The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior.

In the last decade, new non-apoptotic roles have been ascribed to apoptotic caspases. This family of proteins plays an important role in the sculpting of the brain in the early stages of development by eliminating excessive and nonfunctional synapses and extra cells. Consequently, impairments in this process can underlie many neurological and mental illnesses. This view is particularly relevant to dopamine because it plays a pleiotropic role in motor control, motivation, and reward processing. In this study, we analyze the effects of the elimination of caspase-8 (CASP8) on the development of catecholaminergic neurons using neurochemical, ultrastructural, and behavioral tests. To do this, we selectively delete the CASP8 gene in cells that express tyrosine hydroxylase with the help of recombination through the Cre-loxP system. Our results show that the number of dopaminergic neurons increases in the substantia nigra. In the striatum, the basal extracellular level of dopamine and potassium-evoked dopamine release decreased significantly in mice lacking CASP8, clearly showing the low dopamine functioning in tissues innervated by this neurotransmitter. This view is supported by electron microscopy analysis of striatal synapses. Interestingly, behavioral analysis demonstrates that mice lacking CASP8 show changes reminiscent of autism spectrum disorders (ASD). Our research reactivates the possible role of dopamine transmission in the pathogenesis of ASD and provides a mild model of autism.

Valoración de la masa muscular por bioimpedancia en pacientes con EPOC / Assessmen tof musclemassusing bioelectricalimpedance in patients with COPD

OBJETIVO: recientemente se ha descrito un método para estimar la masa muscular total (MMT) a partir de los datos obtenidos en una bioimpedancia corporal. Los objetivos del presente trabajo fueron calcular diversos parámetros de MMT, a partir de los datos de la bioimpedancia y estudiar la relación entre estos parámetros y el resto de parámetros de bioimpedancia, así como su posible relación con parámetros clínicos y funcionales. MÉTODO: el presente trabajo es un estudio observacional transversal sobre pacientes con EPOC estable. A los pacientes incluidos se les realizó una evaluación clínica, funcional y de ejercicio. Mediante bioimpedancia, se calculó la MMT y tres parámetros asociados: su porcentaje respecto al peso total (MMTp), su porcentaje respecto a la masa magra y el índice de MMT. RESULTADOS: el grupo estaba compuesto por 85 pacientes con EPOC (79 hombres; edad 64(7) años; FEV1 61(9)%). Los hombres tenían significativamente mayor MMT que las mujeres (14,7(2,7) Kg vs 24,5(3,7) Kg, p < 0,001). Los valores de MMTp fueron los que tuvieron una mejor relación significativa, con parámetros de capacidad pulmonar (TLC r = 0,461, p < 0,001) y capacidad de ejercicio (consumo de oxígeno r = 0,325 p = 0,024; test 6 minutos r = 0,255; p = 0,019). El estudio multivariante confirmó estas asociaciones (R2 = 0,606, p < 0,001). CONCLUSIÓN: el estudio de la composición corporal por bioimpedancia permite hacer una estimación de la MMT que está relacionada con variables funcionales y de ejercicio en los pacientes con EPOC. La expresión de la MMTp es el parámetro con mayores relaciones con estas variables

OBJECTIVE: Recently, a method has been described to estimate total muscle mass (TMM), based on data obtained from a bioelectrical impedance of the body. The objective of this work was to calculate the various TMM parameters, based on the data provided by bioelectrical impedance, to then study the relationship between these parameters and other bio-impedance parameters, as well as their possible relationship with clinical and functional parameters. METHOD: the work is an observational, transversal study of patients with stable COPD. Patients included in this study underwent a clinical, functional and exercise assessment. Using bioelectrical impedance, TMM was calculated as were three associated parameters: percentage regarding total body weight (TMMp), percentage regarding lean mass and TMM index. RESULTS: the test group included 85 patients with COPD (79 men; 64 years of age (7); FEV1 61(9)%). Males had a significant higher TMM than women (14.7(2.7) Kg. vs. 24.5(3.7) Kg., p < 0.001). The TMMp values had a greater significant relationship with parameters for pulmonary capacity (TLC r = 0.461, p < 0.001) and exercise capacity (oxygen consumption r = 0.325 p = 0.024; test 6 minutes r = 0.255; p = 0.019). The multivariate study confirmed these associations (R2 = 0.606, p < 0.001). CONCLUSION: the body composition study using bioelectrical impedance allows an estimation of TMM to be formulated, which is related to functional variables and exercise in patients with COPD. The expression of TMMp is the parameter with the greatest relationship with these variables

Conciliación de la medicación en el paciente crítico / Medicines reconciliation in critically ill patients

OBJETIVO: La conciliación de la medicación se considera un elemento clave en la seguridad del paciente, no existiendo apenas datos sobre cómo afecta al paciente crítico. En este estudio, se evalúa un programa de conciliación en el paciente crítico liderado por el farmacéutico adscrito a la Unidad de Cuidados Intensivos (UCI).DISEÑO: Estudio prospectivo sobre los errores de conciliación en 50 pacientes. Ámbito: UCI médico-quirúrgica. PACIENTES: Se incluyó a todos los pacientes con estancia en UCI, excluyendo a los pacientes sin tratamiento habitual. INTERVENCIONES: La conciliación de la medicación se realizó en las primeras 24 h tras el ingreso en UCI. En caso de encontrar discrepancias, se contactó con el médico responsable. Variables principales: Se analizó la incidencia, tipo y gravedad de los errores, sus características, las intervenciones realizadas y su aceptación por el médico responsable. RESULTADOS: El 48% de los pacientes presentó algún error de conciliación. La omisión de fármacos supuso el 74% de los mismos, afectando principalmente a fármacos antihipertensivos (33%). El58% de los errores de conciliación corresponden a la categoría D de gravedad. Se realizaron sugerencias al prescriptor en el 98% de los pacientes con discrepancias, aceptándose el 81% de las intervenciones. CONCLUSIONES: Los errores de conciliación en UCI tienen una incidencia y características similares a los referenciados en pacientes no críticos, afectando a grupos terapéuticos de gran significación clínica. Nuestros datos apoyan la incorporación de los procesos de conciliación al cuidado habitual del paciente crítico. El farmacéutico adscrito a la unidad puede llevar a cabo el proceso adecuadamente. (33%). An amount of 58% of reconciliation errors detected corresponded to severity category D. Pharmacist made interventions in the 98% of patients with discrepancies. A total of 81% of interventions were accepted. CONCLUSIONS: The incidence and characteristics of reconciliation errors in ICU are similar to those published in non-critically ill patients, and they affect drugs with high clinical significance. Our data support the importance of the stablishment of medication reconciliation proceedings in critically ill patients. The ICU's pharmacist could carry out this procedure adequately

OBJECTIVE: Medicines reconciliation plays a key role in patient safety. However, there is limited data available on how this process affects critically ill patients. In this study, we evaluate a program of reconciliation in critically ill patients conducted by the Intensive Care Unit's (ICU)pharmacist. DESIGN: Prospective study about reconciliation medication errors observed in 50 patients. Scope: ICU. PATIENTS: All ICU patients, excluding patients without regular treatment. INTERVENTIONS: Reconciliation process was carried out in the first 24 h after ICU admission. Discrepancies were clarified with the doctor in charge of the patient. Main variable: We analyzed the incidence of reconciliation errors, their characteristics and gravity, the interventions made by the pharmacist and their acceptance by physicians. RESULTS: A total of 48% of patients showed at least one reconciliation error. Omission of drugs accounted for 74% of the reconciliation errors, mainly involving antihypertensive drugs (33%). An amount of 58% of reconciliation errors detected corresponded to severity category D. Pharmacist made interventions in the 98% of patients with discrepancies. A total of 81% of interventions were accepted. CONCLUSIONS: The incidence and characteristics of reconciliation errors in ICU are similar to those published in non-critically ill patients, and they affect drugs with high clinical significance. Our data support the importance of the stablishment of medication reconciliation proceedings in critically ill patients. The ICU's pharmacist could carry out this procedure adequately

[Medicines reconciliation in critically ill patients]. / Conciliación de la medicación en el paciente crítico.

OBJECTIVE: Medicines reconciliation plays a key role in patient safety. However, there is limited data available on how this process affects critically ill patients. In this study, we evaluate a program of reconciliation in critically ill patients conducted by the Intensive Care Unit's (ICU) pharmacist. DESIGN: Prospective study about reconciliation medication errors observed in 50 patients. SCOPE ICU PATIENTS: All ICU patients, excluding patients without regular treatment. INTERVENTIONS: Reconciliation process was carried out in the first 24h after ICU admission. Discrepancies were clarified with the doctor in charge of the patient. MAIN VARIABLE: We analyzed the incidence of reconciliation errors, their characteristics and gravity, the interventions made by the pharmacist and their acceptance by physicians. RESULTS: A total of 48% of patients showed at least one reconciliation error. Omission of drugs accounted for 74% of the reconciliation errors, mainly involving antihypertensive drugs (33%). An amount of 58% of reconciliation errors detected corresponded to severity category D. Pharmacist made interventions in the 98% of patients with discrepancies. A total of 81% of interventions were accepted. CONCLUSIONS: The incidence and characteristics of reconciliation errors in ICU are similar to those published in non-critically ill patients, and they affect drugs with high clinical significance. Our data support the importance of the stablishment of medication reconciliation proceedings in critically ill patients. The ICU's pharmacist could carry out this procedure adequately.

[Impact of the creation of a nutritional support team on the quality, safety and effectiveness of total parenteral nutrition]. / Impacto de la creación de un equipo de soporte nutricional en la calidad, seguridad y efectividad de la nutrición parenteral.

INTRODUCTION: Parenteral nutrition (PN) is an essential component in the treatment of many hospitalized patients; however its use is associated to severe complications. The monitoring of these patients has been demonstrated as an effective method for the success of nutrition therapy; therefore, nutritional support teams play an important role to increase the effectiveness and efficiency of the PN. In Spain, there is no data available about the situation of nutritional support teams in hospitals. OBJECTIVE: Develop a nutritional support team in our hospital and analyze the interventions and outcomes in terms of quality, effectiveness and safety. METHODS: Retrospective, cross-sectional study. Patients with PN were selected during two months, corresponding to the period before and after the creation of the nutritional support team (group 1 and 2, respectively). The functions of the nutritional team include: nutritional evaluation, daily monitoring of vital signs and glycemia, detailed analytical control, management of PN complications, between others. RESULTS: 67% of patients in group 1 (n = 24) maintain the PN < 7 days, versus 22% in group 2 (n = 38). In group 1, no patient had a nutritional assessment, neither daily vital signs monitoring (100% in group 2). Detailed analytical control was carried out in the 4% of group 1 and 79% of group 2. In group 2, albumin and prealbumin levels remain stable or increased in the 66% and 88% of patients, respectively. No patient reached triglyceride > 400 mg/dl. 34% of patients showed glycemia > 140 mg/dl (100% of them were solved), and 26% of patients underwent hepatic dysfunction (50% were solved). No refeeding syndrome was reported (thiamine was added to PN in 34% of patients). DISCUSSION: the nutritional support team work has notably increased the quality, safety and effectiveness of PN. This study demonstrates the need to incorporate multidisciplinary nutritional teams in hospitals and the benefit obtained in the patient medical care.

Impacto de la creación de un equipo de soporte nutricional en la calidad, seguridad y efectividad de la nutrición parenteral / Impact of the creation of a nutritional support team on the quality, safety and effectiveness of total parenteral nutrition

Introducción: La nutrición parenteral (NP) es esencial en muchos pacientes hospitalizados, no estando exenta de complicaciones. El seguimiento de estos pacientes constituye un método eficaz para el éxito de la terapia nutricional, por lo que los equipos de soporte nutricional han incrementado la eficacia y eficiencia de la NP. En España, no existen referencias sobre los equipos de soporte nutricional hospitalarios. Objetivos: Crear un equipo nutricional y analizar las intervenciones realizadas y los resultados obtenidos en términos de calidad, efectividad y seguridad en la NP. Métodos: estudio retrospectivo transversal. Se seleccionaron los pacientes con NP durante dos meses, previos y posterior a la creación del equipo (grupo 1 y 2, respectivamente). Las funciones del equipo incluyen: valoración del paciente, seguimiento diario de constantes vitales y glucemia, control analítico completo, manejo de complicaciones metabólicas, electrolíticas y hepáticas, entre otras. Resultados: La duración de la NP fue < 7 días en el 67% del grupo 1 (n = 24) y en el 22% del grupo 2 (n = 38). Ningún paciente fue valorado, ni tuvo seguimiento diario de constantes vitales en el grupo 1 (100% grupo 2). El control analítico completo se realizó en el 4% del grupo 1 y 79% del grupo 2. En el grupo 2, los niveles de albúmina y prealbúmina se mantuvieron estables o aumentaron en el 66% y 88% de los pacientes, respectivamente. Ningún paciente presentó hipertrigliceridemia. El 34% presentó glucemias > 140 mg/dl (100% fueron resueltas) y el 26% presentó complicaciones hepatobiliares (50% fueron resueltas). Ningún paciente presentó síndrome de realimentación (se añadió tiamina al 34%). Discusión: El equipo nutricional ha incrementado notablemente la calidad, seguridad y efectividad de la NP quedando demostrada la necesidad de dichos equipos multidisciplinares a nivel hospitalario (AU)

Introduction: Parenteral nutrition (PN) is an essential component in the treatment of many hospitalized patients; however its use is associated to severe complications. The monitoring of these patients has been demonstrated as an effective method for the success of nutrition therapy; therefore, nutritional support teams play an important role to increase the effectiveness and efficiency of the PN. In Spain, there is no data available about the situation of nutritional support teams in hospitals. Objective: Develop a nutritional support team in our hospital and analyze the interventions and outcomes in terms of quality, effectiveness and safety. Methods: Retrospective, cross-sectional study. Patients with PN were selected during two months, corresponding to the period before and after the creation of the nutritional support team (group 1 and 2, respectively). The functions of the nutritional team include: nutritional evaluation, daily monitoring of vital signs and glycemia, detailed analytical control, management of PN complications, between others. Results: 67% of patients in group 1 (n = 24) maintain the PN < 7 days, versus 22% in group 2 (n = 38). In group 1, no patient had a nutritional assessment, neither daily vital signs monitoring (100% in group 2). Detailed analytical control was carried out in the 4% of group 1 and 79% of group 2. In group 2, albumin and prealbumin levels remain stable or increased in the 66% and 88% of patients, respectively. No patient reached triglyceride > 400 mg/dl. 34% of patients showed glycemia > 140 mg/dl (100% of them were solved), and 26% of patients underwent hepatic dysfunction (50% were solved). No refeeding syndrome was reported (thiamine was added to PN in 34% of patients). Discussion: the nutritional support team work has notably increased the quality, safety and effectiveness of PN. This study demonstrates the need to incorporate multidisciplinary nutritional teams in hospitals and the benefit obtained in the patient medical care (AU)

Respuesta parcial de etanercept en el tratamiento de la hidradenitis supurativa / No disponible

Objetivo Revisión del tratamiento de la hidradenitis pupurativa y papel de etanercept en términos de eficacia y seguridad. Métodos Estudio descriptivo transversal retrospectivo. Se incluyeron pacientes diagnosticados de hidradenitis supurativa tratados con etanercept (indicación fuera de ficha técnica) hasta junio de 2009. Las variables estudiadas fueron: edad, sexo, tratamientos anteriores y posteriores a etanercept, respuesta, efectos adversos, duración y motivo de suspensión. Resultados Como primera línea de tratamiento se emplearon antibióticos, anticonceptivos, corticoides, isotretinoína o sulfonas orales. Ante la falta de respuesta mantenida se solicitó el uso de etanercept. Fue bien tolerado, pero únicamente permitió obtener una mejoría inicial, por lo que fue suspendido. Las siguientes opciones que se emplearon incluyeron corticoides, antibióticos, isotretinoína, anticonceptivos, inmunosupresores y antiandrógenos. Los pacientes tratados con adalimumab e infliximab como alternativa presentaron reactivación de las lesiones. Como última opción se plantea el tratamiento quirúrgico. Actualmente, la mayoría de los pacientes están en terapia de mantenimiento con tratamientos orales. Conclusiones El tratamiento de la hidradenitis supurativa se basa en antibióticos, corticoides o anticonceptivos con los que se obtiene un control transitorio de la enfermedad. El etanercept es bien tolerado, pero su eficacia se limita a una mejoría inicial. Se han obtenido resultados similares con infliximab y adalimumab. La cirugía permite obtener un control en la zona intervenida. Por tanto, el papel de los anti-TNF en el tratamiento de la hidradenitis supurativa es controvertido (AU)

Objective To review the treatment of hidradenitis suppurativa and the role of etanercept in terms of efficacy and safety. Methods Descriptive, cross-sectional and retrospective study. Patients diagnosed with hidradenitis suppurativa who were treated with etanercept (indication not on its Summary of Product Characteristics) until June 2009 were included in the study. The study variables were: age, sex, treatments before and after etanercept, response, adverse effects, duration and reason for stopping treatment. Results Antibiotics, contraceptives, corticosteroids, isotretinoin or oral sulfones were used as the first-line treatment. When patients no longer responded to these treatments, the use of etanercept was requested. It was well tolerated but it only led to an initial improvement. It was, therefore, suspended. The options employed included the following: corticosteroids, antibiotics, isotretinoin, contraceptives, immunosuppressive drugs and antiandrogens. Patients who were treated with adalimumab and infliximab as an alternative treatment found that their lesions flared up. Surgery was considered as a last option. At present, the majority of patients are undergoing maintenance therapy with oral treatments. Conclusions The treatment of hidradenitis suppurativa is based on antibiotics, corticosteroids or contraceptives. These are able to control the disease temporarily. Etanercept is well tolerated but it only results in an initial improvement. Similar results have been found with infliximab and adalimumab. The affected areas can be controlled with surgery. Therefore, the role of TNF inhibitors in the treatment of hidradenitis suppurativa is controversial (AU)