Thrombosis and infections associated with PICC in onco-hematological patients, what is their relevance?

PURPOSE: Peripherally inserted central venous catheters (PICC) in the onco-hematological patients may be associated with thrombosis or infections that may have short- to medium-term repercussions. MATERIAL AND METHODS: Single-centre retrospective analysis of a prospectively collected cohort. Primary objective was to establish the PICC-thrombosis and infections incidence. Secondary objectives were to analyze profile of patients suffering from these complications and variables associated with an increased likelihood of developing these events. RESULTS: 549 patients were recruited. 58.5% (n = 321) were oncology patients and 41.5% (n = 228) hematology patients. The incidence of PICC-associated thrombosis was 3.5% (n = 19). Thrombosis was associated with progression of the underlying malignant pathology in 10.6% (n = 2) of cases. No association was found between clinical variables analysed and development of thrombosis. Incidence of PICC-associated infections was 7.65% (n = 42). In the 30 days prior to PICC infection, 57.1% (n = 24) had a febrile syndrome of another focus, 73.8% (n = 11) had been hospitalized, 49.5% (n = 25) had a neutrophil count of 0-500 cells/mm3 and 47.6% (n = 20) had an episode of neutropenic fever. Variables significantly associated with the development of infection were hematological patients, high-flow PICC, 3-lm PICC or PICC insertion because of administration of vesicant therapy. CONCLUSIONS: Incidence of PICC-associated thrombosis is low and apparently less prognostically aggressive than other forms of thrombosis associated with cancer, without identify predictive factors. Infection was more prevalent and the identification of risk factors in our series could facilitate its prevention.

Influence of oral health on mucositis in patients undergoing hematopoietic progenitor cell transplantation (HPCT).

AIMS: To establish whether or not the state of patient oral health can influence the occurrence and/or severity of oral mucositis during hematopoietic progenitor cell transplantation (HPCT). MATERIALS AND METHODS: The study included 72 patients awaiting HPCT. Prior to transplantation, clinical exploration and radiology were carried out and oral photographs were taken. This evaluated the extent of caries present, the number of missing teeth and the number of dental fillings in each patient; CAO (Caries and Obturations Index) DMFS (Decayed, Missing, and Filled Surfaces) and Restoration Indices were calculated. Gingival pathology was also examined by means of the Ainamo and Bay Gingival Bleeding Index. O'Leary's Plaque Index was used to evaluate the level of patient oral hygiene. This data was analyzed to see if it exercised any influence on the mucositis grade suffered during HPCT. RESULTS: 96,87% of patients suffered some degree of mucositis during their treatment by the Transplant Unit. The grade of mucositis was seen to be influenced by the number of missing teeth (ANOVA p<0.016) and by the DMFS Index (ANOVA p< 0.038). Although this was not one of the aims of this study, patient age and the administration of colony-stimulating factors were also seen to influence these clinical manifestations. CONCLUSIONS: The state of prior oral health can influence decisively the mucositis suffered during transplantation.

Cambra system in patients awaiting hematopoietic progenitor cell transplant and high caries risk.

BACKGROUND: Recent times have witnessed a significant increase in the number of patients affected by problems related to oncological treatment Aims of this study is to evaluate dental affectation among patients awaiting hematopoietic progenitor cell transplant (HPCT), and they showed high caries risk, so it should establish a protocol prior to transplantation. MATERIAL AND METHODS: The study included 72 patients due for HPCT. Clinical and radiological explorations were performed and oral photos taken. The amount of caries, missing teeth and fillings were registered for each patient. CAO, DMFS and Restoration Indices were calculated. RESULTS: 83% of patients presented caries. 48 patients (67%) had lost at least one tooth. Only 32 patients (44%) had received some sort of conservative treatment. The average CAO index value obtained was 10.37. The DMFS index showed an average of 27.06 affected surfaces. Of the 72 patients studied, 40 (56%) showed a restoration index value of zero. CONCLUSIONS: These patients presented a high number of carious teeth and a low restoration index. The presence of so many possible septic foci in an individual, who will later become susceptible to infection, highlights the importance of preventative treatment and bucco-dental restoration within this patient population. These patients with a high caries risk can be treated with CAMBRA system. Key words:Hematopoietic progenitor cell transplantation, high caries risk, state of oral health, haematological disease, CAMBRA system.

[Cost-per-responder analysis comparing romiplostim to rituximab in the treatment of adult primary immune thrombocytopenia in Spain]. / Coste por paciente con respuesta a romiplostim y rituximab en el tratamiento de la trombocitopenia inmune primaria en España.

BACKGROUND AND OBJECTIVE: Romiplostim, a thrombopoietin-receptor agonist, is approved for second-line use in idiopathic thrombocytopenic purpura (ITP) patients where surgery is contraindicated. Anti-CD20 rituximab, an immunosuppressant, is currently used off-label. This analysis compared the cost per responder for romiplostim versus rituximab in Spain. MATERIALS AND METHOD: A decision analytic model was constructed to estimate the 6-month cost per responding patient (achieving a platelet count≥50×10(9)/l) according to the most robust published data. A systematic literature review was performed to extract response rates from phase 3 randomized controlled trials. Romiplostim patients received weekly injections; rituximab patients received 4 weekly intravenous infusions. Medical resource costs were obtained from Spanish reimbursement lists. Treatment non-responders incurred bleeding-related event (BRE) management costs as reported in clinical trials. Medical resource utilization and clinical practice were based on Spanish treatment guidelines and validated by local clinical experts. RESULTS: The literature review identified phase 3 romiplostim trials with a response rate of 83%. Due to a lack of phase 3 controlled rituximab trials, a systematic review of studies was selected as the best source, reporting a response rate of 62.5%. The mean cost per patient for romiplostim was €16,289 and €13,459 for rituximab. Rituximab resulted in a 10% higher cost per responder (€21,535 versus €19,625 for romiplostim). Romiplostim use reduced drug administration, intravenous immunoglobulin, and bleeding-related costs compared to rituximab. CONCLUSIONS: Due to its high level of efficacy leading to lower BRE costs, romiplostim represents an efficient use of resources for adult ITP patients in the Spanish Healthcare System.

[Pharmacodynamic and pharmacokinetic characteristics. Mechanism of action of the new oral anticoagulants]. / Características farmacodinámicas y farmacocinéticas. Mecanismo de acción de los nuevos anticoagulantes orales.

Thromboembolic disease, both arterial and venous, is a major cause of morbidity and mortality in developed countries. The new anticoagulants exert their action by selective, direct and reversible inhibition of a single coagulation factor. Although the results of several phase III trials have demonstrated the safety and efficacy of these drugs, their mechanism of action, as well as the pharmacodynamics and pharmacokinetics of these drugs, need to be understood for their correct use. The present review discusses the features of the new anticoagulants whose clinical development is more advanced, both those designed to block active factor X, such as rivaroxaban or apixaban, and those designed to block thrombin (also active factor II): dabigatran.

[Guidelines for diagnosis, treatment and monitoring of primary immune thrombocytopenia]. / Diagnóstico, tratamiento y seguimiento de la trombocitopenia inmune primaria.

The consensus document on the diagnosis, treatment and monitoring of primary immune thrombocytopenia was developed in 2010 by specialists with recognized expertise in this disease under the auspices of the Spanish Society of Hematology and Hemotherapy and the Spanish Society of Pediatric Hematology and Oncology, with the aim to adapt to Spain the recommendations of the recently published international consensus documents. The decision to start treatment is based on bleeding manifestations and platelet count (<20×10(9)/L). The first-line treatment is corticosteroids, albeit for a limited period of 4-6 weeks. The addition of intravenous immunoglobulin is reserved to patients with severe bleeding. Splenectomy is the most effective second-line treatment. For patients refractory to splenectomy and those with contraindications or patient refusal, the new thrombopoietic agents are the drugs of choice due to their efficacy and excellent safety profile. The other treatment options have highly variable response rates, and the absence of controlled studies does not allow to establish clear recommendations. Monitoring should be individualized. In patients without active treatment, blood counts are recommended every 3-6 months, and the patient should be instructed to consult in case of bleeding, surgery or invasive procedure and pregnancy. In most of the pediatric population, the disease tends to spontaneous remission. High-dose corticosteroids in short course and intravenous immunoglobulin are the treatment of choice. Second- and further-line treatments should be monitored in specialized centers.

Predictive value of peripheral blood lymphocyte count in breast cancer patients treated with primary chemotherapy.

Peripheral blood lymphocyte (PBL) count may reflect the immune status of cancer patients. We retrospectively analyzed the predictive and prognostic impact of baseline and post-chemotherapy PBL counts in a homogeneous group of 103 breast cancer patients treated with neoadjuvant chemotherapy (anthracyclines and taxanes). In univariate analysis, baseline PBL under 1500 × 10(6)/L (p = 0.013; hazard ratio [HR]: 2.80, 95%CI 1.24-6.61), and PBL decrease >200 × 10(6)/L after the first cycle of chemotherapy (p = 0.047; HR: 2.82, 95%CI 1.01-7.86) were significantly related to disease free survival. In multivariate analysis, both baseline PBL count less than 1500 × 10(6)/L (p = 0.034; HR: 3.32, 95%CI 1.09-10.02) and PBL decrease >200 × 10(6)/L after first cycle (p = 0.032; HR: 3.25, 95%CI 1.10-9.56) showed independent prognostic value for worse disease free survival. No effect was observed for overall survival. Our data support the relevance of pre- and post-chemotherapy PBL for breast cancer recurrence after neoadjuvant chemotherapy.

Coste por paciente con respuesta a romiplostim y rituximab en el tratamiento de la trombocitopenia inmune primaria en España / Cost-per-responder analysis comparing romiplostim to rituximab in the treatment of adult primary immune thrombocytopenia in Spain

Fundamento y objetivo: Romiplostim, agonista del receptor de la trombopoyetina, está aprobado para el tratamiento de segunda línea en pacientes con trombocitopenia inmune primaria (PTI). El tratamiento con rituximab no es infrecuente, aunque esta indicación no esté recogida en la ficha técnica. Este análisis compara el coste por paciente respondedor a romiplostim frente a rituximab en España. Materiales y método: Se ha diseñado un modelo para estimar el coste de 6 meses de tratamiento por paciente que responde (recuento plaquetario ≥ 50 × 109/l). Este modelo toma las referencias conforme a los datos publicados más sólidos. Los pacientes tratados con romiplostim recibieron inyecciones semanales; los pacientes tratados con rituximab recibieron 4 infusiones intravenosas semanales. Los precios se obtuvieron de las listas de reembolso españolas. Los pacientes sin respuesta incurrieron en gastos por el tratamiento de episodios relacionados con sangrado (ERS), tal como se notificó en los ensayos clínicos. La utilización de recursos médicos y la práctica clínica se basaron en las guías de tratamiento españolas y fueron validadas por expertos locales. Resultados: Las tasas de respuesta para romiplostim y rituximab fueron del 83 y 62,5%, y el coste medio por paciente fue de 16.289 Euros y 13.459 Euros, respectivamente. Con rituximab el coste por paciente respondedor fue un 10% superior (21.535 Euros) comparado con romiplostim (19.625 Euros). Romiplostim redujo el coste de administración de fármacos, el uso de inmunoglobulina intravenosa y los costes relacionados con ERS comparado con rituximab. Conclusiones: Romiplostim representaría una opción terapéutica eficiente en comparación con rituximab para el tratamiento de pacientes adultos con PTI crónica en el Sistema Nacional de Salud español (AU)

Background and objective: Romiplostim, a thrombopoietin-receptor agonist, is approved for second-line use in idiopathic thrombocytopenic purpura (ITP) patients where surgery is contraindicated. Anti-CD20 rituximab, an immunosuppressant, is currently used off-label. This analysis compared the cost per responder for romiplostim versus rituximab in Spain. Materials and method: A decision analytic model was constructed to estimate the 6-month cost per responding patient (achieving a platelet count ≥ 50 × 109/l) according to the most robust published data. A systematic literature review was performed to extract response rates from phase 3 randomized controlled trials. Romiplostim patients received weekly injections; rituximab patients received 4 weekly intravenous infusions. Medical resource costs were obtained from Spanish reimbursement lists. Treatment non-responders incurred bleeding-related event (BRE) management costs as reported in clinical trials. Medical resource utilization and clinical practice were based on Spanish treatment guidelines and validated by local clinical experts. Results: The literature review identified phase 3 romiplostim trials with a response rate of 83%. Due to a lack of phase 3 controlled rituximab trials, a systematic review of studies was selected as the best source, reporting a response rate of 62.5%. The mean cost per patient for romiplostim was 16,289 Euros and 13,459 Euros for rituximab. Rituximab resulted in a 10% higher cost per responder (21,535 Euros versus 19,625 Euros for romiplostim). Romiplostim use reduced drug administration, intravenous immunoglobulin, and bleeding-related costs compared to rituximab. Conclusions: Due to its high level of efficacy leading to lower BRE costs, romiplostim represents an efficient use of resources for adult ITP patients in the Spanish Healthcare System (AU)

Aspectos clínicos de la hemoglobinuria paroxística nocturna / No disponible

No disponible

Características farmacodinámicas y farmacocinéticas. Mecanismo de acción de los nuevos anticoagulantes orales / Pharmacodynamic and pharmacokinetic characteristics. Mechanism of action of the new oral anticoagulants

La enfermedad tromboembólica, tanto arterial como venosa, constituye una de las principales causas de morbimortalidad en el mundo occidental. Los nuevos anticoagulantes tienen un efecto selectivo en un único factor de la coagulación, actuando de forma directa y reversible. Al margen de los resultados de diversos ensayos en fase III que han demostrado la seguridad y eficacia de estos fármacos, es importante conocer el mecanismo de acción, así como la farmacodinamia y farmacocinética para un correcto uso. A lo largo de esta revisión, repasaremos dichos aspectos de los nuevos anticoagulantes cuyo desarrollo está más avanzado, tanto los destinados a bloquear el factor X activo: rivaroxaban, apixaban, como la trombina (o factor II activo): dabigatran (AU)

Thromboembolic disease, both arterial and venous, is a major cause of morbidity and mortality in developed countries. The new anticoagulants exert their action by selective, direct and reversible inhibition of a single coagulation factor. Although the results of several phase III trials have demonstrated the safety and efficacy of these drugs, their mechanism of action, as well as the pharmacodynamics and pharmacokinetics of these drugs, need to be understood for their correct use. The present review discusses the features of the new anticoagulants whose clinical development is more advanced, both those designed to block active factor X, such as rivaroxaban or apixaban, and those designed to block thrombin (also active factor II): dabigatran (AU)

Influence of oral health on mucositis in patients undergoing hematopoietic progenitor cell transplantation (HPCT)

Aims: To establish whether or not the state of patient oral health can influence the occurrence and/or severity of oral mucositis during hematopoietic progenitor cell transplantation (HPCT).Materials and Methods: The study included 72 patients awaiting HPCT. Prior to transplantation, clinical exploration and radiology were carried out and oral photographs were taken. This evaluated the extent of caries present, the number of missing teeth and the number of dental fillings in each patient; CAO (Caries and Obturations Index)DMFS (Decayed, Missing, and Filled Surfaces) and Restoration Indices were calculated. Gingival pathology was also examined by means of the Ainamo and Bay Gingival Bleeding Index. O’Leary’s Plaque Index was used to evaluate the level of patient oral hygiene. This data was analyzed to see if it exercised any influence on the mucositis grade suffered during HPCT. Results: 96,87% of patients suffered some degree of mucositis during their treatment by the Transplant Unit. The grade of mucositis was seen to be influenced by the number of missing teeth (ANOVA p<0.016) and by the DMFS Index (ANOVA p< 0.038). Although this was not one of the aims of this study, patient age and the administration of colony-stimulating factors were also seen to influence these clinical manifestations. Conclusions: The state of prior oral health can influence decisively the mucositis suffered during transplantation (AU)

Diagnóstico, tratamiento y seguimiento de la trombocitopenia inmune primaria / Guidelines for diagnosis, treatment and monitoring of primary immune thrombocytopenia

El documento de consenso sobre el diagnóstico, tratamiento y seguimiento de la trombocitopenia inmune primaria fue elaborado en 2010 por especialistas con reconocida experiencia en esta enfermedad bajo el auspicio de la Sociedad Española de Hematología y Hemoterapia y la Sociedad Española de Hematología y Oncología Pediátricas, con el fin de adaptar a España las recomendaciones de los documentos de consenso internacional recientemente publicados. La decisión de iniciar tratamiento se basa en las manifestaciones hemorrágicas y en la cifra de plaquetas (<20×109/L). El tratamiento de primera línea son los glucocorticoides, aunque durante un plazo limitado de 4-6 semanas, reservándose la adición de inmunoglobulinas intravenosas para pacientes con hemorragia grave. La esplenectomía es el tratamiento de segunda línea más eficaz. Para los pacientes refractarios a la esplenectomía y para aquellos con contraindicación o rechazo, los nuevos agentes trombopoyéticos son los fármacos de elección por su eficacia y excelente perfil de seguridad. El resto de las opciones terapéuticas presentan tasa de respuesta y duración muy variables, y carecen de estudios controlados que permitan establecer recomendaciones claras. El seguimiento debe individualizarse, aunque, como mínimo, en pacientes sin tratamiento activo, se recomienda un hemograma cada 3-6 meses, y programas de educación al paciente para que consulte en caso de hemorragia, cirugía o procedimiento invasor y gestación. En una considerable proporción de la población pediátrica la enfermedad tiene tendencia a la remisión espontánea. Los glucocorticoides a altas dosis en pauta corta y las inmunoglobulinas intravenosas son el tratamiento de elección. Los tratamientos de segunda línea y los posteriores deben controlarse en centros especializados

The consensus document on the diagnosis, treatment and monitoring of primary immune thrombocytopenia was developed in 2010 by specialists with recognized expertise in this disease under the auspices of the Spanish Society of Hematology and Hemotherapy and the Spanish Society of Pediatric Hematology and Oncology, with the aim to adapt to Spain the recommendations of the recently published international consensus documents. The decision to start treatment is based on bleeding manifestations and platelet count (<20×109/L). The first-line treatment is corticosteroids, albeit for a limited period of 4-6 weeks. The addition of intravenous immunoglobulin is reserved to patients with severe bleeding. Splenectomy is the most effective second-line treatment. For patients refractory to splenectomy and those with contraindications or patient refusal, the new thrombopoietic agents are the drugs of choice due to their efficacy and excellent safety profile. The other treatment options have highly variable response rates, and the absence of controlled studies does not allow to establish clear recommendations. Monitoring should be individualized. In patients without active treatment, blood counts are recommended every 3-6 months, and the patient should be instructed to consult in case of bleeding, surgery or invasive procedure and pregnancy. In most of the pediatric population, the disease tends to spontaneous remission. High-dose corticosteroids in short course and intravenous immunoglobulin are the treatment of choice. Second- and further-line treatments should be monitored in specialized centers (AU)