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.

Paciente joven en hemodiálisis con más de veinte accesos vasculares / Young patient on hemodialysis with more than twenty vascular access

Introducción: El acceso vascular supone un pilar fundamental en el tratamiento dialítico de los pacientes renales. El empleo de catéteres se ha incrementado en los últimos años. Caso clínico: Varón de 49 años que inició tratamiento de hemodiálisis a sus 32 años. Presentó 7 accesos registrados (tiempo medio de uso: 64 días) hasta el primer trasplante y otros 15 accesos (tiempo medio de uso: 162 días) y 11 infecciones por el germen Staphylococcus Epidermidis, hasta recibir el segundo trasplante, que perdió a los 5 días por infarto renal isquémico masivo, volviendo a hemodiálisis con la colocación de un catéter venoso central tunelizado femoral izquierdo, que dura hasta la actualidad sin complicaciones destacables, gracias al diagnóstico posterior de la mutación heterocigótica del factor V de Leiden (que provoca un trastorno de hipercoagulabilidad), comenzando anticoagulación oral con acenocumarol de forma domiciliaria y heparina de bajo peso molecular intradiálisis desde ese momento. Discusión: Tras comenzar el sellado del catéter con Citrato + Heparina sódica (inicialmente incluía también Taurolidina pero se eliminó debido a intolerancia), no presentó más infecciones. Debido al diagnóstico de la mutación heterocigótica del factor V de Leiden, nos planteamos la posibilidad de que los fracasos de los accesos anteriores sean debidos al desconocimiento de esta mutación. Ante la situación demográfica de España se pone de manifiesto la necesidad de equipos multidisciplinares más amplios e incluir un control y seguimiento del acceso tunelizado para reducir sus pérdidas y evitar situaciones altamente invasivas

Introduction: The vascular access is a basic pillar in the dialytic treatment of renal patients. The use of catheters has increased in recent years. Clinical case: 49 year old male who started hemodialysis treatment at 32 years. He presented 7 registered access (average use time: 64 days) until the first transplant and other 15 accesses (average use time: 162 days) and 11 infections by Staphylococcus Epidermidis, until receive the second transplant. He lost the graft 5 days after by massive renal ischemic infarction, returning to hemodialysis with the placement of a central venous catheter tunneled in left femoral, that last to the present day without notable complications, mainly due to the subsequent diagnosis of heterozygous mutation in the factor V Leiden (that causes a hypercoagulability disorder), starting oral anticoagulation with acenocoumarol in his home and intradialytic heparin low molecular weight since that time. Discussion: After starting the sealed catheter with citrate + heparin sodium (initially it also includes Taurolidina, but it was removed due to intolerance), did not give more infections. Because of the diagnosis of heterozygous factor V Leiden mutation, we consider the possibility that the previous access failures are due to ignorance of this mutation. Given the demographic situation in Spain, we highlight the need to expand the multidisciplinary teams and include a protocol of control and monitoring of the tunneled access to reduce their losses and avoid a highly invasive

Características de los tratamientos biológicos en enfermedades reumáticas en Argentina: quinto informe del registro BIOBADASAR / Features of rheumatic diseases biological treatments in Argentina: BIOBADASAR fifth report

Introducción: El proyecto BIOBADASAR (Registro argentino deeventos adversos con tratamientos biológicos en reumatología)comenzó en agosto de 2010, para recabar información a largo plazosobre los eventos adversos en tratamientos biológicos en pacientescon enfermedades reumáticas en la práctica clínica cotidiana enArgentina.Pacientes y método: Se registraron datos de cada paciente,tratamientos y acontecimientos adversos relevantes o importantes.Los pacientes debían tener enfermedad diagnosticada y tratadacon un agente biológico. Cada caso se comparó con un control:un paciente con tratamiento no biológico con característicasdemográficas similares. Se analizaron los datos con análisis de lavarianza, con test de t de Student, Mann Whitney, test chi2, o testexacto de Fisher. El análisis de supervivencia de los tratamientoshasta su discontinuación o interrupción se realizó con el método deKaplan-Meier y test log-rank...

Background: BIOBADASAR (Argentine Registry of Adverse Eventsin Biological Treatments in Rheumatology) was started in August2010 to obtain long-term information of patients with rheumatic diseases,treatments and adverse events in everyday clinical practice.Patients and methods: Data on patients’ demographics,treatments and adverse events were collected. Patients had a diagnosisof a rheumatic disease and were treated with biological agent.To compare information, a control group was included, consisting ofpatients treated with similar demographic characteristics but treatedwith a non-biological agent. Data were analysed with Anova,Student´s t, Mann Whitney, chi2, Fisher´s exact tests, as appropriate.Survival analysis of treatments was performed with Kaplan-Meiercurves and log-rank test...

Tercer reporte de eventos adversos con tratamientos biológicos en Argentina. Informe de registro biobadasar / Thrid report of adverse events with biologics in Argentina. Report from biobadasar registry

Introducción: BIOBADASAR (Registro Argentino de Eventos Adversos con Tratamientos Biológicos en Reumatología) comenzó en agosto de 2010. La importancia de este registro es mostrar datos locales que, probablemente, puedan diferir de otros registros. El objetivo es comunicar los resultados del tercer reporte de BIOBADASAR. Métodos: Todos los pacientes con enfermedades reumáticas que requirieron tratamiento con agentes biológicos y pacientes controles sin estos tratamientos fueron incluidos en la base de datos provenientes de 32 centros participando a lo largo de la Argentina. Tres áreas de datos son analizados: características de los pacientes, tratamientos y eventos adversos...

Introduction: BIOBADASAR (Argentine Registry of Adverse Events with Biological Treatments in Rheumatology) began in August 2010. The importance of this registry is to show local data that may probably differ from other registries. The objective is to communicate the results of the third BIOBADASAR report. Methods: All patients with rheumatic diseases who required treatment with biological agents and control patients without these treatments were included in the database from 32 participating centers throughout Argentina. Three areas of data are analyzed: patient characteristics, treatments and adverse events...

Primer reporte de eventos adversos de tratamientos biológicos en Argentina. Informe de Registro BIOBADASAR / First report of adverse events for biologic treatments in Argentine. BIOBADASAR Register

Introducción: En la actualidad existe gran cantidad de pacientes sometidos a tratamiento con agentes biológicos en enfermedades reumatológicas y se desconocen los efectos adversos predominantes, así como la eficacia y tasa de discontinuación de nuestros pacientes en dichos tratamientos. Objetivo: Comunicar los primeros resultados de BIOBADASAR, Registro Argentino de Acontecimientos Adversos ocasionados por el Uso de Agentes Biológicos en Reumatología. Métodos: Participan del registro 56 centros de Reumatología de Argentina. Se requiere el ingreso de un paciente no tratado con agentes biológicos por cada paciente expuesto ingresado en el registro. Datosdesde el 1 de agosto de 2010 hasta 1 abril 2011. Las variables categóricasse calcularon con chi cuadrado y las continuas con T student. Se calcularon porcentajes de incidencia y por persona/año. Resultados: Se incorporaron 966 pacientes (1132 tratamientos). Mujeres 763 (79%) y hombres 203 (21%). La edad media fue 52 años (3-88); 543 pacientes (56%) fueron tratados con agentes biológicos (casos) y 423 (44%) fueron no tratados con agentes biológicos (controles). 786 pacientes tenían artritis reumatoidea (81,4%) y 79 artritis psoriásica (8,2%), entre otros diagnósticos. La media de tiempo de evolución de enfermedad fue 11 años para los casos y 8,25 años para los controles. El fármaco biológico más utilizado fue el etanercept con 348 tratamientos (50%) y una supervivencia al tratamiento en años cuya media fue 2,90 seguido por el adalimumab con 158 tratamientos (22,7%) y una supervivencia al tratamiento en años cuya media fue 2,15. La causa más frecuente de interrupción de tratamiento en los casos fue ineficacia (42,1%) seguido por eventos adversos (32%).

Estudio del uso del citratopara el sellado de catéteres en hemodiálisis / No disponible

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Characterization of hepatitis B virus genotypes in chronically infected patients

Las mutaciones genómicas presentes durante la transcripción reversa del virus de la hepatitis B (VHB) podrían explicar su variabilidad genéticay ser la causa de la existencia de ocho genotipos distintos que presentan una distribución geográfica diferente. Los objetivos principalesdel presente trabajo fueron determinar la prevalencia de los genotipos del virus de la hepatitis B en pacientes con hepatitis crónica B y buscarla relación entre los genotipos y los factores de riesgo de transmisión con respecto al estado del HBeAg. Se analizaron 14 muestras desuero utilizando el kit INNO-LIPA HBV Genotyping assay. El genotipo D fue el más prevalente (64,3%), seguido del genotipo A (28,6%). Enuna muestra se detectó una coinfección (genotipos D/E) que fue confirmada mediante secuenciación. Todos los pacientes, excepto uno, presentaronHBeAg negativo y anti-HBe positivo. Con respecto a los factores de riesgo de transmisión del VHB, en la mitad de los casos se desconocían;en la otra mitad se observaron transmisiones sexuales, mediante transfusión, verticales e intrafamiliares. Estos resultados demuestranque el genotipo D es el más prevalente en nuestro hospital, seguido del genotipo A. Por otra parte, no hemos encontrado relación entreel estado del HBeAg y el genotipo implicado en la infección(AU)

Genomic mutations occurring during reverse transcription of hepatitis B virus (HBV) could explain its genetic diversity and account for 8genetically distinct genotypes that are geographically distributed quite differently. The main objectives of this study were to determine theprevalence of hepatitis B virus genotypes in patients with chronic hepatitis B and to see if there was a relationship between genotypes andrisk factors for transmission based on HBeAg status. A total of 14 serum samples were analyzed using INNO-LIPA HBV genotyping assay.Genotype D was the most prevalent (64.3%) followed by genotype A (28.6%). There was one case of co-infection (D/E genotypes) that wasconfirmed by PCR sequencing. All patients except one were HBeAg-negative and anti-HBe-positive. The risk factors for HBV transmission wereunknown in half of the cases; in the other half, sexual, transfusion, maternal or interfamilial transmission were observed. The results showthat genotype D is the most prevalent genotype in our hospital, followed by genotype A. On the other hand, no relationship was found betweenHBeAg status and genotype(AU)

Masa abdominal palpable / Palpable abdominal mass

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Characterization of hepatitis B virus genotypes in chronically infected patients.

Genomic mutations occurring during reverse transcription of hepatitis B virus (HBV) could explain its genetic diversity and account for 8 genetically distinct genotypes that are geographically distributed quite differently. The main objectives of this study were to determine the prevalence of hepatitis B virus genotypes in patients with chronic hepatitis B and to see if there was a relationship between genotypes and risk factors for transmission based on HBeAg status. A total of 14 serum samples were analyzed using INNO-LIPA HBV genotyping assay. Genotype D was the most prevalent (64.3%) followed by genotype A (28.6%). There was one case of co-infection (D/E genotypes) that was confirmed by PCR sequencing. All patients except one were HBeAg-negative and anti-HBe-positive. The risk factors for HBV transmission were unknown in half of the cases; in the other half, sexual, transfusion, maternal or interfamilial transmission were observed. The results show that genotype D is the most prevalent genotype in our hospital, followed by genotype A. On the other hand, no relationship was found between HBeAg status and genotype.

[Incidence of influenza and influenza vaccine effectiveness in the 2004-2005 season]. / Incidencia de la gripe y efectividad de la vacuna antigripal en la temporada 2004-2005.

BACKGROUND: To quantify the incidence of flu in different groups of the population of Navarra in the 2004-2005 season, and to evaluate the effectiveness of anti-flu vaccination. METHODS: The analysis of influenza cases in the system of compulsory notificable diseases was complemented by the individualised notifications in the network of sentinel doctors that covers a population of 22,339 inhabitants. The coverage and effectiveness of the vaccine was studied. RESULTS: Vaccine coverage in (3)65 year olds reached 62%. The incidence of influenza was 42.6 cases per 1,000 inhabitants. It reached a maximum in mid-January, exceeding 750 weekly cases per 100,000 inhabitants and 1,900 cases per 100,000 children. The highest rate of influenza was observed in under-15 year olds (49.4 cases per 1,000 inhabitants) and the lowest in non-institutionalised (3)65 year olds (2.6 per 1,000 inhabitants), although it was higher in geriatric residences (62.1 per 1,000; p<0.0001). Seventy-nine percent of the cases from 5 to 64 years resulted in absenteeism from school or work. The flu virus was identified in 42/65 (65%) nasopharyngeal smears, 90% being influenza virus A(H3). The incidence of influenza was 3.08% in the unvaccinated and 0.45% in the vaccinated (p<0.001). The global effectiveness of the anti-flu vaccine was 65%, and in (3)65 years old it was 73%. CONCLUSION: Although its effectiveness is not total, the vaccine is the main measure for preventing influenza. The network of sentinel doctors provide useful information for the coordination of care and public health activities against flu.

Incidencia de la gripe y efectividad de la vacuna antigripal en la temporada 2004-2005 / Incidence of influenza and influenza vaccine effectiveness in the 2004-2005 season

Fundamento. Cuantificar la incidencia de gripe en distintos grupos de la población de Navarra en la temporada 2004-2005 y evaluar la efectividad de la vacunación antigripal.Métodos. El análisis de los casos de gripe del sistema de enfermedades de declaración obligatoria se ha complementado con las notificaciones individualizadas de la red de médicos centinela que atiende a una población de 22.339 habitantes. Se estudió la cobertura y efectividad de la vacuna. Resultados. La cobertura vacunal en Ž65 años alcanzó el 62%. La incidencia de gripe fue de 42,6 casos por 1.000 habitantes. Alcanzó el máximo a mediados de enero, superando 750 casos semanales por 100.000 habitantes y 1.900 casos por 100.000 niños. La mayor tasa de gripe se observó en menores de 15 años (49,4 casos por 1.000 habitantes) y la menor en Ž65 años no institucionalizados (2,6 por 1.000 habitantes), aunque fue mayor en residencias geriátricas (62,1 por 1.000; p<0,0001). El 79% de los casos de 5 a 64 años causó absentismo escolar o laboral. Se identificó el virus de la gripe en 42/65 (65%) frotis nasofaríngeos, siendo el 90% virus gripal A(H3). La incidencia de gripe fue del 3,08% en los no vacunados y del 0,45% en vacunados (p<0,001). La efectividad global de la vacuna antigripal fue del 65%, y en Ž65 años del 73%.Conclusión. Aunque su efectividad no es total, la vacuna es la principal medida para la prevención de la gripe. La red de médicos centinela aporta información útil para la coordinación de actividades asistenciales y de salud pública frente a la gripe

Background. To quantify the incidence of flu in different groups of the population of Navarra in the 2004-2005 season, and to evaluate the effectiveness of anti-flu vaccination. Methods. The analysis of influenza cases in the system of compulsory notificable diseases was complemented by the individualised notifications in the network of sentinel doctors that covers a population of 22,339 inhabitants. The coverage and effectiveness of the vaccine was studied. Results. Vaccine coverage in Ž65 year olds reached 62%. The incidence of influenza was 42.6 cases per 1,000 inhabitants. It reached a maximum in mid-January, exceeding 750 weekly cases per 100,000 inhabitants and 1,900 cases per 100,000 children. The highest rate of influenza was observed in under-15 year olds (49.4 cases per 1,000 inhabitants) and the lowest in non-institutionalised Ž65 year olds (2.6 per 1,000 inhabitants), although it was higher in geriatric residences (62.1 per 1,000; p<0.0001). Seventy-nine percent of the cases from 5 to 64 years resulted in absenteeism from school or work. The flu virus was identified in 42/65 (65%) nasopharyngeal smears, 90% being influenza virus A(H3). The incidence of influenza was 3.08% in the unvaccinated and 0.45% in the vaccinated (p<0.001). The global effectiveness of the anti-flu vaccine was 65%, and in Ž65 years old it was 73%. Conclusion. Although its effectiveness is not total, the vaccine is the main measure for preventing influenza. The network of sentinel doctors provide useful information for the coordination of care and public health activities against flu

Brotes de gripe en población vacunada de residencias geriátricas en la temporada 2004-2005 / Influenza outbreaks in highly-vaccinated older institutionalised people in the 2004-2005 season

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Orogenital transmission of Neisseria meningitidis serogroup C confirmed by genotyping techniques.

Urethritis caused by Neisseria meningitidis in heterosexual patients is presumed to occur via orogenital contact, but confirmation has not been possible in most cases. Presented here is a case of urethritis caused by N. meningitidis, serogroup C, and the isolation of the same microorganism from the nasopharynx and endocervix of the patient's sexual partner. The similarity of the urethral and nasopharyngeal isolates' electrophoretic patterns, obtained using pulsed-field gel electrophoresis, proves the infection was transmitted via orogenital contact.

Systemic lupus erythematosus: mortality and survival in Argentina. A multicenter study.

OBJECTIVE: To analyze the factors associated with mortality, survival and causes of death in patients with systemic lupus erythematosus (SLE) in Argentina. PATIENTS AND METHOD: A series of 366 patients with SLE (45 men and 321 women), mean age 29 y (range 11-70 y) and mean disease duration 6 y, was evaluated from 1990 to 1998. A total of 57 clinical, serological and therapeutic variables were studied. RESULTS: Five- and 10-year survival was 91% and 85% respectively. Forty four patients died (12%): 54% due to sepsis and 32% due to active SLE. Mortality risk factors included heart involvement CRR 3.82), hyperlipidemia (RR 2.72), renal damage (RR 2. 62), infections (RR 2.44), lung disease (RR 2.20) and myositis (RR 2. 07). High-dose prednisone (RR 3.4) or cyclophosphamide (RR 9.19) treatments increased the risk of sepsis (P=0.003) as a cause of death. However, corticosteroids, antimalarial agents and accumulated cyclophosphamide doses proved to be protective factors in overall mortality figures (RR <1). CONCLUSIONS: The main risk factors of death in SLE were heart involvement, hyperlipidemia and renal damage. Treatment with steroids, antimalarial agents and cyclophosphamide improved survival. High-dose corticosteroids and cyclophosphamide were associated with sepsis as a cause of death.

[Description of 165 episodes of fungemia: A multicenter study.]. / Descripción de 165 episodios de fungemia de un estudio multicéntrico.

UNLABELLED: The aim of this article is to describe the main features of fungemia belonged to the Multicenter Study Sepsis Data realised in 34 spanish hospitals. The hospitals were been given a protocol and a software specially designed for this study. 165 episodes of fungemia has been recovered (total: 5,000 episodes of bacteremia). The main results are showed as follows. Sex: male 100 (60.6%); female 65 (39.4%). Areas: medical 64 (38.8%); intensive care unit 48 (29.1%); surgical 39 (23.6%); paediatric 14 (8.5%). Underlying disease: neoplasia 43 (26.1%); HIV infection 28 (16.9%); chronic obtructive pulmonary disease 18 (10.9%); diabetes mellitus and parenteral drug abuse 15 (9.1%) every one. Nosocomial fungemia: 119 (72.1%). Community-acquired fungemia: 42 (25.5%). SOURCES: primary 41 (24.9%); catheter 40 (24.2%); respiratory 23 (13.9%); urinary 17 (10.3%); abdominal 8 (4.9%); skin/soft tissues 4 (4.4%); surgical wound 6 (3.6%). Fungi most often isolated: Candida albicans, 73 isolates (44.2%); Candida parapsilosis, 20 (12.1%); Cryptococcus spp., 12 (7.3%) and Candida glabrata, 6 (3.6%). Polymicrobial fungemia: 19 (11.5%). Fluconazole (54.4%) and amphotericin B (41.9%) were the antifungal agents most often used. Mortality: 33.3%.

[Changes in bone mass and in glucose homeostasis in subjects with high spontaneous fluoride intake]. / Modificaciones en la masa osea y en la homeostasis de la glucosa en residentes de la zona de Bahía Blanca con alta ingesta espontanea de flúor.

This paper reports metabolic data of 24 women and two men, 44-66 years old, ex-residents in an area of endemic fluorosis close to Bahía Blanca city. Fasting fluoremias of these subjects (0.5 to 9.2 microM) and daily urinary fluoride excretion (> 60 mumoles/day) are characteristics of zones with endemic fluorosis. Bone mineral density (BMD) at the lumbar spine (L2-4 1330 +/- 41 mg/cm2) and femoral neck (1045 +/- 10 mg/cm2) were significantly above average of normal subjects of the same age and sex. A significant correlation was observed between the daily excretion of fluoride and BMD L2-4 (r = 0.43, P < 0.05). The Area Under the Curve of insulin during a standard glucose tolerance test showed an inverse relationship with fluoremia. This observation coincides with experiments published elsewhere indicating that fluoride intake at concentrations 5 microM or greater, inhibits the secretion of insulin.