Peritonitis diverticular: ¿Qué nos enseñó Ladies Trial? Análisis metodológico de su diseño, aplicación y resultados / Diverticular peritonitis: What did LADIES Trial teach us? Analysis of design, application and results

Contexto y Antecedentes: LADIES TRIAL es uno de los ensayos más importantes referidos a peritonitis diverticular. A pesar de este y otros ensayos publicados, aún se debate cuáles son los procedimientos adecuados para cada escenario de peritonitis diverticular, haciendo necesaria una revisión profunda de la metodología empleada en los ensayos para validar u objetar sus conclusiones. Objetivos: Analizar la metodología empleada en el diseño, aplicación, análisis de resultados y conclusiones de sus publicaciones. Secundariamente, colaborar en el mejoramiento de la investigación de la peritonitis diverticular y facilitar el análisis del tema por parte de los lectores. Métodos: Se analizaron las partes centrales de toda investigación, desde la pregunta de investigación, elaboración de hipótesis, operacionalización de variables y diseño del ensayo, análisis estadístico de resultados y conclusiones. Se buscaron errores, sesgos y debilidades que pudiesen objetar los hallazgos del estudio. Resultados: LADIES se trató de un estudio randomizado, abierto con análisis de superioridad según intención de tratar modificada en aquellos casos de incumplimiento de los criterios de inclusión y exclusión. Su diseño fue en general correcto, aunque en su aplicación se detectaron errores, debilidades y sesgos. En cuanto a resultados LOLA mostró que en Hinchey III el lavado laparoscópico tiene mayor morbimortalidad temprana que la sigmoidectomía, con un tiempo operatorio menor. Por su parte, DIVA mostró que en Hinchey III y IV la anastomosis primaria tiene mayor sobrevida libre de ostomía con menor morbilidad, combinando la cirugía inicial y cierre ostomía, respecto de la operación de Hartmann. Conclusiones: El no haber llegado al tamaño de muestra calculado hizo que solo grandes diferencias consiguieran significancia estadística. Las bajas frecuencias de eventos adversos acentuaron este problema metodológico. La especialización de los centros y cirujanos intervinientes, como la exclusión de pacientes hemodinámicamente inestables o bajo corticoterapia comprometieron su validación externa.

Background: LADIES TRIAL is considered one of the most important trials related to diverticular peritonitis. Its protocol and results were published in 2010, 2015, 2017, and 2019. Despite this one and other published trials, the proper procedures for each diverticular peritonitis scenario are still being debated, a thorough review of the methodology used in this trial is necessary to validate or reject their conclusions. Aim: To analyze the methodology used in the design, application, analysis of results, and conclusions of all LADIES TRIAL publications. Secondly, to collaborate in the improvement of the research about diverticular peritonitis and to facilitate its analysis by the readers. Methods: The central parts of a research trial were analyzed, from the research question, hypothesis development, operationalization of variables and trial design, statistical analysis of results, to conclusions. Errors, biases and weaknesses were searched for to try and challenge the trial's findings. Results: LADIES was a randomized, open-label, superiority trial analyzed according to intention to treat modified in cases of non-compliance with the inclusion-exclusion criteria. Its design was generally correct, although errors, weaknesses, and biases were detected in its application. Regarding results, LOLA showed that, in Hinchey 3, laparoscopic lavage has a higher rate in early morbidity and mortality than sigmoidectomy, but with a shorter operative time. For its part, DIVA showed that, in Hinchey 3 and 4, the primary anastomosis has higher ostomy-free survival with less morbidity, combining the initial surgery and ostomy closure, compared to the Hartmann procedure. Conclusions: Not having reached the sample size calculated in its design implies that only large effect differences achieved statistical significance. The low frequencies of adverse events accentuated this methodological problem. The specialization of the intervening centers and surgeons, the exclusion of hemodynamically unstable patients or patients undergoing steroid therapy, compromised the external validation of their findings.

Collaborative quality improvement in the congenital heart defects: development of the assist consortium and a preliminary surgical outcomes report

Abstract Objective: ASSIST is the first Brazilian initiative in building a collaborative quality improvement program in pediatric cardiology and congenital heart disease. The purposes of this manuscript are: (a) to describe the development of the ASSIST project, including the historical, philosophical, organizational, and infrastructural components that will facilitate collaborative quality improvement in congenital heart disease care; (b) to report past and ongoing challenges faced; and (c) to report the first preliminary data analysis. Methods: A total of 614 operations were prospectively included in a comprehensive online database between September 2014 and December 2015 in two participating centers. Risk Adjustment for Congenital Heart Surgery (RACHS) 1 and Aristotle Basic Complexity (ABC) scores were obtained. Descriptive statistics were provided, and the predictive values of the two scores for mortality were calculated by multivariate logistic regression models. Results: Many barriers and challenges were faced and overcome. Overall mortality was 13.4%. Independent predictors of in-hospital death were: RACHS-1 categories (3, 4, and 5/6), ABC level 4, and age group (≤ 30 days, and 30 days - 1 year). Conclusion: The ASSIST project was successfully created over a solid base of collaborative work. The main challenges faced, and overcome, were lack of institutional support, funding, computational infrastructure, dedicated staff, and trust. RACHS-1 and ABC scores performed well in our case mix. Our preliminary outcome analysis shows opportunities for improvement.

Plastia valvar mitral com mitraclip(mr): seleção de pacientes, técnica de implante e resultados clínicos / Mitral valve repair with mitraclip(mr): seletion of patients, implant technique and clinical results

A regurgitação mitral (RM) é a doença valvar mais prevalente nos Estados Unidos e sua prevalência aumenta a cada ano devido ao envelhecimento populacional. Independentemente da etiologia, a RM sintomática grave cursa com prognóstico desfavorável. O procedimento cirúrgico ainda é o tratamento padrão para essa patologia; porém, como vários pacientes não são submetidos à cirurgia devido ao alto risco, o tratamento percutâneo com MitraClip surgiu como opção viável. A segurança, eficácia e durabilidade do reparo valvar percutâneo com MitraClip já foram demonstradas em estudos randomizados e, com isso, sua indicação vem-se expandindo

Mitral regurgitation (MR) is the most prevalent valve disease in the United States and its prevalence is increasing every year due to population aging. Regardless of the etiology, severe symptomatic MR presents with an unfavorable prognosis. The surgical procedure is still the standard treatment for this pathology, however, various patients do not receive this treatment because of a high surgical risk, and percutaneous treatment with MitraClip has emerged as a viable option. The safety, efficacy, and durability of percutaneous valve repair with the MitraClip have already been demonstrated in randomized trials, and as a result, its indication has been expanding

Prospective registration and results disclosure of clinical trials in the Americas: a roadmap toward transparency / Registro prospectivo y comunicación de los resultados de los ensayos clínicos en la Región de las Américas

The objective of this article is to propose a roadmap toward transparency of clinical trials in the Americas by their prospective registration and results disclosure. This will broaden access to more complete and accurate data and facilitate evidence-informed decision-making and participation in research. Consequently, it should have a positive impact on people's health and should promote trust in health research. Existing initiatives were identified, registration of trials was analyzed following the World Health Organization (WHO) standards on trial registration, and a roadmap is proposed to address the gaps in advancing transparency. The analysis shows that, in spite of numerous regional and country initiatives, clinical trials taking place in nonEnglish-speaking parts of the Americas are underregistered. A roadmap is proposed to enhance research governance and good research practice by improving the transparency of clinical trials. The proposed roadmap includes strategies for implementing WHO international standards for trial registration, for developing international standards of public disclosure of trial results, and for a potential role of the Pan American Health Organization.

El objetivo de este artículo es proponer una hoja de ruta que fomente la transparencia de los ensayos clínicos en la Región de las Américas mediante el registro prospectivo de los ensayos y la comunicación de sus resultados. Esto brindará un acceso más amplio a datos más completos y exactos, y facilitará la toma de decisiones fundamentada en datos probatorios y la participación en las investigaciones clínicas. En consecuencia, debería tener una repercusión positiva en la salud de la población y promover la confianza en la investigación médica. Después de identificar las iniciativas existentes y analizar los registros de ensayos clínicos según las normas de la Organización Mundial de la Salud (OMS) para el registro de ensayos, se propone una hoja de ruta para salvar las brechas y promover la transparencia. El análisis demuestra que, a pesar de las numerosas iniciativas regionales y de los distintos países, hay un subregistro de los ensayos clínicos que tienen lugar en zonas no anglohablantes de la Región de las Américas. Se propone una hoja de ruta para mejorar la gobernanza en la investigación y las buenas prácticas clínicas mediante una mayor transparencia en los ensayos clínicos. La hoja de ruta propuesta incluye estrategias para ejecutar las normas internacionales de la OMS sobre el registro de los ensayos clínicos, formular normas internacionales de comunicación pública de los resultados de los ensayos, y una función potencial de la Organización Panamericana de la Salud.

The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders: recruitment, assessment instruments, methods for the development of multicenter collaborative studies and preliminary results / Consórcio Brasileiro de Pesquisa em Transtornos do Espectro Obsessivo-Compulsivo: recrutamento, instrumentos de avaliação, métodos para o desenvolvimento de estudos colaborativos multicêntricos e resultados preliminares

OBJECTIVE: To describe the recruitment of patients, assessment instruments, implementation, methods and preliminary results of The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders, which includes seven university sites. METHOD: This cross-sectional study included a comprehensive clinical assessment including semi-structured interviews (sociodemographic data, medical and psychiatric history, disease course and comorbid psychiatric diagnoses), and instruments to assess obsessive-compulsive (Yale-Brown Obsessive-Compulsive Scale and Dimensional Yale-Brown Obsessive-Compulsive Scale), depressive (Beck Depression Inventory) and anxious (Beck Anxiety Inventory) symptoms, sensory phenomena (Universidade de São Paulo Sensory Phenomena Scale), insight (Brown Assessment Beliefs Scale), tics (Yale Global Tics Severity Scale) and quality of life (Medical Outcome Quality of Life Scale Short-form-36 and Social Assessment Scale). The raters' training consisted of watching at least five videotaped interviews and interviewing five patients with an expert researcher before interviewing patients alone. The reliability between all leaders for the most important instruments (Structured Clinical Interview for DSM-IV, Dimensional Yale-Brown Obsessive-Compulsive Scale, Universidade de São Paulo Sensory Phenomena Scale) was measured after six complete interviews. RESULTS: Inter-rater reliability was 96 percent. By March 2008, 630 obsessive-compulsive disorder patients had been systematically evaluated. Mean age (±SE) was 34.7 (±0.51), 56.3 percent were female, and 84.6 percent Caucasian. The most prevalent obsessive compulsive symptom dimensions were symmetry and contamination. The most common comorbidities were major depression, generalized anxiety and social anxiety disorder. The most common DSM-IV impulsive control disorder was skin picking. CONCLUSION: The sample was composed mainly by Caucasian individuals, unmarried, with some kind...

OBJETIVO: Descrever o recrutamento de pacientes, instrumentos de avaliação, métodos para o desenvolvimento de estudos colaborativos multicêntricos e os resultados preliminares do Consórcio Brasileiro de Pesquisa em Transtornos do Espectro Obsessivo-Compulsivo, que inclui sete centros universitários. MÉTODO: Este estudo transversal incluiu entrevistas semi-estruturadas (dados sociodemográficos, histórico médico e psiquiátrico, curso da doença e diagnósticos psiquiátricos comórbidos) e instrumentos que avaliam os sintomas do transtorno obsessivo-compulsivo (Escala para Sintomas Obsessivo-Compulsivos de Yale-Brown e Escala Dimensional para Sintomas Obsessivo-Compulsivos de Yale-Brown), sintomas depressivos (Inventário de Depressão de Beck), sintomas ansiosos (Inventário de Ansiedade de Beck), fenômenos sensoriais (Escala de Fenômenos Sensoriais da Universidade de São Paulo), juízo crítico (Escala de Avaliação de Crenças de Brown), tiques (Escala de Gravidade Global de Tiques de Yale) e qualidade de vida (questionário genérico de avaliação de qualidade de vida, Medical Outcome Quality of Life Scale Short-form-36 e Escala de Avaliação Social). O treinamento dos avaliadores consistiu em assistir cinco entrevistas filmadas e entrevistar cinco pacientes junto com um pesquisador mais experiente, antes de entrevistar pacientes sozinhos. A confiabilidade entre todos os líderes de grupo para os instrumentos mais importantes (Structured Clinical Interview for DSM-IV, Dimensional Yale-Brown Obsessive-Compulsive Scale, Universidade de São Paulo Sensory Phenomena Scale ) foi medida após seis entrevistas completas. RESULTADOS: A confiabilidade entre avaliadores foi de 96 por cento. Até março de 2008, 630 pacientes com transtorno obsessivo-compulsivo tinham sido sistematicamente avaliados. A média de idade (±SE) foi de 34,7 (±0,51), 56,3 por cento eram do sexo feminino e 84,6 por cento caucasianos. Os sintomas obsessivo-compulsivos mais prevalentes foram...

Evaluation of web-based annotation of ophthalmic images for multicentric clinical trials.

An Internet browser-based annotation system can be used to identify and describe features in digitalized retinal images, in multicentric clinical trials, in real time. In this web-based annotation system, the user employs a mouse to draw and create annotations on a transparent layer, that encapsulates the observations and interpretations of a specific image. Multiple annotation layers may be overlaid on a single image. These layers may correspond to annotations by different users on the same image or annotations of a temporal sequence of images of a disease process, over a period of time. In addition, geometrical properties of annotated figures may be computed and measured. The annotations are stored in a central repository database on a server, which can be retrieved by multiple users in real time. This system facilitates objective evaluation of digital images and comparison of double-blind readings of digital photographs, with an identifiable audit trail. Annotation of ophthalmic images allowed clinically feasible and useful interpretation to track properties of an area of fundus pathology. This provided an objective method to monitor properties of pathologies over time, an essential component of multicentric clinical trials. The annotation system also allowed users to view stereoscopic images that are stereo pairs. This web-based annotation system is useful and valuable in monitoring patient care, in multicentric clinical trials, telemedicine, teaching and routine clinical settings.

Coordination of international multicenter studies: governance and administrative structure

A well-conducted multicenter study needs to assure standardization, uniformity of procedures, high data quality, and collaboration across sites. This manuscript describes the organization and dynamics of multicenter studies, focusing on governance and administrative structures among countries of diverse cultures. The organizational structure of a multicenter study is described, and a system for oversight and coordination, along with roles and responsibilities of participants in the multicenter study, are presented. The elements of a governance document are also reviewed, along with guidelines and policies for effective collaboration. The experience of an ongoing multi-country collaboration, the World Studies of Abuse in the Family Environment (WorldSAFE), illustrates the implementation of these guidelines. It is essential that multicenter studies have an objective coordinating center and that the investigators jointly develop a written governance document to enable collaboration and preserve collegiality among participating investigators