Clinical evaluation of rituximab treatment for neuromyelitis optica.

INTRODUCTION: Neuromyelitis optica is an inflammatory and usually relapsing demyelinating autoimmune disease of the central nervous system that targets the optic nerves and spinal cord. Rituximab has been used for different neurological diseases that are probably immune-mediated or involving humoural immunity. The objective of this study is to evaluate the efficacy and safety of rituximab as treatment for neuromyelitis optica in a tertiary hospital. METHODS: Retrospective study of patients with neuromyelitis optica treated with rituximab 1000mg on days 1 and 15, repeated every 6 to 8 months. We recorded EDSS score, relapse rate, overall condition, CD19+ count, presence of anti-NMO antibodies, and possible adverse reactions. RESULTS: Six patients were treated; all were women with a median age of 46 years (range, 38-58). Anti-NMO antibodies were detected in 3 patients (50%). Baseline EDSS was 4 (range 2.0-5.5). Two patients had previously been treated with an immunomodulatory drug. Median time from the first rituximab infusion to first relapse was 3.7 years (range 1.7-6.9). Two patients had infusion reactions after the first dose of rituximab. Four patients remained relapse-free and their EDSS score did not progress during rituximab treatment, one patient showed no clinical improvement, and one patient could not be evaluated. CONCLUSION: Rituximab can be considered an attractive therapeutic alternative for patients with neuromyelitis optica as there are no approved treatments for this disease. Further studies with rituximab are needed to establish the role of this drug in treating neuromyelitis optica.

[Improving inpatient pharmacoterapeutic process by Lean Six Sigma methodology]. / Mejora del proceso farmacoterapéutico del paciente hospitalizado mediante la metodología Lean Seis Sigma.

BACKGROUND: Lean Six Sigma methodology has been used to improve care processes, eliminate waste, reduce costs, and increase patient satisfaction. OBJECTIVE: To analyse the results obtained with Lean Six Sigma methodology in the diagnosis and improvement of the inpatient pharmacotherapy process during structural and organisational changes in a tertiary hospital. SCOPE: 1.000 beds tertiary hospital. DESIGN: prospective observational study. The define, measure, analyse, improve and control (DMAIC), were deployed from March to September 2011. An Initial Project Charter was updated as results were obtained. POPULATION AND SAMPLE: 131 patients with treatments prescribed within 24h after admission and with 4 drugs. VARIABLES: safety indicators (medication errors), and efficiency indicators (complaints and time delays). RESULTS: Proportion of patients with a medication error was reduced from 61.0% (25/41 patients) to 55.7% (39/70 patients) in four months. Percentage of errors (regarding the opportunities for error) decreased in the different phases of the process: Prescription: from 5.1% (19/372 opportunities) to 3.3% (19/572 opportunities); Preparation: from 2.7% (14/525 opportunities) to 1.3% (11/847 opportunities); and administration: from 4.9% (16/329 opportunities) to 3.0% (13/433 opportunities). Nursing complaints decreased from 10.0% (2119/21038 patients) to 5.7% (1779/31097 patients). The estimated economic impact was 76,800 euros saved. CONCLUSIONS: An improvement in the pharmacotherapeutic process and a positive economic impact was observed, as well as enhancing patient safety and efficiency of the organization. Standardisation and professional training are future Lean Six Sigma candidate projects.

Assessment of the effectiveness and safety of natalizumab for treating relapsing-remitting multiple sclerosis.

OBJECTIVE: Assessing the effectiveness and safety of natalizumab for treating relapsing-remitting multiple sclerosis in a tertiary hospital. METHOD: Observational, prospective study of adult patients treated with natalizumab from May 2007 until February 2009. TREATMENT: 300 mg natalizumab every four weeks. Response criteria: assessment of disease progression, appearance of flare-ups and assessment of magnetic resonance images. Adverse reactions during treatment with natalizumab were recorded. RESULTS: Thirty patients (73% female); average age 34 ± 8.4 years; mean baseline EDSS 3.4 ± 1.3; number of flare-ups in the past year 2.1 ± 1.2. TREATMENT was discontinued in five patients, due to refusal in one case, ineffectiveness in two cases and anaphylaxis in the other two cases. Fourteen patients completed one year of treatment with satisfactory results. A lower EDSS score by 36%, 47%, 31%, 54% and 28% was obtained at 3, 6, 9, 12 and 15 months of treatment respectively. The prevalence of relapse-free patients was 94%, 76% and 54% at 3, 6 and 12 months. MRI imaging studies in 11 patients one year after they began treatment showed no new lesions. Two patients suffered severe anaphylactic shock and another one had an outbreak of urticaria. The presence of neutralising antibodies was the reason for suspending treatment in 6.6% of the patients. CONCLUSIONS: The treatment's effectiveness and safety in our patient group suggest that natalizumab is a treatment for refractory patients or those with aggressive types of multiple sclerosis, although we do not yet know about its long-term effects and the evolution of the appearance of neutralising antibodies.

[The effectiveness of rituximab in refractory autoimmune thrombocytopenic purpura and haemolytic anaemia]. / Efectividad de rituximab en púrpura tombocitopénica y anemia hemolítica autoinmune refractarias.

OBJECTIVE: To evaluate the efficacy and safety of treatment with rituximab in patients presenting autoimmune thrombocytopenic purpura and haemolytic anaemia. METHOD: A check was carried out of the medical records of the patients starting treatment with rituximab for compassionate use in 2004 at doses of 375 mg/m2 per week for 4 weeks. The rate of patients achieving full response in accordance with the best criteria found in the bibliography was assessed. All adverse reactions described in the medical records were gathered. RESULTS: Six patients with thrombocytopenic purpura were candidates for treatment. Five began treatment, four of them completed treatment, and three of these patients achieved full response. This response was achieved at different times and was sustained for at least six months. Two patients with autoimmune haemolytic anaemia were treated and both achieved full response again at different times and in this case, it was sustained for at least 8 months. One patient suffered mild adverse reactions to treatment. CONCLUSIONS: Rituximab is a new perspective for the treatment of refractory autoimmune cytopenias, and has a good safety profile.

Efectividad de rituximab en púrpura tombocitopénica y anemia hemolítica autoinmune refractarias / No disponible

Objetivo: Evaluar la efectividad y seguridad del tratamiento con rituximab en pacientes con púrpura trombocitopénica y anemia hemolítica autoinmune. Método: Se han revisado las historias clínicas de los pacientes que iniciaron tratamiento con rituximab como uso compasivo en el año 2004 a dosis de 375 mg/m2 semanal durante 4 semanas. Se evaluó la tasa de pacientes que alcanzó respuesta completa según los mejores criterios encontrados en la bibliografía. Se recogieron las reacciones adversas descritas en la historia clínica. Resultados: Seis pacientes con púrpura trombocitopénica autoinmune fueron candidatos a tratamiento. Cinco iniciaron tratamiento, cuatro de ellos completaron el tratamiento, de los cuales tres obtuvieron respuesta completa. Dicha respuesta es alcanzada en diferentes tiempos y es mantenida al menos durante 6 meses. Dos pacientes con anemia hemolítica autoinmune fueron tratados y ambos alcanzaron respuesta completa también en diferentes tiempos y esta se mantuvo al menos durante 8 meses. Las reacciones adversas al tratamiento que sufrió algún paciente fueron leves. Conclusiones: Rituximab es una nueva expectativa al tratamiento de citopenias autoinmunes refractarias, con un buen perfil de seguridad

Objective: To evaluate the efficacy and safety of treatment with rituximab in patients presenting autoimmune thrombocytopenic purpura and haemolytic anaemia. Method: A check was carried out of the medical records of the patients starting treatment with rituximab for compassionate use in 2004 at doses of 375 mg/m2 per week for 4 weeks. The rate of patients achieving full response in accordance with the best criteria found in the bibliography was assessed. All adverse reactions described in the medical records were gathered. Results: Six patients with thrombocytopenic purpura were candidates for treatment. Five began treatment, four of them completed treatment, and three of these patients achieved full response. This response was achieved at different times and was sustained for at least six months. Two patients with autoimmune haemolytic anaemia were treated and both achieved full response again at different times and in this case, it was sustained for at least 8 months. One patient suffered mild adverse reactions to treatment. Conclusions: Rituximab is a new perspective for the treatment of refractory autoimmune cytopenias, and has a good safety profile

[Managing methotrexate toxicity: a case report]. / Manejo de la intoxicación por metotrexato: a propósito de un caso.

High-dose methotrexate is included in chemotherapy regimens used to treat a number of malignant neoplasms. Methotrexate plasma concentration is considered the best toxicity predictor. Monitoring methotrexate plasma concentrations is standard practice in the identification of at-risk patients, the titration of folinic acid doses, and the establishment of corrective measures. Methotrexate is a kidney-cleared weak acid, and renal function impairment may retard methotrexate clearance. A case of severe methotrexate-induced toxicity secondary to renal failure is reported in a patient with non-Hodgkin s lymphoma receiving methotrexate at a dose of 1 g/m2. Corrective measures included folinic acid rescue therapy, cholestyramine resin administration, hydration and urine alkalinization, urine pH monitoring, and extracorporeal clearance techniques.

[Pharmacokinetic monitoring of 24-hour infusion of methotrexate in an adult population with non-Hodgkin lymphoma]. / Monitorización farmacocinética del metotrexato en infusión de 24 horas en una población adulta afectada de linforma no Hodgkin.

OBJECTIVES: To describe the behavior and variability of methotrexate (MTX) pharmacokinetic parameters in patients with non-Hodgkin lymphoma (NHL) and to suggest a monitoring system to optimize sample collection using a bayesian method. METHOD: Two adult patient groups diagnosed with different NHL types were studied. Group I was made up of 9 patients aged 53 +/- 16 years who received MTX at a mean dose of 1.652 +/- 327 mg per course. Group II was made up of 7 patients aged 53 +/- 14 years who received MTX at a mean dose of 1.862 +/- 220 mg per course. No statistically significant differences between groups were seen. Serum MTX measurements were performed using polarized immunofluorescence (TDx system). The pharmacokinetic analysis was performed using Abbottbase Pharmacokinetics Systems (PKS) software, adjusting experimental data according to a bicompartmental linear model for intravenous delivery using non-linear regression in Group I and Bayesian estimates in Group II. By estimating mean square error and linear regression between predicted and experimental concentrations, the capability of the Bayesian method implemented in PKS to predict plasma MTX concentration at 48 hours post-infusion was evaluated. The safety of MTX therapy was assessed using patient medical histories and then scoring toxicity using the WHO scale. RESULTS: Pharmacokinetic parameters obtained for group I included: alpha (h(-1)) = 0.38 +/- 0.12; beta (h(-1)) = 0.07 +/- 0.03; K12 (h(-1)) = 0.02 +/- 0.02; K21 (h(-1)) = 0.09 +/- 0.09; K13 (h(-1)) = 0.34 +/- 0.12; Vc (l/kg) = 0.53 +/- 0.23; Vss (l/kg) = 0.62 +/- 0.26; Cl (l/kg.h) = 0.16 +/- 0.06. The error for the PKS population model in measuring plasma MTX concentration at 48 hours post-infusion in Group II was calculated in accordance with three sampling schemes -12 h, 24 h, and both. It was -14.58 x 10(-3), -15.70 x 10(-3) and -14.67 x 10(-3), respectively. Eqm was 9.58 x 10(-3), 2.39 x 10(-3), and 1.02 x 10(-3), respectively. CONCLUSION: An MTX monitoring scheme is suggested based on a Bayesian method implementing pharmacokinetic parameters obtained from an adult population with NHL, which allows therapy safety and the clearance profile of MTX to be predicted from a single sample collected at 24 hours post-infusion.