Abstract Objectives: Bicuspid aortic valve (BAV) is an important aetiology of aortic stenosis and the use of transcatheter aortic valve implantation (TAVI) has not been fully explored in this cohort. This systematic review and meta-analysis compared the outcomes of TAVI in stenotic BAV against tricuspid aortic valve (TAV). Methods: An electronic literature search was performed in PubMed, MEDLINE, EMBASE, and Scopus to identify all studies comparing TAVI in stenotic BAV versus TAV. Only studies comparing TAVI in BAV versus TAV were included, without any limit on the study date. Primary endpoints were 30-day and 1-year mortality, while secondary endpoints were postoperative rates of stroke, acute kidney injury (AKI), and permanent pacemaker (PPM) requirement. A trial sequential analysis (TSA) was performed for all endpoints to understand their significance. Results: Thirteen studies met the inclusion criteria (917 BAV and 3079 TAV patients). The BAV cohort was younger (76.8±7.43 years vs. 78.5±7.12 years, P=0.02), had a higher trans-aortic valve gradient (P=0.02), and larger ascending aortic diameters (P<0.0001). No significant difference was shown for primary (30-day mortality [P=0.45] and 1-year mortality [P=0.41]) and secondary endpoints (postoperative stroke [P=0.49], AKI [P=0.14], and PPM requirement [P=0.86]). The BAV group had a higher rate of significant postoperative aortic regurgitation (P=0.002). TSA showed that there was sufficient evidence to conclude the lack of difference in PPM requirements, and 30-day and 1-year mortality between the two cohorts. Conclusion: TAVI gives satisfactory outcomes for treating stenotic BAV and should be considered clinically.

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

El protocolo de un ensayo clínico es la base para planificar, ejecutar, publicar y evaluar el ensayo. Sin embargo, los protocolos y las guías que existen para su elaboración varían enormemente en cuanto a su calidad y contenido. En este artículo se describe la elaboración sistemática y el alcance de la Declaración SPIRIT 2013 (denominada así por la sigla en inglés de Standard Protocol items: Recommendations for Interventional Trials o Elementos estándares de un protocolo: recomendaciones para los ensayos de intervención), una guía en la que se establecen los contenidos mínimos que debe tener el protocolo de un ensayo clínico. La lista de comprobación de la declaración SPIRIT, que consta de 33 elementos, se aplica a los protocolos de todos los ensayos clínicos y se centra más en el contenido que en el formato. En esta lista se recomienda hacer una descripción completa de lo que se ha planificado, aunque no se establece cómo diseñar o ejecutar un ensayo. Al brindar orientación sobre los contenidos fundamentales, las recomendaciones SPIRIT procuran facilitar la redacción de protocolos de alta calidad. El cumplimiento de las recomendaciones SPIRIT debería mejorar la transparencia y la exhaustividad de los protocolos de los ensayos en beneficio de los investigadores, los participantes, los pacientes, los patrocinadores, los financiadores, los comités de ética de la investigación o las juntas de revisión institucionales, los revisores, las revistas biomédicas, los registros de ensayos, los formuladores de políticas, los organismos reguladores y otras partes interesadas clave.

摘要 问题 在资源贫乏的环境中，艾滋病（AIDS）相关的巨细胞病毒（CMV）视网膜炎仍然是被疏忽的失明原因。主要问题在于缺乏在患者接受护理并诊断了所有其他机会性感染的临床环境中诊断CMV视网膜炎的能力。 方法 我们开发和实...

Résumé Problème La rétinite à cytomégalovirus (CMV) liée au syndrome d'immunodéficience acquise (SIDA) continue à être une source négligée de cécité dans les zones à faibles ressources. Le principal problème est la capacité insuffisante à diagnostiquer la rétinite à CMV dans les établissements cliniques où les patients reçoivent des soins et où les autres infections opportunistes sont diagnostiquées. Approche Nous avons développé et mis en œ...

Резюме Проблема Цитомегаловирусный (ЦМВ) ретинит, ассоциированный с синдромом приобретенного иммунодефицита (СПИД...

Problem Acquired immunodeficiency syndrome (AIDS)-related cytomegalovirus (CMV) retinitis continues to be a neglected source of blindness in resource-poor settings. The main issue is lack of capacity to diagnose CMV retinitis in the clinical setting where patients receive care and all other opportunistic infections are diagnosed. Approach We developed and implemented a four-day workshop to train clinicians working in human immunodeficiency virus (HIV) clinics how to perform binocular indirect ophthalmoscopy and diagnose CMV retinitis. Workshops comprised both classroom didactic instruction and direct clinical eye examinations in patients with advanced AIDS. Between 2007 and 2013, 14 workshops were conducted in China, Myanmar and the Russian Federation. Local setting Workshops were held with local clinicians at HIV clinics supported by nongovernmental organizations, public-sector municipal hospitals and provincial infectious disease referral hospitals. Each setting had limited or no access to locally- trained ophthalmologists, and an HIV-infected population with advanced disease. Relevant changes Clinicians learnt how to do binocular indirect ophthalmoscopy and to diagnose CMV retinitis. One year after the workshop, 32/38 trainees in Myanmar did systematic eye examination for early diagnosis of CMV retinitis as standard care for at-risk patients. In China and the Russian Federation, the success rates were lower, with 10/15 and 3/5 trainees, respectively, providing follow-up data. Lessons learnt Skills necessary for screening and diagnosis of CMV retinitis can be taught in a four-day task-oriented training workshop. Successful implementation depends on institutional support, ongoing training and technical support. The next challenge is to scale up this approach in other countries.

ملخص المشكلة ما زال التهاب شبكية العين الناجم عن الفيروسة المضخمة للخلايا ذات الصلة بمتلازمة العوز المناع...

Resumen Situación La retinitis por citomegalovirus (CMV) relacionada con el síndrome de inmunodeficiencia adquirida (SIDA) sigue siendo una fuente desatendida de ceguera en entornos con recursos insuficientes. El problema principal es la falta de capacidad para diagnosticar la retinitis por CMV en el entorno clínico donde los pacientes reciben atención y se diagnostican el resto de infecciones oportunistas. Enfoque Desarrollamos y pusimos en práctica un taller de cuatro días para formar a médicos que trabajan en clínicas en las que se trata el virus de inmunodeficiencia humana (VIH) en la realización de la oftalmoscopia indirecta binocular y en el diagnóstico de la retinitis por CMV. Los talleres incluyeron una instrucción didáctica en el aula y exámenes oftalmológicos clínicos directos en pacientes con SIDA avanzado. Entre 2007 y 2013, se llevaron a cabo 14 talleres en China, Myanmar y la Federación de Rusia. Marco regional Se realizaron talleres con médicos locales en las clínicas del VIH con el apoyo de organizaciones no gubernamentales, hospitales municipales públicos y hospitales provinciales de enfermedades infecciosas. Todos los emplazamientos presentaban un acceso a oftalmólogos formados a nivel local limitado o nulo y una población de personas infectadas por el VIH con enfermedad avanzada. Cambios importantes Los médicos aprendieron a realizar la oftalmoscopia indirecta binocular y a diagnosticar la retinitis por CMV. Un año después del taller, 32/38 aprendices en Myanmar realizaban el examen oftalmológico sistemático para el diagnóstico precoz de la retinitis por CMV como parte de la atención estándar para los pacientes en riesgo. En China y la Federación de Rusia, las tasas de éxito fueron menores, con 10/15 y 3/5 aprendices, respectivamente, que proporcionaban datos de seguimiento. Lecciones aprendidas Las competencias necesarias para la detección y el diagnóstico de la retinitis por CMV pueden enseñarse en un taller de formación especializada de cuatro días de duración. El éxito de la puesta en práctica depende del apoyo institucional, de la formación continua y de la asistencia técnica. El próximo desafío consistirá en extender este enfoque a otros países.

This article analyzes alternative forms of mediation available to foreign enterprises for resolving their commercial disputes in China, highlighting the defining characteristics of each form of mediation. Institutional commercial mediation is an out-of-court private mediation process conducted through a professional mediation institution. This form of mediation is consistent with the usual characteristics of modern mediation, but for various reasons it is underutilized by foreign enterprises. Despite some individual lapses, the med-arb procedure (i.e. mediation procedure within an arbitration) is generally in line with international practice. Court mediation remains the most problematic form of conciliatory dispute resolution method. Local protectionism, the policy preference for settling lawsuits and the absence of judicial independence have made court mediation structurally deficient. As long as the principle of voulntariness is upheld, mediation is a cost-effective way for resolving commercial disputes in China.

Este artículo analiza las alternativas de que dispone una empresa extranjera para resolver sus disputas comerciales en China. La falta de independencia judicial y la tendencia de los tribunales populares hacia el proteccionismo de las empresas locales, vuelven preferible acudir a las Soluciones Alternativas de Confictos. El arbitraje en CIETAC cumple con los estándares internacionales. Pero si una de las partes no cumple voluntariamente el laudo, surgen problemas al intentar el cumplimiento forzado ante los tribunales chinos porque estos pueden rechazar la ejecución. La mediación aparece como la mejor opción en China. Los acuerdos alcanzados en una mediación comercial suelen ser cumplidos volutariamente, esquivando las dificultades de la ejecución judicial. Además, el Centro de Mediación y la mediación durante un arbitraje en CIETAC (med-arb) también cumplen estándares internacionales, superando los prejuicios que podría tener un observador externo.

Nós revisamos evidências epidemiológicas relacionadas à exposição ocupacional a pesticidas e à incidência de câncer no Estudo da Saúde Agrícola (AHS). Descobertas relacionadas com a vida-dia e / ou intensidade do tempo de vida-dia do uso de agrotóxicos são o foco principal desta revisão, porque estas medidas permitem a avaliação do potencial das relações de exposição-resposta. A maioria dos 32 pesticidas examinados não foram fortemente associados à incidência de câncer em aplicadores de pesticidas. Um aumento da taxa e padrões de resposta-exposição positivos foram reportados em 12 pesticidas registrados atualmente nos Estados Unidos e Canadá. A classificação de exposição incorreta também é uma preocupação para o AHS e pode limitar a análise dos padrões de resposta-exposição. É necessário um acompanhamento contínuo para clarificar as associações reportadas até hoje. Em particular, é necessária uma avaliação mais profunda dos pesticidas registrados.

We reviewed epidemiologic evidence related to occupational pesticide exposures and cancer incidence in the Agricultural Health Study (AHS) cohort. Studies were identified from the AHS publication list available on a Medline/PubMed database search in March 2009. Findings related to lifetime-days and/or intensity-weighted lifetime-days of pesticide use are the primary focus of this review, because these measures allow for the evaluation of potential exposureresponse relationships. Most of the 32 pesticides examined were not strongly associated with cancer incidence in pesticide applicators. Increased rate ratios and positive exposureresponse patterns were reported for 12 pesticides currently registered in Canada and/or the United States. Exposure misclassification is also a concern in the AHS and may limit the analysis of exposureresponse patterns. Epidemiologic evidence outside the AHS remains limited with respect to most of the observed associations, but animal toxicity data support the biological plausibility of relationships observed six pesticides. Continued follow-up is needed to clarify associations reported to date. In particular, further evaluation of registered pesticides is warranted.

Nós revisamos evidências epidemiológicas relacionadas à exposição ocupacional a pesticidas e à incidência de câncer no Estudo da Saúde Agrícola (AHS). Descobertas relacionadas com a vida-dia e / ou intensidade do tempo de vida-dia do uso de agrotóxicos são o foco principal desta revisão, porque estas medidas permitem a avaliação do potencial das relações de exposição-resposta. A maioria dos 32 pesticidas examinados não foram fortemente associados à incidência de câncer em aplicadores de pesticidas. Um aumento da taxa e padrões de resposta-exposição positivos foram reportados em 12 pesticidas registrados atualmente nos Estados Unidos e Canadá. A classificação de exposição incorreta também é uma preocupação para o AHS e pode limitar a análise dos padrões de resposta-exposição. É necessário um acompanhamento contínuo para clarificar as associações reportadas até hoje. Em particular, é necessária uma avaliação mais profunda dos pesticidas registrados.

We reviewed epidemiologic evidence related to occupational pesticide exposures and cancer incidence in the Agricultural Health Study (AHS) cohort. Studies were identified from the AHS publication list available on a Medline/PubMed database search in March 2009. Findings related to lifetime-days and/or intensity-weighted lifetime-days of pesticide use are the primary focus of this review, because these measures allow for the evaluation of potential exposureresponse relationships. Most of the 32 pesticides examined were not strongly associated with cancer incidence in pesticide applicators. Increased rate ratios and positive exposureresponse patterns were reported for 12 pesticides currently registered in Canada and/or the United States. Exposure misclassification is also a concern in the AHS and may limit the analysis of exposureresponse patterns. Epidemiologic evidence outside the AHS remains limited with respect to most of the observed associations, but animal toxicity data support the biological plausibility of relationships observed six pesticides. Continued follow-up is needed to clarify associations reported to date. In particular, further evaluation of registered pesticides is warranted.