Intravitreal antivascular endothelial growth factor in diabetic macular oedema: scoping review of clinical practice guidelines recommendations.

BACKGROUND: Diabetic macular oedema (DME) is a worldwide major cause of low vision and blindness. Intravitreal antivascular endothelial growth factor (anti-VEGF) constitutes an effective treatment. Clinical practice guidelines (CPGs) are synthesis documents that seek to improve patient care. OBJECTIVES: To identify CPGs that make anti-VEGF recommendations for DME and to assess their reporting quality and their considerations when making recommendations. ELIGIBILITY CRITERIA: CPGs published between December 2009 and December 2019 that make explicit anti-VEGF recommendations in DME. SOURCES OF EVIDENCE: Sensitive search strategy in Embase, Google Scholar and hand-searching on 165 websites. METHODS: We extracted information from each CPG with a previously piloted sheet. Two independent authors applied theAppraisal of Guidelines, Research and Evaluation tool (AGREE-II) assessment for each CPG. RESULTS: The 21 included CPGs recommend anti-VEGF for DME, but there is a wide variation among the clinical aspects included, such as location of DME, visual acuity required, therapeutical alternatives or discontinuation. Most have a poor quality of reporting based on the AGREE-II tool assessment, especially those developed by ophthalmological societies, those that have an exclusive content about DME, and those where most of their authors disclose conflict of interest (COI) with pharmaceutical industry or where their authors did not report COIs. Pharmaceutical-sponsored CPGs did not use systematic reviews (SRs) to support their recommendations. Very few recommendations consider patient values and preferences, equity, acceptability and feasibility of the intervention. CONCLUSIONS: Most of the CPGs that made recommendations of anti-VEGF for DME have poor quality of reporting, do not use SRs and do not consider patients' values and preferences.

Evaluación de la terapia de reproducción médicamente asistida en 9 años: estudio de cohorte retrospectivo / Medically assisted reproductive therapy assessment in 9 years: retrospective cohort study

OBJETIVO: Describir las tasas de recién nacidos vivos (RNV) y embarazo de la terapia de reproducción médicamente asistida de baja complejidad del Centro de Reproducción Humana de la Universidad de Valparaíso, Chile. MÉTODO: Estudio retrospectivo de todos los ciclos de estimulación ovárica controlada con inseminación intrauterina (IIU) completados, entre los años 2011 y 2019. Se evaluaron las características clínicas basales y los resultados en IIU homólogas y heterólogas según el ciclo inseminado, la causa de infertilidad, el rango etario y el índice de masa corporal (IMC). El desenlace principal fue la tasa de RNV por ciclo inseminado. RESULTADOS: Se estudiaron 1415 ciclos en 700 parejas. La tasa acumulativa de RNV fue del 19,6%, un 18,3% en IIU homóloga y un 39,0% en IIU heteróloga. La tasa de RNV fue del 10,0% al primer ciclo, del 5,8% al segundo ciclo y del 3,7% al tercer o más ciclos. Al separar por IIU heteróloga, esta aumenta al 24,4% al primer ciclo y al 14,6% al segundo ciclo. La tasa de RNV es significativamente mejor en pacientes menores de 35 años (23,7%) y con IMC < 29 (20,8%). CONCLUSIONES: El tratamiento de baja complejidad en pacientes infértiles es una opción terapéutica vigente con una aceptable tasa de RNV por ciclo inseminado. Los resultados están influenciados por la edad y por el IMC.

OBJECTIVE: To describe the rates of live newborns (LNB) and pregnancy of the low complexity therapy of the Centre for Human Reproduction of Universidad de Valparaíso, Chile. METHOD: Retrospective study of all cycles of controlled ovarian stimulation with intrauterine insemination (IUI) completed between 2011-2019. The baseline clinical characteristics and results in homologous and heterologous IUI were evaluated according to inseminated cycle, cause of infertility, age range and body mass index (BMI). The main outcome was rate of LNB per inseminated cycle. RESULTS: 1415 cycles were studied in 700 couples. The cumulative rate of LNB was 19.6%, 18.3% in homologous IUI and 39.0% in heterologous IUI. The LNB rate was 10.0% at the first cycle, 5.8% at the second cycle, 3.7% at the third or more cycles. When separating by heterologous IUI, it increases to 24.4% in the first cycle and 14.6% in the second cycle. The LNB rate is significantly better in patients under 35 years of age (23.7%) and with a BMI less than 29 (20.8%). CONCLUSIONS: Treatment of low complexity in selected infertile patients is a current therapeutic option with an acceptable rate of LNB per inseminated cycle. The results are influenced by age and BMI.

Graphical Representation of Overlap for OVErviews: GROOVE tool.

Overlap of primary studies among systematic reviews (SRs) is one of the main methodological challenges when conducting overviews. If not assessed properly, overlapped primary studies may mislead findings, since they may have a major influence either in qualitative analyses or in statistical weight. Moreover, overlapping SRs may represent the existence of duplicated efforts. Matrices of evidence and the calculation of the overall corrected covered area (CCA) are appropriate methods to address this issue, but they seem to be not comprehensive enough. In this article we present Graphical Representation of Overlap for OVErviews (GROOVE), an easy-to-use tool for overview authors. Starting from a matrix of evidence, GROOVE provides the number of included primary studies and SRs included in the matrix; the absolute number of overlapped and non-overlapped primary studies; and an overall CCA assessment. The tool also provides a detailed CCA assessment for each possible pair of SRs (or "nodes"), with a graphical and easy-to-read representation of these results. Additionally, it includes an advanced optional usage, incorporating structural missingness in the matrix. In this article, we show the details about how to use GROOVE, what results it achieves and how the tool obtains these results. GROOVE is intended to improve the overlap assessment by making it easier, faster, and more friendly for both authors and readers. The tool is freely available at http://doi.org/10.17605/OSF.IO/U2MS4 and https://es.cochrane.org/es/groovetool.

Embolización de la arteria renal: serie de casos y revisión de la literatura / Renal artery embolization: case series and literature review

Resumen Introducción: La embolización de arteria renal (EAR) es un procedimiento percutáneo que ocluye la arteria renal, con la consecuente isquemia del territorio vascular. Sus indicaciones más comunes son la hematuria y el manejo paliativo en cáncer renal metastásico. A pesar del desarrollo técnico y de la experiencia progresiva, los estudios incluyen un número reducido de pacientes y en nuestro país se revisan casos aislados. Objetivo: Describir la experiencia en el Servicio de Salud Valparaíso San Antonio y revisar la literatura existente. Materiales y Método: Realizamos un estudio descriptivo de los pacientes sometidos a EAR por anemia severa secundaria a hematuria, durante los años 2012 a 2020. Posteriormente, realizamos una revisión de la literatura en PubMed, hasta abril de 2020. Resultados: Incluimos 9 pacientes, 6 (66,7%) hombres y 3 (33,3%) mujeres. La mediana de edad fue de 69 años (RIC = 18). La principal causa de la hematuria fue cáncer renal avanzado (7 pacientes). No hubo complicaciones, y se logró éxito clínico en todos los pacientes. Nuestra búsqueda de literatura arrojó 571 referencias y 24 cumplieron con nuestros criterios de elegibilidad. La edad de los pacientes y las causas subyacentes de hematuria fueron variadas. La menor tasa de éxito clínico fue de 65%, sin embargo, 15 estudios (62,5%) reportaron un éxito igual o mayor al 90%. Seis estudios reportaron más de un 10% de pacientes con alguna complicación. Conclusión: Nuestros resultados y la evidencia revisada muestran que la EAR parece ser segura y eficaz en el manejo de anemia severa secundaria a hematuria.

Introduction: Renal artery embolization (RAE) is a percutaneous procedure that occludes the renal artery, with consequent ischemia of the vascular territory. The most common indications include hematuria and palliation for metastatic renal cancer. Despite technical development and progressive experience, studies include a small number of patients and few cases have been published in our country. Aim: To share our experience at Valparaíso-San Antonio Health Service and to review the existing literature. Materials and Method: We performed a retrospective descriptive review of medical records of patients with severe anemia due to hematuria managed with RAE, between 2012 and 2020. Subsequently, we conducted a literature search in PubMed, from inception until April 2020. Results: We included 9 patients. There were 6 (66.7%) males and 3 (33.3%) females with a median age of 69 years (IQR = 18). Main cause of hematuria was advanced kidney cancer (7 patients). There were no complications and clinical success was achieved in all patients. Our literature search yielded 571 references, 24 met our eligibility criteria. The age of patients and the underlying causes of hematuria were varied. The lowest clinical success rate was 65%, however, 15 studies (62.5%) reported a success equal to or greater than 90%. Six studies reported more than 10% of patients with complications. Conclusión: Our results and the studies reviewed show that RAE appears to be safe and effective in the management of patients with severe anemia due to hematuria.

Key concepts for searching evidence: an introduction for healthcare professionals. / Conceptos clave para la búsqueda de evidencia: una introducción para profesionales de la salud.

The currently abundant bibliography on healthcare can make the search process an exhausting and frustrating experience. For this reason, it is essential to learn the basic concepts of research question formulation, information sources, and search strategies to make this process more efficient and user-friendly. The search strategy is an iterative process that allows the incorporation of tools and terms in the strategy design to optimize evidence retrieval. Each strategy varies according to the questions, the language used, the source of information accessed, and the available tools. This article is part of a methodological series of narrative reviews on biostatistics and clinical epidemiology. This narrative review describes the essential elements for developing a literature search strategy and identifying the relevant evidence concerning a clinical question through familiar and accessible sources (such as Google and Google Scholar), as well as search interfaces and technical-scientific databases focused on biomedical knowledge (PubMed and The Cochrane Library).

La abundante bibliografía disponible actualmente sobre una determinada temática puede hacer que el proceso de búsqueda se vuelva una experiencia extenuante y frustrante. Por esta razón, resulta necesario tener presente los conceptos básicos sobre formulación de preguntas, fuentes de información y estrategias de búsqueda a fin de hacer más eficaz y amigable a este proceso. La generación de una estrategia de búsqueda es un proceso iterativo que permite incorporar herramientas y términos en el diseño de esta para optimizar la recuperación de evidencia. Cada estrategia variará según la pregunta formulada, el lenguaje utilizado, la fuente de información a la cual se accede y las herramientas utilizadas que se encuentren disponibles en dichas fuentes. Este artículo es parte de una serie metodológica de revisiones narrativas sobre aspectos relacionados con bioestadística y epidemiología clínica. El objetivo de esta revisión es detallar y brindar múltiples herramientas para la búsqueda aplicada al ámbito clínico, analizando paso a paso su formulación y aplicación tanto en fuentes comunes y accesibles (como Google y Google Académico), como en interfaces de búsqueda y bases de datos centradas en conocimiento biomédico de carácter técnico-científico (PubMed y The Cochrane Library).

Efficacy of systemic oncological treatments in patients with advanced pancreatic cancer at high risk of dying in the short or medium-term: overview of systematic reviews.

BACKGROUND: Patients with advanced pancreatic cancer (PC) have a high risk of dying in the short or medium-term. This overview aimed to assess the evidence regarding systemic oncological treatments (SOT) versus supportive care for advanced PC. METHODS: We searched for systematic reviews (SRs) in MEDLINE, Embase, The Cochrane Library, Epistemonikos, and PROSPERO. Two authors assessed eligibility independently. Data extraction and methodological quality assessment were conducted by one author and cross-checked by another one. We evaluated the overlap of primary studies, performed a de novo meta-analysis, and assessed the certainty of evidence. Primary outcomes were overall survival (OS), quality of life (QoL), functional status (FS), and toxicity. RESULTS: We identified three SRs that assessed SOT versus supportive care in patients with advanced PC. All SRs had critically low methodological quality. At 12 months, OS improved with chemotherapy, radiotherapy followed by chemotherapy, and immunotherapy, but the certainty of the evidence supporting these findings is very low. The evidence on chemotherapy is very uncertain about its effects on QoL; it suggests a slight increase in toxicity and little to no difference in FS. The evidence on immunotherapy is very uncertain about its effects in toxicity. CONCLUSIONS: The identified evidence is very uncertain about the benefits of oncological treatments on OS and QoL in patients with advanced PC with a high risk of dying in the short or medium-term, so its use should be proposed only to selected patients. Further studies that include a thorough assessment of patient-centred outcomes are needed.

Patient decision aids for adults with advanced chronic kidney disease with a medical recommendation to start dialysis: a scoping review protocol.

OBJECTIVE: This review will identify and describe the content and assess the quality of available decision aids aimed at adults with advanced chronic kidney disease with medical indication to start dialysis who need to choose one of the two dialysis modalities. INTRODUCTION: The lack of evidence regarding the superiority of the different options for dialysis, hemodialysis, and peritoneal dialysis, indicated in advanced chronic kidney disease, makes the shared decision-making process especially important. INCLUSION CRITERIA: We will include decision aids from published studies and non-published material aimed at adults with advanced chronic kidney disease. METHODS: We will perform searches in MEDLINE, CINAHL, Embase, PsycINFO, the Cochrane Library, and Epistemonikos. In addition, we will search unpublished studies in OpenGrey, ClinicalTrials.gov, and Open Access Theses and Dissertations. We will also identify decision aids through a specific search in Google and by searching websites of nephrology societies or associations. We will include decision aids in English or Spanish aimed at adults with advanced chronic kidney disease with medical indication to start dialysis. Two independent reviewers will screen, select, and extract the data. General aspects and attributes of the decision aids will be collected. Their quality will be evaluated, and their recommendations for implementation in clinical practice will be analyzed.

The GRADE approach, Part 2: Evidence to decision frameworksoutlining decision-making in health. / Metodología GRADE, parte 2: de la evidencia a la decisión—esquematizando la toma de decisiones en salud.

The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology provides a framework for assessing the certainty of the evidence and making recommendations. The Evidence to Decision Framework (EtD) is a transparent and structured system for formulating health recommendations. Once the problem is identified and the certainty of the evidence is assessed, EtD provides several criteria for formulating a recommendation. These criteria include the trade-off between benefits and harms, patients values and preferences, acceptability, feasibility, resource use, and impact on equity. The resulting recommendations may differ in strength (strong or weak) and direction (for or against). The process is transparent, allowing other users to adjust the framework of recommendations by modifying the criteria to fit the desired context through an adaptation-adoption process. Given the extensive information available on EtD and the GRADE methodology in general, this narrative review seeks to explain the main concepts involved in decision-making in health by using simplified and friendly descriptions, accompanied by practical examples, thus facilitating its understanding by inexperienced readers.

La metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) provee un método para valorar la certeza de la evidencia y para la formulación de recomendaciones que ayuden en la toma de decisiones en salud. Una vez identificado el problema y valorada la certeza de la evidencia, los marcos de la evidencia a la decisión (Evidence to decision frameworks o EtD) utilizan un sistema transparente y estructurado para formular recomendaciones, en que se consideran criterios como el balance entre beneficios y daños, valores y preferencias de los pacientes, aceptabilidad, factibilidad, equidad y uso de recursos para establecer una recomendación en salud. Esta podrá tener distinta fuerza (fuertes o débiles) y dirección (a favor o en contra). La transparencia de este proceso permite que otros usuarios puedan adaptar un marco de recomendaciones según el contexto deseado, mediante un proceso de adaptación-adopción. Ante la extensa información disponible sobre marcos de la evidencia a la decisión y la metodología GRADE en general, esta revisión narrativa busca entregar una explicación acerca de los principales conceptos involucrados en la toma de decisiones en salud, a través de descripciones simplificadas, amigables y con ejemplos prácticos, con el fin de facilitar su entendimiento por lectores inexpertos.

Graphical representation of the body of the evidence: the essentials for understanding the evidence gap map approach. / Graficando el cuerpo de la evidencia: lo esencial para comprender el enfoque de los mapas de brecha de evidencia.

The significant increase in scientific evidence production has led to the creation of methods to facilitate evidence review and synthesis. This has turned, this has resulted in the emergence of different designs depending on the reviews objective. Evidence gap maps constitute a novel approach for literature review. They are thematic collections of a broad field of evidence, using a systematic search strategy that identifies gaps in knowledge and engages, early on, the target audience to design a friendly graphic product. Evidence maps are a tool to be considered in the roster of options available for research funders in that they are particularly useful for evidence-based decision-making and evidence-based policy development. The most commonly used formats to display the findings of evidence gap search designs are the bubble plot and the intervention-outcome framework. This article corresponds to the sixth of a series of narrative reviews on general topics of biostatistics and clinical epidemiology. The purpose of this review is to describe the principal features of evidence gap maps, highlighting their main objectives and utility, exploring the most commonly used mapping formats, and comparing this approach with other evidence synthesis designs.

El gran aumento en la producción de evidencia científica ha llevado a la creación de métodos para facilitar su revisión y síntesis, surgiendo distintos diseños según el objetivo principal que se busque cumplir. Los mapas de brecha de evidencia constituyen un enfoque novedoso de revisión de literatura. Corresponden a colecciones temáticas de un amplio campo de evidencia, utilizando una estrategia de búsqueda sistemática que destaca por identificar brechas o lagunas en el cuerpo de la evidencia disponible y por involucrar tempranamente a la audiencia definida como blanco para el diseño de un producto gráfico amigable. Se han establecido como una herramienta a considerar para guiar la agenda y el financiamiento de futuras investigaciones, y como apoyo en la toma de decisiones y en la creación de políticas basadas en evidencia. Los formatos más utilizados para representar sus hallazgos son el gráfico de burbujas y la grilla intervención-desenlace. Este artículo corresponde al sexto de una serie de revisiones narrativas acerca de tópicos generales en bioestadística y epidemiología clínica, y tiene por objetivo describir las características generales de los mapas de brecha de evidencia, destacar sus principales objetivos y utilidades, explorar los formatos de mapeo más utilizados y comparar este enfoque con otras propuestas de síntesis.

The Perspectives of Patients with Chronic Diseases and Their Caregivers on Self-Management Interventions: A Scoping Review of Reviews.

BACKGROUND: Self-management (SM) interventions are supportive interventions systematically provided by healthcare professionals, peers, or laypersons to increase the skills and confidence of patients in their ability to manage chronic diseases. We had two objectives: (1) to summarise the preferences and experiences of patients and their caregivers (informal caregivers and healthcare professionals) with SM in four chronic diseases and (2) to identify and describe the relevant outcomes for SM interventions from these perspectives. METHODS: We conducted a mixed-methods scoping review of reviews. We searched three databases until December 2020 for quantitative, qualitative, or mixed-methods reviews exploring patients' and caregivers' preferences or experiences with SM in type 2 diabetes mellitus (T2DM), obesity, chronic obstructive pulmonary disease (COPD), and heart failure (HF). Quantitative data were narratively synthesised, and qualitative data followed a three-step descriptive thematic synthesis. Identified themes were categorised into outcomes or modifiable factors of SM interventions. RESULTS: We included 148 reviews covering T2DM (n = 53 [35.8%]), obesity (n = 20 [13.5%]), COPD (n = 32 [21.6%]), HF (n = 38 [25.7%]), and those with more than one disease (n = 5 [3.4%]). We identified 12 main themes. Eight described the process of SM (disease progression, SM behaviours, social support, interaction with healthcare professionals, access to healthcare, costs for patients, culturally defined roles and perceptions, and health knowledge), and four described their experiences with SM interventions (the perceived benefit of the intervention, individualised care, sense of community with peers, and usability of equipment). Most themes and subthemes were categorised as outcomes of SM interventions. CONCLUSION: The process of SM shaped the perspectives of patients and their caregivers on SM interventions. Their perspectives were influenced by the perceived benefit of the intervention, the sense of community with peers, the intervention's usability, and the level of individualised care. Our findings can inform the selection of patient-important outcomes, decision-making processes, including the formulation of recommendations, and the design and implementation of SM interventions.

Angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers for COVID-19: A living systematic review of randomized clinical trials.

OBJECTIVE: This living systematic review aims to provide a timely, rigorous, and continuously updated summary of the evidence available on the role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in the treatment of patients with COVID-19. DATA SOURCES: We conducted searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralized repository in L·OVE (Living OVerview of Evidence), which retrieves articles from multiple sources such as PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, among other pre-print and protocols repositories. In response to the COVID-19 emergency, L·OVE (Living OVerview of Evidence) was adapted to expand the range of evidence and customized to group all COVID-19 evidence in one place on a daily search basis. The search covered a period of time up to July 31, 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: We adapted an already published standard protocol for multiple parallel living systematic reviews to this question's specificities. We included randomized trials evaluating the effect of either suspension or indication of angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers as monotherapy, or in combination versus placebo or no treatment in patients with COVID-19. We searched for randomized trials evaluating the effect of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers versus placebo or no treatment in patients with COVID-19. Two reviewers independently screened each study for eligibility, extracted data, and assessed the risk of bias. We pooled the results using meta-analysis and applied the GRADE system to assess the certainty of the evidence for each outcome. We will resubmit results every time the conclusions change or whenever there are substantial updates. RESULTS: We screened 772 records, but none was considered for eligibility. We identified 55 ongoing studies, including 41 randomized trials evaluating angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for patients with COVID-19. CONCLUSIONS: We did not find a randomized clinical trial meeting our inclusion criteria, and hence there is no evidence for supporting the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in the treatment of patients with COVID-19. A substantial number of ongoing studies would provide valuable evidence to inform researchers and decision-makers in the near future. PROSPERO REGISTRATION NUMBER: CRD42020182495. PROTOCOL PREPRINT DOI: 10.31219/osf.io/vp9nj.

OBJETIVO: Esta revisión sistemática viva tiene como objetivo proporcionar un resumen oportuno, riguroso y continuamente actualizado de la evidencia disponible sobre el rol de los inhibidores de la enzima convertidora de angiotensina (iECA) y los bloqueadores del receptor de angiotensina II (ARA-II) en el tratamiento de pacientes con COVID-19. FUENTES DE DATOS: Realizamos búsquedas en PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), literatura gris y en el repositorio centralizado L·OVE (Living OVerview of Evidence) que recupera artículos de múltiples fuentes como PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, entre otros repositorios de preprints y protocolos. En respuesta a la emergencia de COVID-19, L·OVE (Living OVerview of Evidence) se adaptó para ampliar el rango de información que cubre y se personalizó para agrupar toda la evidencia en torno a COVID-19 en un solo lugar, en una base de búsqueda diaria. La búsqueda cubrió el período hasta el 31 de julio de 2020. CRITERIOS DE ELEGIBILIDAD PARA LA SELECCIÓN DE ESTUDIOS Y MÉTODOS: Adaptamos un protocolo común ya publicado para múltiples revisiones sistemáticas vivas paralelas a las especificidades de esta pregunta. Se incluyeron ensayos aleatorizados que evaluaban el efecto de la suspensión o la indicación de inhibidores de la enzima convertidora de angiotensina o bloqueadores de los receptores de angiotensina II, como monoterapia o en combinación, versus placebo o ningún tratamiento, en pacientes con COVID-19. Se buscaron ensayos aleatorizados que evaluaran el efecto de los inhibidores de la enzima convertidora de angiotensina/bloqueadores del receptor de angiotensina II versus placebo o ningún tratamiento en pacientes con COVID-19. Dos revisores examinaron de forma independiente la elegibilidad de cada estudio, extrajeron los datos y evaluaron el riesgo de sesgo. Los resultados se agruparon mediante un metanálisis y se aplicó GRADE para evaluar la certeza de la evidencia para cada resultado. Cada vez que cambien las conclusiones o hayan actualizaciones sustanciales, volveremos a enviar un reporte. RESULTADOS: Analizamos 772 artículos, pero ninguno cumplió con los criterios de inclusión. Identificamos 55 estudios en curso, incluidos 41 ensayos aleatorizados que evaluaban inhibidores de la enzima convertidora de angiotensina/bloqueadores del receptor de angiotensina II para pacientes con COVID-19. CONCLUSIONES: No encontramos ningún ensayo clínico aleatorizado que cumpliera con nuestros criterios de inclusión y, por lo tanto, no hay pruebas que respalden el papel de los inhibidores de la enzima convertidora de angiotensina y los bloqueadores de los receptores de angiotensina II en el tratamiento de pacientes con COVID-19. Identificamos un número considerable de estudios en curso que podría proporcionar evidencia valiosa para informar a los investigadores y a los responsables de la toma de decisiones en un futuro próximo.

Maternal and perinatal outcomes related to COVID-19 and pregnancy: An overview of systematic reviews.

INTRODUCTION: Evidence about coronavirus disease 2019 (COVID-19) and pregnancy has rapidly increased since December 2019, making it difficult to make rigorous evidence-based decisions. The objective of this overview of systematic reviews is to conduct a comprehensive analysis of the current evidence on prognosis of COVID-19 in pregnant women. MATERIAL AND METHODS: We used the Living OVerview of Evidence (L·OVE) platform for COVID-19, which continually retrieves studies from 46 data sources (including PubMed/MEDLINE, Embase, other electronic databases, clinical trials registries, and preprint repositories, among other sources relevant to COVID-19), mapping them into PICO (population, intervention, control, and outcomes) questions. The search covered the period from the inception date of each database to 13 September 2020. We included systematic reviews assessing outcomes of pregnant women with COVID-19 and/or their newborns. Two authors independently screened the titles and abstracts, assessed full texts to select the studies that met the inclusion criteria, extracted data, and appraised the risk of bias of each included systematic review. We measured the overlap of primary studies included among the selected systematic reviews by building a matrix of evidence, calculating the corrected covered area, and assessing the level of overlap for every pair of systematic reviews. RESULTS: Our search yielded 1132 references. 52 systematic reviews met inclusion criteria and were included in this overview. Only one review had a low risk of bias, three had an unclear risk of bias, and 48 had a high risk of bias. Most of the included reviews were highly overlapped among each other. In the included reviews, rates of maternal death varied from 0% to 11.1%, admission to intensive care from 2.1% to 28.5%, preterm deliveries before 37 weeks from 14.3% to 61.2%, and cesarean delivery from 48.3% to 100%. Regarding neonatal outcomes, neonatal death varied from 0% to 11.7% and the estimated infection status of the newborn varied between 0% and 11.5%. CONCLUSIONS: Only one of 52 systematic reviews had a low risk of bias. Results were heterogeneous and the overlap of primary studies was frequently very high between pairs of systematic reviews. High-quality evidence syntheses of comparative studies are needed to guide future clinical decisions.

Macrolides for the treatment of COVID-19: a living, systematic review. / Macrólidos para el tratamiento de COVID-19: Una revisión sistemática viva.

OBJECTIVE: This living, systematic review aims to provide a timely, rigorous, and continuously updated summary of the evidence available on the role of macrolides for treating patients with COVID-19. DESIGN: A living, systematic review. DATABASE: We conducted searches in the centralized repository L·OVE (Living OVerview of Evidence). L·OVE is a platform that maps PICO questions to evidence from the Epistemonikos database. In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it covers and customized to group all COVID-19 evidence in one place. Today it is maintained through regular searches in 39 databases. METHODS: We included randomized trials evaluating the effect of macrolides as monotherapy or in combination with other drugs versus placebo or no treatment in patients with COVID-19. Randomized trials evaluating macrolides in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomized studies in COVID-19 were searched in case we found no direct evidence from randomized trials. Two reviewers independently screened each study for eligibility, extracted data, and assessed the risk of bias. Measures included all-cause mortality; the need for invasive mechanical ventilation; extracorporeal membrane oxygenation, length of hospital stay, respiratory failure, serious adverse events, time to SARS-CoV-2 RT-PCR negativity. We applied the GRADE approach to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates. RESULTS: The search in the L·OVE platform retrieved 424 references. We considered 260 as potentially eligible and were reviewed in full texts. We included one randomized clinical trial that evaluated the use of azithromycin in combination with hydroxychloroquine compared to hydroxychloroquine alone in hospitalized patients with COVID 19. The estimates for all outcomes evaluated resulted in insufficient power to draw conclusions. The quality of the evidence for the main outcomes was low to very low. CONCLUSIONS: Macrolides in the management of patients with COVID 19 showed no beneficial effects compared to standard of care. The evidence for all outcomes is inconclusive. Larger trials are needed to determine the effects of macrolides on pulmonary and other outcomes in COVID-19 patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registration number: CRD42020181032 Protocol preprint DOI: 10.31219/osf.io/rvp59.

OBJETIVO: Proporcionar un resumen oportuno, riguroso y continuamente actualizado de la evidencia disponible sobre el papel de los macrólidos para el tratamiento de pacientes con COVID-19. DISEÑO: Revisión sistemática viva. BASE DE DATOS: La búsqueda de evidencia se realizó en el repositorio centralizado L·OVE (Living OVerview of Evidence) COVID-19; una plataforma que mapea las preguntas PICO para identificar la evidencia en 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 hoy se mantiene a través de búsquedas regulares en 39 bases de datos. MÉTODOS: Se incluyeron estudios experimentales que evaluaban el efecto de los macrólidos, como monoterapia o en combinación con otros fármacos, versus placebo o ningún tratamiento en pacientes con sospecha o confirmación de COVID-19. Se buscó identificar experimentos clínicos aleatorizados que evaluaran macrólidos en infecciones causadas por otros coronavirus, como MERS-CoV y SARS-CoV. Dos revisores examinaron de forma independiente la elegibilidad de cada estudio, extrajeron los datos y evaluaron el riesgo de sesgo. Se evaluó el efecto de los macrólidos sobre la mortalidad por todas las causas; necesidad de ventilación mecánica invasiva; oxigenación por membrana extracorpórea, duración de la estancia hospitalaria, insuficiencia respiratoria, eventos adversos graves, tiempo hasta la negatividad de la RT-PCR del SARS-CoV-2. La certeza de la evidencia para cada desenlace se evaluó siguiendo la aproximación GRADE. Esta revisión se mantendrá viva y disponible abiertamente durante la pandemia de COVID-19. Se someterán actualizaciones de su publicación cada vez que cambien las conclusiones o cuando haya actualizaciones sustanciales. RESULTADOS: Se identificó un experimento clínico aleatorio que evaluó el uso de azitromicina en combinación con hidroxicloroquina en comparación con el uso de hidroxicloroquina sola, en pacientes hospitalizados por COVID 19. Las estimaciones para todos los resultados evaluados resultaron en un poder estadístico insuficiente para llegar a conclusiones válidas. La calidad de la evidencia para los resultados principales fue baja a muy baja. CONCLUSIONES: El uso de macrólidos en el tratamiento de pacientes con COVID 19 no ha mostrado efectos beneficiosos en comparación con el tratamiento estándar. La evidencia para todos los desenlaces no es concluyente. Se necesitan estudios sobre un mayor número de pacientes con COVID 19, para determinar los efectos del uso de macrólidos sobre los desenlaces relacionados con la enfermedad. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registration number: CRD42020181032 Protocol preprint DOI: 10.31219/osf.io/rvp59.

Macrólidos para el tratamiento de COVID-19: una revisión sistemática viva / Macrolides for the treatment of COVID-19: a living, systematic review

OBJETIVO Proporcionar un resumen oportuno, riguroso y continuamente actualizado de la evidencia disponible sobre el papel de los macrólidos para el tratamiento de pacientes con COVID-19. DIDEÑO Revisión Sistemática Viva. BASE DE DATOS: La búsqueda de evidencia se realizó en el repositorio centralizado L·OVE (Living OVerview of Evidence) COVID-19; una plataforma que mapea las preguntas PICO para identificar la evidencia en 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 hoy se mantiene a través de búsquedas regulares en 39 bases de datos. MÉTODOS: Se incluyeron estudios experimentales que evaluaban el efecto de los macrólidos, como monoterapia o en combinación con otros fármacos, versus placebo o ningún tratamiento en pacientes con sospecha o confirmación de COVID-19. Se buscó identificar experimentos clínicos aleatorizados que evaluaran macrólidos en infecciones causadas por otros coronavirus, como MERS-CoV y SARS-CoV. Dos revisores examinaron de forma independiente la elegibilidad de cada estudio, extrajeron los datos y evaluaron el riesgo de sesgo. Se evaluó el efecto de los macrólidos sobre la mortalidad por todas las causas; necesidad de ventilación mecánica invasiva; oxigenación por membrana extracorpórea, duración de la estancia hospitalaria, insuficiencia respiratoria, eventos adversos graves, tiempo hasta la negatividad de la RT-PCR del SARS-CoV-2. La certeza de la evidencia para cada desenlace se evaluó siguiendo la aproximación GRADE. Esta revisión se mantendrá viva y disponible abiertamente durante la pandemia de COVID-19. Se someterán actualizaciones de su publicación cada vez que cambien las conclusiones o cuando haya actualizaciones sustanciales. RESULTADOS: Se identificó un experimento clínico aleatorio que evaluó el uso de azitromicina en combinación con hidroxicloroquina en comparación con el uso de hidroxicloroquina sola, en pacientes hospitalizados por COVID 19. Las estimaciones para todos los resultados evaluados resultaron en un poder estadístico insuficiente para llegar a conclusiones válidas. La calidad de la evidencia para los resultados principales fue baja a muy baja. CONCLUSIONES: El uso de macrólidos en el tratamiento de pacientes con COVID 19 no ha mostrado efectos beneficiosos en comparación con el tratamiento estándar. La evidencia para todos los desenlaces no es concluyente. Se necesitan estudios sobre un mayor número de pacientes con COVID 19, para determinar los efectos del uso de macrólidos sobre los desenlaces relacionados con la enfermedad.

OBJECTIVE This living, systematic review aims to provide a timely, rigorous, and continuously updated summary of the evidence available on the role of macrolides for treating patients with COVID-19. DESIGN: a living, systematic review. DATABASE: We conducted searches in the centralized repository L·OVE (Living OVerview of Evidence). L·OVE is a platform that maps PICO questions to evidence from the Epistemonikos database. In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it covers and customized to group all COVID-19 evidence in one place. Today it is maintained through regular searches in 39 databases.METHODS: We included randomized trials evaluating the effect of macrolides ­ as monotherapy or in combination with other drugs ­ versus placebo or no treatment in patients with COVID-19. Randomized trials evaluating macrolides in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomized studies in COVID-19 were searched in case we found no direct evidence from randomized trials. Two reviewers independently screened each study for eligibility, extracted data, and assessed the risk of bias. Measures included all-cause mortality; the need for invasive mechanical ventilation; extracorporeal membrane oxygenation, length of hospital stay, respiratory failure, serious adverse events, time to SARS-CoV-2 RT-PCR negativity. We applied the GRADE approach to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates. RESULTS: The search in the L·OVE platform retrieved 424 references. We considered 260 as potentially eligible and were reviewed in full texts. We included one randomized clinical trial that evaluated the use of azithromycin in combination with hydroxychloroquine compared to hydroxychloroquine alone in hospitalized patients with COVID 19. The estimates for all outcomes evaluated resulted in insufficient power to draw conclusions. The quality of the evidence for the main outcomes was low to very low. CONCLUSIONS: Macrolides in the management of patients with COVID 19 showed no beneficial effects compared to standard of care. The evidence for all outcomes is inconclusive. Larger trials are needed to determine the effects of macrolides on pulmonary and other outcomes in COVID-19 patients.

Adherence to breast cancer guidelines is associated with better survival outcomes: a systematic review and meta-analysis of observational studies in EU countries.

BACKGROUND: Breast cancer (BC) clinical guidelines offer evidence-based recommendations to improve quality of healthcare for patients with or at risk of BC. Suboptimal adherence to recommendations has the potential to negatively affect population health. However, no study has systematically reviewed the impact of BC guideline adherence -as prognosis factor- on BC healthcare processes and health outcomes. The objectives are to analyse the impact of guideline adherence on health outcomes and on healthcare costs. METHODS: We searched systematic reviews and primary studies in MEDLINE and Embase, conducted in European Union (EU) countries (inception to May 2019). Eligibility assessment, data extraction, and risk of bias assessment were conducted by one author and crosschecked by a second. We used random-effects meta-analyses to examine the impact of guideline adherence on overall survival and disease-free survival, and assessed certainty of evidence using GRADE. RESULTS: We included 21 primary studies. Most were published during the last decade (90%), followed a retrospective cohort design (86%), focused on treatment guideline adherence (95%), and were at low (80%) or moderate (20%) risk of bias. Nineteen studies (95%) examined the impact of guideline adherence on health outcomes, while two (10%) on healthcare cost. Adherence to guidelines was associated with increased overall survival (HR = 0.67, 95%CI 0.59-0.76) and disease-free survival (HR = 0.35, 95%CI 0.15-0.82), representing 138 more survivors (96 more to 178 more) and 336 patients free of recurrence (73 more to 491 more) for every 1000 women receiving adherent CG treatment compared to those receiving non-adherent treatment at 5 years follow-up (moderate certainty). Adherence to treatment guidelines was associated with higher costs, but adherence to follow-up guidelines was associated with lower costs (low certainty). CONCLUSIONS: Our review of EU studies suggests that there is moderate certainty that adherence to BC guidelines is associated with an improved survival. BC guidelines should be rigorously implemented in the clinical setting. TRIAL REGISTRATION: PROSPERO ( CRD42018092884 ).

Guidelines in Low and Middle Income Countries Paper 2: Quality assessment of Chilean guidelines: need for improvement in rigor, applicability, updating, and patients' inclusion.

OBJECTIVES: The Chilean health system mandates providers to ensure assistance under a guaranteed system, the Explicit Guarantees in Healthcare (EGH) program. The Health Ministry has developed clinical practice guidelines (CPGs), but independent assessment of their quality is lacking. STUDY DESIGN AND SETTING: We assessed all CPGs of the EGH program using Appraisal of Guidelines for Research & Evaluation II (AGREE II) tool for appraising quality, validity period, and last update. RESULTS: Eighty-six CPGs were published between 2005 and 2016. Only 15 (17.4%) were updated. The overall mean raw score was 4.18 (±0.98). The scaled scores for each domain were: Scope and objectives 79.7%, Stakeholder involvement 46.2%, Rigor of development 36.3%, Clarity of presentation 82.8%, Applicability 23.5%, and Editorial independence 39.2%. The highest items were: overall objectives described, population described, options for management clearly presented, and key recommendations easily identifiable. The worst evaluated items were: views and preferences of the target population, strengths and limitations of the body of evidence, methods for formulating the recommendations, external review by experts, and description of facilitators and barriers to application. CONCLUSION: Most Chilean CPGs included in the EGH program are outdated and show items that should be improved, mainly through a more rigorous methodology, the inclusion of patients in its development, and appropriate consideration of its applicability.

Physicians perspectives about medical sources of information: protocol for an overview of systematic reviews. / Perspectivas médicas sobre las fuentes de información: protocolo de una revisión panorámica de revisiones sistemáticas.

INTRODUCTION: Despite the growing availability of evidence and sources of information, it is not clear what are the physicians preferences for filling gaps in their medical knowledge. OBJECTIVE: To summarize the available evidence about physicians preferences and perceived barriers and facilitators about sources of information. METHODS: We will undertake an overview of systematic reviews according to PRISMA guidelines. We will search Epistemonikos from inception until March 2019. We will also search PROSPERO, and we will perform a forward citation search in Scopus. Inclusion criteria will consider systematic reviews (qualitative, quantitative, or mixed methods) focusing on physicians preferences about sources of information, as well as perceived barriers and facilitators. Two authors will independently screen and select records for inclusion. We will appraise the quality of included systematic reviews using the Joanna Briggs Institute checklist, and the overlap of primary studies according to the corrected covered area formula. We will conduct a narrative synthesis of quantitative data and a thematic analysis of qualitative findings. DISCUSSION: We expect that our findings will contribute to improving the evidence-based general practice by identifying physicians perspectives about different sources of medical information.

INTRODUCCIÓN: Pese a la creciente cantidad y disponibilidad de evidencia, así como de fuentes de información, no existe claridad respecto a las fuentes de información de preferencia utilizadas por los médicos para dar respuesta a sus preguntas clínicas. OBJETIVO: Resumir la evidencia disponible acerca de las fuentes de información que prefieren los médicos para dar respuesta a las interrogantes surgidas de la práctica médica, además de las barreras y facilitadores percibidos sobre su uso. MÉTODOS: Realizaremos una revisión panorámica de revisiones sistemáticas, de acuerdo con las guías PRISMA. Buscaremos en Epistemonikos desde el inicio hasta marzo de 2019. También utilizaremos PROSPERO y efectuaremos una búsqueda de citas en Scopus. Los criterios de inclusión considerarán revisiones sistemáticas (métodos cualitativos, cuantitativos o mixtos) centrados en las preferencias de los médicos sobre las fuentes de información, así como las barreras y facilitadores percibidos. Dos autores examinarán y seleccionarán de forma independiente los estudios para su inclusión. Evaluaremos la calidad de las revisiones sistemáticas incluidas utilizando la lista de verificación del Instituto Joanna Briggs y la superposición de los estudios primarios, de acuerdo con la fórmula del área cubierta corregida. Realizaremos una síntesis narrativa de datos cuantitativos y un análisis temático de hallazgos cualitativos. DISCUSIÓN: Esperamos que nuestros hallazgos contribuyan a mejorar la práctica médica basada en la evidencia, mediante la identificación de las perspectivas médicas sobre las diversas fuentes de información médicas disponibles.

Thromboprophylaxis in elective spinal surgery: A protocol for systematic review.

BACKGROUND: Venous thromboembolism (VTE) is a serious, sometimes life-threatening complication that can occur following spine surgery. The incidence of VTE, and the optimal type and timing of thromboprophylaxis for this complication in elective spine surgery is a matter of debate. OBJECTIVE: To perform a systematic review with the aim of clarifying the efficacy and adverse effects of mechanical and chemical prophylaxis for preventing thromboembolic complications in elective spine surgery for conditions other than trauma and malignant disease. METHODS/DESIGN: A search strategy of related articles up to March 2018 was designed and executed in Medline and Embase. PATIENTS: adolescents (>10 years) and adults undergoing elective surgery for spinal deformity or degenerative disease (from C1 to S1). INTERVENTION: Perioperative mechanical and chemical thromboprophylaxis. Studies could be randomized controlled trials or observational studies that reported data on any relevant clinical outcomes. RESULTS: In total, 2451 uniquecitations were identified and 35 studies were ultimately included in the systematic review. The overall mean incidence of complications was 3.7% for deep venous thrombosis, 0.0% for pulmonary embolism, and 3.7% for bleeding in chemoprophylaxis group; 2.9% for deep venous thrombosis, 0.4% for pulmonary embolism and 0.0% for bleeding in mechanoprophylaxis; and 0.7% for deep venous thrombosis, 0.1% for pulmonary embolism and 0.2% for bleeding in mixed prophylaxis group with no specific data on these rates for the type of patient and type and location of surgery. None of the articles retrieved provided information on the adolescent population. DISCUSSION AND CONCLUSIONS: The poor design and high variability among the studies regarding characteristics of study population, details of interventions, and definitions of outcomes, determines a low quality of the available evidence and limits the interpretation of the results. We were unable to identify a clear advantage of one type of thromboprophylaxis over the other, although there was an increased risk of bleeding with chemoprophylaxis, which could favor the use of mechanoprophylaxis in this scenario.

Healthcare providers' adherence to breast cancer guidelines in Europe: a systematic literature review.

PURPOSE: Clinical guidelines' (CGs) adherence supports high-quality care. However, healthcare providers do not always comply with CGs recommendations. This systematic literature review aims to assess the extent of healthcare providers' adherence to breast cancer CGs in Europe and to identify the factors that impact on healthcare providers' adherence. METHODS: We searched for systematic reviews and quantitative or qualitative primary studies in MEDLINE and Embase up to May 2019. The eligibility assessment, data extraction, and risk of bias assessment were conducted by one author and cross-checked by a second author. We conducted a narrative synthesis attending to the modality of the healthcare process, methods to measure adherence, the scope of the CGs, and population characteristics. RESULTS: Out of 8137 references, we included 41 primary studies conducted in eight European countries. Most followed a retrospective cohort design (19/41; 46%) and were at low or moderate risk of bias. Adherence for overall breast cancer care process (from diagnosis to follow-up) ranged from 54 to 69%; for overall treatment process [including surgery, chemotherapy (CT), endocrine therapy (ET), and radiotherapy (RT)] the median adherence was 57.5% (interquartile range (IQR) 38.8-67.3%), while for systemic therapy (CT and ET) it was 76% (IQR 68-77%). The median adherence for the processes assessed individually was higher, ranging from 74% (IQR 10-80%), for the follow-up, to 90% (IQR 87-92.5%) for ET. Internal factors that potentially impact on healthcare providers' adherence were their perceptions, preferences, lack of knowledge, or intentional decisions. CONCLUSIONS: A substantial proportion of breast cancer patients are not receiving CGs-recommended care. Healthcare providers' adherence to breast cancer CGs in Europe has room for improvement in almost all care processes. CGs development and implementation processes should address the main factors that influence healthcare providers' adherence, especially patient-related ones. REGISTRATION: PROSPERO (CRD42018092884).

The perspectives of patients and their caregivers on self-management interventions for chronic conditions: a protocol for a mixed-methods overview.

Introduction: Self-management (SM) interventions are complex interventions and one of the main components of high-quality chronic disease care for which the incorporation of the perspectives of patients and their informal caregivers is crucial. We aim to identify, appraise and synthesise the evidence exploring patients' and caregivers' perspectives on SM interventions. More precisely, we aim to 1) describe how they value the importance of outcomes of SM interventions, and 2) identify the factors that might impact on acceptability and feasibility of SM interventions based on their preferences and experiences. Methods and analysis: We will conduct four mixed-methods overviews as part of COMPAR-EU, a European Union (EU) funded project aimed to identify the most effective and cost-effective SM interventions for chronic obstructive pulmonary disease (COPD), heart failure (HF), obesity, and type 2 diabetes mellitus (T2DM). We will search in MEDLINE, CINAHL, and PsycINFO for systematic reviews of studies addressing patients' preferences on outcomes, or their experiences with SM alongside their disease trajectory or with SM interventions, published in English. Selection of studies and data extraction will be conducted in pairs. We will assess the overlap of studies and methodological quality. We will follow a three-step synthesis process: 1) narrative synthesis for quantitative evidence, 2) thematic synthesis for qualitative evidence, and 3) integration of findings in the interpretation phase. Additionally, we will consult on the relevance of findings with patients and their caregivers. Systematic review registration: PROSPERO CRD42019117867.