Preferencias del tratamiento en pacientes con Espondiloartritis axial / Treatment preferences in patients with axial spondyloarthritis

Introducción: Una de las premisas del Treat to Target (T2T) es la decisión conjunta del tratamiento entre el reumatólogo y el paciente. Por esta razón las preferencias del paciente juegan un rol fundamental en el éxito del tratamiento a corto y largo plazo. El objetivo de este estudio fue evaluar las preferencias de tratamiento de los pacientes con Espondiloartritis axial (EsPax) e identificar factores asociados a su elección. Material y métodos: Estudio de corte transversal de la cohorte ESPAXIA de pacientes ≥18 años de edad con EsPax (según criterios ASAS 2009). Se consignaron datos sociodemográficos, comorbilidades, características de la enfermedad, y tratamientos recibidos. Se administró un cuestionario especialmente diseñado, en modalidad de elección múltiple y/o respuesta categorizada según orden de importancia de los enunciados. Análisis estadístico: Estadística descriptiva. Test T de Student, test de Chi2 y análisis de regresión logística múltiple. Se consideró significativo un valor de p<0,05. Resultados: Se incluyeron 70 pacientes con una edad mediana (m) de 46,5 años (RIC: 38-57) y un tiempo m de evolución de 13,5 años (RIC: 7,75-23,25). Los aspectos más importantes en la elección del tratamiento fueron: la capacidad de mejoría en la calidad de vida, seguido por mejoría en la inflamación articular, el dolor y la función física. Las vías de administración elegidas en orden decreciente de frecuencia fueron: vía oral (VO) 51,4%, subcutánea (SC) 41,4%, intramuscular (IM) 4,3% y endovenosa (EV) 2,9%. El intervalo entre dosis más votado en la VO fue 1 comprimido semanal (61,1%), y en la SC, 1 aplicación mensual (34,5%). La elección de la VO, se asoció con: preferencia por la autoaplicación, preferencia de aplicación en el hogar y mayor nivel de escolaridad. La elección de la vía SC, fue más frecuente en los pacientes con EA. Los pacientes que recibían tratamiento biológico por vía SC, así como aquellos que tenían la actividad de su enfermedad más controlada, tuvieron mayor conformidad con el tratamiento. Conclusión: La vía de administración de la medicación preferida en nuestra cohorte de pacientes con EsPax fue la oral. Los pacientes con mayor conformidad de tratamiento fueron aquellos que recibían el tratamiento biológico por vía SC y los que tenían menor actividad de la enfermedad.

Background: One of the premises of the Treat to Target (T2T) is the shared treatment decision between the rheumatologist and the patient. For this reason, patient preferences play a fundamental role in the success of treatment in the short and long term. The aims of this study were to evaluate the treatment preferences of patients with Axial Spondyloarthritis (axSpA) and to identify the factors associated with their choice. Material and methods: Cross sectional study. Patients ≥18 years old that fulfilled the ASAS 2009 criteria for axSpA were included. Sociodemographic data, comorbidities, disease characteristics, and treatments received were recorded. A specially designed questionnaire in both, multiple choice modality and response mode listed in order of priority of the statements was administered. Statistical analysis: Descriptive statistics. Student's T-test, Chi2 test and multiple logistic regression analysis. A value of p <0.05 was considered significant. Results: Seventy patients were included with a median age (m) of 46.5 years (IQR: 38-57), 55 males (78.6%) and a median disease duration of 13.5 years (IQR: 7.75-23.25). The relevant aspects for choosing a treatment were: the ability to improve the quality of life (32.9%), followed by improvement in joint inflammation (22.9%), pain (21.4%) and physical function (14.3%). The chosen administration routes in decreasing order of frequency were: oral (51.4%), subcutaneous (SC) (41.4%), intramuscular (IM) 4.3% and intravenous (IV) 2.9%. The preferred frequency of oral administration was one tablet per week (61.1%) and SC administration, once a month (34.5%). The choice of oral route was associated with: preference for self-administration, preference for receiving the medication at home and higher level of education. The choice of the SC route was independently associated with the type of axSpA (AS) and a lower educational level. The patients under biological SC treatment and with lower disease activity, showed higher level of treatment satisfaction. Conclusion: The most preferred way of administration by patients with axSpA was the oral route. Lower disease activity and SC biological treatment were associated with treatment greater compliance.

Tolerancia, sobrevida y adherencia al tratamiento con Metotrexato en pacientes con artritis reumatoidea / Tolerance, survival and adherence to Methotrexate treatment in patients with rheumatoid arthritis

Introducción: Metotrexato (MTX) es la medicación más utilizada en pacientes con Artritis Reumatoidea (AR). Sin embargo, varios autores han cuestionado su éxito debido a la frecuente presencia de eventos adversos y la consiguiente falta de adherencia al tratamiento. Objetivos: Determinar la sobrevida al tratamiento con MTX, eventos adversos y causas de discontinuación en pacientes con AR. Material y métodos: Se incluyeron pacientes ≥18 años de edad con diagnóstico de AR (criterios ACR/EULAR 2010), en forma consecutiva, que hubiesen iniciado en algún momento tratamiento con MTX. Se consignaron datos sociodemográficos, clínicos y terapéuticos. Se determinó fecha de inicio y suspensión de MTX, forma de administración, tratamientos concomitantes, consumo de café y tabaco, como también presencia de eventos adversos (EA). La adherencia se evaluó utilizando el cuestionario Compliance Questionnaire Rheumatology de 5 ítems (CQR5). Análisis estadístico: Estadística descriptiva. Test Chi² o test exacto de Fisher. Sobrevida del tratamiento por Kaplan-Meier y log Rank. Regresión logística múltiple. Una p <0,05 se consideró significativa. Resultados: Se incluyeron 118 pacientes, 101 mujeres (85,6%), con una edad mediana (m) de 56 años (RIC 49-64) y tiempo m de evolución de 10 años (RIC 6-18). Ochenta y cinco pacientes (72%) recibieron MTX por vía oral. 43,2% presentaron EA asociados al MTX, donde solo 20 pacientes (16,9%) tuvieron que discontinuar. La intolerancia digestiva fue el EA más frecuente (27,1%), seguida por alteraciones del laboratorio (12,7%). 86,6% de los pacientes presentaron una adherencia ≥80%. La supervivencia mediana acumulada del tratamiento con MTX fue de 348 meses (IC 95%: 235-460,9). En los análisis uni y multivariados no se encontró asociación de la sobreviva del MTX con variables sociodemográficas, características de la enfermedad, tratamiento concomitante, vía de administración, consumo de café y nivel de adherencia. Conclusión: En nuestra cohorte, la adherencia y sobrevida del tratamiento con MTX fueron buenas. La sobrevida acumulada fue de casi 30 años. La presencia de EA no determinó la suspensión del tratamiento en la mayoría de los casos.

Background: Methotrexate (MTX) is the most frequently used medication in patients with Rheumatoid Arthritis (RA). However, several authors have questioned its success due to the presence of adverse events and the lack of adherence. Objectives: To determine cumulative survival of MTX, frequency and type of adverse events and causes of discontinuation in patients with RA. Methods: Consecutive patients 18 years and older with a diagnosis of RA (ACR/EULAR 2010 criteria), who had begun treatment with MTX during their disease were included. Sociodemographic, clinical and therapeutic data were collected. Date of initiation and suspension of MTX, route of administration, concomitant treatments, consumption of coffee and tobacco, presence of adverse events (AE) were all consigned. Adherence was evaluated using the Compliance Questionnaire Rheumatology questionnaire 5-item summary version (CQR5). Statistical analysis: Descriptive statistics. Chi² test or Fisher's exact test; Survival of treatment by Kaplan-Meier and log Rank. Multiple logistic regression. A p value <0.05 was considered significant. Results: We included 118 patients, 101 were women (85.6%), with a median age (m) of 56 years (IQR 49-64) and disease duration m 10 years (IQR 6-18). Thirty-five patients (29.7%) were smokers and 56 patients (47.5%) consumed coffee. Eighty-five patients (72%) received MTX orally. 43.2% presented AE associated with MTX, but only 20 patients (16.9%) had to discontinue MTX. Gastrointestinal intolerance was the most frequent AE (27.1%), followed by laboratory test abnormalities (12.7%). 86.6% of the patients presented an adherence ≥80%. The median cumulative survival of MTX treatment was 348 months (95% CI: 235-460.9). In the univariate and multivariate analysis, there was no association of survival of MTX with sociodemographic variables, disease characteristics, concomitant treatment, route of administration, coffee consumption nor level of adherence. Conclusions: In our cohort, adherence and survival of MTX treatment were good. The cumulative survival was almost 30 years. The presence of AE did not determine the suspension of treatment in most cases.

Seasonal composition, abundance and biomass of the subestuarine fish assemblage in Solís Chico (Río de la Plata estuary, Uruguay) / Composição, abundância e biomasa sazonal da assembleia de peixes no subestuário do Solís Chico (Estuário do Río de la Plata, Uruguay)

Abstract The large estuaries can present long narrow branches called subestuaries or tidal creeks. These types of subsystems are distributed along the Uruguayan coast of the Río de la Plata estuary and are very important as nursery and refuge areas for fish. For the first time, the seasonal composition and abundance of the fish community of the Solís Chico subestuary was studied by using beach and gill nets. Fourteen species, mainly euryhaline (86%) presented a significant representation of juvenile stages. The fish community was dominated by Odontesthes argentinensis, Platanichthys platana, Mugil liza, Brevoortia aurea, Micropogonias furnieri and Paralichthys orbignyanus, similar to adjacent subestuaries. While Micropogonias furnieri and B. aurea were the most abundant species, some other species were rarely caught. A seasonal variation of the fish assemblage abundance was detected, with higher values in autumn showing a positive correlation with temperature. Species that complete their life cycle in the Río de la Plata estuary, some of which are relevant to fisheries (64% of the analyzed species) were captured in the Solís Chico subestuary. The importance of this environment as a transitional system for some estuarine fish species is advised.

Resumo Os grandes estuários podem apresentar longos ramos estreitos chamados subestuários e riachos de maré. Estes subsistemas estão distribuídos ao longo da costa uruguaia no estuário do Río de la Plata e são muito importantes como áreas de reprodução e refúgio para os peixes. Pela primeira vez, a composição sazonal e abundância da comunidade de peixes do subestuário Solís Chico foi estudada usando redes de arrasto de praia e rede de emalhar. Quatorze espécies com predominância das eurialinas foram capturadas, havendo uma representação significativa das fases juvenis e espécies alvo para a pesca. A comunidade de peixes foi dominada por Odontesthes argentinensis, Platanichthys platana, Mugil liza, Brevoortia aurea, Micropogonias furnieri e Paralichthys orbignyanus, semelhante aos subestuários adjacentes. Enquanto, M. furnieri e B. aurea foram as espécies com maior número de individuos. Solís Chico apresentou espécies exclusivas com baixa abundância e ocorrência. Foi verificada uma variação sazonal da abundância de peixes, com valores maiores no outono, mostrando uma correlação positiva com a temperatura. Algumas espécies relevantes para a pesca que completam seu ciclo de vida no estuário do Río de la Plata foram capturadas (64% das espécies estudadas) no subestuário Solís Chico, indicando a importância deste ambiente como um sistema transitório para algumas espécies estuarinas de peixes.

Hemorragia alveolar difusa asociada a vasculitis ANCA positiva, manejo con plasmaféresis. reporte de un caso / ANCA vasculitis associated diffuse alveolar hemorrhage treated with plasmapheresis: a case report

Presentamos el caso de una paciente femenina de 43 años con vasculitis tipo ANCA con severo compromiso pulmonar por desarrollo de hemorragia alveolar difusa (HAD) e insuficiencia respiratoria. Debido al rápido deterioro clínico y pobre respuesta a inmunosupresores (ciclofosfamida y metilprednisolona) se le practicó plasmaféresis resultando en rápida mejoría, permitiendo la liberación en la ventilación mecánica y mejoría radiológica. En la actualidad se puede sugerir esta terapia en pacientes con diagnóstico de vasculitis tipo ANCA con compromiso pulmonar severo.

We describe a 43 years old woman who was diagnosed of ANCAassociated vasculitides (AAV) with onset of diffuse alveolarhemorrhage and poor pulmonary function. She developed a clinicaldeterioration in spite of cyclophosphamide and methylprednisolonetreatment, and plasmapheresis was performed. She was successfullytreated with timely plasma exchange and immunosuppressivetreatment. Early plasmapheresis with immunosuppressant therapycan rescue this fatal complication.

Isolation and characterization of a serine proteinase with thrombin-like activity from the venom of the snake Bothrops asper

A serine proteinase with thrombin-like activity was isolated from the venom of the Central American pit viper Bothrops asper. Isolation was performed by a combination of affinity chromatography on aminobenzamidine-Sepharose and ion-exchange chromatography on DEAE-Sepharose. The enzyme accounts for approximately 0.13 percent of the venom dry weight and has a molecular mass of 32 kDa as determined by SDS-PAGE, and of 27 kDa as determined by MALDI-TOF mass spectrometry. Its partial amino acid sequence shows high identity with snake venom serine proteinases and a complete identity with a cDNA clone previously sequenced from this species. The N-terminal sequence of the enzyme is VIGGDECNINEHRSLVVLFXSSGFL CAGTLVQDEWVLTAANCDSKNFQ. The enzyme induces clotting of plasma (minimum coagulant dose = 4.1 µg) and fibrinogen (minimum coagulant dose = 4.2 µg) in vitro, and promotes defibrin(ogen)ation in vivo (minimum defibrin(ogen)ating dose = 1.0 µg). In addition, when injected intravenously in mice at doses of 5 and 10 µg, it induces a series of behavioral changes, i.e., loss of the righting reflex, opisthotonus, and intermittent rotations over the long axis of the body, which closely resemble the `gyroxin-like' effect induced by other thrombin-like enzymes from snake venoms.

Evaluation of antivenoms in the neutralization of hyperalgesia and edema induced by Bothrops jararaca and Bothrops asper snake venoms

Neutralization of hyperalgesia induced by Bothrops jararaca and B. asper venoms was studied in rats using bothropic antivenom produced at Instituto Butantan (AVIB, 1 ml neutralizes 5 mg B. jararaca venom) and polyvalent antivenom produced at Instituto Clodomiro Picado (AVCP, 1 ml neutralizes 2.5 mg B. aspar venom). The intraplantar injection of B. jararaca and B. asper venoms caused hyperalgesia, which peaked 1 and 2 h after injection, respectively. Both venoms also induced edema with a similar time course. When neutralization assays involving the independent injection of venom and antivenom were performed, the hyperalgesia induced by B. jararaca venom was neutralized only when bothropic antivenom was administered iv 15 min before venom injection, whereas edema was neutralized when antivenom was injected 15 min or immediately before venom injection. On the other hand, polyvalent antivenom did not interfere with hyperalgesia or edema induced by B. asper venom, even when administered prior to envenomation. The lack of neutralization of hyperalgesia and edema induced by B. asper venom is not attributable to the absence of neutralizing antibodies in the antivenom, since neutralization was achieved in assays involving preincubation of venom and antivenom. Cross-neutralization of AVCP or AVIB against B. jararaca and B. asper venoms, respectively, was also evaluated. Only bothropic antivenom partially neutralized hyperalgesia induced by B. asper venom in preincubation experiments. The present data suggest that hyperalgesia and edema induced by Bothrops venoms are poorly neutralized by commercial antivenoms even when antibodies are administered immediately after envenomation

Effect of adjuvants on the antibody response of mice to Bothrops asper (Terciopelo) snake venom

The adjuvant of several immunostimulant molecules on the murine antibody response to Bothrops asper snake venom were evaluated. Mice receiving venom together with either sodium alginate, calcium alginate, aluminum hydroxide, muramyl dipeptide, killed Brucella abortus or B. abortus smooth lipopolysaccharide developed a similar antibody response. Despite the fact that in some cases animals injected with venom and Salmonella montevideo lipopolysaccharide developed a significantly higher antibody titer when compared to other experimental groups, no statistically significant differences were observed in most of the comparisons.

Neutralization of coral snake Micrurus nigrocinctus venom by a monovalent antivenom

The neutralizing ability of a monovalent anti-Micrurus nigrocinctus (coral snake) antivenom produced in Costa Rica was tested against the letal, myotoxic and phospholipase A, activities of homologous venom. In addition, immunodiffusion and Western blot analyses were performed. in experiments where venom and antivenom were incubated prior to the test, antivenom was effective in neutralizing lethal, myotoxic and phospholipase A2, activities, with Effective Doses 50% of 2700 *l antivenom/mg venom, 1840 *l antivenom/mg venom, and 3630 *l antivenom, respectively. When coral snake antivenom was administered different times after coral snake venom injection, neutralization of lethality was achieved ehen antivenom was injected iv immediately and 15 min after venom. In contrast, lethaly was not reduced when antivenom was administered by the route. Only partial neutralization of myotoxixity was observed even when antivenom was injected iv immediately after envenomation. Immunodiffusion and immunoblot analyses demonstrated the presence of antibodies in antivenom against several, but not all, venom components

South American snake venom proteins antigenically related to bothrops asper myotoxins

1. the presence of proteins antigenically related to Bothrops asper myotoxins in various snake venoms, mainly from South America, was investigated by using poluclonal and monoclonal antibodies. 2. Myotoxin-like components were detected in the bothrops venoms from South america, and in the venoms of Crotalus atrox (North america), Trimerusurus flavoviridis (Japan), and Micrurus alleni (Costa Rica). 3. Cross-reactive components detected in several Bothrops venoms show a common subunit of 15-16 LDa by sodium dodcyl sulphate-polyacrylamide gel electrophoresis, although significant charge variations are evident by immunoelectrophoresis. 4. It is concluded that proteins antigenically related to B. asper nyotoxins are relatively common in the genus Bothrops and, in the light of findings discussed, are likely to posses myotoxic activity

Tuberculosis extrapulmonar. Analisis de 450 casos. / Extrapulmonary tuberculosis. Analysis of 450 cases

Se comenta la experiencia recogida del analisis de 450 casos de tuberculosis extrapulmonar, que por trabajar en un hospital general integrado al programa de control de la tuberculosis y contar con los medios de diagnostico y seguimiento necesarios pudimos comprobar en el termino de nueve anos(1973-1981). Se destaca en especial la metodologia seguida en la confirmacion diagnostica, efectuando un juicio critico de la misma. El estudio histopatologico y el cultivo del material obtenido por biopsia han sido los metodos de eleccion en nuestra experiencia y por ello los propiciamos

Las actividad proteolitica de los venenos de serpientes de Costa Rica sobre la caseina. / Proteolytic activity of snake venoms of Costa Rica on casein

Se establecen las condiciones optimas para la determinacion comparativa de la actividad proteolitica de los venenos de serpientes costarricenses sobre la caseina y se describe dicha actividad para 13 venenos diferentes. Los venenos mostraron marcadas diferencias de actividad entre las diversas especies y aun entre los venenos de ejemplares de distintas zonas geograficas dentro de una misma especie