Safe Reduction in CD4 Cell Count Monitoring in Stable, Virally Suppressed Patients With HIV Infection or HIV/Hepatitis C Virus Coinfection.

BACKGROUND: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/µL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression. METHODS: The PISCIS Cohort study included data from 14 539 patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain) since January 1998. All patients who had at least one period of 6 months of continuous HIV suppression were included in this analysis. Cumulative probabilities with 95% confidence intervals were calculated using the Kaplan-Meier estimator stratified by the initial CD4 cell count at the period of continuous suppression initiation. RESULTS: A total of 8695 patients were included. CD4 cell counts fell to <200 cells/µL in 7.4% patients, and the proportion was lower in patients with an initial count >350 cells/µL (1.8%) and higher in those with an initial count of 200-249 cells/µL (23.1%). CD4 cell counts fell to <200 cells/µL in 5.7% of monoinfected and 11.1% of coinfected patients. Of monoinfected patients with an initial CD4 cell count of 300-349 cells/µL, 95.6% maintained counts ≥200 cells/µL. In the coinfected group with the same initial count, this rate was lower, but 97.6% of coinfected patients with initial counts >350 cells/µL maintained counts ≥200 cells/µL. CONCLUSIONS: From our data, it can be inferred that CD4 cell count monitoring can be safely performed annually in HIV-monoinfected patients with CD4 cell counts >300 cells/µL and HIV/HCV-coinfected patients with counts >350 cells/µL.

[Cerebrovascular accident with haemorrhagic transformation in a patient on antiplatelet treatment subjected to surgery of a hypophyseal macroadenoma]. / Accidente cerebrovascular con transformación hemorrágica en una paciente con tratamiento antiagregante intervenida de macroadenoma hipofisario.

The case is presented of a 51 year-old woman, proposed for endoscopic endonasal transsphenoidal resection of a hypophyseal macroadenoma diagnosed in the context of a stroke suffered 10 weeks before the date of the surgery. During this time, she had been treated with antiplatelet drugs, which were withdrawn 5 days before the surgery. The surgical procedure was performed without any incidents. On the second day after the surgery, the patient had an ischaemic infarction of the left cerebellar hemisphere, with signs of hydrocephaly and a posterior haemorrhagic transformation, with brain death 5 days after the operation. There are no definitive guidelines on the use of antiplatelet drugs in the perioperative period of neurosurgery. Also, there is no agreement as regards the waiting time between a cerebrovascular event and surgery, it appears that between 4 and 12 weeks would be the most advisable. The importance of an individual assessment of each patient before surgery is emphasised, as well as a review of the antiplatelet management of the patient with a risk of thrombosis in the context of neurosurgery, and their possible postoperative complications.

A simple algorithm for differential diagnosis in hemodynamic shock based on left ventricle outflow tract velocity-time integral measurement: a case series.

Echocardiography has gained wide acceptance among intensive care physicians during the last 15 years. The lack of accredited formation, the long learning curve required and the excessive structural orientation of the present algorithms to evaluate hemodynamically unstable patients hampers its daily use in the intensive care unit. The aim of this article is to show 4 cases where the use of our simple algorithm based on VTI, was crucial. Subsequently, to explain the benefit of using the proposed algorithm with a more functional perspective, as a means for clinical decision-making. A simple algorithm based on left ventricle outflow tract velocity-time integral measurement for a functional hemodynamic monitoring on patients suffering hemodynamic shock or instability is proposed by Spanish Critical Care Ultrasound Network Group. This algorithm considers perfusion and congestion variables. Its simplicity might be useful for guiding physicians in their daily decision-making managing critically ill patients in hemodynamic shock.

Diploma on Basic Echocardiography training and competencies for Intensive Care and Emergency medicine: Consensus document of the Spanish Society of Anesthesiology and Critical Care (SEDAR) and the Spanish Society of Emergency Medicine (SEMES).

Cardiac ultrasound has become an essential tool for diagnosis and hemodynamic monitoring in critically ill patients. Scientific societies need to work toward developing a training program that will allow clinicians to acquire competence in performing cardiac ultrasound and understanding its indications. The Clinical Ultrasound for Intensive Care task force of the Spanish Society of Anesthesiology and Critical Care (SEDAR) and the Spanish Society of Emergency Medicine (SEMES) have drawn up this position statement defining the learning objectives and training required to acquire the competencies recommended for basic ultrasound management in the intensive care and emergency setting in order to obtain a diploma in Basic Ultrasound in Intensive Care and Emergency Medicine. This document defines the training program and the competencies needed for basic skills in ultrasound in Intensive Care and Emergency Medicine-part of the Diploma in Ultrasound for Intensive Care and Emergency Medicine awarded by SEDAR/SEMES. The Spanish Society of Anesthesia (SEDAR), Spanish Society of Internal Medicine (SEMI) and Spanish Society of Emergency Medicine (SEMES) have drawn up a position statement determining the competencies and training program for a diploma in ultrasound (lung, abdominal and vascular) in Intensive Care and Emergency Medicine. To obtain the SEDAR/SEMES Diploma in Ultrasound in Intensive Care and Emergency Medicine, clinicians must have completed the SEDAR, SEMI and SEMES Diploma in basic ultrasound and the Diploma in lung, abdominal, and vascular ultrasound.

[Estimating cardiac output. Utility in the clinical practice. Available invasive and non-invasive monitoring]. / Estimación del gasto cardíaco. Utilidad en la práctica clínica. Monitorización disponible invasiva y no invasiva.

This aim of this review is to provide a detailed review of the physiologic conditions and variables of the cardiac output, as well as review the different techniques available for its measurement. We also want to establish the clinical situations in which the measurement of cardiac output can add valuable information for the management of critically ill patients. The Fick technique, used in the beginning to calculate cardiac output, has been replaced today by thermodilution techniques (transcardiac or transpulmonary), lithium dilution, bioreactance, Doppler technique or echocardiography. Pulse wave analysis allows a continuous minimally invasive cardiac output measurement. Other methods, such bioreactance, Doppler technique or echocardiography currently provide a valid, fast and non-invasive measurement of cardiac output.

Disseminated intravascular coagulation as a form of presentation of coronavirus-19 disease. Clinical case. / Coagulación intravascular diseminada como forma de presentación de la enfermedad por coronavirus-19. Caso clínico.

The covid-19 disease (coronavirus disease 2019) is a novel disease causing a world pandemic. Its presentation varies from an asymptomatic infection to a pneumonia with acute respiratory distress syndrome. We present a case presenting initially as a covid-19 pneumonia together with a disseminated intravascular coagulopathy consisting of arterial and venous thrombosis in different locations and a shock requiring admission in the intensive care unit. The abnormal coagulation test in covid-19 patients have been described since the first cases observed in Wuhan, China, as well as an increased incidence of venous thrombosis. On the contrary, a higher incidence of arterial thrombosis has not been described in these patients. The unusual case we present could be a manifestation of this altered tests.

Diploma on Ultrasound training and competency for Intensive Care and Emergency Medicine: Consensus document of the Spanish Society of Anesthesia (SEDAR), Spanish Society of Internal Medicine (SEMI) and Spanish Society of Emergency Medicine (SEMES). / Documento de consenso de la Sociedad Española de Anestesiología y Reanimación (SEDAR), Sociedad Española de Medicina Interna (SEMI) y Sociedad Española de Medicina de Urgencias y Emergencias (SEMES) para la definición de competencias mínimas de ecografía en Cuidados Intensivos y Urgencias y la obtención del Diploma acreditativo.

The use of ultrasound as a clinical diagnostic tool and guide of bedside procedures has become an indispensable examination in the acute critically ill patient. The training of professionals in minimum skills of knowledge, management and indications of use of ultrasound required to be defined by the Scientific Societies. The Intensive Care Ultrasound Working Group of the Spanish Society of Anesthesiology and Resuscitation (SEDAR), of the Spanish Society of Internal Medicine (SEMI) and the Spanish Society of Emergency Medicine (SEMES) has developed this consensus document in which the recommended training program and the minimum competencies to be achieved with regard to the use of Ultrasound in Intensive Care, Anesthesia and Emergency medicine are defined. This document defines the training program and the skills to acquire in order to achieve the diploma in lung, abdominal and vascular ultrasound. This document can serve as a guide to define the skills to be acquired in the training programs of residents (MIRs) of specialists working in intensive care, anesthesia, and emergency medicine.

[Near-infrared spectroscopy in the postanesthesia recovery care unit: noninvasive monitoring of peripheral perfusion]. / Espectroscopia cercana al infrarrojo en la reanimación: medición no invasiva de la perfusión periférica.

Clinical signs of recovery, such as blood pressure or heart rate, do not accurately reflect the perfusion of organs and tissues in patients in critical condition. Of the various means for monitoring perfusion, regional monitors are the most sensitive. Near-infrared spectroscopy (NIRS), which analyzes infrared light detected after it has passed through red blood cells in tissues, provides a measure of oxygen saturation that is the most appropriate method for clinical situations. In patients with sepsis or multiple injuries, tissue oxygen saturation can be useful as an early indicator of shock, as a marker of recovery or need for transfusion, or as a prognostic factor. In spite of widespread interest in NIRS, however, there are gaps to fill in our understanding of clinical signs and physiology in relation to this technique before peripheral tissue monitoring can become routine in postanesthesia recovery care units.

[Adjuvant methadone or fentanyl in spinal anesthesia with bupivacaine: a randomized, double-blind, placebo-controlled trial]. / Metadona frente a fentanilo como adyuvante en anestesia subaracnoidea con bupivacaína. Estudio doble ciego, controlado con placebo, comparativo, aleatorizado.

OBJECTIVE: To compare the effect of combining spinal bupivacaine with either of 2 lipophilic opioids (fentanyl or methadone), testing the hypothesis that methadone would give longer-lasting analgesia. METHODS: Randomized, double-blind, placebo-controlled trial enrolling 69 women undergoing vaginal hysterectomy under spinal anesthesia (13 mg of 0.5% bupivacaine). The patients were randomized to 3 groups for use of different adjuvants: normal saline (placebo), 15 µg [DOSAGE ERROR CORRECTED] of fentanyl, or 3 mg of methadone. The main outcome was duration of analgesic effect measured as time elapsing until need for the first analgesic dose. The characteristics of the spinal blocks and adverse events were secondary outcome variables. RESULTS: Methadone significantly prolonged the duration of analgesia in comparison with the other adjuvants; with methadone, the effect was 1.9 times longer than in the placebo group and 1.5 times longer than in the fentanyl group. Duration of the sensory-motor block was significantly shorter in the methadone group (mean difference, 30 minutes). No differences in the incidences of adverse events were observed between the 2 opioid groups. No signs or symptoms suggestive of direct neurologic toxic effects were observed. CONCLUSIONS: The addition of methadone to bupivacaine significantly prolonged the postoperative analgesic effect of spinal anesthesia and shortened sensory-motor block duration, enhancing patient comfort after surgery.

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%.

Coagulación intravascular diseminada como forma de presentación de la enfermedad por coronavirus-19. Caso clínico / Disseminated intravascular coagulation as a form of presentation of coronavirus-19 disease. Clinical case

La enfermedad covid-19 (coronavirus disease 2019) es una infección de reciente aparición que está causando una pandemia a nivel mundial. La forma de presentación varía desde una infección asintomática hasta una neumonía con síndrome de distrés respiratorio. Presentamos el caso de un paciente que presentó una neumonía por covid-19 junto a una coagulación intravascular diseminada con trombosis arterial y venosa en múltiples localizaciones y un estado de choque que requirió ingreso en unidad de cuidados intensivos. La alteración de las pruebas de coagulación en pacientes afectos de covid-19 se ha descrito desde los primeros casos observados en Wuhan, China, así como una mayor incidencia de trombosis venosas. Al contrario, una mayor incidencia de trombosis arterial no ha sido descrita en estos pacientes. El caso inusual que presentamos podría representar una manifestación de estas alteraciones.(AU)

The covid-19 disease (coronavirus disease 2019) is a novel disease causing a world pandemic. Its presentation varies from an asymptomatic infection to a pneumonia with acute respiratory distress syndrome. We present a case presenting initially as a covid-19 pneumonia together with a disseminated intravascular coagulopathy consisting of arterial and venous thrombosis in different locations and a shock requiring admission in the intensive care unit. The abnormal coagulation test in covid-19 patients have been described since the first cases observed in Wuhan, China, as well as an increased incidence of venous thrombosis. On the contrary, a higher incidence of arterial thrombosis has not been described in these patients. The unusual case we present could be a manifestation of this altered tests.(AU)

Implicación en Cataluña de los Servicios de Anestesiología y Reanimación en la pandemia por SARS-CoV-2. Una solución real coste-efectiva para una crisis sanitaria sin precedentes / Involvement in Catalonia of the Anaesthesiology and Resuscitation Services in the SARS-CoV-2 pandemic. A real, cost-effective solution to an unprecedented health crisis

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Coagulación intravascular diseminada como forma de presentación de la enfermedad por coronavirus-19. Caso clínico / Disseminated intravascular coagulation as a form of presentation of coronavirus-19 disease. Clinical case

La enfermedad covid-19 (coronavirus disease 2019) es una infección de reciente aparición que está causando una pandemia a nivel mundial. La forma de presentación varía desde una infección asintomática hasta una neumonía con síndrome de distrés respiratorio. Presentamos el caso de un paciente que presentó una neumonía por covid-19 junto a una coagulación intravascular diseminada con trombosis arterial y venosa en múltiples localizaciones y un estado de choque que requirió ingreso en unidad de cuidados intensivos. La alteración de las pruebas de coagulación en pacientes afectos de covid-19 se ha descrito desde los primeros casos observados en Wuhan, China, así como una mayor incidencia de trombosis venosas. Al contrario, una mayor incidencia de trombosis arterial no ha sido descrita en estos pacientes. El caso inusual que presentamos podría representar una manifestación de estas alteraciones

The covid-19 disease (coronavirus disease 2019) is a novel disease causing a world pandemic. Its presentation varies from an asymptomatic infection to a pneumonia with acute respiratory distress syndrome. We present a case presenting initially as a covid-19 pneumonia together with a disseminated intravascular coagulopathy consisting of arterial and venous thrombosis in different locations and a shock requiring admission in the intensive care unit. The abnormal coagulation test in covid-19 patients have been described since the first cases observed in Wuhan, China, as well as an increased incidence of venous thrombosis. On the contrary, a higher incidence of arterial thrombosis has not been described in these patients. The unusual case we present could be a manifestation of this altered tests

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%

CDP-choline reduces pro-caspase and cleaved caspase-3 expression, nuclear DNA fragmentation, and specific PARP-cleaved products of caspase activation following middle cerebral artery occlusion in the rat.

Citicoline has been demonstrated to be beneficial in several models of cerebral ischaemia. We tested the hypothesis that citicoline may provide apoptotic pathways following focal cerebral ischaemia. Focal cerebral ischaemia was produced by distal, permanent middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. The animals were randomised into four groups: (B+A) Citicoline 500 mg/kg IP 24 and 1 h before MCAO, and 23 h after MCAO; (A) citicoline 500 mg/kg IP, within 30 min after MCAO, and 23 h after MCAO; (C) vehicle IP; and (D) sham-operated. The animals were sacrificed at 12 h (n=8 per group) and 24 h (n=8 per group) after MCAO. Immunohistochemistry was performed on free-floating tissue sections with goat polyclonal antibodies to procaspase-1, -2, -3, -6 and -8, and in paraffin-embedded sections processed for cleaved caspase-3 (17 kDa) immunohistochemistry. Finally, some sections were stained with the method of in situ end-labelling of nuclear DNA fragmentation. For gel electrophoresis and Western blotting, antibodies to poly (ADP-ribose) polymerase (PARP) products of 89 kDa were used to reveal specific cleavage substrates of caspases. MCAO induced the expression of all procaspases and the expression of PARP products of 89 kDa, as well as cells with nuclear DNA fragmentation, at 12 and 24 h, in the infarcted core and penumbra. Citicoline reduced the expression of all procaspases at 12 and 24 h after MCAO, as well as the expression of cleaved caspase-3 in cells in the penumbra area. This was accompanied by a reduction in the number of cells bearing nuclear DNA fragments. The expression of caspase-cleaved products of PARP (PARP 89 kDa) was reduced in citicoline-treated ischaemic rats. These results show that citicoline inhibits the expression of proteins involved in apoptosis following MCAO.

Prednicarbate versus fluocortin for inflammatory dermatoses. A cost-effectiveness study.

The purpose of this study was to compare, from a societal perspective, the cost effectiveness of topical prednicarbate 0.25% and fluocortin 0.75% in the treatment of inflammatory dermatoses, such as dermatitis and eczema, in Spain. Effectiveness and tolerability were determined by means of a meta-analysis of 17 randomised double-blind controlled clinical trials, using a MEDLINE search and a second-level reference search. The data were obtained on the basis of a per-protocol assessment system, and the Mantel-Haenszel method (as modified by Peto) was used to make the statistical analysis. In terms of economic assessment, a model was developed in which the expected total cost was determined by the cost of the medicine (adjusted to the recommended dosage) plus the costs derived from the ineffectiveness and/or adverse effects associated with the different treatments. A sensitivity analysis was carried out on the basis of changes in: (i) clinical effectiveness; (ii) price of prednicarbate; (iii) incidence of adverse reactions; (iv) costs associated with ineffectiveness and/or adverse effects; and (v) the regimen under which prednicarbate was administered. The meta-analysis showed that there was a statistically significant difference between the 2 alternatives (p = 0.001). The value of a combined odds ratio [and 95% confidence interval (95% CI)] for the combined studies of prednicarbate was 1.54 (95% CI 1.10 to 2.15), compared with 0.73 (95% CI 0.60 to 0.89) for fluocortin relative to moderate or moderate-to-high potency corticosteroids. Effectiveness was 84.9% for prednicarbate and 69.7% for fluocortin, while frequency of adverse effects was 3.5% for prednicarbate and 4.9% for fluocortin. The total expected cost per patient treated was found to be 4600 Spanish pesetas (Pta) [$US37.10; 1996 values] for prednicarbate and Pta5778 ($US46.60; 1996 values) for fluocortin. The total expected cost per patient successfully treated was Pta5608 ($US45.20) for prednicarbate and Pta8680 ($US70) for fluocortin. Prednicarbate has been shown to have a favourable cost-effectiveness ratio, when compared with fluocortin, for the treatment of dermatitis and eczema in Spain. Additional pharmacoeconomic studies on topical corticosteroids are required, including the use of new variables, long term analysis and/or the measurements of the effect of the drug on patients' quality of life.

A method to select an instrument for measurement of HR-QOL for cross-cultural adaptation applied to dermatology.

OBJECTIVE: The objective of this study was to develop a process to obtain an instrument to measure dermatology specific health-related quality of life (HR-QOL), and to adapt it into another culture, namely the Spanish-speaking community. DESIGN AND SETTING: By consensus, a multi-disciplinary team determined the qualities of an 'ideal' questionnaire as follows: need (absence of any such instrument), utility, multi-dimensionality, psychometric development, simplicity, high degree of standardisation, and accessibility. A bibliographic search was conducted on Medline, EMBASE and IME (Spanish Medical Index), using 'dermatology' and 'quality of life' as the key words, from January 1990 through to September 1997, supplemented by a second level reference search, to identify the instruments already in existence. Rather than develop a questionnaire ex novo, it was decided to make a cultural adaptation of an existing one. The questionnaires identified in the literature search were classified according to their generic or specific scope and it was decided to adapt a dermatology specific instrument. To select and compare the instruments, a model was developed which would provide an Adaptation Index (ADAPT), which includes the degree of development of psychometric properties, the formal design and the degree of standardisation at a given moment in time. RESULTS: Six dermatology specific scales were identified: Impact of Skin Disease Scale (IMPACT), Dermatology Life Quality Index (DLQI), Skindex, Dermatology Quality-of-Life Scales (DQOLS), Dermatology Specific Quality of Life (DSQL) and Qualita di Vita Italiana in Dermatologia (QUAVIDERM). The ADAPT Index for each of the above was determined at the time of the study and the DLQI was chosen for adaptation (ADAPT = 77, October 1997). CONCLUSIONS: The study showed the utility of ADAPT Index to assist in the selection process of the questionnaire to adapt. The results of the analysis indicate that in order to introduce and systematically use dermatology specific HR-QOL instruments, the indices require consolidation and improvement. There is a special need for an effort to be made in developing transculturally equivalent instruments suitable for international research.

[A controlled, double-blind, randomized pilot clinical trial of nicardipine as compared with a placebo in patients with moderate or severe head injury]. / Ensayo clínico piloto, controlado, doblemente ciego, aleatorizado de nicardipino frente a placebo en pacientes afectados de traumatismo craneal grave o moderado.

INTRODUCTION: One of the factors involved in the occurrence of ischemic cerebral lesions following head injury is cerebral vasospasm. We analyze the effect of intravenous nicardipine on the prevention and treatment of posttraumatic cerebral vasospasm. PATIENTS AND METHODS: We made a placebo-controlled, randomised, double-blind pilot study of the effect of nicardipine (intravenously 5 mg/hour for one week) on patients with moderate or severe head injury who presented with cerebral vasospasm, defined as an average Doppler flow velocity (DFV) of 100 cm/second or more. The main variable assessed was the evolution of the DFV and the secondary criteria were the evolution of the arterial blood pressure, coma scales, the findings on the Glasgow Coma Scale and the safety of the drug. RESULTS: Eleven patients were included in each homogeneous group. The DFV was found to have become normal on the first day of treatment with nicardipine and on the third day with the placebo (p = 0.023). During the first day of treatment the percentage of cerebral hemispheres diagnosed as having suspected spasm was 11.1% for nicardipine and 64.3% for the placebo (p = 0.02881). The average time for recovery (DFV < 100 cm/second) was 3.33 days with the placebo and 1.22 days with nicardipine (p = 0.0039). The patients treated with nicardipine had 8.89 times more chance of recovery from vasospasm. The incidence of adverse effects was greater with the placebo (p = 0.014). CONCLUSION: Nicardipine is effective in the reversal and prevention of increased Doppler flow velocity in patients with moderate or severe head injury.

[Subarachnoid hemorrhage, cerebral ischemia and endothelin-1]. / Hemorragia subaracnoidea, isquemia cerebral y endotelina-1.

INTRODUCTION: Cerebral vasospasm is involved in the development of delayed ischemic lesions in patients with subarachnoid hemorrhage. We developed an integral theoretical model to explain the pathophysiology of cerebral vasospasm, in which endothelin-1 has a pivotal role in the development of both cerebral vasospasm and delayed ischemic neurological deficits (DIND). OBJECTIVE: The objective of this study is to analyze the relationship between temporal profile of plasma endothelin-1 levels and the development of cerebral vasospasm and DIND. PATIENTS AND METHODS: We analyzed sequentially plasma endothelin-1 levels in 17 patients with aneurysmatic subarachnoid hemorrhage. All the patients had complete clinical and neuroradiological studies. Patients were classified according to Fisher's score. RESULTS: Patients (4 males and 13 females, aged 48.1 +/- 20.3 years) had a good clinical condition (Hunt-Hess < 4, GCS > 10). Two weeks after bleeding, patients had higher plasma endothelin-1 levels than healthy volunteers (p = 0.024). Patients who developed DIND had higher plasma endothelin-1 levels (p = 0.034) and a different evolution (p = 0.0146) than patients without DIND. There is a significant correlation (p = 0.02) between basal plasma endothelin-1 levels and GOS score. Multiple regression analysis shows a significant dependence between plasma endothelin-1 levels and Fisher's score (p = 0.0195), development of DIND (p = 0.0095), and GOS score (p = 0.0319). Logistic regression analysis finds a predictive relation between Fisher's score and plasma endothelin-1 levels for the development of DIND (overall predicted = 74.24%; p = 0.0148). CONCLUSIONS: Plasma endothelin-1 levels are increased in patients after subarachnoid hemorrhage and are associated with the development of cerebral vasospasm and DIND.