Evidence and decision-making in times of pandemic / Evidencias y decisiones en tiempos de pandemia

In December 2019, an outbreak of a respiratory desease caused by a new coronavirus strain was detected in Wuhan, China. The disease spread rapidly around the world and was recognized as a pandemic by the World Health Organization in March 2020. From the very beginning of the pandemic, society was faced with a scenario fraught with uncertainty: a new disease with severe effects on some patients and no specific treatment. The medical community reacted promptly and undertook the quest for treatment options, some based on prior experiences with diseases caused by other coronavirus strains or related viruses, and other approaches based on potential pathophysiological mechanisms promising at the time but without any supporting scientific evidence.

En diciembre de 2019, se detectó en Wuhan (China) un brote de una enfermedad respiratoria causada por una nueva cepa de coronavirus. La enfermedad se extendió rápidamente por todo el mundo y fue reconocida como pandemia por la Organización Mundial de la Salud en marzo de 2020. Desde el principio de la pandemia, la sociedad se enfrentó a un escenario cargado de incertidumbre: una nueva enfermedad con graves efectos en algunos pacientes y sin tratamiento específico. La comunidad médica reaccionó rápidamente y emprendió la búsqueda de opciones de tratamiento, algunas basadas en experiencias previas con enfermedades causadas por otras cepas de coronavirus o virus relacionados, y otras aproximaciones basadas en posibles mecanismos fisiopatológicos prometedores en ese momento pero sin ninguna evidencia científica que los respaldara.

Filariasis mamaria: a propósito de un caso / Breast filariasis: case report

INTRODUCCIÓN: La filariasis con afectación mamaria es una enfermedad endémica de áreas tropicales y subtropicales de África, Asia, el Pacífico y América, que afecta a unos 120 millones de personas. Aunque es una patología rara en España, dado el aumento de pacientes procedentes de dichos países, debemos conocerla para saber diagnosticarla y tratarla adecuadamente. OBJETIVO DE REPORTAR EL CASO: Dar a conocer la filariasis con afectación mamaria, sus manifestaciones clínicas y radiológicas principales, a través de un caso clínico de nuestras consultas de ginecología. DESCRIPCIÓN DEL CASO: Paciente de 43 años, procedente de Guinea Ecuatorial que acude a la consulta de Ginecología por mastalgia bilateral y aumento del volumen de las mamas de semanas de evolución. La exploración es anodina por lo que se solicita mamografía bilateral en la que describen calcificaciones compatibles con filariasis. A pesar de que el resto de pruebas fueron negativas, dada la alta sospecha clínica y radiológica se diagnosticó de filariasis mamaria. CONCLUSIONES: A pesar de la actual campaña mundial para eliminar la filariasis, el aumento de migración global incrementa la probabilidad de padecer casos importados de filariasis mamaria. Por tanto, el conocimiento de las diferentes parasitosis es imprescindible para realizar un buen diagnóstico diferencial con otras entidades clínicamente similares, e instaurar el tratamiento más adecuado.

INTRODUCTION: Breast filariasis is an endemic disease from tropical and subtropical areas of Africa, Asia, the Pacific and America affecting about 120 million people. Although it is a rare pathology in Spain, given the increase in patients from the referred countries, we must be aware of it in order to know how to diagnose and treat it properly. OBJECTIVE OF REPORTING THE CASE: To raise awareness of filariasis with breast involvement and its main clinical and radiological manifestations, through a clinical case of our gynecology consultations. CASE REPORT: 43-year-old patient from Equatorial Guinea who comes to the Gynecology consultation for bilateral mastalgia and breast enlargement of weeks of evolution. The examination is anodyne, so bilateral mammography is requested in wich calcifications compatible with filariasis are described. Despite the rest of the tests are negative, given the high clinical and radiological suspicion, the diagnosis of breast filariasis is made. CONCLUSIONS: Despite the current worldwide campaign to eliminate filariasis, the increase in global migration enhances the probability of suffering from imported cases of breast filariasis Therefore, the knowledge of the different parasitoses is essential to make a correct differential diagnosis with other clinically similar entities, and to establish the most appropriate treatment.

Bacteriemia con afectación inflamatoria pélvica y miositis secundaria a histeroscopia diagnóstica. Reporte de un caso / Bacteremia with pelvic inflamatory involvement and secondary myositis due to diagnostic hysteroscopy. A case report

Resumen ANTECEDENTES: Las complicaciones infecciosas secundarias a la histeroscopia diagnóstica ambulatoria son bajas (0.6%). CASO CLÍNICO: Paciente de 46 años que a los 6 días posthisteroscopia diagnóstica ambulatoria por pólipos endometriales ingresó al servicio de Ginecología debido a un cuadro de piomiositis del músculo piriforme izquierdo, secundario a bacteriemia por Streptococcus pyogenes luego de un procedimiento ginecológico. Se trató con una dosis subcutánea de 40 mg de enoxaparina al día, y 2 g de ceftriaxona intravenosa cada 24 h, 240 mg de gentamicina intravenosa una vez al día. En las siguientes 48 horas se retiró la gentamicina y se prescribió 1 g de amoxicilina cada 8 h, por vía oral más 300 mg de clindamicina cada 8 h, también por vía oral que la paciente continuó durante 7 días más. En la resonancia magnética de control tomada a los 10 días quedó de manifiesto la tromboflebitis séptica en la vena iliaca interna izquierda y la persistencia del cuadro de piomiositis, con colección pélvica intra y extramuscular. Se decidió reingresarla para tratarla con el siguiente esquema: 1 g de amoxicilina por vía intravenosa cada 8 horas y 900 mg de clindamicina con igual pauta; se suspendió a las 24 h enseguida de la valoración por el infectólogo. Se indicó nuevo tratamiento antitrombótico con 0.5 mL de fraxiparina forte cada 24 horas, por vía subcutánea. El eco-Doppler descartó la trombosis venosa profunda; los hemocultivos que resultaron negativos. La paciente fue dada de alta con prescripción de fraxiparina Forte a dosis de 0.5 mL cada 24 horas durante 6 semanas; la evolución clínica fue favorable. La resonancia magnética de control a los 30 días reportó la desaparición completa del proceso inflamatorio. Luego de un año, la paciente permanece asintomática y continúa en seguimiento médico anual. CONCLUSIONES: La histeroscopia diagnóstica ambulatoria es una técnica eficaz y segura aunque excepcionalmente pueden sobrevenir complicaciones infecciosas derivadas de la técnica. Esto se previene con profilaxis antibiótica. La valoración previa a la histeroscopia es indispensable para advertir factores de riesgo que puedan controlarse o contraindiquen la realización del procedimiento.

Abstract BACKGROUND: Infectious complications due to diagnostic hysteroscopy are uncommon, being only 0.6% of all complications. CLINICAL CASE: A 46-year-old patient who, 6 days after performing an outpatient diagnostic hysteroscopy due to endometrial polyps, was admitted to the Gynecology Department, due to pyomyositis of the left piriformis muscle secondary to Streptococcus pyogenes bacteremia after gynecological procedure. Antithrombotic treatment was initiated with Enoxaparin 40 mg, 1/24h subcutaneously and antibiotic therapy with Ceftriaxone 2g/24h intravenously (iv) and Gentamicin 240 mg/24h iv, which 48 hours later were changed to Amoxicillin 1g/8h orally (VO) and Clindamycin 300 mg/8 hours orally for another 7 days. In the 10-day control magnetic resonance imaging (MRI), septic thrombophlebitis was seen in the left internal iliac vein as well as persistence of the pyomyositis condition, with intra and extramuscular pelvic collections. Therefore, a new admission was decided to start antibiotic therapy again with Amoxicillin 1g/8h IV and Clindamycin 900 mg/8h IV, which was suspended 24 hours after assessment by the Infectious Diseases Unit; and new antithrombotic treatment with Fraxiparin Forte 0.5 mL/24h subcutaneous, by consensus with the Vascular Surgery Service. ECO-DOPPLER was performed, which ruled out Deep Venous Thrombosis (DVT); and negative blood cultures. The patient was discharged with Fraxiparina Forte 0.5 mL/24h for 6 weeks presenting good clinical evolution. A new MRI control was scheduled for the following month, finding a complete resolution of the inflammatory process. Currently, one year later, the patient is asymptomatic and continues in annual follow-up in our consultations. CONCLUSIONS: Outpatient diagnostic hysteroscopy is an effective and safe technique. Infectious complications derived from the technique are infrequent, which is why it is not necessary to perform an antibiotic prophylaxis in patients who are going to undergo this test

Efectos de una intervención de educación emocional en alumnos de un programa universitario para mayores / Effects of an Emotional Education Intervention in Students of University Programs for Older Students

RESUMEN Los programas universitarios para mayores tienen como objetivo la potenciación de las capacidades cognitivas, emocionales y sociales, así como la mejora de la calidad de vida y el bienestar personal. Las competencias emocionales, por su impacto a múltiples niveles, se deben desarrollar y fomentar a lo largo de todo el ciclo vital. No obstante, hasta el momento, en España existen escasos trabajos que implementen programas de intervención de educación emocional para mayores y que al mismo tiempo evalúen empíricamente su posible impacto. El principal objetivo de este trabajo fue examinar el efecto de un programa de educación emocional en alumnos de un programa universitario para mayores. Se utilizó un grupo experimental (n = 28) y dos grupos control (n = 23; n 2 = 15) que fueron evaluados en dos momentos temporales, a través del TMMS-24 y MSCEIT Los resultados mostraron que, tras un periodo de 4 meses de intervención, el grupo experimental no difirió de forma estadísticamente significativa del grupo control en las puntuaciones medias de inteligencia emocional entre el pretest y el postest. A pesar de los resultados obtenidos, es necesario promocionar las habilidades emocionales y sociales a lo largo del ciclo vital. Es sumamente interesante que se adquieran y potencien las habilidades emocionales en este sector de la población, con la finalidad de mejorar el ajuste personal y la calidad de vida, así como el desarrollo integral de la persona. Futuros estudios deberían utilizar muestras más representativas, así como llevar a cabo un seguimiento longitudinal.

ABSTRACT University programs for older students aim at enhancing the cognitive, emotional and social skills as well as improving the quality of life and personal well-being. The emotional competencies, due to their impact at multiple levels on individual well-being, should be developed and promoted throughout all stages across the lifespan. However, there is a paucity of studies in Spain that have conducted intervention programs and, at the same time, have empirically assessed their impact. The main goal of the present study was to examine the effects of an emotional education program on older students. An experimental (n = 28) and two control groups (nj = 23; n 2 = 15) were used and assessed at two time points using the TMMS-24 and the MSCEIT The results showed that, after a period of 4 months of intervention, the experimental group did not differ significantly from the control group mean scores of measures of emotional intelligence between the pre-test and post-test. These findings, although inconclusive, highlight the importance of promoting social and emotional skills throughout the whole lifespan. It is very interesting to enhance the emotional and social competences in this sector of the population in order to improve their personal adjustment and quality of life. Future studies should use representative sampling as well as include long term follow-up.

Costos de la rehidratación oral y nasogástrica comparadas con la rehidratación endovenosa en niños con diarrea en Colombia / Costs of oral and nasogastric rehydration compared to intravenous rehydration in children under 5 years of age with diarrhea in Colombia

RESUMEN Objetivo Evaluar los costos de las terapias de rehidratación oral (TRO) y de rehidratación nasogástrica (TRN) comparadas con la terapia de rehidratación endovenosa (TRE) para corregir la deshidratación por diarrea en niños. Metodología Análisis de minimización de costos desde la perspectiva del Sistema de Salud colombiano comparando TRO (seguida de TRN ante falla de la TRO), con la TRE. El horizonte temporal fue la duración de la rehidratación. La medida de efectividad se extrajo de una revisión sistemática de literatura. Para determinar costos, se construyó un caso típico y un árbol de decisiones, a partir de revisión de guías e historias clínicas, validado con expertos. Los costos unitarios se obtuvieron de bases de datos colombianas. Costos fueron calculados en pesos colombianos (COP) y dólares americanos (USD). Se realizaron análisis de sensibilidad de una y dos vías. Resultados La TRO y la TRE son similares en efectividad para prevenir hospitalización y lograr rehidratación. En el caso base, el costo de la TRO fue $91,221COP (40.5 USD) y para TRE $112,944COP (50.14USD), es decir, un ahorro de $21,723 COP (9.64 USD). En los análisis de sensibilidad por regímenes de aseguramiento y complejidad del hospital, la TRO suele ser la estrategia menos costosa. Discusión Ambas intervenciones son similares en efectividad, pero la TRO, seguida de TRN ante falla de la primera resulta menos costosa que la TRE. La TRO es recomendable como primera opción para corregir la deshidratación. Deberían continuarse esfuerzos por implementar TRO y TRN en los servicios de salud en Colombia.(AU)

ABSTRACT Objective To evaluate the costs of oral rehydration therapy (ORT) and nasogastric rehydration therapy (NRT) compared with intravenous rehydration therapy (IRT) to treat dehydration in children under 5 years of age with diarrhea. Methodology Cost-minimization analysis from the perspective of the Colombian Health System, comparing ORT, (followed by NRT when ORT fails), with IRT. The time horizon was the duration of rehydration. The effectiveness measure was obtained from a systematic review of the literature. To determine costs, a typical case was created based on current guidelines and medical records; this case was validated by experts. Unit costs were obtained from Colombian databases and were provided in Colombian pesos (COP) and US dollars (USD) for 2010. One- and two-way sensitivity analyzes were performed. Results ORT and ERT are similarly effective to prevent hospitalization and to achieve rehydration. In the base case, the expected cost of ORT was $91,221 COP (40.5 USD) and for IRT was $112,944 COP ($50.14 USD), saving $21,723 COP ($9.64 USD) per case. In the sensitivity analyzes by health insurance and hospital level, ORT is often the least costly strategy. Discussion Both interventions are similarly effective, but ORT, followed by NRT when ORT fails, is less costly than IRT. ORT is recommended as the first option to treat dehydration since it is effective and less expensive. Efforts should be continued to implement TRO and NRT in the health services of Colombia.(AU)

Programas Educativos Universitarios Para Mayores: Evaluación de su Impacto en la Autopercepción del Apoyo Social y la Salud Mental / University Education Programs for Older Adults: Evaluation of Their Impact on Individual Perceptions of Social Support and Mental Health / Programas Educativos Universitários Para Idosos: Avaliação de Seu Impacto na Autopercepção do Apoio Social e da Saúde Mental

Algunos estudios indican que los programas universitarios para mayores pueden tener un impacto positivo en la autopercepción del apoyo social y la salud de los participantes. Sin embargo, dichos estudios no evalúan estas variables con instrumentos de medida estandarizados y grupos de control dentro y fuera del programa. En el presente trabajo se utilizó un grupo experimental y dos grupos control que fueron evaluados en dos momentos con instrumentos estandarizados. Los resultados no confirmaron los efectos beneficiosos esperados de los programas. Es necesario seguir profundizando en esta línea de actuación y explorar el efecto de variables socioafectivas en estudios longitudinales.

Some studies indicate that university programs for older adults can have a positive impact on the participants' perceptions of social support and health. However, those studies fail to evaluate these variables with standardized measurement instruments and control groups, both within and outside the program. This study used an experimental group and two control groups that were evaluated at two different moments, using standardized instruments. The results did not confirm the expected beneficial effects of the programs. Thus, it is necessary to continue in-depth research along these lines and explore the effect of socio-affective variables in longitudinal studies.

Alguns estudos indicam que os programas universitários para idosos podem ter um impacto positivo na autopercepção do apoio social e da saúde dos participantes. Contudo, esses estudos não avaliam essas variáveis com instrumentos de medidas padronizados e grupos de controle dentro e fora do programa. No presente trabalho, utilizaram-se um grupo experimental e dois grupos de controle que foram avaliados em dois momentos com instrumentos padronizados. Os resultados não confirmaram os efeitos benéficos esperados dos programas. É necessário continuar aprofundando nessa linha de atuação e explorar os efeitos de variáveis socioafetivas em estudos longitudinais.

Cost effectiveness of Zinc Supplementation for the Treatment of Acute Diarrhoea in Children under 5 Years in Colombia.

Objectives: To determine the relative cost-effectiveness of zinc supplementation for the treatment of acute diarrhoea in children under five years in Colombia. Methods: Cost-effectiveness analysis from the perspective of the Colombian Health System. We evaluated standard treatment with addition of zinc versus standard treatment without zinc supplement for children from birth to five years. The time horizon was the duration of the diarrhoea. Effectiveness information was extracted from a Cochrane systematic review and Colombian databases and observational studies. Identification and measurement of resource use was based in clinical guidelines, protocols and expert opinion. Unit costs were obtained from Colombian tariff manuals. We performed deterministic sensitivity analysis to assess the impact of changes in the cost and effectiveness of the strategies on the results of the model. Results: The average treatment cost of one diarrhoea episode in Colombia is USD $40.77 using standard treatment, and USD $32.96 with zinc supplementation, a reduction of $7.81 USD. Additionally, zinc supplementation is more effective than standard treatment without zinc: it reduces diarrhoea-related mortality and incidence of persistent diarrhoea. The results are sensitive to changes in the probability of hospitalization and persistent diarrhoea, but conclusions do not change substantially. Conclusions: Zinc for the treatment of acute diarrhoea is a highly cost-effective strategy from the perspective of the Colombian Health System. It is more cost-effective in children with higher risk of persistent diarrhoea and hospitalization.

Incidencia de meningitis en lactantes con crisis febriles simples. Experiencia en un hospital de 3er nivel / Incidence of meningitis in infants with simple febrile seizures. Experience in a 3th level hospital

IINTRODUCCIÓN. Se denominan convulsiones febriles (CF) simples aquellas crisis generalizadas, autolimitadas, de menos de 15 minutos de duración, sin recurrencia en las primeras 24 horas y sin alteración neurológica postictal. Las CF constituyen el cuadro convulsivo más frecuente en niños menores de 5 años y se caracterizan por ser eventos benignos y autolimitados. Aproximadamente 2-4% de los niños tienen al menos una CF en algún momento de la vida. OBJETIVO. Determinar la incidencia de meningitis en niños menores de 18 meses de edad con un primer episodio de convulsión febril simple. MATERIAL Y MÉTODOS. Revisión retrospectiva de historias clínicas de pacientes entre 3 y 18 meses que consultaron a urgencias del Hospital Universitario San Vicente Fundación (HUSVF), en Medellín, por un primer episodio de convulsión febril simple, entre 2006 y 2011. RESULTADOS. Se revisaron 286 registros de pacientes con diagnóstico de convulsión febril, 79 (27%) correspondían a CF simple. 50 niños (63%) tenían menos de 12 meses, Se realizó punción lumbar en 45 (57%), y se identificaron 6 casos con pleocitosis, uno de los cuáles fue considerado meningitis bacteriana y tres como meningitis aséptica. Dos casos adicionales se consideraron meningitis parcialmente tratada. Los niños con meningitis o meningitis parcialmente tratada tenían sígnos clínicos sospechosos, habían recibido antibióticos o tenía vacunación incompleta. CONCLUSIÓN. La meningitis en niños con CF simple es poco frecuente y los casos sospechosos pueden detectarse con los criterios de la Academia Americana de Pediatría; si se realiza punción lumbar a niños que han recibido antibióticos, con vacunas incompletas o con signos clínicos neurológicos. La punción lumbar no debe ser rutinaria en casos de CF. Debe estudiarse el perfil epidemiologico de las de las infecciones por neumococo en Colombia, luego de la inclusión de la vacuna de 10 serotipos, para determinar su efecto en el riesgo de meningitis.

INTRODUCCTION. Febrile seizures (FS) are defined as generalized, self limited crisis lasting less than 15 minutes with no recurrence in 24 hours and without neurological inpairment in the post ictal period. FS are the most common cause for convulsions in patients less than 5 years old. These type of crisis are benign and self-limited . FS Lifetime incidence has been calculated between 2-4% in pediatric population. OBJECTIVE. To determine the inicidence of meningitis in children under 18 months with first simple febrile seizure (FS). Materials and METHODS. A retrospective review of medical records of patients 3 to 18 months of age who visited the emergency room at the Hospital Universitario San Vicente Fundación (HUSVF) after first episode of simple febrile seizure (FS), between January 2005 and December 2010. RESULTS. We analized 286 clinical records of patients between 3 and 18 months of age with febrile seizures, 79 (27%) were considered a single FS. Fifty-patients were under 12 months of age (63%). Lumbar puncture was performed in 45 children (57%) and there were 6 children with pleocytosis, one of them was considered as bacterial meningitis, and three as aseptic meningitis. Two cases had diagnosis of partially treated meningitis. Children with suspected meningitis had abnormal neurological signs, had previously received antibiotics or had incomplete vaccination. CONCLUSION. Meningitis in children with simple FS is not frequent and all cases could be detected according to the criteria of the American Academy of Pediatrics to perform lumbar puncture in children who previously received antibiotics, had incomplete vaccination or have positive neurological signs. Routine lumbar puncture in children with simple CF must be discouraged. The current state of pneumococcal infections in Colombia after implementation of immunization 10 serotypes vaccine must be assessed, in order to know the effect of vaccination status on the risk of meningitis in children with FS.

Immunosupressive therapy in children with steroid-resistant nephrotic syndrome: single center experience / Tratamento com imunossupressores em crianças com síndrome nefrótica resistente a corticosteróide: experiência de um único centro

INTODUCTION: Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA) is one of the treatments used in such situations. OBJECTIVE: To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS) and to assess the therapeutic response to MA. METHODS: This was a retrospective and descriptive study. RESULTS: 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS). The immunosuppresive drugs used were: Mycophenolate mofetil (MMF) 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4). This median became 1 (p25: 1 - p75: 3.25) after using this medication (p = 0.08). Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62) mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55) mg/k/day (p < 0.001), in 8 patients prednisolone was stopped. CONCLUSION: In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage.

INTRODUÇÃO: A síndrome nefrótica é uma das mais frequentes doenças glomerulares em crianças e o tratamento com corticosteróides ainda é o tratamento de escolha. Apesar disso, 10 a 15% dos pacientes são resistentes a corticosteróides, e o melhor tratamento para tais casos ainda não foi definido. O ácido micofenólico (AM) é um dos tratamentos usados em tais situações. OBJETIVO: Descrever o comportamento clínico de crianças diagnosticadas com síndrome nefrótica resistente a corticosteróide (SNRC) e avaliar a resposta terapêutica ao AM. MÉTODOS: Esse foi um estudo retrospectivo e descritivo. RESULTADOS: 26 registros de pacientes com SNRC; 70% homens e 30% mulheres. Todos os pacientes foram submetidos a biópsias renais, o que mostrou predominância de glomeruloesclerose segmentar focal (GESF). Os medicamentos imunossupressores utilizados foram: Mofetil Micofenolato (MMF) 100%; Ciclosporina 69,2%; Ciclosfosfamida 23,1%; e Rituximabe 23%. Um mês após início do tratamento com MMF, 61,5% tiveram remissão. A mediana das recidivas por ano para os pacientes foi de 3 (p25: 2,75 - p75: 4). Essa mediana se tornou 1 (p25: 1 - p75: 3,25) após o uso da medicação (p = 0,08). Além disso, antes do início do tratamento com MMF, a mediana da dose de corticosteróide foi de 1 (p25: 0.5 - p75: 1.62) mg/k/ dia. Após a utilização do MMF, essa mediana se tornou 0,07 (p25: 0 - p75: 0,55) mg/k/dia (p < 0,001), em 8 pacientes a prednisolona foi interrompida. CONCLUSÃO: em nossa casuística, o tratamento com MMF mostrou resultados positivos, tais como a redução na frequência de recidivas, menos proteinúria, e redução da dose de corticosteróide administrada sem deterioração nas taxas de filtração glomerular. Entretanto, mais estudos são necessários para se avaliar a eficácia, segurança e otimização da dosagem.