Eficacia y seguridad de antipsicóticos en el síndrome confusional / Efficacy and safety of antipsychotics in delirium

RESUMEN El objetivo del tratamiento del delirium es conocer y tratar la causa desencadenante, siendo el tratamiento farmacológico sintomático. La fisiopatología del delirium no es del todo conocida; se ha asociado a un déficit de acetilcolina en el sistema nervioso central así como a un exceso de dopamina y en este motivo es que se ha basado el uso de antipsicóticos. El objetivo de este trabajo es conocer la evidencia sobre eficacia y seguridad de los antipsicóticos en la prevención y el tratamiento del delirium Se realizó una revisión limitada a ensayos clínicos, revisiones sistemáticas y metaanálisis para evaluar la eficacia de los antipsicóticos en la prevención y en el tratamiento del delirium. Para evaluar seguridad se incluyeron además estudios observacionales, serie de casos y alertas. Se encontró un número limitado de ensayos clínicos que evaluaron eficacia entre diferentes antipsicóticos y comparado con placebo. La mayoría de los estudios analizados demuestran que en la profilaxis del delirium no existen diferencias clínicamente significativas en la incidencia entre los pacientes que recibieron antipsicóticos o placebo. Para el tratamiento sintomático del delirium, los antipsicóticos han mostrado beneficio en cuanto a reducción de severidad y duración de síntomas, no encontrándose diferencias significativas entre haloperidol y antipiscóticos atípicos.

ABSTRACT The main goal in delirium treatment is to identify and treat the triggering causes, being the pharmacological treatment mainly symptomatic. Delirium physiopathology is still unknow, and has been associated with an acetylcholine deficit and a dopamine excess in central nervous system. Those are the therapeutic targets that justify the use of antipsychotics. Our objective was to review the evidence on efficacy and safety of antipsychotics in the treatment and prevention of delirium. A sistematic literature review was caried out in the main databases, including randomise clinilal trials, systematic reviews and meta-analyzes to evaluate the efficacy of antipsychotics in the prevention and treatment of delirium. Observational studies, case reports and international drug alerts were also included to evaluate safety. We found a limited number of clinical trials evaluating efficacy between diferent antipsychotics and compared with placebo. Most of the analyzed studies show that in prophylaxis there are no clinically significant differences in the incidence of delirium among patients receving antipsychotics or placebo. For the symptomatic treatment of delirium, antipsychotics have shown benefits in reducing severity and duration of symptoms, with no significant differences between haloperidol and atypical antipsychotics.

Pneumocistis jiroveccii como causa de fiebre de origen desconocido en paciente con dermatomiositis y tromboembolismo pulmonar / Pneumocystis jiroveccii as a cause of fever of unknown origin in a patient with dermatomyositis and pulmonary thromboembolism

La dermatomiositis (DM) al igual que otras enfermedades autoinmunes ha sido reportada en varios estudios como un factor de riesgo para enfermedad tromboembólica venosa (ETEV). A su vez, debido a las alteraciones en la inmunidad causadas por la propia enfermedad, sumado a la inmunodepresión propia del tratamiento, estos pacientes son propensos a complicaciones infecciosas, muchas de ellas por gérmenes oportunistas como el Pneumocistis jirovecci (PJ). Los criterios diagnósticos de fiebre de origen desconocido (FOD) han estado durante largo tiempo en debate. En los últimos años se han propuesto nuevas categorías distintas a la FOD clásica, como ser la que afecta a pacientes inmunodeprimidos, donde tanto las etiologías como las formas de presentación de las mismas varía. Se han descrito más de 200 causas de FOD dentro de las cuales se incluye PJ. Se presenta el caso clínico de una paciente a la cual se le realizó diagnóstico de DM y que pese a la tromboprofilaxis presentó un episodio de tromboembolismo pulmonar. A su vez, durante la internación presentó una FOD. Luego de una búsqueda exhaustiva se aisló PJ y se realizó tratamiento para el mismo con excelente respuesta clínica.

Dermatomyositis (DM), the same as other auto-immune diseases, has been reported in several studies as a risk factor for a venous thromboembolic disease. Also, given immunity alterations caused by the disease itself, along with the immunodepression that characterizes treatment, these patients are likely to present infectious complications, many of them due to opportunistic germs such as Pneumocystis jirovecci (PJ). Diagnostic criteria for fever of unknown origin (FUO) have been long discussed. Lately, new categories that are different to the classic FUO have been proposed, as is the one affecting immunodepressed patients, where both the etiology and presentation vary. Over 200 causes for FUO have been described, PJ being among them. The clinical case of a female patient diagnosed with DM is described in the study, who, in spite of thromboprofilaxis presented a pulmonary thromboembolism episode. Likewise, during hospitalization, the patient evidenced FUO. After an extensive search, PJ was isolated and treatment was applied, resulting in an excellent clinical response.

A dermatomiosite (DM), assim como outras patologias, tem sido descrita como um fator de risco para doença tromboembólica venosa (DTEV). As alterações da imunidade causadas poresta patologia, associadas à imunodepressão própria do tratamento fazem com que os pacientes sejam propensos a complicações infecciosas, muitas delas por microrganismos oportunistas como o Pneumocistis jirovecci (Pj). Durante muito tempo os critérios diagnósticos de febre de origem indeterminada (FOI) foram causa de discussão. Nos últimos anos foram propostas novas categorias diferentes da FOI clássica, como por exemplo, a que afeta pacientes imunodeprimidos, nas quais, tanto as etiologias como as formas de apresentação variam. Mais de 200 causas de FOI, incluindo Pj, foram descritas. Apresenta-se o caso clínico de uma paciente diagnosticada com DM e que, apesar da profilaxia tromboembólica, apresentou um episódio de tromboembolismo pulmonar. Durante a internação apresentou FOI; Pj foi isolado depois de uma exaustiva busca. A paciente recebeu o tratamento correspondente com excelente resposta clínica.

Uso de rituximab en trombocitopenia inmune: experiencia en el Hospital de Clínicas / Use of rituximab in immune thrombocytopenia at the University Hospital

Introducción: rituximab es un anticuerpo monoclonal que se une específicamente al antígeno CD20 expresado en los linfocitos B. El uso de rituximab en el tratamiento de la trombocitopenia inmune refractaria no se encuentra aprobado en su ficha técnica. Objetivo: describir las características clínicas, la respuesta terapéutica y los aspectos vinculados a la seguridad con el uso de rituximab en los pacientes con trombocitopenia inmune refractaria asistidos en la Cátedra de Hematología del Hospital de Clínicas y revisar la evidencia sobre el beneficio clínico esperado en este grupo de pacientes. Material y método: se realizó un estudio descriptivo de los pacientes con trombocitopenia inmune refractaria asistidos en la Cátedra de Hematología del Hospital de Clínicas a quienes se les prescribió rituximab. Se realizó una búsqueda bibliográfica en PubMed sobre el uso de rituximab en este tipo de patología. Resultados: se trataron cuatro pacientes con trombocitopenia inmune refractaria con rituximab. Se obtuvo respuesta en tres de cuatro pacientes. La media de tiempo de respuesta fue 9,25 semanas. La respuesta se ha mantenido en los tres pacientes. No se registraron efectos adversos durante la perfusión de rituximab. La evidencia publicada se limita a estudios observacionales, en adultos, con pocos pacientes, habiendo mostrado respuestas favorables. Conclusiones: existen limitaciones en la evidencia sobre el tratamiento de la trombocitopenia inmune refractaria, pero rituximab constituye una alternativa efectiva. Es indispensable la integración clínica para monitorizar la efectividad y seguridad del uso de anticuerpos monoclonales, especialmente en indicaciones no aprobadas...

Medicina basada en evidencia en laformación de grado: experiencia de enseñanza en un laboratorio de habilidades clínicas / Evidence based medicine in the graduates training: teaching experience in a clinical skills laboratory

Introducción: la Facultad de Medicina se encuentra transitando un proceso de reforma en su plan de estudios. En esecontexto se desarrollaron experiencias piloto destinadas a mejorar la formación de los estudiantes e incorporar innova-ciones educativas. Entre estas, el desarrollo de un laboratorio de habilidades clínicas, una de cuyas áreas fue la enseñanza de la medicina basada en evidencias (MBE).Objetivo: describir la experiencia del curso de MBE, sus principales fortalezas y debilidades. Material y método: un total de 230 estudiantes de los cursosclínicos se incorporaron a esta experiencia piloto. De estos, se conformó una cohorte de 80 estudiantes que fueron evaluados sobre el conocimiento y uso de las bases de datos biomédicos, aplicabilidad de los contenidos y nivel de satisfacción con el curso. Asimismo, se evaluó la opinión de los tutores participantes del curso.Resultados: antes del curso la mayoría de los estudiantes encuestados no conocían las principales bases de datos de información biomédica. En relación con la aplicabilidad, fue evaluada como buena o muy buena por 37 estudiantes(46,8%), satisfactoria por 26 (33%) y no aplicable por 16 (20,2%). El cumplimiento de las expectativas fue evaluado como bueno o muy bueno por 28 estudiantes (35,4%), satisfactorio por 39 (49,3%) y no satisfactorio por 11 (15,3%). Todos los tutores consideraron la experiencia como buena o muy buena. Conclusiones: la experiencia fue ampliamente satisfactoria, sugiriendo que la incorporación de la enseñanza de la MBEen los cursos de grado puede resultar favorable para los estudiantes.

Introduction: the School of Medicine is undergoing a reform process of its studies plan. Within this context,pilot experiences were devised geared to improving the training of students and incorporating educational innovations. Among these experiences we find the creation of a clinical skills laboratory which includes the teaching of evidence based medicine. Objective: to describe the weaknesses and strengths of the evidence based medicine course.Method: a total of 230 students of the clinical courses were included in this pilot experience. Out of these, an 80 student cohort group was formed to be evaluated on knowledge and the use of biomedical data, the applicability of contents and the level of satisfaction of the course. Likewise, the opinion of the tutors participating in the course was evaluated. Results: before the course most students in the survey did not know the main biomedical information data bases. In terms of applicability, it was evaluated as good or very good by 37 students (46.8%), satisfactory by 26(33%) and not applicable by 16 (20.2%). Meeting the expectations was seen as good or very good by 28 students (35.4%), satisfactory by 39 (49.3%) and non-satisfactory by 11 (15.3%). All tutors regarded theexperience as good or very good.Conclusions: the experience was highly satisfactory, what suggests the inclusion of evidence based medicine in the graduate courses may be positive forstudents.

Introdução: no contexto da reforma do programa de ensino da Faculdade de Medicina da Universidad de la República, foram realizadas experiências piloto com o objetivo de melhorar a formação dos estudantes e incorporar inovações educativas. Entre estas a criação de umlaboratório de habilidades clínicas no qual uma das áreas desenvolvidas foi a medicina baseada na evidencia (MBE).Objetivo: descrever a experiência do curso de MBE, suas fortalezas e debilidades. Material e método: 230 estudantes dos cursos clínicos foram incorporados a esta experiência piloto. Uma coorte de 80 estudantes foi avaliada sobre o conhecimento e uso das bases de dados biomédicos, aplicabilidade do conteúdo das mesmas e o nível de satisfação com o curso. A opinião dos tutores participantes docurso também foi avaliada.Resultados: antes do inicio do curso a maioria dos estudantes entrevistados não conheciam as principais bases de dados de informação biomédica. A aplicabilidade destas foi avaliada como boa ou muito boa por 37 estudantes (46,8%), satisfatória por 26 (33%) e não aplicável por 16 (20,2%). A satisfação das expectativas foi avaliada como boa ou muito boa por 28 estudantes (35,4%), satisfatória por 39 (49,3%) e não satisfatória por 11 (15,3%). Todos os tutores consideraram a experiência como boa ou muito boa.Conclusões: a experiência foi satisfatória, sugerindo que a incorporação da MBE nos cursos de graduação pode ser favorável para os estudantes.

[Rational use of antibiotics in the Department of Internal Medicine from a university hospital: results of a pilot experience]. / Uso racional de antimicrobianos en el departamento de medicina interna de un hospital universitario: resultados de una experiencia piloto.

INTRODUCTION: The programs of rational use of antibiotics are designed to optimize antimicrobial therapy and minimize the emergence of bacterial resistance. In order to optimize the use of antibiotics we implemented an educational program based on the application of a checklist criteria for the rational use of these drugs. METHOD: We performed a cohort study unpaired in the Department of Internal Medicine, during three months. We compared a prospective cohort (A) which used a checklist, with a retrospective cohort (B) in wich prescription was based on usual clinical practice. RESULTS: We included 227 prescriptions of antibiotics. In cohort A compared to B, there was a higher proportion of switch to oral antibiotics agents and adjustment of the antimicrobial therapy to the susceptibility in the antibiogram and reduced use of associated antibiotics. Total antibiotic consumption was 117.7 DDD/100 bed-days (Defined Daily Doses). Consumption in cohorts A and B was 46.1 DDD/100 bed-days and 71.6 DDD/100 bed-days (reduction, 35.6%). There was also a reduction in consumption of ceftriaxone, ceftazidime, quinolones, vancomycin and carbapenems. Costs were reduced by 55%. There was no difference in the average hospital stay. CONCLUSIONS: The implementation of an educational strategy based on a checklist allowed the optimum use of antibiotics.

Uso racional de antimicrobianos en el departamento de medicina interna de un hospital universitario: resultados de una experiencia piloto / Rational use of antibiotics in the department of internal medicine from a university hospital: results of a pilot experience

Introduction: The programs of rational use of antibiotics are designed to optimize antimicrobial therapy and minimize the emergence of bacterial resistance. In order to optimize the use of antibiotics we implemented an educational program based on the application of a checklist criteria for the rational use of these drugs. Method: We performed a cohort study unpaired in the Department of Internal Medicine, during three months. We compared a prospective cohort (A) which used a checklist, with a retrospective cohort (B) in wich prescription was based on usual clinical practice. Results: We included 227 prescriptions of antibiotics. In cohort A compared to B, there was a higher proportion of switch to oral antibiotics agents and adjustment of the antimicrobial therapy to the susceptibility in the antibiogram and reduced use of associated antibiotics. Total antibiotic consumption was 117.7 DDD/100 bed-days (Defined Daily Doses). Consumption in cohorts A and B was 46.1 DDD/100 bed-days and 71.6 DDD/100 bed-days (reduction, 35.6%). There was also a reduction in consumption of ceftriaxone, ceftazidime, quinolones, vancomycin and carbapenems. Costs were reduced by 55%. There was no difference in the average hospital stay. Conclusions: The implementation of an educational strategy based on a checklist allowed the optimum use of antibiotics.

Introducción: Los programas de uso racional de antimicrobianos tienen la finalidad de optimizar la terapia antimicrobiana y minimizar la aparición de resistencia bacteriana. Con el objetivo de optimizar el uso de antimicrobianos se implementó un programa educativo basado en la aplicación de una lista de verificación (check list) conteniendo criterios establecidos de uso racional de estos fármacos. Método: Se realizó un estudio de cohortes no pareadas en el Departamento de Medicina Interna, durante tres meses. Se comparó una cohorte prospectiva (A) en que se aplicó la lista de verificación, con una cohorte retrospectiva (B) con prescripción de acuerdo a la práctica clínica habitual. Resultados: Se incluyeron 227 prescripciones de antimicrobianos. En la cohorte A, hubo mayor proporción de paso a vía oral y adecuación del antimicrobiano al antibiograma y menor uso de asociación de antimicrobianos, con respecto a la cohorte B. El consumo total de antimicrobianos fue de 117,7 DDD/100 días-cama (Dosis Diaria Definida). El consumo en las cohortes A y B fue de 46,1 DDD/100 días-cama y 71,6 DDD/100 días-cama respectivamente (reducción de un 35,6%). También hubo una reducción en el consumo de ceftriaxona, ceftazidima, quinolonas, vancomicina y carbapenem. Los costos se redujeron en 55%. No hubo diferencias en la estadía media hospitalaria. Conclusiones: La aplicación de una estrategia educativa basada en una lista de verificación permitió optimizar el uso de antimicrobianos.

Reacciones adversas cutáneas a medicamentos: Vigilancia durante un año en un Hospital Universitario. Uruguay 2008-2009 / Adverse cutaneous reactions to Drugs among hospitalized patients: A one year surveillance

Background: Adverse cutaneous reactions to Drugs (CDRs) are of particular interest among all adverse Drug reactions (ADR) due to their frequency, potential severity and because of the importance of an early diagnosis. Antimicrobial agents, anticonvulsants and non-steroidal anti-inflammatory Drugs are the Drugs associated to the highest risk of CDRs. Aim: To assess CDRs in hospitalized patients and identify the Drugs involved. Material and Methods: All patients hospitalized in the Hospital de Clínicas in Montevideo, Uruguay, with suspected CDRs, detected during one year, were included in this prospective study. The imputability was established using the Karch and Lasagna algorithm modified by Naranjo. We analyzed age, gender, Drugs involved, causal disease, severity, latency and evolution. Results: Seventeen patients, aged 17 to 85 years (15 females) with CDRs were identifed. Twelve had morbilliform exanthemas, four had reactions with eosinophilia and systemic symptoms and one had a Stevens Johnson syndrome. The Drugs involved were antimicrobials in nine cases, hypouricemic agents in four cases, anticonvulsants in three cases and aspartic insulin in one. Twelve patients had a life threatening reaction and one required admission to the intensive care unit. No deaths occurred. Conclusions: CDRs were more common in women and most of them were caused by antimicrobial agents.

[Adverse cutaneous reactions to drugs among hospitalized patients: a one year surveillance]. / Reacciones adversas cutáneas a medicamentos: Vigilancia durante un año en un Hospital Universitario. Uruguay 2008-2009.

BACKGROUND: Adverse cutaneous reactions to Drugs (CDRs) are of particular interest among all adverse Drug reactions (ADR) due to their frequency, potential severity and because of the importance of an early diagnosis. Antimicrobial agents, anticonvulsants and non-steroidal anti-inflammatory Drugs are the Drugs associated to the highest risk of CDRs. AIM: To assess CDRs in hospitalized patients and identify the Drugs involved. MATERIAL AND METHODS: All patients hospitalized in the Hospital de Clínicas in Montevideo, Uruguay, with suspected CDRs, detected during one year, were included in this prospective study. The imputability was established using the Karch and Lasagna algorithm modified by Naranjo. We analyzed age, gender, Drugs involved, causal disease, severity, latency and evolution. RESULTS: Seventeen patients, aged 17 to 85 years (15 females) with CDRs were identifed. Twelve had morbilliform exanthemas, four had reactions with eosinophilia and systemic symptoms and one had a Stevens Johnson syndrome. The Drugs involved were antimicrobials in nine cases, hypouricemic agents in four cases, anticonvulsants in three cases and aspartic insulin in one. Twelve patients had a life threatening reaction and one required admission to the intensive care unit. No deaths occurred. CONCLUSIONS: CDRs were more common in women and most of them were caused by antimicrobial agents.