Evaluation of neutropenia secondary to mycophenolate mofetil associated with valganciclovir in liver transplant patients.

OBJECTIVE: Immunosuppressive drugs are necessary to avoid or reduce the risk of rejection of transplanted organs. The immunosuppression generated may result in these patients needing  antibiotics and antivirals to be prescribed to them in conjunction with their immunosuppressants to avoid the risk of infection. This has generated an increase in neutropenia in patients treated with mycophenolate mofetil in combination with valganciclovir. The purpose of this study is to estimate the risk of neutropenia attributable to combination treatment of mycophenolate mofetil with valganciclovir in patients with a transplanted liver. METHOD: This is a retrospective cohort study. It included patients who received a liver transplant between 2012 and 2017 and who were treated with mycophenolate mofetil or with a combination of mycophenolate mofetil and valganciclovir. Minimum follow-up was 100 days posttransplantation. Children under 16 years of age and patients who died during follow-up were excluded. Binary logistic regression analysis was used to determine the association of neutropenia with sex, age, diabetes, creatinine at baseline and at discharge, and concomitant treatment of mycophenolate mofetil with valganciclovir. Relative risk and 95% CI were calculated using logistic regression coefficients. RESULTS: 144 patients were analyzed, 87 were treated with mycophenolate mofetil and 57 received mycophenolate mofetil and valganciclovir together. An overall risk of neutropenia of 37% [95% CI (29- 45)] was observed. The risk was significantly higher in patients who received the combination of mycophenolate mofetil and valganciclovir (56%) than in those treated with mycophenolate mofetil alone (24%), p = 0.001. Binarylogistic-regression analysis revealed that concomitant use of mycophenolate mofetil with valganciclovir was associated with an increased risk of neutropenia: Relative risk = 4.97, 95% CI [2.25-11.00]. CONCLUSIONS: Our study shows that concomitant use of mycophenolate mofetil and valganciclovir increases the risk of neutropenia in patients with a transplanted liver.

Objetivo: Los fármacos inmunosupresores son necesarios para evitar o reducir el riesgo de rechazo de órganos trasplantados. La inmunosupresión generada puede dar lugar a que estos pacientes necesiten recibir antibióticos y antivíricos con los inmunosupresores para evitar el riesgo de infecciones. Esto ha generado un incremento de neutropenia en pacientes tratados conjuntamente con micofenolato de mofetilo y valganciclovir. El objetivo de este estudio es estimar el riesgo de neutropenia atribuible al tratamiento concomitante de micofenolato de ofetilo y valganciclovir en pacientes trasplantados hepáticos.Método: Estudio de cohorte retrospectiva. Se incluyeron pacientes receptores de hígado entre 2012 y 2017 tratados con micofenolato de mofetilo o con la combinación de micofenolato de mofetilo y valganciclovir, con al menos 100 días de seguimiento postrasplante. Se excluyeron menores de 16 años y pacientes fallecidos durante el seguimiento. El análisis de regresión logística binaria se utilizó para determinar la asociación del riesgo de neutropenia con el sexo, edad, diabetes, creatinina basal y al alta, y tratamiento concomitante de micofenolato de mofetilo y valganciclovir. El riesgo relativo y los IC 95% se calcularon mediante los coeficientes de regresión logística.Resultados: Un total de 144 pacientes fueron analizados, 87 se trataron con micofenolato de mofetilo y 57 recibieron conjuntamente micofenolato de mofetilo y valganciclovir, observándose un riesgo de neutropenia del 37%, IC 95% [29-45]. Este riesgo fue significativamente mayor en pacientes que recibieron la combinación de micofenolato de mofetilo y valganciclovir (56%) respecto a los tratados solo con micofenolato de mofetilo (24%), p = 0,001. El análisis de regresión logística binaria reveló que el uso concomitante de micofenolato de mofetilo y valganciclovir se asociaba a un mayor riesgo de neutropenia: riesgo relativo = 4,97, IC 95% [2,25-11,00].Conclusiones: Nuestro estudio demuestra que el uso concomitante de micofenolato de mofetilo y valganciclovir aumenta el riesgo de neutropenia en pacientes trasplantados hepáticos.

Extended Stability of Reconstituted Lyophilized Erwinia L-asparaginase in Vials.

BACKGROUND/AIM: L-Asparaginase (L-ASNase) is used as a tumor-inhibitory drug on paediatric acute lymphoblastic leukemia (ALL). ERW-ASNase is commercialised as a lyophilized powder stable only for 8 hours once reconstituted and, consequently, the leftover is usually discarded. The aim of this study will be to analyse the stability of the reconstituted lyophilised ERW-ASNase. MATERIALS AND METHODS: In the present study, we analysed the enzymatic stability of reconstituted ERW-ASNase after conservation in three different temperature conditions for 2 and 5 days. RESULTS: Our results show that ERW-ASNase is stable at 4°C, -20°C and -80°C for up to 5 days, retaining 95% of the initial enzymatic activity in all three storage temperatures tested. CONCLUSION: It is feasible to reuse the remaining content of ERW-ASNase vial after reconstitution, which allows the optimization of the content of ERW-ASNase vials use and reduces the cost of this formulation usage, making it more accessible.

Clinical-economic impact of the change of protocol for use of basiliximab in liver transplant.

OBJECTIVE: Evaluation of the clinical and economic impact after the protocol  change of basiliximab use in orthohepatic transplant. METHOD: Retrospective study in which all liver transplant patients were included  during the years 2013, 2014 and until February 15, 2015. The study was divided into two stages according to the protocol used: 1) administration of basiliximab  only if factors of previous risk, and 2) administration of the first dose of  basiliximab to all transplant patients and the second dose if it had risk factors. RESULTS: 83 patients were included, 34 according to protocol 1 and 49 according  to protocol 2. No significant differences were found in the clinical  variables evaluated or in the variables related to health outcomes. Considering  that the percentage of patients without risk factors who received basiliximab was 43% and without differences in the stays, we could estimate an additional cost  for the universal use of basiliximab in orthohepatic transplant of € 21,400.00. CONCLUSIONS: In our population, the protocol change making universal the first  dose of basiliximab has not shown the expected benefits, but an increase in  costs, so the suitability of the new protocol in consensus with the medical team  must be reconsidered. The evidence regarding the use of basiliximab in  orthohepatic transplant remains limited and although its benefit seems clear in  patients with risk factors, especially renal failure, recommendations about its use universally remains controversial.

Objetivo: Evaluación del impacto clínico y económico tras el cambio de protocolo de uso de basiliximab en el trasplante ortohepático. Método: Estudio retrospectivo en el que se incluyó a todos los pacientes trasplantados de hígado durante los años 2013, 2014 y hasta el 15 de  febrero de 2015. El estudio se dividió en dos etapas según el protocolo  empleado: 1) administración de basiliximab solo si existían factores de riesgo  previos, y 2) administración de la primera dosis de basiliximab a todos los  pacientes trasplantados y de una segunda dosis si existían factores de riesgo. Resultados: Se incluyeron 83 pacientes, 34 según el protocolo 1 y 49 según el  protocolo 2. No se encontraron diferencias significativas en las variables clínicas  evaluadas ni en las variables relacionadas con los resultados en salud.  Considerando que el porcentaje de pacientes sin factores de riesgo que recibieron basiliximab fue del 43% y sin diferencias en las estancias,  podríamos estimar un coste adicional por el empleo universal de basiliximab en  el trasplante ortohepático de 21.400 €.Conclusiones: En nuestra población, el cambio de protocolo haciendo universal  la primera dosis de basiliximab no ha mostrado los beneficios esperados, pero sí  un aumento de los costes, por lo que debe replantearse la idoneidad del nuevo  protocolo en consenso con el equipo médico. La evidencia en relación con el  empleo de basiliximab en el trasplante ortohepático sigue siendo limitada y  aunque parece claro su beneficio en pacientes con factores de riesgo,  especialmente fallo renal, las recomendaciones acerca de su uso de forma  universal sigue siendo controvertido.

The use of adalimumab, etanercept, golimumab and infliximab in rheumatic pathologies: variation between label dosage and real-world use.

Rheumatoid arthritis (AR), psoriatic arthritis (PSA) and ankylosing spondylitis (AS) are autoimmune systemic diseases characterized by inflammation, pain and joint degeneration. The objective of this study is to evaluate, under the actual conditions of use, dosing patterns of adalimumab, etanercept, golimumab and infliximab in these pathologies, and compare them with the label regimens recommended, as well as evaluating the financial implications of these regimen modifications. The study population included all adult patients diagnosed with RA, PSA or AS who had been treated with adalimumab, etanercept, golimumab and infliximab for at least 6 months between 1 January 2011 and 31 December 2013. The main variable of this study was to assess the dose dispensed for drugs administered subcutaneously and the dose prepared/administered for drugs administered intravenously, and the annual costs of the treatment. A total of 5,428 episodes were included. The mean weekly dose was lower than the standard dose in the three pathologies studied in the patients treated with adalimumab and etanercept (84.3% vs 81.2% for RA, 85.0% vs 78.0% for PSA and 87.8% vs 81.6% for AS). The drugs with highest dose optimization in RA are etanercept (46.3%) followed by adalimumab (46%); however, the highest percentage of patients with major dose optimization corresponds to etanercept (11.6%). Both in the PA and the AS group, we also observed that etanercept is the drug more optimized, corresponding to 53.9 and 43% of patients, respectively. By contrast, 48.5% of patients with RA treated with infliximab required dose intensification; however, infliximab dose intensification in PSA and AS is not so pronounced. The practice of optimization of dose regimens in patients with rheumatic diseases under treatment with anti-TNFα is spreading among professionals, resulting in annual cost reduction in the treatment of rheumatic arthropathies. However, long term follow-up will be necessary to assess the influence of this optimization on health outcomes.

Severe ifosfamide-induced neurotoxicity: a case report.

INTRODUCTION: Ifosfamide is an alkylating agent used in the treatment of several neoplasias. Ifosfamide metabolites accumulation can produce neurotoxicity, which sometimes manifests as a severe clinical picture. CASE DESCRIPTION: We describe the case of a male with a mixed cellularity subtype classical Hodgkin's lymphoma, treated with ifosfamide after other chemotherapy drugs failure. After the first Ifosfamide cycle, the patient showed severe neurological toxicity that resolved 3 weeks later with supportive therapy. DISCUSSION: Among the risk factors described in the literature, our patient had previously received cisplatin chemotherapy, had low albumin serum levels, and had received ifosfamide as a rapid intravenous infusion. The management of the neurotoxicity is symptomatic although some drugs, like methylene blue and albumin, have also been used. CONCLUSION: This case highlights that clinicians should be aware of the possibility of severe neurological toxicity after the administration of ifosfamide and may control the risk factors associated.

[Perioperative pharmacological treatment recommendations]. / Recomendaciones sobre el tratamiento farmacológico perioperatorio.

Despite the advances in surgical techniques and anaesthesia, there are still a significant number of postoperative complications in surgery, the most common being, surgical wound infections, sepsis, respiratory and cardiovascular complications, and thromboembolic events. All of these complications increase hospital stay, health costs and mortality. Different pharmacological perioperative strategies have been employed to reduce their incidence, but these have varied widely between hospitals, and even among professionals in the same hospital. In this article we review the recommendations of clinical practice guidelines on the medication routinely used in this situation, such as antibiotics, antithrombotics, analgesics and antiemetics.