Intermittent androgen deprivation therapy: recommendations to improve the management of patients with prostate cancer following the GRADE approach.

PURPOSE: The purpose of this study was to provide evidence-based recommendations of intermittent androgen deprivation therapy (IADT) compared with continuous androgen deprivation therapy (CADT) for men with prostate cancer (PCA). METHODS: We conducted a comprehensive search in MEDLINE, EMBASE, The Cochrane Library, CINAHL, and ECONLIT, from the database inception to December 2017. We adhered to the Grading of Recommendations, Assessment, Development and Evaluation framework to assess the quality of the evidence and to formulate recommendations. RESULTS: We included one systematic review with 15 trials as well as three additional studies that assessed IADT versus CADT, all of them focused on PCA patients in advanced stages. The findings did not show differences for critical and important outcomes, including adverse events. Trials reported the benefits of IADT in terms of selected domains of health-related quality of life, although with high heterogeneity. Evidence quality was considered moderate or low for most of the assessed outcomes. We identified a patient preference study reporting a high preference for IADT, due to issues related to quality of life, general well-being, and side effects, among others. We did not identify economic studies comparing these regimes. We formulate four recommendations: one no-recommendation, one conditional recommendation, and two good practice points. CONCLUSION: For men in early stages of PCA, it is not possible to make any recommendation about the preferable use of IADT or CADT due to the lack of available evidence. For men in advanced stages of the disease, an IADT should be considered as soon as clinically reasonable (weak recommendation and low certainty of the evidence). Clinicians should discuss the risks and benefits of IADT and CADT with their patients, taking into account their values and preferences.

Is intravenous ketamine effective for postoperative pain management in adults? / ¿Es efectiva la ketamina endovenosa para el manejo del dolor postoperatorio en adultos?

Ketamine is a N-Metil-D-Aspartate receptor antagonist that has been used as adjuvant in the acute postoperative pain management because of its analgesic properties. However, its role is not clearly determined. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple information sources. We identified 19 systematic reviews including 226 randomized trials overall. We extracted data and generated a summary of findings table using the GRADE approach. We concluded intravenous ketamine probably has little or no effect in reducing postoperative pain.

La ketamina es un antagonista de los receptores de N-metil-D-aspartato que ha sido utilizada como adyuvante en el manejo agudo del dolor postoperatorio debido a sus propiedades analgésicas. Sin embargo, su rol no está claramente determinado. Para aclarar esta interrogante utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en multiples fuentes de información. Identificamos 19 revisiones sistemáticas que en conjunto incluyen 226 ensayos aleatorizados. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de ketamina endovenosa probablemente no produce una disminución del dolor postoperatorio, o esta es clínicamente irrelevante.

Is primary prevention with antiepileptic drugs effective in brain tumors or brain metastases? / ¿Es efectiva la prevención primaria con anticonvulsivantes en tumores o metástasis cerebrales?

Patients with brain tumors –primary or metastatic- have an increased risk of presenting seizures during the course of their disease. So, prophylactic antiepileptic drugs have been proposed. However, the effects of this intervention are not yet clear. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple databases. We identified 12 systematic reviews including 80 studies overall. Twelve corresponded to randomized trials, but only two answered the question of interest. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE method. We concluded primary prevention with antiepileptic drugs might not reduce the risk of seizures, and it is associated to frequent adverse effects.

Los pacientes con tumores cerebrales, primarios o metastásicos, presentan riego de desarrollar convulsiones durante la evolución de su enfermedad, por lo que se ha propuesto el uso profiláctico de anticonvulsivantes. Sin embargo, el efecto de esta intervención no está claro. Para responder esta pregunta utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos. Identificamos 12 revisiones sistemáticas que en conjunto incluyen ochenta estudios primarios. Doce corresponden a estudios aleatorizados, pero sólo dos responden la pregunta de interés. Extrajimos los datos, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Concluimos que la prevención primaria con anticonvulsivantes podría no disminuir el riesgo de convulsiones en tumores o metástasis cerebrales, y se asocia a efectos adversos frecuentes.

Is electroconvulsive therapy effective as augmentation in clozapine-resistant schizophrenia? / ¿Es efectivo el uso de terapia electroconvulsiva en el tratamiento de pacientes con esquizofrenia resistente que usan clozapina?

Clozapine is considered to be the most effective antipsychotic drug for patients with treatment resistant schizophrenia, but up to a third of the patients do not respond to this treatment. Various strategies have been tried to augment the effect of clozapine in non-responders, one of these strategies being electroconvulsive therapy. However, its efficacy and safety are not yet clear. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 55 studies, among them six randomized controlled trials addressing clozapine-resistant schizophrenia. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded electroconvulsive therapy probably augments response to clozapine in patients with treatment resistant schizophrenia, but it is not possible to determine if it leads to cognitive adverse effects because the certainty of the evidence is very low.

Are cannabinoids effective for treatment of pain in patients with active cancer? / ¿Son efectivos los cannabinoides para el tratamiento del dolor en pacientes con cáncer activo?

Cannabinoids have been proposed for the treatment of patients with cancer pain, especially if standard treatment does not control symptoms. Using Epistemonikos database, which is maintained by searching 30 databases, we identified nine systematic reviews including seven trials that answer the question of interest, of which six are randomized trials. We performed a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded it is unclear whether cannabinoids decrease pain and improve quality of life in patients with refractory cancer pain because the certainty of the evidence is very low, and it probably increases adverse effects substantially.

El uso de cannabinoides ha sido propuesto para el tratamiento de pacientes con dolor oncológico, principalmente para aquellos en quienes el tratamiento habitual no es suficiente. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos nueve revisiones sistemáticas que en conjunto incluyen siete estudios que responden la pregunta de interés, de los cuáles seis corresponden a estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que no está claro si los cannabinoides producen una disminución del dolor o una mejoría en la calidad de vida en pacientes con dolor oncológico refractario porque la certeza de la evidencia es muy baja, pero probablemente se asocian a efectos adversos importantes.