Effectiveness of a specific follow up program for the management of the mental components of post-intensive care syndrome and chronic pain after COVID-19: results from the PAIN-COVID randomized clinical trial.

BACKGROUND: Critical COVID-19 survivors are at risk of developing Post-intensive Care Syndrome (PICS) and Chronic ICU-Related Pain (CIRP). We determined whether a specific care program improves the quality of life (QoL) of patients at risk of developing PICS and CIRP after COVID-19. METHODS: The PAIN-COVID trial was a parallel-group, single-centre, single-blinded, randomized controlled trial. The intervention consisted of a follow up program, patient education on PICS and pain, and a psychological intervention based on Rehm's self-control model in patients with abnormal depression scores (≥8) in the Hospital Anxiety and Depression Scale (HADS) at the baseline visit. QoL was evaluated with the 5-level EQ 5D (EQ 5D 5 L), mood disorders with the HADS, post-traumatic stress disorder (PTSD) with the PCL-5 checklist, and pain with the Brief Pain Inventory short form, the Douleur Neuropathique 4 questionnaire, and the Pain Catastrophizing Scale. The primary outcome was to determine if the program was superior to standard-of-care on the EQ visual analogue scale (VAS) at 6 months after the baseline visit. The secondary outcomes were EQ VAS at 3 months, and EQ index, CIRP incidence and characteristics, and anxiety, depression, and PTSD at 3 and 6 months after baseline visits. CONCLUSIONS: This program was not superior to standard care in improving QoL in critical COVID-19 survivors as measured by the EQ VAS. However, our data can help establish better strategies for the study and management of PICS and CIRP in this population. TRIAL REGISTRATION: # NCT04394169, registered on 5/19/2020.

Stroke units could be a valid alternative to intensive care units for patients with low-grade aneurysmal subarachnoid haemorrhage.

BACKGROUND AND PURPOSE: According to current guidelines, patients with aneurysmal subarachnoid haemorrhage (aSAH) are mostly managed in intensive care units (ICUs) regardless of baseline severity. We aimed to assess the prognostic and economic implications of initial admission of patients with low-grade aSAH into a stroke unit (SU) compared to initial ICU admission. METHODS: We reviewed prospectively registered data from consecutive aSAH patients with a World Federation of Neurosurgery Societies grade <3, admitted to our Comprehensive Stroke Centre between April 2013 and September 2018. Clinical and radiological baseline traits, in-hospital complications, length of stay (LOS) and poor outcome at 90 days (modified Rankin Scale score > 2) were compared between the ICU and SU groups in the whole population and in a propensity-score-matched cohort. RESULTS: Of 131 patients, 74 (56%) were initially admitted to the ICU and 57 (44%) to the SU. In-hospital complication rates were similar in the ICU and SU groups and included rebleeding (10% vs. 7%; P = 0.757), angiographic vasospasm (61% vs. 60%; P = 0.893), delayed cerebral ischaemia (12% vs. 12%; P = 0.984), pneumonia (6% vs. 4%; P = 0.697) and death (10% vs. 5%; P = 0.512). LOS did not differ between groups (median [interquartile range] 22 [16-30] vs. 19 [14-26] days; P = 0.160). In adjusted multivariate models, the location of initial admission was not associated with long-term poor outcome either in the whole population (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.32-4.19; P = 0.825) or in the matched cohort (OR 0.98, 95% CI 0.24-4.06; P = 0.974). CONCLUSIONS: A dedicated SU, with care from a multidisciplinary team, might be an optimal alternative to ICU for initial admission of patients with low-risk aSAH.

Características, evolución clínica y factores asociados a la mortalidad en UCI de los pacientes críticos infectados por SARS-CoV-2 en España: estudio prospectivo, de cohorte y multicéntrico / Patient characteristics, clinical course and factors associated to ICU mortality in critically ill patients infected with SARS-CoV-2 in Spain: a prospective, cohort, multicentre study

ANTECEDENTES: No se ha reportado plenamente la evolución clínica de los pacientes críticos de COVID-19 durante su ingreso en la unidad de cuidados intensivos (UCI), incluyendo las complicaciones médicas e infecciosas y terapias de soporte, así como su asociación con la mortalidad en ICU. OBJETIVO: El objetivo de este estudio es describir las características clínicas y la evolución de los pacientes ingresados en UCI por COVID-19, y determinar los factores de riesgo de la mortalidad en UCI de dichos pacientes. MÉTODOS: Estudio prospectivo, multi-céntrico y de cohorte, que incluyó a los pacientes críticos de COVID-19 ingresados en 30 UCIs de España y Andorra. Se incluyó a los pacientes consecutivos de 12 de Marzo a 26 de Mayo de 2020 si habían fallecido o habían recibido el alta de la UCI durante el periodo de estudio. Se reportaron los datos demográficos, síntomas, signos vitales, marcadores de laboratorio, terapias de soporte, terapias farmacológicas, y complicaciones médicas e infecciosas, realizándose una comparación entre los pacientes fallecidos y los pacientes dados de alta. RESULTADOS: Se incluyó a un total de 663 pacientes. La mortalidad general en UCI fue del 31% (203 pacientes). Al ingreso en UCI los no supervivientes eran más hipoxémicos [SpO2 sin mascarilla de no reinhalación, de 90 (RIC 83-93) vs 91 (RIC 87-94); p < 0,001] y con mayor puntuación en la escala SOFA - Evaluación de daño orgánico secuencial - [SOFA, 7 (RIC 5-9) vs 4 (RIC 3-7); p < 0,001]. Las complicaciones fueron más frecuentes en los no supervivientes: síndrome de distrés respiratorio agudo (SDRA) (95% vs 89%; p = 0,009), insuficiencia renal aguda (IRA) (58% vs 24%; p < 10−16), shock (42% vs 14%; p < 10−13), y arritmias (24% vs 11%; p < 10−4). Las súper-infecciones respiratorias, infecciones del torrente sanguíneo y los shock sépticos fueron más frecuentes en los no supervivientes (33% vs 25%; p = 0,03, 33% vs 23%; p = 0,01 y 15% vs 3%, p = 10−7), respectivamente. El modelo de regresión multivariable reflejó que la edad estaba asociada a la mortalidad, y que cada año incrementaba el riesgo de muerte en un 1% (95%IC: 1-10, p = 0,014). Cada incremento de 5 puntos en la escala APACHE II predijo de manera independiente la mortalidad [OR: 1,508 (1,081, 2,104), p = 0,015]. Los pacientes con IRA [OR: 2,468 (1,628, 3,741), p < 10−4)], paro cardiaco [OR: 11,099 (3,389, 36,353), p = 0,0001], y shock séptico [OR: 3,224 (1,486, 6,994), p = 0,002] tuvieron un riesgo de muerte incrementado. CONCLUSIONES: Los pacientes mayores de COVID-19 con puntuaciones APACHE II más altas al ingreso, que desarrollaron IRA en grados II o III y/o shock séptico durante la estancia en UCI tuvieron un riesgo de muerte incrementado. La mortalidad en UCI fue del 31%

BACKGROUND: The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as their association with in-ICU mortality has not been fully reported. OBJECTIVE: This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients. METHODS: Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12th to May 26th, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients. RESULTS: A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic [SpO2 with non-rebreather mask, 90 (IQR 83-93) vs 91 (IQR 87-94); p < 0.001] and with higher sequential organ failure assessment score [SOFA, 7 (IQR 5-9) vs 4 (IQR 3-7); p < 0.001]. Complications were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs 89%; p = 0.009), acute kidney injury (AKI) (58% vs 24%; p < 10−16), shock (42% vs 14%; p < 10−13), and arrhythmias (24% vs 11%; p < 10−4). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs 25%; p = 0.03, 33% vs 23%; p = 0.01 and 15% vs 3%, p = 10−7), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1-10, p = 0.014). Each 5-point increase in APACHE II independently predicted mortality [OR: 1.508 (1.081, 2.104), p = 0.015]. Patients with AKI [OR: 2.468 (1.628, 3.741), p < 10−4)], cardiac arrest [OR: 11.099 (3.389, 36.353), p = 0.0001], and septic shock [OR: 3.224 (1.486, 6.994), p = 0.002] had an increased risk-of-death. CONCLUSIONS: Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades II or III and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%

Patient characteristics, clinical course and factors associated to ICU mortality in critically ill patients infected with SARS-CoV-2 in Spain: A prospective, cohort, multicentre study. / Características, evolución clínica y factores asociados a la mortalidad en UCI de los pacientes críticos infectados por SARS-CoV-2 en España: estudio prospectivo, de cohorte y multicéntrico.

BACKGROUND: The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as their association with in-ICU mortality has not been fully reported. OBJECTIVE: This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients. METHODS: Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12th to May 26th, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients. RESULTS: A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic [SpO2 with non-rebreather mask, 90 (IQR 83 to 93) vs. 91 (IQR 87 to 94); P<.001] and with higher sequential organ failure assessment score [SOFA, 7 (IQR 5 to 9) vs. 4 (IQR 3 to 7); P<.001]. Complications were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs. 89%; P=.009), acute kidney injury (AKI) (58% vs. 24%; P<10-16), shock (42% vs. 14%; P<10-13), and arrhythmias (24% vs. 11%; P<10-4). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs. 25%; P=.03, 33% vs. 23%; P=.01 and 15% vs. 3%, P=10-7), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1 to 10, P=.014). Each 5-point increase in APACHE II independently predicted mortality [OR: 1.508 (1.081, 2.104), P=.015]. Patients with AKI [OR: 2.468 (1.628, 3.741), P<10-4)], cardiac arrest [OR: 11.099 (3.389, 36.353), P=.0001], and septic shock [OR: 3.224 (1.486, 6.994), P=.002] had an increased risk-of-death. CONCLUSIONS: Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades ii or iii and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%.

Identificación por catálogo y detección molecular de bovinos Holstein portadores de braquiespina en Uruguay / Identification through sire catalogues analysis and molecular detection of brachyspina carriers in Uruguayan Holstein

Resumen El síndrome de braquiespina es una condición genética de la raza Holstein, detectada en el año 2006. Es causado por una deleción de 3.3 Kb en el gen FANCI localizado en el cromosoma bovino 21. La mutación fue identificada en poblaciones de Holstein de Europa, América del Norte y Asia. Dada la importancia económica del defecto y su amplia distribución mundial, el objetivo de este trabajo ha sido la identificación de animales portadores en el núcleo de selección genética de la raza en Uruguay y el diagnóstico molecular del alelo deletéreo en animales del rodeo nacional. En el presente estudio se analizaron 2598 registros de toros Holstein del catálogo de padres del sistema de evaluación genética lechera, los registros de toros pertenecientes a los catálogos de semen Holstein disponible para Uruguay de los años 2014 al 2018; y 71 vacas pertenecientes al rodeo general. Se encontraron 28 toros portadores de braquiespina de un total de 377 toros con información genética del catálogo de padres y cuatro vacas portadoras de un total de 71 genotipificadas en nuestro laboratorio. Se demostró una disminución en el ingreso de semen de animales portadores al país entre los años 2014 y 2018. La frecuencia significativa de animales portadores en Uruguay evidencia la necesidad de implementar estrategias que permitan eliminar gradualmente el defecto de la población.

Abstract Brachyspina syndrome is a hereditary recessive disease of recent identification in the Holstein breed. It is caused by a deletion of 3.3Kb in the FANCI gene located in the bovine chromosome 21. The mutation was identified in Holstein populations of Europe, North America and Asia. Given the economic importance of the defect and its wide distribution, the objective of this work was the identification of carrier animals in the genetic selection nucleus of the breed in Uruguay and the molecular verification of the deleterious allele in animals of the national herd. In the present study, 2598 records of Holstein bulls were analyzed from the list of parents of the dairy genetic evaluation system, records of bulls belonging to the Holstein semen catalogs available for Uruguay from 2014 to 2018; and 71 cows belonging to the general herd. Twenty-eight brachyspina carrier bulls were found of a total of 377 bulls with genetic information from the list of parents and four carrier cows of a total of 71 genotyped in our laboratory. A decrease in the income of semen from carrier animals to the country between 2014 and 2018 was demonstrated. The significant frequency of carrier animals in Uruguay evidences the need to implement strategies to gradually eliminate the population defect.

Time-domain induced polarization as a tool to image clogging in treatment wetlands.

During the last decade, treatment (artificial) wetlands have flourished all over Europe for the treatment of sewages from small communities thanks to their low cost of operation. The clogging of the filter of these wetlands is an issue affecting their efficiency and considered as their main operational problem. The present work shows the results of the application of a geophysical method called time-domain induced polarization. It is used to non-intrusively image, in 3D, the clogging of the gravel filters in a quick and efficient way. Induced polarization characterizes the ability of a porous material to reversibly store electrical charges when submitted to an electrical field. The material property characterizing this ability is called normalized chargeability. A set of laboratory experiments allows to determine an empirical relationship between the normalized chargeability and the weight amount of clogging. Induced polarization measurements have been performed in the field over a treatment wetland to get a 3D reconstructed image (tomography) of the normalized chargeability. From this tomography and the previously defined relationship, we are able to image in 3D the distribution of clogging and where it is concentrated in the filter. We can therefore identify the areas requiring preventive measures to minimize this clogging issue.

ESTABLECIMIENTO DEL SISTEMA DE REGENERACIÓN POR EMBRIOGÉNESIS SOMÁTICA DE Azadirachta indica A. Juss. / Establishment of Regeneration System for Somatic Embryogenesis of Azadirachta Indica A. Juss.

Azadirachta indica, es una planta con múltiples aplicaciones tanto forestal como farmacológica. Por ende, el establecimiento del sistema de cultivo in vitro por embriogénesis somática ofrece diversas y variadas ventajas, tales como obtener plantas altamente productivas en metabolitos. En este estudio, se utilizaron secciones foliares y cotiledonares, inducidas en medios MS (1962) suplementados con: BAP sólo y combinado con ANA / 2,4-D, TDZ sólo y con ABA. La regeneración fue con MS sólo o con K + AIA y BAP + AIA. Como resultado se estableció un sistema eficiente con secciones de cotiledones, observándose organogénesis a bajas concentraciones de BAP, mientras a altos niveles de BAP (2,5 mg.L-1), así como con TDZ + ABA (0,02 + 1 mg.L-1) respectivamente favorecieron la embriogénesis somática primaria y secundaria en un 96 % y 71 % respectivamente. La regeneración fue 71 % con MS, mientras que el enraizamiento fue de 86,67 % con MS½, obteniéndose plantas completas a corto plazo.

Azadirachta indica, is a plant with multiple forest and pharmacological application. Therefore, the establishment of in vitro culture system for somatic embryogenesis offers several distinct advantages such as obtaining highly productive plant metabolites. In this study, were used sections cotyledon and leaf, induced on MS medium (1962) supplemented with: BAP alone and combined with NAA / 2,4-D, TDZ alone and ABA. Regeneration was with MS alone or with K + BAP + IAA and IAA. As a result was established an efficient system with cotyledon sections, being observed organogenesis at low concentrations of BAP, while high levels of BAP (2.5 mg.L-1) with 96 % and TDZ + ABA (0.02 + 1 mg.L-1) with 71 %, favoring the primary and secondary somatic embryogenesis. Regeneration was 71 % with MS; rooting was 86.67 % with MS½, presenting whole plants obtained short term.

Safety of specific immunotherapy using a depigmented and polymerised extract of Dermatophagoides pteronyssinus in children under five years of age

Background: Different opinion documents point to a patient age of under five years as a relative contraindication to specific immunotherapy, arguing that this age group has a greater risk of developing anaphylaxis, and that specially trained personnel are needed to deal with the problem if it occurs. However, insufficient evidence exists to support such an affirmation. Patients and methods: A retrospective follow-up observational study was made of patients aged 60 months or younger who had been subjected to specific immunotherapy. We included 77 children with a diagnosis of extrinsic bronchial asthma (n=68), extrinsic spasmodic cough (n=5) and allergic rhinitis (n=4) confirmed by clinical criteria and prick-test, with specific IgE positivity to Dermatophagoides pteronyssinus. All patients received specific immunotherapy with an extract of depigmented D. pteronyssinus polymerised with glutaraldehyde, involving an initial cluster protocol of two weeks and monthly maintenance doses. All observed adverse reactions were recorded, and classified according to European Academy of Allergy and Clinical Immunology (EAACI) criteria. Results: A total of 1837 doses were administered to the 77 patients, with four adverse reactions being observed in three patients. Three reactions (0.16% of the administered doses) were local and immediate, while one was systemic and of grade 2 (0.05% of the administered doses) – consisting of an episode of nocturnal wheezing. Conclusions: Specific immunotherapy in children under five years of age with the extract used is safe. We consider that further studies are needed, involving other types of extracts, to allow reconsideration of the relative contraindication of patient age for the administration of immunotherapy (AU)

Factors associated with blood pressure control in diabetic patients treated in nephrology units. PRESDIAB Study.

BACKGROUND AND OBJECTIVE: Most hypertensive patients do not reach target blood pressure (BP), especially if they are diabetic. The objective of the study is to assess the percentage of tight BP control, defined as BP<130/80mm Hg and identify factors associated with it in diabetic type 2 (DM2) patients treated in nephrology units. PATIENTS AND METHODS: Observational and cross-sectional study; we included 526 patients with DM2 and arterial hypertension (AHT). We collected data on: demographics, anthropometrics, harmful habits, history of cardiovascular disease (CVD), blood pressure, kidney function, glycaemic control, lipid profile, and drug treatment, among others. RESULTS: The mean age (SD) was 66 (10.6) years, 61% were male, 12.8% were smokers, 39.4% had a history of CVD, 72% had hypercholesterolemia, and 44% were obese. Seventeen point five percent of patients had tight BP control (<130/80mm Hg) (95% confidence interval [CI]:14.3-21.0), while 36.9% had BP below 140/85mm Hg. Seventy-one percent of patients were prescribed two or more anti-hypertensive treatments. Several factors are associated with tight BP control not being achieved, and the logistic regression analysis revealed that LDL cholesterol levels were significantly associated (odds ratio [OR] 0.55; 95% CI:0.41-0.75 for one standard deviation increase). CONCLUSIONS: Of the DM2 patients that attended the nephrology units, less than 20% achieved a tight BP control. Cholesterol levels seem to be the main factor associated with unsatisfactory BP control within our study population.

Factores asociados al control de la presión arterial en pacientes con diabetes tratados en unidades de nefrología. Estudio PRESDIAB / Factors associated with blood pressure control in diabetic patients treated in nephrology units. PRESDIAB Study

Fundamento y objetivo: La mayoría de pacientes hipertensos no alcanza los objetivos de control de la presión arterial (PA), especialmente si son diabéticos. El objetivo del estudio fue evaluar el porcentaje de control estricto de la PA definida como PA <130/80 mmHg e identificar factores asociados al mismo en pacientes diabéticos tipo 2 (DM2) tratados en unidades de nefrología. Pacientes y método: Estudio observacional y transversal, en el que se incluyeron 526 pacientes con DM2 e hipertensión arterial (HTA). Se recogieron datos demográficos, antropométricos, hábitos tóxicos, antecedentes de enfermedad cardiovascular (ECV), medidas de PA, función renal, control glicémico, perfil lipídico y tratamiento farmacológico, entre otros. Resultados: La edad media (DE) fue de 66 (10,6) años, con un 61% de hombres, un 12,8% de fumadores, un 39,4% con antecedentes de ECV, un 72% con hipercolesterolemia, y 44% con obesidad. El porcentaje de control estricto de la PA (<130/80 mmHg) fue del 17,5% (intervalo de confianza [IC] 95%: 14,3-21,0), mientras que un 36,9% tenían la PA por debajo de 140/85 mmHg. Un 71,1% de pacientes recibía dos o más tratamientos antihipertensivos. Diversos factores se asociaron con falta de control estricto de la PA, de los cuales, tras análisis de regresión logística, destacaban los valores de colesterol LDL (odds ratio [OR] 0,55; IC 95%: 0,41-0,75 para un aumento de 1 DE). Conclusiones: En pacientes con DM2 atendidos en unidades de nefrología, el porcentaje del control estricto de la PA es inferior al 20% en la clínica. Los niveles de colesterol parece el principal factor asociado con el control insuficiente de PA en la población estudiada (AU)

Background and objective: Most hypertensive patients do not reach target blood pressure (BP), especially if they are diabetic. The objective of the study is to assess the percentage of tight BP control, defined as BP<130/80mm Hg and identify factors associated with it in diabetic type 2 (DM2) patients treated in nephrology units. Patients and methods: Observational and cross-sectional study; we included 526 patients with DM2 and arterial hypertension (AHT). We collected data on: demographics, anthropometrics, harmful habits, history of cardiovascular disease (CVD), blood pressure, kidney function, glycaemic control, lipid profile, and drug treatment, among others. Results: The mean age (SD) was 66 (10.6) years, 61% were male, 12.8% were smokers, 39.4% had a history of CVD, 72% had hypercholesterolemia, and 44% were obese. Seventeen point five percent of patients had tight BP control (<130/80mm Hg) (95% confidence interval [CI]:14.3-21.0), while 36.9% had BP below 140/85mm Hg. Seventy-one percent of patients were prescribed two or more anti-hypertensive treatments. Several factors are associated with tight BP control not being achieved, and the logistic regression analysis revealed that LDL cholesterol levels were significantly associated (odds ratio [OR] 0.55; 95% CI:0.41-0.75 for one standard deviation increase). Conclusions: Of the DM2 patients that attended the nephrology units, less than 20% achieved a tight BP control. Cholesterol levels seem to be the main factor associated with unsatisfactory BP control within our study population (AU)

Safety of specific immunotherapy using a depigmented and polymerised extract of Dermatophagoides pteronyssinus in children under five years of age.

BACKGROUND: Different opinion documents point to a patient age of under five years as a relative contraindication to specific immunotherapy, arguing that this age group has a greater risk of developing anaphylaxis, and that specially trained personnel are needed to deal with the problem if it occurs. However, insufficient evidence exists to support such an affirmation. PATIENTS AND METHODS: A retrospective follow-up observational study was made of patients aged 60 months or younger who had been subjected to specific immunotherapy. We included 77 children with a diagnosis of extrinsic bronchial asthma (n=68), extrinsic spasmodic cough (n=5) and allergic rhinitis (n=4) confirmed by clinical criteria and prick-test, with specific IgE positivity to Dermatophagoides pteronyssinus. All patients received specific immunotherapy with an extract of depigmented D. pteronyssinus polymerised with glutaraldehyde, involving an initial cluster protocol of two weeks and monthly maintenance doses. All observed adverse reactions were recorded, and classified according to European Academy of Allergy and Clinical Immunology (EAACI) criteria. RESULTS: A total of 1837 doses were administered to the 77 patients, with four adverse reactions being observed in three patients. Three reactions (0.16% of the administered doses) were local and immediate, while one was systemic and of grade 2 (0.05% of the administered doses) - consisting of an episode of nocturnal wheezing. CONCLUSIONS: Specific immunotherapy in children under five years of age with the extract used is safe. We consider that further studies are needed, involving other types of extracts, to allow reconsideration of the relative contraindication of patient age for the administration of immunotherapy.

Effects of 5-azacytidine on lymphocyte-metaphases of Creole cows carrying the rob(1;29).

The Robertsonian translocation rob(1;29) is the most important chromosomal abnormality in cattle. It has been demonstrated that carriers of this chromosomal alteration exhibit reduced fertility due to an early embryonic loss. In the present study we analyzed the effects of DNA methylation inhibitor 5-azacytidine (5-aza-C) on metaphase lymphocytes from Uruguayan Creole cows carrying the rob(1;29). The analysis was focused on the chromatin structure of rob(1;29) comparing it to active and inactive BTAX chromosomes. Lymphocyte cultures were treated with 5-aza-C (1 x 10(-3)M) for 2 h to analyze regions of chromatin decondensation. A comparative analysis of chromatin decondensation among rob(1;29), active BTAX and inactive BTAX showed significant differences (p=1.07 x 10(-7)). Post-hoc pair-wise comparisons using the Mann-Whitney U-test showed significant differences between rob(1;29) and active BTAX (p=1.97 x 10(-5)) and between the active BTAX and inactive BTAX (p=2.55 x 10(-7)). Nevertheless, rob(1;29) did not show significant differences when compared to inactive BTAX (p=0.078). Robertsonian translocation rob(1;29) showed a despiralization pattern similar to the inactive X chromosome. Pericentromeric despiralization in rob(1;29) and the inactive X chromosome was similar, with an average value and standard error of 0.75+/-0.11 and 0.75+/-0.083, respectively. A single condensed region was observed in the inactive X chromosome, whereas in rob(1;29) two regions of condensation, one proximal to the centromere and another proximal to the telomere were detected. Our results show that rob(1;29) and the inactive X chromosome present instability regions susceptible to 5-aza-C. Further studies will be needed to understand the nature and expression pattern of genes located in chromatin condensed regions of rob(1;29).

Seroprevalencia de anticuerpos IgG anti Toxoplasma gondii en receptorespretrasplante renales cubanos, Holguin, 2005: [carta al editor] / Seroprevalence of IgG antibodies against Toxoplasma gondii in cuban receptors: [letter to the editor]

Estudios recientes han permitido observar que entre un 30-50% de los pacientes infectadosdesarrolla una toxoplasmosis cerebral durante su evolución7,8 siendo los de mayor riesgo los quetienen cifras de CD4+ por debajo de 100/mm3. Si bien es cierto que las contraindicaciones para larealización de un trasplante renal son pocas, no podemos negar que buena parte del éxito de estaopción terapéutica radica en una correcta selección de los receptores, donde la toxoplasmosispuede estar asociada5. En Cuba se ha reportado hasta un 65,4% de prevalencia de anticuerposanti-Toxoplasma gondii en pacientes con insuficiencia renal crónica9

Effectiveness of virosomal subunit influenza vaccine in preventing influenza-related illnesses and its social and economic consequences in children aged 3-14 years: a prospective cohort study.

To evaluate the effectiveness of a virosomal subunit influenza vaccine in preventing influenza-related illnesses and its social and economic consequences in children aged 3-14 years, a prospective cohort study was carried out during the 2004-2005 influenza season in 11 private pediatric clinics in the Barcelona metropolitan area. One dose of a virosomal subunit inactivated influenza vaccine (Inflexal V Berna) was given during September and October 2004 to healthy children aged 3-14 years attended in 5 of the 11 clinics. Who comprised the vaccinated cohort (n=966). The non-vaccinated cohort (n=985) was comprised of children attended in the other six clinics. Informed consent was obtained from all parents. The follow up was performed between 1 November 2004 and 31 March 2005. Using a self-administered questionnaire, information was collected from parents or guardians on any type of acute, febrile respiratory illness suffered by their children during the study period, including antibiotic use, and absence from school or work-loss of parents as a result of the illness. RT-PCR (influenza A+B+C) was carried out on pharyngeal and nasal samples obtained from children attended by pediatricians during this period in these clinics with the following symptoms: fever> or =38.5 degrees lasting at least 72h, cough or sore throat (influenza-like illness). Adjusted vaccination effectiveness was 58.6% (95% CI 49.2-66.3) in preventing acute febrile respiratory illnesses, 75.1% (95% CI 61.0-84.1) in preventing cases of influenza-like illnesses and 88.4% (95% CI 49.2-97.3) in preventing laboratory-confirmed cases of influenza A. The adjusted vaccination effectiveness in reducing antibiotic use (18.6%, 95% CI -4.2 to 3.64), absence from school (57.8%, 95% CI 47.9-65.9) and work-loss of parents (33.3%, 95% CI 8.9-51.2) in children affected by an acute febrile respiratory illness was somewhat lower. Vaccination of children aged 3-14 years in pediatric practices with one dose of virosomal subunit inactivated influenza vaccine has the potential to considerably reduce the health and social burdens caused by influenza-related illnesses.

Clinical pharmacokinetics of parenteral dexketoprofen trometamol in healthy subjects.

Dexketoprofen trometamol, a highly water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug used for pain relief. Two studies were conducted to determine the pharmacokinetics of the drug in healthy subjects following single intravenous (i.v.) and intramuscular (i.m.) doses of dexketoprofen. In the first study, 6 male and 6 female volunteers received 50 mg dexketoprofen (74 mg dexketoprofen trometamol) by i.v. bolus. In the second one, another 6 male and 6 female subjects received 25 mg and 50 mg of dexketoprofen by the i.m. route. Dexketoprofen plasma concentrations were determined by reverse-phase high-performance liquid chromatography (HPLC). No serious adverse events were observed and all volunteers completed the study. The main pharmacokinetic parameters were determined by a noncompartmental approach. Following the i.v. bolus, mean (+/- SEM) area under the curve AUC0-x and clearance (CL) were 9005 +/- 422 ng.h/ml and 0.089 +/- 0.004 l/h/kg. Volumes of distribution Vi and Vss averaged 0.060 +/- 0.006 l/kg and 0.104 +/- 0.003 l/kg. Mean elimination half-life (t1/2e) and MRT were 1.05 +/- 0.04 h and 1.18 +/- 0.05 h. Following single i.m. 25 mg and 50 mg dexketoprofen, a rapid absorption was observed, with tmax values ranging from 0.17 h to 0.75 h. The corresponding Cmax averaged 1851 +/- 182 ng/ml and 3813 +/- 169 ng/ml, and mean AUC0-x were 3033 +/- 193 ng.h/ml and 5878 +/- 228 ng.h/ml, respectively. No significant differences by gender were obtained following both parenteral routes. A dose proportionality in Cmax and AUC0-x was observed. Dexketoprofen pharmacokinetics following i.v. and i.m. routes, together with the availability of a single 2 ml formulation, allows for a potential advantageous rapid switch to the oral formulation when clinically possible.

Single and repeated dose pharmacokinetics of dexketoprofen trometamol in young and elderly subjects.

Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) widely used for pain relief. This study was conducted to determine the pharmacokinetics of this analgesic agent in elderly subjects and to compare them with young volunteers following single and repeated oral doses. Twelve healthy young and 12 elderly subjects received 25 mg oral dexketo- profen (equivalent to 37 mg of its tromethamine salt) as a single dose (day 1) and 3-day repeated doses (1 dose every 8 h for a total of 10 doses). Serial concentrations of dexketoprofen were determined in plasma and urine by a reverse-phase HPLC/ultraviolet procedure over 24 h on day 1 and after the last 10th repeated t.i.d. dose. Compared to young subjects, elderly subjects showed significant increases in AUC and t1/2,z and decreases in CL/F following single and repeated doses. After single dosing, the corresponding mean +/- SD values were 5106.6 +/- 1873.0 vs. 3605.4 +/- 897.9 ng.h/ml (p = 0.015); 1.59 +/- 0.40 vs. 1.12 +/- 0.20 h (p < 0.001); and 1.11 +/- 0.29 vs. 1.63 +/- 0.36 ml/min/kg (p < 0.001). After the repeated dose, AUC, t1/2,z and CL/F averaged 5067.8 +/- 1373.4 vs. 3194.4 +/- 694.3 ng.h/ml (p < 0.001); 1.65 +/- 0.44 vs. 1.11 +/- 0.29 h (p < 0.005); and 1.12 +/- 0.23 vs. 1.87 +/- 0.42 ml/min/kg (p < 0.001). Median tmax was 0.5 h. Cumulative excretions in urine up to 24 h of unbound, conjugated and total dexketoprofen were similar among the groups. These results suggest that dexketoprofen elimination is reduced in the elderly. Although no drug accumulation in plasma was observed after single and repeated dosing, the renal function decline in elderly patients calls for a cautious dose-adjustment in this population.

Pharmacokinetics of dexketoprofen trometamol in subjects with mild and moderate chronic renal insufficiency.

The influence of mild to moderate chronic renal insufficiency on the pharmacokinetics of dexketoprofen trometamol was evaluated. Dexketoprofen was administered to volunteers with mild (n = 8) or moderate (n = 8) renal impairment and to healthy subjects (n = 8), as a single 12.5 mg oral dose (equivalent to 18.5 mg of the tromethamine salt). All subjects completed the study and no serious adverse events were recorded. Mild and moderate renal insufficiency increased Cmax by approximately 22% and 37%, respectively, as related to normal subjects (p < 0.05 for moderate renal dysfunction). No statistically significant differences between groups were obtained for tmax, AUC, CL/F, renal CL and V/F. The cumulative urinary excretion of unchanged dexketoprofen, assessed up to 24 hours postdose, was similar in all groups (median values of 7.0%, 8.1% and 9.7% of the administered dose). On the contrary, cumulative urinary excretions of conjugated dexketoprofen decreased in subjects with mild or moderate renal insufficiency when compared to healthy controls (median and 95% CI for differences: -3.3% (-14.8% to 2.6%) and -7.3% (-22.2% to -0.2%), respectively). Conservatively, a dose adjustment of dexketoprofen in patients with impaired renal function is recommended.

Single and repeated dose pharmacokinetics of dexketoprofen trometamol in patients with impaired liver function.

Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain relief. This study compared the pharmacokinetics of dexketoprofen in patients with impaired liver function and normal subjects following single and repeated oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label and parallel study. They received 25 mg dexketoprofen (equivalent to 37 mg of its tromethamine salt) as a single (day 1) and a 3-day repeated dose (1 dose every 8 hours for a total of 10 doses). Dexketoprofen concentrations were determined in plasma and urine by reverse-phase high performance liquid chromatography (HPLC). Model-independent pharmacokinetic parameters were obtained. All subjects completed the study. No serious adverse events were recorded. Following the single dose, mean (+/- SEM) Cmax were 3027.7 +/- 429.3 ng/ml (healthy subjects), 2856.3 +/- 340.3 ng/ml (Child-Pugh A) and 1937.2 +/- 328.0 ng/ml (Child-Pugh B). Median tmax were 0.49 h (0.33-0.68) h, 0.50 h (0.33-0.67) h and 0.67 h (0.33-1.50) h. AUC0-x averaged 3778.0 +/- 439.0 ng.h/ml, 4890.4 +/- 539.1 ng.h/ml and 3985.0 +/- 712.0 ng.h/ml. Mean CL/F were 101.1 +/- 11.3 ml/h/kg, 73.3 +/- 9.9 ml/h/kg and 88.8 +/- 15.5 ml/h/kg and V/F averaged 0.192 +/- 0.018 l/kg, 0.162 +/- 0.006 l/kg and 0.214 +/- 0.044 l/kg. Following the repeated administration, similar results were obtained showing no drug accumulation. As related to the administered dose, median excretions of unchanged and conjugated dexketoprofen in urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced urinary excretion of conjugated dexketoprofen in hepatic patients, more evident in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared with healthy volunteers (median and 95% CI for differences: -5.4% [-19.9% to 2.0%] and -19.4% [-45.6% to 0.4%]). Conservatively, a dose adjustment of dexketoprofen trometamol in patients with impaired hepatic function is recommended.

ITS-2 rDNA sequencing of Gnathostoma species (Nematoda) and elucidation of the species causing human gnathostomiasis in the Americas.

From several gnathostome species the complete internal transcribed spacer ITS-2 ribosomal DNA (rDNA) repeat sequence and a fragment of the 5.8S rDNA were obtained by direct polymerase chain reaction cycle-sequencing and silver-staining methods. The size of the complete ITS-1 sequence in agarose gel electrophoresis was also obtained. The ITS-2 enabled the differentiation of Gnathostoma spinigerum from Thailand and Gnathostoma binucleatum from Mexico and Ecuador and confirmed the validity of the latter. Gnathostoma turgidum, Gnathostoma sp. I (=Gnathostoma procyonis sensu Almeyda-Artigas et al., 1994), and Gnathostoma sp. II (=G. turgidum sensu Foster, 1939 pro parte), all from Mexico, proved to be independent species, but Gnathostoma sp. III, also from Mexico, could not be differentiated from G. turgidum. In Mexico and Ecuador, gnathostomes involved in human infection and that had been classified as G. spinigerum belong to G. binucleatum. The 5.8S rDNA sequences of the 6 Gnathostoma species studied were identical. The results of the ITS-1 agreed with those results of ITS-2.

Cisapride treatment changes the evolution of infant asthma with gastroesophageal reflux.

Gastroesophageal reflux has been named as a possible etiologic factor in infant asthma. We studied 28 boys and six girls aged 19.4 +/- 4.8 months whose asthma began at the age of 7.5 months (1 to 28 months). A common protocol including allergy tests and 24-h intraesophageal pH monitoring (IEpHM) was used. Patients with pathologic 24-h IEpHM were treated with cisapride while the rest were considered the control group. Symptoms score and drug consumption were evaluated in both groups, and 24-h IEpHM was repeated at 4 months. IEPHM was pathologic in 65.6% of the infants. In the cisapride group, wheezing crisis frequency decreased from 4.9 +/- 2 to 0.75 +/- 1.2 (p < 0.0002), and only 10% of patients needed basic pharmacologic treatment. The second IEpHM was normal in eight cases, pathologic in six and was not performed in seven. In the controls, wheezing crisis frequency decreased from 4.6 +/- 2.4 to 0.75 +/- 1.8 (p < 0.01), but 44% needed basic pharmacologic treatment (p < 0.05). In conclusion, gastroesophageal reflux is a frequent but not universal finding in infants with asthma; and cisapride treatment spectacularly reduces wheezing crisis frequency and antiasthmatic drug consumption in these patients.