivariado (regresión logística múltiple) para evaluar los factores asociados al pobre estado de salud (ASAS-HI ≥12). Para analizar la validez de constructo de la herramienta se realizó correlación de Spearman entre el ASAS-HI y otros parámetros de evaluación de la enfermedad. Resultados: Se incluyeron 274 pacientes con EspA, con una edad media de 49 (±14) años y una duración mediana de la enfermedad de 62 meses (p25-75: 24-135), 155 (56,6%) de los pacientes eran de sexo masculino, 129 pacientes (47%) con EspAax y 145 (52,9%) EspAp. Según el ASAS-HI 119 pacientes (43,4%) presentaban buen estado de salud, 117 (42,7%) tenían estado de salud moderado y 38 (13.9%) pobre estado de salud. En los pacientes con EspAp el valor de ASAS-HI mediano fue de 7 (p25-75: 3-10). El ASAS-HI correlacionó positivamente con: DAS28: rho: 0.5 (p<0.001) y HAQ: rho: 0.54 (p<0.001). La variable asociada de manera independiente con pobre estado de salud fue el DAS28 (OR: 1.9, IC95% 1.1-3.4, p: 0.029). En los pacientes con EspAax el valor de ASAS-HI mediano fue de 6 (p25-75: 2.75-10). El ASAS-HI mostró correlación con: BASDAI: rho: 0.7 (p<0.001), ASDAS-ERS: rho: 0.7 (p<0,001), ASQoL: rho: 0.8 (p<0.001), BASFI rho: 0.75 (p<0.001). La variable que se asoció de manera independiente a pobre estado de salud fue el ASDAS-ERS (OR 6.6, IC95% 2-22, p 0.002). Conclusión: Un pobre estado de salud se asoció independientemente a mayor actividad de la enfermedad en pacientes con EspAax y EspAp. El ASAS-HI correlacionó con otros parámetros de la enfermedad, lo que refuerza la validez de constructo de esta nueva herramienta.

Introduction: The "Assessment of Spondyloarthritis International Society Health Index" (ASAS-HI) questionnaire was developed to globally measure function and health status in patients with spondyloarthritis (SpA). Cut-off points have been proposed to determine different health states that were poorly evaluated in real-life patients. Objectives: To describe the health status measured by ASAS-HI in Argentine patients with axial SpA (AxSpA) and peripheral SpA (SpAp) in daily practice and to evaluate the factors associated with poor health. Materials and methods: Cross-sectional, analytical and multicenter study. Patients with SpAax and SpAp were consecutively included according to ASAS criteria, from 15 Argentine centers. Statistical analysis: Descriptive statistics, bivariate and multivariate analysis (multiple logistic regression) were performed to evaluate the factors associated with poor health status (ASAS-HI ≥12). To analyze the construct validity of the tool, Spearman correlation was performed between the ASAS-HI and other disease evaluation parameters. Results: 274 patients with SpA were included, with a mean age of 49 (± 14) years and a median duration of the disease of 62 months (p25-75: 24-135), 155 (56.6%) were male, 129 patients (47%) with AxSpA and 145 (52.9%) SpAp. According to the ASAS-HI, 119 patients (43.4%) had good health, 117 (42.7%) had moderate health and 38 (13.9%) had poor health. In patients with SpAp, the mean ASAS-HI value was 7 (p25-75: 3-10). The ASAS-HI positively correlated with: DAS28: rho: 0.5 (p <0.001) and HAQ: rho: 0.54 (p <0.001). The variable independently associated with poor health status was DAS28 (OR: 1.9, 95% CI 1.1-3.4, p: 0.029). In patients with AxSpA, the mean ASAS-HI value was 6 (p25-75: 2.75-10). The ASAS-HI showed correlation with: BASDAI: rho: 0.7 (p <0.001), ASDAS-ERS: rho: 0.7 (p <0.001), ASQoL: rho: 0.8 (p <0.001), BASFI rho: 0.75 (p <0.001). The variable that was independently associated with poor health was the ASDAS-ERS (OR 6.6, 95% CI 2-22, p 0.002). Conclusion: Poor health status was independently associated with higher disease activity in patients with AxSpA and SpAp. The ASAS-HI correlated with other parameters of the disease, which reinforces the construct validity of this new tool.

Sexto reporte de eventos adversos con tratamientos biológicos en Argentina: Informe del registro BIOBADASAR / Sixth report of adverse events with biological treatments in Argentina: Report of the BIOBADASAR registry

Objetivo: Actualizar los resultados del registro BIOBADASAR sobre seguridad, duración y causas de interrupción del tratamiento luego de 8 años de seguimiento. Métodos: BIOBADASAR es un registro de seguridad de terapias biológicas establecido por la Sociedad Argentina de Reumatología. Se presenta la descripción de BIOBADASAR 3.0, una cohorte compuesta por 53 centros de Argentina seguidos prospectivamente desde agosto de 2010 hasta enero de 2018. Resultados: Se registraron 4656 pacientes, 6234 tratamientos [3765 casos (terapia con biológicos) y 2469 controles (terapia no biológicos)]. Se interrumpió el tratamiento en el 44,6% en los casos vs. 27,9% en los controles. Causa principal de discontinuación fue por ineficacia (40% casos vs. 32% controles). Se presentaron 3154 eventos adversos (2230 en casos vs. 924 en controles), de los cuales el 13,6% fueron graves (9,8% en casos y 3,7% en controles). El evento adverso (EA) más frecuente en ambos grupos fueron las infecciones (43,56% en casos vs. 34,31% en los controles, RR: 3,42; IC 95%: 3,02-3,88), y de ellas las de vías aéreas superiores (14,5%). Las neoplasias se presentaron en 78 casos vs. 45 en controles (RR: 1,98; IC 95%: 1,37-2,86). Conclusiones: En este sexto reporte no se observan tendencias diferentes sobre seguridad, duración y causas de interrupción del tratamiento respecto a informes previos. Las infecciones fueron el principal EA y la ineficacia, seguido por EA y la pérdida de pacientes las principales causas de suspensión del tratamiento. El advenimiento de nuevos agentes biológicos y la necesidad de control en seguridad a largo plazo, fortalece el uso de este tipo de registro.

Objective: Update the results of the BIOBADASAR registry on safety, duration and causes of treatment interruption after 8 years of follow-up. Methods: BIOBADASAR is a safety record of biological therapies established by the Argentine Society of Rheumatology. The description of BIOBADASAR 3.0 is presented, a cohort of 53 centers in Argentina followed prospectively from August 2010 to January 2018. Results: 4656 patients were registered, 6234 treatments [3765 cases (therapy with biologicals) and 2469 controls (non-biological therapy)]. Treatment was interrupted in 44.6% in cases vs. 27.9% in controls. Main cause of discontinuation was due to inefficiency (40% cases vs. 32% controls). There were 3154 adverse events (2230 in cases vs. 924 in controls), of which 13.6% were tombs (9.8% in cases and 3.7% in controls). The most frequent adverse event (AE) in both groups were infections (43.56% in cases vs. 34.31% in controls, RR: 3.42, 95% CI: 3.02-3.88), and the upper airway pathways (14.5%). Neoplasms were published in 78 cases versus 45 controls (RR: 1.98, 95% CI: 1.37-2.86). Conclusions: In this article, there are no different trends regarding safety, duration and causes of interruption of treatment compared to previous reports. Infections were the main causes of treatment discontinuation. The advent of new biological agents and the need for control over long-term security, strengthens the use of this type of registration.

Concordancia de los nuevos criterios ACR/EULAR y los ACR 1980 para la clasificación de la esclerosis sistémica / Concordance of the new ACR/EULAR criteria and the ACR 1980 for the classification of systemic sclerosis

Objetivo: Evaluar cumplimiento, y así mismo concordancia y discordancia de los criterios de clasificación de Esclerosis Sistémica (ES) ACR/EULAR 2013 y ACR 1980 en pacientes con diagnóstico clínico de la enfermedad. Método: Se incluyeron 169 pacientes con diagnóstico de Esclerosis Sistémica. Resultados: El 72,2 por ciento cumplía los criterios ACR 1980, y el 99,4 por ciento (168 pacientes) cumplía los criterios ACR/EULAR 2013. La concordancia absoluta de toda la muestra fue 72,7 por ciento, para el subtipo limitado 35,2 por ciento, y 100 por ciento el difuso. Se subanalizaron los pacientes con limitada que sólo cumplían criterios ACR/EULAR 2013, y se comparó con el resto de las limitadas. Los primeros presentaron en forma estadísticamente significativa menor esclerodactilia distal a MCF, menor presencia de úlceras digitales y pitting scars, menor afectación intersticial pulmonar, y mayor daño microvascular en la capilaroscopia. Conclusión: Los nuevos criterios de clasificación de Esclerosis Sistémica serían más adecuados para detectar esclerodermias limitadas, siendo dicho hallazgo estadísticamente significativo.

Objective: To evaluate the performance, and likewise concordance and discordance of the classification criteria of Systemic Sclerosis ACR/EULAR 2013 and ACR 1980 in a group of patients with clinical diagnosis of SSc. Methods: We enrolled 169 patients with diagnosis of Systemic Sclerosis. Results: 72.2 percent met the 1980 ACR criteria, and 99.4 percent met the ACR/EULAR 2013 criteria. The absolute agreement of the entire sample was 72.7 percent, 35.2 percent for the limited subtype, and 100 percent for the diffuse. Those patients with limited subtype who only met the ACR/EULAR 2013 criteria were compared with the rest of limited patients. The first group had statistically significantly lower sclerodactyly distal to MCF, lower presence of digital ulcers and pitting scars, less interstitial lung involvement, and greater abnormal nail fold capillaries. Conclusion: The new classification criteria for systemic sclerosis seem to be more suitable for detecting limited scleroderma. In the present study, statistically significant discrepancy was found in the limited subtype.

Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial.

UNLABELLED: Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p < 0.01) and QCT (5.7%, p < 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p < 0.0001), total hip (10.8%, p < 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p < 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.

[Effect of low doses of oral pamidronate (APD) on the calcemia of osteopenic or osteoporotic patients]. / Efecto de bajas dosis del pamidronato (APD) oral sobre la calcemia de pacientes osteopenicas u osteoporoticas.

Oral pamidronate (APD) at high doses (400-900 mg/day) is employed as antiresorptive agent for the treatment of Paget's disease. In some occasions hypocalcemia may occur, and is interpreted as a relative overdosage. To avoid this complication and the consequent PTH release, supplementation with calcium salts is recommended. In osteoporotic syndromes, APD is prescribed at a lower dosage (200 mg/day) and currently calcium or vitamin D are also systematically added. But at this low dose the antiresorptive activity is partial and transient. In order to observe the effects on calcemia of multiple therapy, data from 129 postmenopausal women with the diagnosis of osteopenia or osteoporosis treated with 200 mg/day of APD soft capsules during 6-10 months, were gathered retrospectively. The first group (n: 13) received APD alone; the second group was supplemented with 1 g/day calcium salts (n: 61); the third group received 0.015-0.025 mg/day vitamina D (n: 10); and the fourth received both calcium plus vitamin D (n: 45). In samples of 24 h, urine, calcium, creatinine, hydroxyproline, and serum total calcium were measured before and after therapy. No hypocalcemia was detected. All groups, except the one treated with APD alone, showed a significant trend to increase their calcemia values between normal ranges (Table 1, 2). Only in one patient treated with APD + Ca + vitamin D, hypercalcemia was detected. Measuring HOP/Cr and Ca/Cr in urine as resorption markers, showed that 27% of the APD + Ca group and 33% of the APD + Ca + vitamin D group showed scant or any repercussion on mentioned resorption indexes, meaning that the response to APD could be hindered in those cases. In conclusion, while using low doses of oral APD, calcium salts should not be systematically recommended. There is no trend to hypocalcemia. Furthermore, calcium salts may favor drug interactions and so induce digestive side effects or poor responses. Calcium supplementation should be prescribed only on the basis of low calcium diet and not to prevent APD collateral effects on calcemia.

Serum kinetics, bioavailability and bone scanning of 99mTc-labelled sodium olpadronate in patients with different rates of bone turnover.

The activity of olpadronate labelled with technetium-99m(99mTc) was monitored in plasma and urine samples after single oral (925 MBq 99mTc/10 mg, coadministered with 50 mg cold drug) and intravenous (925 MBq 99mTc/5 mg) administrations to two groups of patients with different rates of bone turnover. The first group comprised high bone turnover (HBTO) patients suffering from Paget's bone disease; the second group comprised patients with normal to low bone turnover (NBTO) having the diagnosis of rheumatoid arthritis and secondary osteoporosis. Kinetic variables were correlated with anthropomorphometric variables, biological markers of bone metabolism and plasma proteins. Data were also obtained after repeatedly dosing the HBTO patients. Additionally, Paget's bone and healthy bone (PB/HB) uptake before and after low-dose oral treatment were assessed by means of scintigraphy. Results showed that most of the kinetic variables did not differ between the two groups of patients, except for a greater Vss and smaller blood area under the curve AUC in the patients with HBTO. After a repeated-dose administration period, the blood AUC activity and Whole Body Retention (WBR) of the HBTO patients tended to be similar to those of the NBTO patients. In both groups, after oral dosing, the Cmax was 20 times lower than the C0.5 after i.v. injection, and the oral bioavailability ranged from 3% to 4%. Finally, the plasma t1/2 beta ranged from 9 to 14 h. Correlation coefficients were obtained from multiple regression analysis; kinetic variables showed very low correlations with anthropomorphometric measurements. In contrast the Vss and WBR were significantly correlated with serum alkaline phosphatase levels and the Vss also with urine hydroxyproline levels. Plasma protein concentration was also correlated with excretion parameters such as CLP and plasma t1/2 beta after an oral dose. Scintigraphic studies in the HBTO group allowed bone selectivity to be seen through skeletal drug uptake. The 15 Pagetic lesions analysed in the HBTO group showed a decrease in PB/HB ratio from 3.8 in the basal study to 2.7 after olpadronate administration for 30 days at the rate of 50 mg/day. In conclusion, the kinetic profile of 99mTc-labelled olpadronate, mainly AUC and WBR, showed a dependence upon bone metabolism and seemed unrelated to body size variables. HBTO patients showed a lower blood AUC but a higher Vss. Both variables may have been reflecting the fact that the drug binds selectively with calcified tissues and, in turn, with the target compartment. Scintigraphy confirmed the labelled-compound bone selectivity as a desirable feature for a bone-scanning agent.

[Kinetics of chemoluminiscence of rat intestine during ischemia and reperfusion]. / Cinética de la quimioluminescencia del intestino de la rata durante isquemia y reperfusión.

Oxygen free radicals are involved in ischemic and reperfusion tissular injuries. Chemiluminescence of organs reflects the steady state level of peroxy radicals, usually generated by oxygen radicals. In this study, chemiluminescence of intestine has been determined in rats subjected to 2, 5 or 10 min of occlusive ischemia by ligation. During the ischemic period, chemoluminescence tends to decrease. After delegation, a constant response, a chemiluminescence overshoot, can be obtained only in the group of rats subjected to 2 min of ligation. This methodology does not provide constant results with longer periods of ligation. In other groups of rats subjected to 2 min of ligation and then delegated, the kinetics of the organ emission in function of time show a mean overshoot of about 44% after 3 min of reperfusion. This early excess of chemiluminescence is maintained for the first 10 to 20 min after delegation, but not for longer periods. The administration of a free radical scavenger, thioctic acid 100 mg/kg i.p., prevents or reduces the amount of the overshoot previously described during the 20 min postdelegation follow-up period. These data suggest that excessive oxygen radical generation occurs in vivo during the early minutes of reperfusion and may be the consequence of very fast enzymatic changes during the short-term previous hypoxic period. Further studies are needed to demonstrate the subsequent functional alteration and the pathological implication of this phenomenon.

Cinetica de la quimioluminescencia del intestino de la rata durante isquemia y reperfusion / Kinetics of luminiscence of rat intestine during ischemia and reperfusion

En este estudio se determina in vivo la quimioluminescencia del intestino de rata sometido a isquemia provocada por una ligadura oclusiva y luego durante la reperfusión al desligar el órgano. La quimioluminescencia del órgano en función del tiempo, en animales sometidos a 2, 5 y 10 minutos de isquemia tiende a disminuir rápidamente. En intestinos de ratas ligados durante 2 minutos y luego desligados, comparados con intestinos no ligados, se muestra un exceso medio de quimioluminescencia del 44% aproximadamente luego de 2 a 3 minutos de iniciada la reperfusión. Este exceso inicial de quimioluminescencia se mantiene entre los primeros 10 a 20 minutos posteriores a la desligadura, no habiéndose registrado períodos más prolongados. la administración de un atrapador de radicales libres, ácido tióctico 100 mg/kg, i.p. evita o reduce el exceso de quimioluminescencia descripto, por un período de por lo menos 20 minutos. Estos datos concuerdan con la sugerencia de que la generación excesiva de radicales del oxígeno tiene lugar in vivo desde los minutos iniciales de la reperfusión y puede ser la consecuencia de cambios enzimáticos producidos muy rápidamente durante el anterior período hipóxico

Cinetica de la quimioluminescencia del intestino de la rata durante isquemia y reperfusion / Kinetics of luminiscence of rat intestine during ischemia and reperfusion

En este estudio se determina in vivo la quimioluminescencia del intestino de rata sometido a isquemia provocada por una ligadura oclusiva y luego durante la reperfusión al desligar el órgano. La quimioluminescencia del órgano en función del tiempo, en animales sometidos a 2, 5 y 10 minutos de isquemia tiende a disminuir rápidamente. En intestinos de ratas ligados durante 2 minutos y luego desligados, comparados con intestinos no ligados, se muestra un exceso medio de quimioluminescencia del 44% aproximadamente luego de 2 a 3 minutos de iniciada la reperfusión. Este exceso inicial de quimioluminescencia se mantiene entre los primeros 10 a 20 minutos posteriores a la desligadura, no habiéndose registrado períodos más prolongados. la administración de un atrapador de radicales libres, ácido tióctico 100 mg/kg, i.p. evita o reduce el exceso de quimioluminescencia descripto, por un período de por lo menos 20 minutos. Estos datos concuerdan con la sugerencia de que la generación excesiva de radicales del oxígeno tiene lugar in vivo desde los minutos iniciales de la reperfusión y puede ser la consecuencia de cambios enzimáticos producidos muy rápidamente durante el anterior período hipóxico (AU)

Cinética de la quimioluminescencia del intestino de la rata durante isquemia y reperfusión. / [Kinetics of chemoluminiscence of rat intestine during ischemia and reperfusion]

Oxygen free radicals are involved in ischemic and reperfusion tissular injuries. Chemiluminescence of organs reflects the steady state level of peroxy radicals, usually generated by oxygen radicals. In this study, chemiluminescence of intestine has been determined in rats subjected to 2, 5 or 10 min of occlusive ischemia by ligation. During the ischemic period, chemoluminescence tends to decrease. After delegation, a constant response, a chemiluminescence overshoot, can be obtained only in the group of rats subjected to 2 min of ligation. This methodology does not provide constant results with longer periods of ligation. In other groups of rats subjected to 2 min of ligation and then delegated, the kinetics of the organ emission in function of time show a mean overshoot of about 44

after 3 min of reperfusion. This early excess of chemiluminescence is maintained for the first 10 to 20 min after delegation, but not for longer periods. The administration of a free radical scavenger, thioctic acid 100 mg/kg i.p., prevents or reduces the amount of the overshoot previously described during the 20 min postdelegation follow-up period. These data suggest that excessive oxygen radical generation occurs in vivo during the early minutes of reperfusion and may be the consequence of very fast enzymatic changes during the short-term previous hypoxic period. Further studies are needed to demonstrate the subsequent functional alteration and the pathological implication of this phenomenon.

[Gastrointestinal involvement in progressive systemic sclerosis]. / Compromiso gastrointestinal en la esclerosis sistémica progresiva.

25 patients with clinical, radiological and manometrical features of PSS in the gastrointestinal tract were reviewed, looking mainly for the esophageal involvement. All of the data obtained in our serie agreed with those of most of the authors. Outlining: The lack of relationship between the evolution of the skin involvement and GI tract involvement. The high incidence of esophageal involvement, especially functional alterations even in the absence of clinical and/or radiological symptomatology. The usefulness of manometric method in the diagnosis of motor involvement of esophages, especially for the evaluation of lower esophageal esphincter. Although the esophageal and intestinal involvement are more frequent and well known, any area of the GI tract may be damaged during the course of this disease. Since up to now, an ethiological therapy to stop the course of the disease is not known, it's important to search for earlier alterations in order to start with a pathophysiological and symptomatic treatment to avoid complications.