Available evidence and outcome of off-label use of rituximab in clinical practice

Purpose: To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost. Methods: This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated. Results: A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.568.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 24 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 1230months) in 69.2%of patients showing a short-term response. Median cost per patient was 5,187.5 (IQR 5,187.57,781.3). Conclusions: In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice.

Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis

Hepatorenal syndrome (HRS) is a serious complication of end-stage liver disease, occurring mainly in patients with advanced cirrhosis and ascites, who have marked circulatory dysfunction,1 as well as in patients with acute liver failure.2 In spite of its functional nature, HRS is associated with a poor prognosis,3 4 and the only effective treatment is liver transplantation. During the 56th Meeting of the American Association for the Study of Liver Diseases, the International Ascites Club held a Focused Study Group (FSG) on HRS for the purpose of reporting the results of an international workshop and to reach a consensus on a new definition, criteria for diagnosis and recommendations on HRS treatment. A similar workshop was held in Chicago in 1994 in which standardised nomenclature and diagnostic criteria for refractory ascites and HRS were established.5 The introduction of innovative treatments and improvements in our understanding of the pathogenesis of HRS during the previous decade led to an increasing need to undertake a new consensus meeting. This paper reports the scientific rationale behind the new definitions and recommendations. The international workshop included four issues debated by four panels of experts (see Acknowledgements). The issues were: (1) evidence-based HRS pathogenesis; (2) treatment of HRS using vasoconstrictors; (3) other HRS treatments using transjugular intrahepatic portosystemic stent-shunt (TIPS) and extracorporeal albumin dialysis (ECAD); and (4) new definitions and diagnostic criteria for HRS and recommendations for its treatment.

El síndrome metabólico en el paciente renal

Se defi ne como síndrome metabólico al conjunto de factores que se dan en un individuo que le llevan a presentar resistencias a la insulina con hiperinsulinismo compensador que se asocia a trastornos del metabolismo hidrocarbonado, hipertensión arterial, alteraciones lipídicas y obesidad. Esta demostrado que este síndrome aumenta la posibilidad de padecer una enfermedad cardiovascular o diabetes mellitus por lo que se considera un factor de riesgo cardiovascular y de mortalidad en la población general. En pacientes...

El ejercicio físico y el paciente renal crónico

Durante estos últimos años estamos asistiendo a un rápido y continuo desarrollo tecnológico en las terapias de hemodiálisis (HD). Este hecho produce el consecuente aumento en la esperanza de vida de los pacientes con enfermedad renal terminal, aumentando la supervivencia y mejorando el alivio de los síntomas urémicos. Sin embargo, la debilidad que sufren estos pacientes es bien conocida; siendo la causante de que haya una tendencia a llevar un estilo de vida sedentario, pese a que existen estudios que refieren que el ejercicio durante la HD es seguro incluso en pacientes de edad avanzada con múltiples comorbilidades1. Por este motivo, uno de los pilares de la atención que...

Available evidence and outcome of off-label use of rituximab in clinical practice

Purpose: To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost. Methods: This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated. Results: A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.5-68.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 2-4 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 12-30months) in 69.2%of patients showing a short-term response. Median cost per patient was 5,187.5 (IQR 5,187.5-7,781.3). Conclusions: In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice.

Revisión de conocimientos sobre el fracaso renal agudo en el contexto del paciente crítico

El fracaso renal agudo afecta entre un 1 y un 25% de los pacientes ingresados en unidades de cuidados intensivos, cifras que varían según la población y los criterios estudiados. Las complicaciones derivadas del fracaso renal agudo (hipervolemia, acidosis metabólica, hiperpotasemia, hemorragias) se tratan pero la mortalidad sigue siendo elevada a pesar de los avances tecnológicos de los últimos años ya que, habitualmente, el fracaso renal agudo está asociado a sepsis, insuficiencia respiratoria, heridas graves, complicaciones quirúrgicas o coagulopatías de consumo. El rango de mortalidad va desde un 30 a un 90%. Aunque no disponemos de una definición universalmente aceptada, la clasificación RIFLE aporta una herramienta operativa tanto para definir el grado de fracaso renal agudo como para homogeneizar el inicio de las técnicas de depuración extrarrenal y evaluar los resultados obtenidos. En consecuencia, las enfermeras que trabajan en una unidad de cuidados intensivos deben estar familiarizadas con esta afección, con su tratamiento (farmacológico o sustitutivo) y con la prevención de las posibles complicaciones. De igual manera han de ser capaces de detectar las manifestaciones de dependencia de cada una de las necesidades básicas e identificar los problemas de colaboración para conseguir un plan de cuidados individualizado.

Hematoma renal en paciente monorreno: caso clínico

Descrito en 1856 por Wunderlich, el hematoma perirrenal espontáneo es una patología infrecuente, en la que a pesar de llegar al diagnóstico de una manera relativamente sencilla con estudios imagen, el poder determinar la etiología representa un reto y es motivo de múltiples estudios y procedimientos invasivos, algunas veces sin poder llegar a esclarecer la causa1. Los hematomas renales y esplénicos están asociados con frecuencia a traumatismos abdominales y más raramente se deben a alteraciones de la coagulación e infecciones. Otras causas menos frecuentes son procesos inflamatorios, diátesis sanguínea,...

Tropical diseases screening in immigrant patients with HIV infection in a European country.

Prospective observational study of all HIV infected immigrants visited at the Infectious Diseases Department of the Hospital Universitari Vall d’Hebron from June 2010 to May 2011. Screening of most prevalent tropical diseases was performed according to geographical origin. 190 patients were included. Overall, 36.8% (70/190) patients had at least one positive result for any parasitic disease, including Chagas disease, schistosomiasis, strongyloidiasis, leishmaniasis, intestinal parasitosis and malaria. We propose a screening and management strategy of latent parasitic infections in immigrant HIV infected patients.

Measuring the child mortality impact of official aid for fighting infectious diseases, 2000-2010

Aid for fighting infectious and parasitic diseases has had a statistically significant role in the under-five mortality reduction in the last decade. Point estimates indicate a country average reduction of 1.4 deaths per thousand under fives live-born attributable to aid at its average level in 2000-2010. The effect would be an average drop of 3.3 in the under-five mortality rate at the aid levels of 2010. By components, a dollar per capita spent in fighting malaria has caused the largest average impact, statistically higher than a dollar per capita spent in STD/HIV control. We do not find statistically significant effects of other infectious disease aid, including aid for the control of tuberculosis.

Analysis and Monte Carlo simulations of a model for the spread of infectious diseases in heterogeneous metapopulations

We present a study of the continuous-time equations governing the dynamics of a susceptible infected-susceptible model on heterogeneous metapopulations. These equations have been recently proposed as an alternative formulation for the spread of infectious diseases in metapopulations in a continuous-time framework. Individual-based Monte Carlo simulations of epidemic spread in uncorrelated networks are also performed revealing a good agreement with analytical predictions under the assumption of simultaneous transmission or recovery and migration processes

Vascular endothelial growth factor and angiopoietin-2 play a major role in the pathogenesis of vascular leakage in cirrhotic rats.

Background and aims: The extent and molecular mechanisms governing plasma extravasation and formation of ascites in cirrhosis are unknown. Vascular endothelial growth factor-A (VEGF-A) and angiopoietin-2 (Ang-2) are endogenous substances with powerful vascular permeability effects. We assessed regional blood flow, vascular leakage, mRNA and tissular expression of VEGF-A and Ang-2 and vascular permeability following VEGF receptor 2 blockade in control and cirrhotic rats to define the vascular territories showing altered vascular permeability in cirrhosis and to determine whether VEGF-A and Ang-2 are involved in this phenomenon. Methods: Arterial blood flow was analysed with the coloured microsphere method. Vascular leakage was measured and visualised with the dye Evan¿s Blue and colloidal carbon techniques, respectively. VEGF-A and Ang-2 expression were determined by real-time polymerase chain reaction (RT-PCR), immunohistochemistry and western blot. The effect on vascular permeability induced by VEGFR2 blockade was assessed by administration of the receptor inhibitor SU11248. Results: Arterial blood flow was increased in the mesentery, pancreas and small intestine but not in the kidney and spleen of cirrhotic rats as compared to controls. Increased vascular leakage was observed in the mesentery and liver, where colloidal carbon spread from microvessels to the adjacent fibrotic tracts. Increased hepatic and mesenteric expression of VEGF-A and Ang-2 was found in cirrhotic rats as compared to controls. Blockade of VEGFR2 markedly reduced hepatic and mesenteric vascular leakage in cirrhotic rats. Conclusions: Enhanced endothelial permeability is restricted to the hepatic and mesenteric vascular beds in cirrhotic rats with ascites and VEGF-A and Ang-2 are key factors in the signalling pathways regulating this dysfunction.