Comparación de la eficacia y toxicidad del estibogluconato de sodio y antimoniato de meglumina en el tratamiento de leishmaniasis cutánea en Perú / Efficacy and safety of sodium stibogluconate compared to meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru

Objetivos : Comparar la eficacia y toxicidad del antimoniato de meglumina (AM) y estibogluconato sódico (EGS) en el tratamiento de leishmaniasis cutánea (LC) en un hospital general. Material y métodos : Serie de casos comparativa de 193 pacientes con LC tratados en tres ensayos clínicos con AM (n=69) y EGS (n=124) durante 2001-2010. La administración de ambas drogas fue vía endovenosa lenta de 20 mg Sb5+/kg/día por 20 días consecutivos siguiendo las normativas de la OPS y OMS. La información clínica, toxicidad y eficacia fue obtenida de las historias clínicas almacenadas en el centro de investigación según la normativa local e internacional. Resultados : Las características demográficas fueron similares entre grupos, pero el tamaño y número de lesiones fueron mayores en el grupo AM. La eficacia del tratamiento con AM fue 76,0% versus 68,4% con EGS (p=0,340) y 55,1% versus 50,8% (p=0,570) en el análisis por protocolo y de intención de tratar, respectivamente. No se observaron efectos adversos inmediatos. Los síntomas más frecuentemente reportados fueron disgeusia (37,0%), mareos (32,0%), cefalea (36,0%), artralgias (31,0%) y linfangitis (21,0%). Los tres primeros síntomas, así como elevación de transaminasas, leucopenia, trombocitopenia y QTc prolongado fueron frecuentes en el grupo EGS, pero clínica y estadísticamente no significativos. El tratamiento fue suspendido definitivamente por toxicidad severa únicamente con EGS por emesis refractaria (2 participantes) y QTc prolongado con extrasístoles (1 participante). Conclusiones : La eficacia del tratamiento con AM y EGS fue comparable. La administración endovenosa de ambos no produjo efectos adversos inmediatos, aunque sí alteraciones clínicas y laboratoriales usuales.

SUMMARY Objectives : To compare the efficacy and safety of sodium stibogluconate (SS) and meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL) in a general hospital. Methods: Case-series of 193 patients with CL treated in three clinical trials with MA (n=69) and SS (n=124) during 2001-2010. Both study drugs were administered intravenously at a slow speed at 20 mg Sb5+/kg/day for 20 consecutive days following WHO-PAHO recommendations. Clinical and safety data were gathered from clinical files. Results: Demographic characteristics were similar between the study groups, but the size and number of lesions were higher in the MA group. Efficacy was 76.0% in the MA vs. 68.4% in the SS group (p=0.340) and 55.1% vs. 50.8% (p=0.570) in the per protocol and intention to treat analysis. respectively. Side effects more frequently reported were dysgeusia (37.0%). dizziness (32.0%). headache (36.0%). arthralgia (31.0%) and lymphangitis (21.0%). These first three symptoms as well as elevation of transaminases, leukopenia, thrombocytopenia and prolonged QTc were numerically more frequent in the SS group but without reaching statistical significance. Treatment was stopped definitively for severe toxicity in the SS group due to refractory emesis (two patients) and prolonged QTc (one patient). Conclusions: The efficacy of MA and SS is comparable. The intravenous administration of these compounds did not produce immediate reactions, but it was associated with unusual clinical and laboratory abnormalities.

Ensaios clínicos de pacientes únicos em homeopatia: aspectos técnicos, educacionais e éticos / Single-case studies in homeopathy: technical, educational and ethical aspects

ensaio clínico de pacientes únicos (ECPU/ensaio n-de-1) consiste na observação sistemática de condutas terapêuticas adotadas para otimizar o restabelecimento da saúde em um único paciente, com múltiplos cruzamentos ao longo do tratamento, podendo ter adicionalmente propósito de pesquisa clínica. Foi proposto há décadas e tem sido mais utilizado nas áreas de psicologia clínica, recebendo maior atenção em estudos médicos nos últimos anos. Embora seja considerado como o tipo de estudo com maior força para tomada de decisões terapêuticas, ainda são escassas as publicações sobre o seu emprego em medicina. Este artigo aborda as possibilidades dos ECPUs na avaliação dos resultados clínicos da homeopatia, explorando seus aspectos metodológicos, éticos e educacionais característicos em comparação aos ensaios clínicos randomizados tradicionais. Em pesquisa clínica, diferentemente dos ensaios convencionais, os ECPUs permitem a participação mais direta do paciente na escolha dos procedimentos e acompanhamento dos resultados, com possibilidade de alterações imediatas e sem que seja necessária sua exclusão do estudo, além de implicações de ordem econômica, política e ética. Podem ser utilizados no teste de medicamentos usados de modo off label, sem as restrições impostas à inclusão de pacientes vulneráveis nos estudos clínicos habituais, com excessiva artificialização no delineamento experimental. Poderiam ser ainda adotados nas diversas fases de teste clínico dos medicamentos, reduzindo a exposição de grande número de participantes aos riscos da pesquisa e baixa margem de extrapolação clínica dos resultados ao conjunto da população. Em homeopatia, podem ajudar a aprimorar o conhecimento dos medicamentos já em uso ou a melhor detectar os efeitos de novas substâncias testadas em ensaios patogenéticos homeopáticos. Em função do seu propósito principal de otimização do tratamento individual ­ e do alinhamento com os princípios éticos da autonomia e beneficência associados à prática da medicina centrada-no-paciente ou de precisão - podem ser desenvolvidos em conjunto com o paciente e familiares, sem a obrigatoriedade de aprovação prévia por Comissões de Ética Médica ou Comitês de Ética em Pesquisa.

The single-patient clinical trial (n-of-1 trial) is primarily designed to systematically observe outcomes from different therapeutic options to optimize the restoration of health in a single patient, with multiple crossovers throughout the treatment. They may additionally have a clinical research purpose. They have been proposed for decades and were mostly used in clinical psychology, receiving greater attention in medical studies in recent years. Although it is considered the type of study with the greatest strength for therapeutic decision-making, there are still few publications with its application in medicine. This article discusses the possibilities of single-patient clinical trials in assessing homeopathy outcomes, exploring their characteristic methodological, educational and ethical aspects compared to traditional randomized clinical trials. In clinical research, unlike conventional trials, single-patient clinical trials allow for more direct patient participation in choosing procedures and monitoring results, with the possibility of immediate changes without the need for their exclusion from the study, in addition to economic, political and ethical implications. They can be used in testing off-label drugs without the restrictions imposed on the inclusion of vulnerable patients in usual clinical studies, with excessive artificiality in the experimental design. They could also be adopted in the various clinical trial phases of drugs, reducing the exposure of many participants to the risks of research and low margin of clinical extrapolation of the results to the entire population. In homeopathy, they can help refine the knowledge of medications already in use or better detect the effects of new substances tested in homeopathic pathogenetic trials. Due to their purpose of optimizing individual treatment ­ and alignment with the principles of patient-centered or precision medicine ­ they can be developed jointly with the patient and her family without the mandatory prior approval by Medical Ethics Committees or Research Ethics Committees.

Tamización primaria con prueba ADN-VPH en mujeres menores de 30 años: evaluación de tecnología sanitaria / Primary HPV-DNA screening in women under 30 years of age: health technology assessment

Antecedentes A partir del 2014 en Colombia se incorporó la Tamización primaria con prueba de Virus del Papiloma Humano (VPH) desde los 30 hasta los 65 años, cuando la prueba es positiva se hace triage con citología para remisión a colposcopia. Actualmente se discute la conveniencia de iniciar la tamización con prueba de ADN de VPH a partir de los 25 años. De esta manera, el objetivo de esta evaluación de tecnologías sanitarias es analizar la evidencia disponible en torno a la seguridad, efectividad, costoefectividad, valores y preferencias, dilemas éticos y aspectos relacionados con la implementación para el contexto colombiano de la prueba ADN-VPH como estrategia de tamización cervical en mujeres menores de 30 años. Dominios a evaluar Eficacia clínica y seguridad 1. Tasa acumulada de neoplasia intraepitelial cervical (NIC) grado 2 o más avanzado luego de 2 rondas de tamización. 2. Tasas acumuladas de cáncer invasor de cérvix luego de 2 rondas de tamización. 3. Seguridad: remisión a colposcopia. Costo-efectividad Costo efectividad para Colombia. Otros dominios considerados Aspectos éticos asociados a la tamización cervical en mujeres menores de 30 años. Aspectos organizacionales y del individuo. Barreras y facilitadores relacionados con la implementación en el contexto colombiano de la tamización cervical en mujeres menores de 30 años. Métodos Evaluación de efectividad y seguridad clínicas Se realizó una búsqueda sistemática de la literatura en MEDLINE, Embase y CENTRAL de revisiones sistemáticas y ensayos clínicos. Se calificó el cuerpo de la evidencia con la aproximación GRADE. Posteriormente, se convocó a un grupo interdisciplinario a una mesa de trabajo en donde se presentó la evidencia recuperada, dando paso a la discusión y a la construcción de las conclusiones, siguiendo los lineamientos de un consenso formal acorde a la metodología RAND/UCLA. Estudio económico Se hizo una búsqueda sistemática de la literatura de estudios que hubieran evaluado el costo-efectividad para Colombia. Resultados De 7.659 referencias recuperadas se incluyeron 8 estudios. Resultados clínicos Se realizó un análisis integrativo de 5 ensayos clínicos aleatorizados que cumplieron con los citerios de inclusión. Cuando se compara frente a la citología, la tamización primaria con ADN-VPH en mujeres menores de 30 años, podría asociarse con una mayor frecuencia de detección de lesiones NIC2+ durante la primera ronda de cribado (RR: 1.57; IC: 1,20 a 2,04; certeza en la evidencia baja), con una menor incidencia de NIC2+ (RR:0,67; IC: 0,48 a 0,92; certeza en la evidencia baja) y se asocia con una menor frecuencia de carcinoma invasor al término del seguimiento (RR: 0,19; IC: 0,07 a 0,53; certeza en la evidencia alta). Resultados económicos Desde el punto de vista económico, la alternativa de ADN-VPH y triage con citología desde los 25 años quizás representa la alternativa más costo-efectiva para Colombia (razón costo-efectividad incremental $8.820.980 COP año 2013). Otras implicaciones Dos estudios sugieren que las barreras de implementación, atribuibles a circunstancias de intermediación, de orden público y de carácter geográfico, podrían ser solventadas por nuevas tecnologías o estrategias de cribado. Es importante considerar alternativas de forma de administración y de prestación de servicios para solventar algunas barreras de aceptabilidad y acceso. Todo programa de tamización cervical debe contemplar los principios éticos de no maleficencia, beneficencia, autonomía y equidad. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años. Conclusiones El uso de la prueba ADN-VPH como estrategia de tamización en mujeres menores de 30 años es una intervención probablemente efectiva y costoefectiva para Colombia. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años.

Background Primary screening with Human Papilloma Virus (HPV) testing was introduced in Colombia in 2014 for individuals between 30 and 65 years of age. When the result is positive, cytology triage is performed for colposcopy referral. The convenience of initiating HPV-DNA testing for screening at 25 years of age is currently a subject of discussion. Therefore, the objective of this health technology assessment (HTA) is to analyze the available evidence regarding safety, efficacy, cost-effectiveness, values and preferences, ethical dilemmas and considerations pertaining to the implementation of the HPV-DNA test as a cervical screening strategy in women under 30 years of age in the Colombian context. Domains to be assessed Clinical efficacy and safety 1. Cumulative rate of cervical intraepithelial neoplasia (CIN) grade 2 or high-er after 2 screening rounds. 2. Cumulative rates of invasive cancer of the uterine cervix after 2 screening rounds. 3. Safety: referral to colposcopy Cost-effectiveness Cost-effectiveness for Colombia. Other domains considered Ethical considerations associated with cervical screening in women under 30 years of age. Organizational and individual considerations. Barriers and facilitators pertaining to the implementation of cervical screening in women under 30 years of age in the Colombian context. Methods Clinical efficacy and safety assessment A systematic literature search of systematic reviews and clinical trials was conducted in MEDLINE, Embase and CENTRAL. The body of evidence was rated using the GRADE approach. An interdisciplinary team was then convened to create a working group to review the retrieved evidence. This led to the discussion and construction of the conclusions following the guidelines of a formal consensus in accordance with the RAND/UCLA methodology. Economic study Systematic literature research of studies that had assessed cost-effectiveness for Colombia. Results Out of the 7,659 references retrieved, 8 studies were included. Clinical outcomes An integrative analysis of 5 randomized clinical trials that met the inclusion critera was performed. Compared with cytology, primary HPV-DNA testing in women under 30 years of age could be associated with a lower frequency of CIN+2 lesions during the first screening round (RR: 1.57; CI: 1.20 to 2.04; low evidence certainty), and a lower incidence of CIN+2 (RR: 0.67; CI: 0.48 to 0.92; low evidence certainty). Moreover, it is associated with a lower frequency of invasive carcinoma at the end of follow-up (RR: 0.19; CI: 0.07 to 0.53; high evidence certainty). Economic results From the financial point of view, the use of HPVDNA testing plus cytology-based triage starting at 25 years of age is perhaps the most cost-effective option for Colombia (incremental cost-effectiveness ratio, COP 8,820,980 in 2013). Other implications Two studies suggest that barriers to implementation attributable to intermediation, public unrest and geographic considerations could be overcome with the use of new screening technologies or strategies. It is important to consider administration and service provision alternatives in order to overcome some acceptability and access barriers. Any cervical screening program must take into consideration ethical principles of nonmaleficence, beneficence, autonomy and equity. Future studies should focus on analyzing new screening techniques with emphasis on the population under 30 years of age. Conclusions The use of HPV-DNA testing as a screening strategy in women under 30 years of age is a potentially efficacious and cost-effective intervention for Colombia. Future studies should focus on analyzing new screening technologies, with emphasis on the population under 30 years of age.

Compreensão do consentimento informado em pesquisa clínica de vacina contra o Zika vírus: estudo transversal / Understanding of informed consent in clinical research for a vaccine against Zika virus: a cross-sectional study / Comprensión del consentimiento informado en la investigación clínica de una vacuna contra el virus del Zika: un estudio transversal

OBJETIVO: avaliar a compreensão das informações do Termo de Consentimento Livre e Esclarecido pelos participantes de uma pesquisa clínica de vacina contra o Zika vírus. MÉTODO: estudo transversal com amostra por conveniência e participação de 101 voluntários de uma pesquisa clínica em Belo Horizonte, Minas Gerais. Utilizou-se um questionário estruturado. A análise dos dados foi realizada no programa R, segundo a estatística descritiva e inferencial. RESULTADOS: a média de acertos dos participantes sobre as informações do documento de consentimento foi de 66,9%. A maioria dos participantes assinou o documento sem o conhecimento suficiente das informações da pesquisa. O Índice de compreensão foi maior entre os participantes que tinham se voluntariado em pesquisas prévias (p=0,039). CONCLUSÃO: verificaram-se limitações importantes na compreensão dos participantes sobre informações do termo de consentimento, o que comprometeu a decisão autônoma. São necessárias adaptações e melhorias nos processos de consentimento informado em prol da sua validade.

OBJECTIVE: to assess the understanding of the information contained in the Informed Consent Form by the participants of a clinical trial of a vaccine against the Zika virus. METHOD: cross-sectional study using intentional sampling, including a total of 101 volunteers in clinical research in Belo Horizonte, Minas Gerais. A structured questionnaire was used. Data analysis was performed using R software, according to descriptive and inferential statistics. RESULTS: the mean of correct answers of the participants regarding the information in the consent form was 66.9%. Most participants signed the document without sufficient knowledge of the research information. The comprehension index was higher among participants who had volunteered in previous research (p=0.039). CONCLUSION: there were important limitations in the participants' understanding of information in the consent form, which compromised the autonomous decision. Adaptations and improvements are necessary in the processes of informed consent for its validity.

OBJETIVO: evaluar la comprensión de las informaciones contenidas en el Término de Consentimiento Libre e Informado por los participantes de un ensayo clínico de una vacuna contra el virus del Zika. MÉTODO: estudio transversal con muestra de conveniencia y participación de 101 voluntarios en una investigación clínica en Belo Horizonte, Minas Gerais. Se utilizó un cuestionario estructurado. El análisis de datos se realizó mediante el programa R, según estadística descriptiva e inferencial. RESULTADOS: el promedio de aciertos de los participantes con respecto a las informaciones del documento de consentimiento fue de 66,9%. La mayoría de los participantes firmó el documento sin conocimiento suficiente de las informaciones de la investigación. El índice de comprensión fue mayor entre los participantes que se habían ofrecido como voluntarios en investigaciones anteriores (p=0,039). CONCLUSIÓN: hubo limitaciones importantes en la comprensión de las informaciones del formulario de consentimiento por parte de los participantes, lo que comprometió la decisión autónoma. Son necesarias adecuaciones y mejoras en los procesos de consentimiento informado para su validez.

Does Virtual Reality Affect Children's Dental Anxiety, Pain, And Behaviour? A Randomised, Placebo-Controlled, Cross-Over Trial

ABSTRACT Objective: To evaluate the effect of virtual reality (VR) on dental anxiety, pain, and behaviour at different time points among children undergoing dental treatment under local anaesthesia. Material and Methods: This randomised, two‐armed, within-subject, cross-over, placebo-controlled trial included 76 children. Eligible participants were treated in two dental visits using the following methods: with protective glasses only, without distraction (attention placebo-controlled - APC); and with the treatment condition (i.e., VR). Primary outcomes were dental anxiety and pain; secondary outcome was dental visit behaviour. Heart rate scores were recorded as an objective measure to evaluate dental anxiety and pain. Subjective measurements for each variable were also performed. Results: Significant reduction in dental pain and anxiety was observed in the VR group, according to the heart rate scores; however, no statistical differences were observed according to the self-reported measures. Decreased dental anxiety and pain were associated with the first visit sequence with VR. Dental pain and anxiety scores were lower during local anaesthesia in the VR group than in the APC group. Conclusion: Virtual reality significantly reduced pain and anxiety during local anaesthesia in children undergoing dental treatment; therefore, it may be recommended during dental treatment in school-age children.

Uso das técnicas de acupuntura para tratamento da dor lombar crônica não específica no Brasil: revisão integrativa da literatura / Use of acupuncture techniques for the treatment of chronic non-specific low back pain in Brazil: an integrative literature review

A acupuntura representa uma prática complementar de intervenção em saúde que aborda de modo integral e dinâmico o processo saúde-doença no ser humano, podendo ser usada isoladamente ou de forma integrada com outros recursos terapêuticos. Esta investigação consiste em uma revisão integrativa da literatura, realizada com o objetivo de analisar as evidências científicas acerca do uso de técnicas de acupuntura para o tratamento da lombalgia crônica não específica no Brasil. Para a elaboração da presente revisão integrativa, foram seguidas seis etapas: elaboração da questão norteadora; amostragem; extração dos dados dos estudos primários; avaliação dos estudos primários incluídos na revisão; análise e síntese dos resultados; apresentação da revisão integrativa. A busca nas bases de dados resultou, inicialmente, em 3552 estudos; desse total, nove (0,25%) estudos foram incluídos nesta revisão, atendendo aos critérios de inclusão. Um artigo foi publicado em 2006; um artigo foi publicado em 2015; um artigo foi publicado em 2016; dois artigos foram publicados em 2018 e quatro artigos foram publicados em 2020. Quanto ao tipo de população, um estudo foi realizado com idosos; um, com gestantes; um, com funcionários de uma cadeia pública feminina e seis estudos foram realizados com adultos entre 18 e 80 anos, todos portadores de lombalgia crônica não específica, no Brasil. Quanto ao nível de evidência, cinco estudos (56%) foram classificados no nível de evidências II por representarem estudos clínicos randomizados controlados e quatro estudos (44%) foram provenientes de ensaios clínicos não-randomizados, sendo classificados no nível de evidências III. Observou-se que a maioria dos estudos foram realizados utilizando a técnica de acupuntura sistêmica, seguida pela técnica de eletroacupuntura, acupuntura auricular e ventosaterapia. Os resultados de todos os estudos demonstraram a efetividade das técnicas de acupuntura para o tratamento da lombalgia crônica não específica, indicando melhora da intensidade da dor, da amplitude dos movimentos da região lombar e do quadro emocional geral do paciente, como diminuição de estresse e sintomas de ansiedade e depressão. Apesar da identificação da efetividade da acupuntura para o tratamento da lombalgia crônica não específica, considera-se fundamental a realização de um maior número de estudos clínicos baseados na utilização de protocolos rigorosos e internacionalmente reconhecidos para o uso destas práticas complementares, no intuito de comprovar a eficácia destes métodos de tratamento principalmente para o alívio da dor, na perspectiva da integralidade da saúde

Acupuncture represents a complementary practice of health intervention that comprehensively and dynamically addresses the health-disease process in humans, and can be used alone or in an integrated way with other therapeutic methods. This investigation consists of an integrative literature review, carried out with the aim of analyzing the scientific evidence about the use of acupuncture techniques for the treatment of chronic non-specific low back pain in Brazil. For the elaboration of this integrative review, six steps were followed: elaboration of the guiding question; sampling; extraction of data from primary studies; evaluation of the primary studies included in the review; analysis and synthesis of the results; presentation of the integrative review. The search in the databases resulted, initially, in 3552 studies; of this total, nine (0.25%) studies were included in this review, considering the inclusion criteria. One article was published in 2006; one article was published in 2015; one article was published in 2016; two articles were published in 2018 and four articles were published in 2020. As for the type of population, a study was carried out with the elderly; one, with pregnant women; one, with employees of a female public chain and six studies were carried out with adults between 18 and 80 years old, all with chronic non-specific low back pain, in Brazil. Related the level of evidence, five studies (56%) were classified at level of evidence II because they represented randomized controlled clinical trials and four studies (44%) came from non-randomized controlled clinical trials and were classified at level III of evidence. It was observed that most studies were carried out using the systemic acupuncture technique, followed by the electroacupuncture, auricular acupuncture technique and suction therapy. The results of all studies demonstrated the effectiveness of acupuncture techniques for the treatment of chronic non-specific low back pain, indicating improvement in pain intensity, range of motion in the lower back and the patient's general emotional condition, such as reduced stress and symptoms of anxiety and depression. Despite the identification of the effectiveness of acupuncture for the treatment of chronic non-specific low back pain, it is considered essential to carry out a greater number of clinical studies based on the use of rigorous and internationally recognized protocols for the use of these complementary practices, in order to prove the effectiveness of these treatment methods mainly for pain relief, from the perspective of comprehensive health

Transmisión sexual del virus SARS-CoV-2 y su rol en la propagación de COVID-19: protocolo de una revisión sistemática viva / Sexual transmission of SARS-CoV-2 virus and its role in the spread of COVID-19: a living systematic review protocol

Objetivo Proporcionar una revisión de la literatura sobre la presencia de SARS-CoV-2 en los fluidos sexuales de pacientes con COVID-19 y su posible transmisión sexual de manera oportuna, rigurosa y continuamente actualizada. Fuentes de datos Realizaremos búsquedas en PubMed / Medline, Embase, Registro Cochrane Central de Ensayos Controlados (CENTRAL), literatura gris y en un repositorio centralizado en L · OVE (Living OVerview of Evidence). L · OVE es una plataforma que mapea las preguntas PICO a la evidencia de la base de datos Epistemonikos. En respuesta a la emergencia de COVID-19, L · OVE se adaptó para ampliar el rango de evidencia que cubre y se personalizó para agrupar todas las pruebas de COVID-19 en un solo lugar. La búsqueda cubrirá el período hasta el día anterior al envío a una revista. Criterios de elegibilidad para la selección de estudios y métodos Adaptamos un protocolo común ya publicado para múltiples revisiones sistemáticas paralelas a las especificidades de esta pregunta. Incluiremos ensayos aleatorios que evalúen la transmisión sexual del virus SARS-CoV-2. Se buscarán ensayos aleatorizados que evalúen la transmisión sexual de otros coronavirus, como MERS-CoV y SARS-CoV, y estudios no aleatorizados en COVID-19 en caso de que no se encuentre evidencia directa de ensayos aleatorizados, o si la evidencia directa proporciona una - o certeza muy baja para resultados críticos. Dos revisores evaluarán de forma independiente la elegibilidad de cada estudio, extraerán datos y evaluarán el riesgo de sesgo. Realizaremos metanálisis de efectos aleatorios y utilizaremos GRADE para evaluar la certeza de la evidencia para cada resultado. Una versión viva basada en la web de esta revisión estará disponible abiertamente durante la pandemia de COVID-19. Lo volveremos a enviar si las conclusiones cambian o hay actualizaciones sustanciales Registro PROSPERO (CRD42020189368).

Uso de testosterona en mujeres: un comentario sobre el consenso global sobre el uso de la terapia de testosterona para mujeres / Global consensus position statement on the use of testosterone therapy for women

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)

There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)

Miotomia peroral (POEM) ou cirúrgica para o tratamento da acalasia: revisão sistemática e metanálise / Peroral (poem) or surgical myotomy for the treatment of achalasia: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Achalasia is a neurodegenerative motility esophageal disorder characterized by failure of lower esophageal sphincter relaxation. The conventional treatment option for achalasia has been laparoscopic Heller myotomy (LHM). However, in 2010, Inoue et al. described peroral endoscopic myotomy (POEM), a minimally invasive procedure, as an alternative therapy. To date, some studies with small sample sizes have aimed to compare outcomes of LHM vs POEM. OBJECTIVE: Thus, the aim of this study is to perform a systematic review and meta-analysis to better evaluate the efficacy and safety of these two techniques. METHODS: Individualized search strategies were developed from inception through April 2019 in accordance with PRISMA guidelines. Variables analyzed included operative time, overall adverse events rate, post-procedure gastroesophageal reflux disease (GERD), hospitalization length, post-procedure pain score, and Eckardt Score reduction. RESULTS: Twelve cohort trials were selected, consisting of 893 patients (359 in POEM group and 534 in LHM.) No randomized clinical trials were available. There was no difference in operative time (MD= -10,26, 95% CI (-5,6 to 8,2), P<0.001) or Post-Operative Gastroesophageal Reflux (RD: -0.00, 95%CI: (-0.09, 0.09), I2: 0%). There was decreased length of hospital stay for POEM (MD: -0.6, 95% CI (-1.11, -0.09), P=0.02), and an increased mean reduction in Eckardt score in POEM patients (MD = -0.257, 95% CI: (-0.512 to -0.002), P=0.048), with similar rates of adverse events. CONCLUSION: POEM demonstrated similar results compared to laparoscopic Heller myotomy with regards to improvement of dysphagia, post-procedure reflux, and surgical time, with the benefit of shorter length of hospital stay. Therefore, POEM can be considered an option for patients with achalasia.

RESUMO CONTEXTO: A acalasia é um distúrbio esofágico da motilidade neurodegenerativa caracterizado por falha no relaxamento do esfíncter esofágico inferior (EEI). A opção de tratamento convencional para acalasia tem sido a miotomia laparoscópica de Heller (LHM). No entanto, em 2010, Inoue et al. descreveram a miotomia endoscópica peroral (POEM), um procedimento minimamente invasivo, como uma terapia alternativa. Até o momento, poucos estudos com amostras pequenas tiveram como objetivo comparar os resultados do LHM versus POEM. OBJETIVO: Assim, o objetivo deste estudo é realizar uma revisão sistemática e metanálise para melhor avaliar a eficácia e segurança dessas duas técnicas. MÉTODOS: Estratégias de busca individualizadas foram desenvolvidas desde o início até abril de 2019, de acordo com as diretrizes do PRISMA. As variáveis analisadas incluíram tempo operatório, taxa global de eventos adversos, doença de refluxo gastroesofágico (DRGE) pós-procedimento, tempo de internação, escore de dor pós-procedimento e redução do escore de Eckardt. RESULTADOS: Doze estudos de coorte foram selecionados, consistindo em 893 pacientes (359 no grupo POEM e 524 no LHM). Nenhum ensaio clínico randomizado estava disponível. Não houve diferença no tempo operatório (MD = -10,26, IC 95% (-5,6 a 8,2), P<0,001) ou refluxo gastroesofágico pós-operatório (RD: -0,00, 95% IC: (-0,09, 0,09), I2: 0%). Houve diminuição do tempo de permanência hospitalar para POEM (MD: -0,6, 95% CI (-1,11, -0,09), P=0,02) e um aumento da redução média no escore de Eckardt em pacientes POEM (MD= -0,257, IC95%: (-0,512 a -0,002), P=0,048), com taxas similares de eventos adversos. CONCLUSÃO: O POEM demonstrou resultados semelhantes aos da miotomia a Heller por videolaparoscopia, com melhora da disfagia, do refluxo pós-procedimento e tempo cirúrgico, com o benefício de menor tempo de internação hospitalar. Portanto, o POEM pode ser considerado uma opção para pacientes com acalasia.

Governança global, regulamentação flexível e os ensaios clínicos na medicina regenerativa no Reino Unido e na União Europeia / Global Governance, Flexible Regulation and Clinical Trials in Regenerative Medicine in the United Kingdom and the European Union

Resumo A medicina regenerativa encontra-se em fase de desenvolvimento dos ensaios clínicos em terapias celulares (TC), na sua manufatura e na sua adoção gradual dentro dos sistemas de saúde. Entretanto, há uma série de lacunas e contradições na governança e regulamentação na área e o objetivo principal deste artigo é sua discussão dentro das tendências globais, já que esses processos afetam de modo substantivo a saúde coletiva global e encontram-se ainda escassamente resolvidos. O texto foca nos processos prevalentes nos ensaios clínicos com TC em duas lideranças internacionais, o Reino Unido e a União Europeia, utilizando a análise bibliográfica e de conteúdo. O texto conclui com uma discussão das principais vantagens e desvantagens para a saúde coletiva global da transição de um modelo científico de comprovação das novas terapias celulares para, eventualmente, outro baseado na inovação médica ou clínica. O último procede desde a fase pré-clínica com animais à aplicação das novas terapias a grupos pequenos de pacientes e, logo a seguir, a sua inserção no mercado. Muitas vezes, esse modelo se associa a flexibilidades regulatórias, a serem ilustradas no artigo, e especialmente desenhadas para aumentar a rapidez no desenvolvimento e aplicação das terapias.

Abstract Regenerative medicine is at present in a stage of development of clinical trials in cell therapies (CT), their manufacture and gradual adoption by health systems. However, there are several gaps and contradictions in governance and regulation in the area and the main aim of this article is their discussion within global trends, as these processes remain still ill- resolved while substantively affecting collective global health. The text focuses on an analysis of prevailing processes in clinical trials with CT by two leading actors, the United Kingdom, and the European Union, and is based upon bibliographical and content analyses. The article concludes with a discussion of the main advantages and disadvantages for collective global health of the transition from a conventional scientific model to test the new therapies to, eventually, one based on medical or clinical innovation. The latter proceeds from the pre-clinical research phase with animals to clinical trials with small groups of patients and subsequently, to the entrance of cell therapies into the market. Often this model is associated to flexible regulations, to be illustrated in the article, which are specifically designed to diminish time-lags between therapy development and its full application.

Use of dupilumab on the treatment of moderate-to-severe asthma: a systematic review

SUMMARY OBJECTIVE The objective of this article was to conduct a systematic review of the treatment of moderate-to-severe asthma by administrating Dupilumab. METHODS A search on the online databases EBSCO, Scielo, PubMed, Medline Bireme, Lilacs, and The New England Journal of Medicine was conducted, publications from 2010 to 2018 were selected. The inclusion criteria were articles which contained control groups, tested the validity of Dupilumab, and verified the response of patients through controlled tests. For the search of such articles, the following keywords were used: "Dupilumab", "asthma", "Bronchial Asthma" AND "Asthma, Bronchial" AND their correspondent in Portuguese "asma", "Asma brônquica" and "Asma brônquica". The exclusion criteria were literature reviews, news, articles without control groups, articles on different subjects, Dupilumab studies on other diseases, articles concerning asthma without the use of Dupilumab, and repeated articles on the databases were discarded. RESULTS The literature considers that the medication shows a good response for the treatment of moderate-to-severe asthma and assists in the improvement of lung function, aside from resulting in few side effects. It presents good efficacy, safety, and tolerance by patients. CONCLUSIONS Dupilumab is promising for the treatment of asthma, whereas conventional therapy is deemed to be insufficient. More additional studies are needed to confirm the long-term safety and effectiveness.

RESUMO OBJETIVO Este artigo teve como objetivo fazer uma revisão sistemática sobre o tratamento da asma moderada a grave, administrando Dupilumabe. MÉTODOS Foi realizada uma busca nas plataformas on-line Ebsco, SciELO, PubMed, Medline Bireme, Lilacs e New England Journal of Medicine. Foram selecionadas publicações de 2010 a 2018 referentes a artigos que continham grupos controle, que testaram a validade de Dupilumabe e verificaram a resposta dos pacientes por meio de testes controlados. Para a busca desses artigos, foram utilizadas as seguintes palavras-chave: "Dupilumab", "asthma", "Bronchial Asthma" and "Asthma, Bronchial". E o correspondente em português: "asma", "Asma brônquica" and "Asma brônquica". Os critérios de exclusão, revisões de literatura, notícias, artigos sem grupos de controle, artigos sobre diferentes assuntos, estudos de Dupilumabe sobre outras doenças, artigos sobre asma sem uso de Dupilumabe e artigos repetidos em plataformas de busca foram descartados. RESULTADOS A literatura aponta que a medicação apresenta boa resposta no tratamento da asma moderada a grave e auxilia na melhora da função pulmonar, além de resultar em poucos efeitos colaterais. Apresenta boa eficácia, segurança e tolerância pelos pacientes. CONCLUSÕES Dupilumabe é promissor para o tratamento da asma em que a terapia convencional se revela insuficiente. Maiores estudos adicionais são necessários para confirmar a segurança e a eficácia em longo prazo.

Análisis crítico de un ensayo clínico de no-inferioridad / Critical analysis of a noninferiority trial

In the era of diseases with highly efficacious treatments, the publication of randomized noninferiority clinical trials is increasingly frequent. However, users of medical literature are less familiar with this type of studies. The aim of this article is to give an introduction to the critical assessment of noninferiority clinical trials, through the solving of a therapeutic dilemma, which will be addressed through the analysis of a recently published trial of this type.

The efficacy and safety of ciclesonide for the treatment of perennial allergic rhinitis: a systematic review and meta-analysis / Eficácia e segurança da ciclesonida no tratamento da rinite alérgica perene: uma revisão sistemática e metanálise

Abstract Introduction: Allergic rhinitis is a chronic inflammatory disease which affects 1 out of 6 individuals. Perennial allergic rhinitis accounts for 40% of AR cases. Ciclesonide is one of the relatively new intranasal steroid for allergic rhinitis. Objective: The purpose of this study was to evaluate the efficacy and safety of ciclesonide in the treatment of perennial allergic rhinitis. Methods: We searched Pubmed, Scientific Citation Index, Embase, Clinical Trial Registries for randomized controlled trials and Cochrane Central Register of Controlled Trials to find out the randomized controlled Trial comparing ciclesonide with placebo for PAR. Results: Eight studies were included. In comparison with placebo groups, ciclesonide groups significantly decreased Reflective Total Nasal Symptom Score (MD = −0.56; 95% CI −0.72 to 0.39, p < 0.00001) with heterogeneity (p = 0.19, I2 = 24%), Instantaneous Total Nasal Symptom Score (MD = −0.57; 95% CI −0.75 to −0.39, p < 0.00001) with heterogeneity (p = 0.34, I2 = 11%). A significant effect for Reflective Nasal Symptom Score Subtotal (MD = −0.15; 95% CI −0.18 to −0.13, p < 0.00001) with heterogeneity (p = 0.12, I2 = 24%) was also demonstrated. Rhinoconjunctivitis quality of life questionnaire score (RQLQs) (MD = −0.27; 95% CI −0.39 to −0.15, p < 0.00001) with heterogeneity (p = 0.58, I 2 = 0%) in the treatment of ciclesonide was also significantly reduced. In addition, the difference in Treatment-Emergent Adverse Events between the two groups was not significant. Conclusion: Ciclesonide can improve perennial allergic rhinitis without increasing adverse events. Ciclesonide may be another valuable choice for perennial allergic rhinitis in the future.

Resumo Introdução: A rinite alérgica é uma doença inflamatória crônica que afeta um a cada seis indivíduos. A rinite alérgica perene é responsável por 40% dos casos de rinite alérgica. A ciclesonida é um dos corticosteroides intranasais mais novos para o tratamento dessa condição clínica. Objetivo: Avaliar a eficácia e segurança da ciclesonida no tratamento da rinite alérgica perene. Método: Uma busca foi feita nos bancos de dados Pubmed, Scientific Citation Index, Embase e Clinical Trial Registries por ensaios clínicos randomizados e Cochrane Central Register of Controlled Trials por estudos controlados randomizados que comparassem ciclesonida com placebo no tratamento da rinite alérgica perene. Resultados: Oito estudos foram incluídos. Em comparação com os grupos placebo, os grupos ciclesonida mostraram diminuição significante no escore do Reflective Total Nasal Symptom Score (DM = −0,56; IC 95%: −0,72 a −0,39, p < 0,00001) com heterogeneidade (p = 0,19, I2 = 24%), do Instantaneous Total Nasal Symptom Score (DM = −0,57; IC95%: −0,75 a −0,39, p < 0,00001) com heterogeneidade (p = 0,34, I2 = 11%). Um efeito significante no escore do Reflective Nasal Symptom Score Subtotal (DM = −0,15; IC 95%: −0,18 a −0,13, p < 0,00001) com heterogeneidade (p = 0,12, I2 = 24%) também foi demonstrado. O escore do Rhinoconjunctivitis Quality of Life Questionnaire score (RQLQs) (DM = −0,27; IC 95%: −0,39 a −0,15, p < 0,00001) com heterogeneidade (p = 0,58, I2 = 0%) também foi significantemente reduzido no tratamento com ciclesonida. Além disso, a diferença em relação aos eventos adversos emergentes do tratamento entre os dois grupos não foi significante. Conclusão: A ciclesonida pode melhorar a rinite alérgica perene sem aumentar os eventos adversos. Esse fármaco pode ser outra opção valiosa para a rinite alérgica perene no futuro.

Efectividad de ejercicio físico intervalado de alta intensidad en las mejoras del fitness cardiovascular, muscular y composición corporal en adolescentes: una revisión / High intensity interval training in teenagers

This review analyzes the effects of high intensity interval training (HIIT) on muscle and cardiovascular fitness and body composition in teenagers. A search was carried out in international databases, finding 145 papers and selecting five for analysis. In all the reviewed manuscripts, peak oxygen uptake improved after HIIT. In the three manuscripts that measured muscle strength, it also increased. We conclude that HIIT improves muscle strength and cardiovascular fitness in school age children. A 12 weeks protocol with three 12-minute sessions per week would be ideal.

Impact of immediately loaded implant-supported maxillary full-arch dental prostheses: a systematic review

Abstract The immediate loading of implant-assisted fixed prostheses in edentulous maxillae may achieve favorable success rates with reduced treatment time. An evidence summary of clinical trials is key to recommend loading protocols in these cases. Objectives To compare immediately loaded, fully implant-supported complete dentures to early and conventional/delayed loading in the edentulous maxillae of adult patients by a systematic review of controlled clinical trials (CCT). Methodology CCTs reports were identified up to January 17, 2019 from Cochrane Oral Health Group's Trial register, Cochrane Central Register of controlled trials (CENTRAL), MEDLINE (Ovid), BIOSIS, EMBASE, CINAHL, Web of Science, and DARE. Two independent reviewers screened titles/abstracts and confirmed inclusion using full texts. Data were extracted and quality assessed (Cochrane Risk of Bias tool) independently and in duplicate. Study heterogeneity prevented pooling by meta-analysis. Results Out of 1,052 candidate studies, four CCTs were included. Two trials had patient satisfaction as an outcome: (1) A randomized trial compared immediately and early loaded fixed dentures and found more satisfaction with the first after 12 months; (2) A non-randomized study found better satisfaction with immediate fixed dentures compared to conventional loading after 3 months (no more at 12 months). Regarding implant success and prosthetic complications, three trials did not report significant differences comparing immediate loading to other protocols. Conclusions This review found weak evidence of differences between immediate load and other loading regimens, regarding patient satisfaction and maintenance events/adversities. The potential of immediate loading for favorable results in edentulous maxillae reinforces the need for well-designed RCTs, for solid clinical guidelines. Registration number CRD42018071316 (PROSPERO database).

Efeito de suplemento dietético à base de fitosterol associado à Dieta Passo II do NCEP sobre o LDL em crianças e adolescentes dislipidêmicos: Ensaio clínico randomizado cruzado, duplo cego / Effect of phytosterol dietary supplement associated with NCEP step II diet on LDL in dyslipidemic children and adolescents: double-blind, cross-over trial

Apesar das evidências do efeito dos esteróis vegetais entre adultos dislipidêmicos , dados sobre o uso de cápsulas com fitosteróis em crianças são limitados. O presente estudo teve como objetivo avaliar o efeito de suplemento dietético à base de fitosterol associado à dieta Passo II no NCEP no LDL de crianças e adolescentes dislipidêmicos em um hospital universitário no Rio de Janeiro. Deste modo, foi realizado um ensaio clínico randomizado cruzado, duplo cego com uso de placebo durante vinte semanas utilizando como critério de inclusão valores de lipoproteína de baixa densidade (LDL) maoir que 110mg/dL. Cinquenta e três crianças com idade entre 7 e 14 anos foram recrutadas, das quais 40 eram elegíveis para participar do estudo, sendo submetidas ao período do run in durante quatro semanas onde receberam orientações para seguir as recomendações da dieta Passo II do NCEP. Ao final do run in trinta e uma crianças e adolescentes permaneceram com LDL superior a 110mg/dL e foram randomizados para participar do estudo. O grupo intervenção recebeu cápsulas contendo 1,5mg/dia de fitosteróis na forma livre e esterificada e o grupo controle recebeu cápsulas contendo 2g/dia de óleo de girassol durante o período de oito semanas. Os participantes foram submetidos ao período do wash out durante quatro semanas. Foram coletados bioquímicos incluindo glicose, colesterol total, LDL, lipoproteína de alta densidade (HDL), triglicerídeos e dados antropométricos nas semanas 0, 8, 12 e 20. Foi realizada análise por intenção de tratar através dos modelos generalizados lineares mistos, usando o software SAS. Ao final do run in 9 participantes reduziram o LDL à menos 110 mg/dL, representando 25% da amostra. Foi observado ainda a prevalência de obesidade em 66,7% dos participantes que reduziram o LDL no run in. Após oito semanas, os participantes do grupo intervenção reduziram o LDL em 6,5%, enquanto o grupo controle apresentou redução de 1,7%. O HDL aumentou em 15,2% no grupo intervenção e 0,1% no grupo controle. 35% dos participantes do grupo intervenção alcançaram os valores considerados desejáveis para o LDL. Contudo, nenhuma destas variações foi significativamente diferente entre os grupos. Apesar do estudo não observar diferença estatisticamente significativa nas reduções do LDL entre os grupos o uso de suplementos a base de fitosteróis por meio de cápsulas mostrou-se seguro no tratamento das dislipidemias na infância e adolescência. Nota-se ainda que a dieta Passo II do NCEP mostrou-se efetiva na redução do LDL nas crianças e adolescentes obesos, sendo este um resultado relevante para redução do risco cardiovascular. Os resultados apresentados no presente estudo reforçam a necessidade de novos estudos envolvendo suplementação de fitosterol por meio de cápsulas, para que estes possam ser comparados.

Even with the evidence of lipid-lowering effect of plant sterols among dyslipidemic adults, the use of capsules with phytosterols in children is limited. The objective of the present study was evaluate the effect of phytosterol-based dietary supplementation associated with the Step II diet NCEP, in LDL of dyslipidemic children and adolescents at university hospital in Rio de Janeiro. A randomized, double-blind, crossover clinical trial with placebo was realized for 20 weeks. Thirty-one children and adolescents between seven and fourteen years old participated in the study. The intervention group received capsules containing 1.5g / day of phytosterols in the free and esterified form and the control group received capsules containing 2g / day of sunflower oil during the eight-week period. The partitipants were submited to wash out during four weeks. Biochemical data were collected including glucose, total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides; anthropometric measures at weeks 0, 8, 12 and 20. Intention-to-treat analysis were performed, using the proc mixed procedure in SAS. In the end of run in 9 participats reduced LDL above 110mg/dL, representing 25% sample size. The prevalence of obesity was also observed in 66.7% of the participants who reduced LDL in the run-in. Intention-to-treat analysis were performed, using the proc mixed procedure in SAS. After eight weeks, participants in the intervention group reduced LDL by 6.48%, while the control group had a reduction of 1.68%. HDL increased by 15.2% in the intervention group and 0.07% in the control group. 35% of participants in the intervention group achieved values considered desirable for LDL. However, none of these variations was significantly different between groups. Even the study did not achieve significantly statistic diference on reduction of LDL between the groups, the intake of phytosterol´s capsule showed safe on dislipidemic in child and youth treatment. It is also noted that the step II diet of the NCEP proved to be effective in reducing LDL in obese children and adolescents, which is a revealing result for reducing cardiovascular risk.The results presented in the present study reinforce the need for new studies involving supplementation of phytosterol with capsules, so that they can be compared.

Efeito do exercício físico nas funções cognitivas e motoras de idosos com doença de Alzheimer: uma revisão / Effect of physical exercise on the cognitive and motor functions of the older people with Alzheimer's disease: a review

OBJETIVO: Analisar o efeito do exercício físico nos aspectos cognitivos e motores de idosos com doença de Alzheimer. MÉ- TODOS: Foi realizada busca nas seguintes bases de dados: Pub- Med, MEDLINE, LILACS, Periódico CAPES e Web of Science ™, no período de 2011 a 2016. Foram utilizadas as seguintes palavras-chave: "physical exercise", "exercise", "training", "motor intervention", "aged", "older", "elderly", "Alzheimer's dementia", "Alzheimer's disease", "Alzheimer", "Cognition", "cognitive performance", "motor" e "motor performance". RESULTADOS: Além da busca em base de dados, foi realizada busca manual nas listas de referências dos artigos selecionados. Foram encontrados três estudos que preencheram todos os critérios de inclusão adotados neste trabalho. Todos demonstraram melhoras tanto no desempenho cognitivo quanto motor de idosos com doença de Alzheimer submetidos a exercícios físicos. CONCLUSÃO: Observou-se melhora e/ou manutenção das funções cognitivas e motoras em todos os estudos. Apesar disso, não houve consenso sobre o tipo de exercício, sua intensidade e a duração adequada para idosos com doença de Alzheimer. (AU)

OBJECTIVE: To analyze the effect of physical exercise on the cognitive and motor aspects of older people with Alzheimer's disease. METHODS: The following databases were searched: Pubmed, Medline, Lilacs, CAPES Journal, and Web of Science from 2011 to 2016. The following keywords were used: "Physical exercise", "exercise", "training "" Motor intervention "," Aged "," older "," elderly","Alzheimer's dementia","Alzheimer's disease","Alzheimer", "Cognition", "cognitive performance", "Motor". RESULTS: In addition to database search, a manual search was performed in the reference lists of the selected articles. Three studies were found that fulfilled all the inclusion criteria adopted in this study. All of them demonstrated improvements in both the cognitive and motor performance of older people with Alzheimer's disease undergoing physical exercises. CONCLUSION: Improvement and/or maintenance of cognitive and motor functions was observed in all studies. Despite this, there was no consensus on the type of exercise, its intensity and adequate duration for elderly people with Alzheimer's disease. (AU)

Ensayos clínicos publicados en el Boletín Médico del Hospital Infantil de México: un análisis crítico / Clinical trials published in the Boletín Médico del Hospital Infantil de México: a critical analysis

Resumen Introducción: El ensayo clínico es la manera más rigurosa de conducir los experimentos en seres humanos. Desde su introducción en investigación biomédica se han implementado cambios en el modo de establecer las bases para el diagnóstico, pronóstico y la terapéutica en la práctica clínica. Se han realizado estudios para identificar los ensayos clínicos publicados en diferentes áreas médicas, pero hasta el momento ninguno había identificado los ensayos clínicos publicados en el Boletín Médico del Hospital Infantil de México (BMHIM). El objetivo de este trabajo fue identificar y describir los ensayos clínicos controlados (ECC) publicados en el BMHIM. Métodos: Se realizó búsqueda manual y sistemática en cada uno de los números y volúmenes del BMHIM de 1968 a 2016. Se registraron los ECC para obtener sus principales características. Adicionalmente, se evaluó su calidad metodológica mediante la herramienta de riesgo de sesgo. Los resultados se presentan de forma descriptiva, gráfica y temporal. Resultados: Se revisaron 73 números con 363 volúmenes, analizando 4925 artículos. La proporción de ECC identificados en el BMHIM fue del 1% (67/4925). En general, los ensayos clínicos se realizaron en el contexto nacional, en el tercer nivel de atención, con un tamaño de muestra reducido, y las intervenciones farmacológicas fueron las más utilizadas. La calidad metodológica de los estudios fue baja, con alto riesgo de sesgo. Conclusiones: Los ensayos clínicos representan el 1% de todos los artículos de investigación originales publicados en el BMHIM. Aún existen áreas de investigación pediátrica, las cuales requieren del desarrollo de ECC para mejorar la práctica clínica, así como para elevar la calidad de la investigación.

Abstract Background: Controlled clinical trials (CCT) are the study design with the highest accuracy and evidence level. From its introduction in biomedical research, changes have been implemented in the way of establishing the basis for diagnosis, prognosis and treatment in clinical practice. Studies to identify published CCTs regarding different medical fields have been carried out. To date, none of them has identified the clinical trials that have been published in the Boletín Médico del Hospital Infantil de México (BMHIM). The aim of this study was to identify and describe the controlled clinical trials published in the BMHIM. Methods: A manual and systematic search was performed in each of the volumes of the BMHIM from 1968 to 2016. CCTs were recorded to obtain their main characteristics. Additionally, their methodological quality was assessed through the "risk of bias" tool. Results are presented in a descriptive, graphic and time-based manner. Results: In total, 73 issues with 363 volumes were reviewed, and 4925 articles were analyzed. The proportion of CCTs identified in the BMHIM was 1% (67/4925). In general, clinical trials were performed in the national context and in the third-level of medical care. CCTs also presented reduced sample sizes; pharmacological interventions were the most frequent. The methodological quality of the studies was low with a high risk of bias. Conclusions: Clinical trials represented 1% of all the original research articles published in the BMHIM. There are still pediatric research fields that require CCTs to be developed in order to improve clinical practice, as well as to increase the quality of the research.

Terapêutica anestésica para o alívio da dor aguda pós-colecistectomia videolaparoscópica: revisão sistemática / Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review

RESUMO A terapêutica inadequada da dor pós-operatória em colecistectomia videolaparoscópica pode levar a mobilização tardia, insatisfação do paciente, atraso na alta hospitalar e desenvolvimento de dor crônica. Objetivou-se identificar qual a melhor estratégia terapêutica disponível ao anestesiologista na terapia da dor aguda pós-operatória de pacientes submetidos à colecistectomia videolaparoscópica eletiva. Trata-se de revisão sistemática que incluiu 36 artigos completos indexados nas bases de dados Medline, Scopus, Web of Science e LILACS, com recorte temporal de cinco anos (2012 a 2016), resultantes de estudos controlados e randomizados que foram submetidos à análise qualitativa. Em uma proposta de analgesia multimodal, é importante considerar as contraindicações, os efeitos adversos, a dose e o momento ideal das intervenções. Utiliza-se fármacos não opioides, como anti-inflamatórios não esteroides (AINES)/inibidores da ciclo-oxigenase-2 (COX-2), gabapentina/pregabalina, antagonistas dos receptores N-methyl-D-aspartato (NMDA), entre outras. Os opioides podem ser utilizados em doses baixas associadas ou não a terapia multimodal e/ou ficarem restritos aos casos em que a analgesia multimodal não opioide for insuficiente. Conclui-se que não há consenso sobre qual a melhor estratégia analgésica a ser implementada na dor aguda pós-operatória da colecistectomia videolaparoscópica, o que requer sua aplicabilidade de forma individualizada, com base nas evidências científicas encontradas na literatura. Aponta-se como contribuições para o ensino e a prática profissional o enriquecimento teórico das opções medicamentosas analgésicas disponíveis para a terapêutica da dor pós-operatória de pacientes submetidos à colecistectomia videolaparoscópica eletiva, além de alertar a equipe para considerar os efeitos adversos das intervenções implementadas.

ABSTRACT Inappropriate therapy of postoperative pain in laparoscopic cholecystectomy may lead to late mobilization, patient dissatisfaction, delayed hospital discharge, and chronic pain development. Our objective was to identify the best therapeutic strategy available to the anesthesiologist for the acute postoperative pain of patients submitted to elective laparoscopic cholecystectomy. This is a systematic review that included 36 complete articles indexed in the Medline, Scopus, Web of Science and LILACS databases, with a five-year time cut (2012 to 2016), resulting from controlled and randomized studies that were submitted to qualitative analysis. In a proposal for multimodal analgesia, it is important to consider the contraindications, adverse effects, dose and optimal timing of interventions. Non-opioid drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs)/cyclooxygenase-2 (COX-2) inhibitors, gabapentin/pregabalin, N-methyl-D-aspartate (NMDA) receptor antagonists, and others. Opioids may be used at low doses associated with multimodal therapy or are restricted to cases where non-opioid multimodal analgesia is insufficient. We conclude that there is no consensus as to the best analgesic strategy to be implemented in the acute postoperative pain of laparoscopic cholecystectomy, which requires its applicability in an individualized way, based on the scientific evidence found in the literature. As contribution to medical learning and practice, we point out the theoretical enrichment of the analgesic drug options available for the therapy of postoperative pain in patients submitted to elective laparoscopic cholecystectomy, and alert the team to consider the adverse effects of the interventions implemented.

Comparative efficacy and safety of contact force-sensing catheter and second-generation cryoballoon ablation for atrial fibrillation: a meta-analysis

This meta-analysis compared the efficacy and safety of the contact force (CF)-sensing catheter and second-generation cryoballoon (CB) ablation for treating atrial fibrillation (AF). Six controlled clinical trials comparing ablation for AF using a CF-sensing catheter or second-generation CB were identified from PubMed, EMBASE, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. The procedure duration was significantly lower in the CB group compared with that in the CF group [mean difference (MD)=29.4; 95%CI=17.84-40.96; P=0.01], whereas there was no difference between the groups for fluoroscopy duration (MD=0.59; 95%CI=-4.48-5.66; P=0.82). Moreover, there was no difference in the incidence of non-lethal complications (embolic event, tamponade, femoral/subclavian hematoma, arteriovenous fistula, pulmonary vein stenosis, phrenic nerve palsy, and esophageal injury) between the CB and the CF groups (8.38 vs 5.35%; RR=0.66; 95%CI=0.37-1.17; P=0.15). Transient phrenic nerve palsy occurred in 17 of 326 patients (5.2%) of the CB group vs none in the CF group (RR=0.12; 95%CI=0.03-0.43; P=0.001). A comparable proportion of patients in CF and CB groups suffered from AF recurrence during the 12-month follow-up after a single ablation procedure [risk ratio (RR)=1.03; 95%CI=0.78-1.35; P=0.84]. AF ablation using CF-sensing catheters and second-generation CB showed comparable fluoroscopy duration and efficacy (during a 12-month follow-up), with shorter procedure duration and different complications in the CB group.