Consistency of covid-19 trial preprints with published reports and impact for decision making: retrospective review

Objective To assess the trustworthiness (ie, complete and consistent reporting of key methods and results between preprint and published trial reports) and impact (ie, effects of preprints on meta-analytic estimates and the certainty of evidence) of preprint trial reports during the covid-19 pandemic. Design Retrospective review. Data sources World Health Organization covid-19 database and the Living Overview of the Evidence (L-OVE) covid-19 platform by the Epistemonikos Foundation (up to 3 August 2021). Main outcome measures Comparison of characteristics of covid-19 trials with and without preprints, estimates of time to publication of covid-19 preprints, and description of differences in reporting of key methods and results between preprints and their later publications. For the effects of eight treatments on mortality and mechanical ventilation, the study comprised meta-analyses including preprints and excluding preprints at one, three, and six months after the first trial addressing the treatment became available either as a preprint or publication (120 meta-analyses in total, 60 of which included preprints and 60 of which excluded preprints) and assessed the certainty of evidence using the GRADE framework. Results Of 356 trials included in the study, 101 were only available as preprints, 181 as journal publications, and 74 as preprints first and subsequently published in journals. The median time to publication of preprints was about six months. Key methods and results showed few important differences between trial preprints and their subsequent published reports. Apart from two (3.3%) of 60 comparisons, point estimates were consistent between meta-analyses including preprints versus those excluding preprints as to whether they indicated benefit, no appreciable effect, or harm. For nine (15%) of 60 comparisons, the rating of the certainty of evidence was different when preprints were included versus being excluded—the certainty of evidence including preprints was higher in four comparisons and lower in five comparisons. Conclusion No compelling evidence indicates that preprints provide results that are inconsistent with published papers. Preprints remain the only source of findings of many trials for several months—an unsuitable length of time in a health emergency that is not conducive to treating patients with timely evidence. The inclusion of preprints could affect the results of meta-analyses and the certainty of evidence. Evidence users should be encouraged to consider data from preprints.

COVID-19 Living Overview of Evidence repository is highly comprehensive and can be used as a single source for COVID-19 studies.

BACKGROUND AND OBJECTIVE: The coronavirus disease 2019 Living OVerview of Evidence (COVID-19 L·OVE) is a public repository and classification platform for COVID-19 articles. The repository contains more than 430,000 articles as of September 20, 2021 and intends to provide a one-stop shop for COVID-19 evidence. Considering that systematic reviews conduct high-quality searches, this study assesses the comprehensiveness and currency of the repository against the total number of studies in a representative sample of COVID-19 systematic reviews. METHODS: Our sample was generated from all the studies included in the systematic reviews of COVID-19 published during April 2021. We estimated the comprehensiveness of COVID-19 L·OVE repository by determining how many of the individual studies in the sample were included in the COVID-19 L·OVE repository. We estimated the currency as the percentage of studies that was available in the COVID-19 L·OVE repository at the time the systematic reviews conducted their own search. RESULTS: We identified 83 eligible systematic reviews that included 2,132 studies. COVID-19 L·OVE had an overall comprehensiveness of 99.67% (2,125/2,132). The overall currency of the repository, that is, the proportion of articles that would have been obtained if the search of the reviews was conducted in COVID-19 L·OVE instead of searching the original sources, was 96.48% (2,057/2,132). Both the comprehensiveness and the currency were 100% for randomized trials (82/82). CONCLUSION: The COVID-19 L·OVE repository is highly comprehensive and current. Using this repository instead of traditional manual searches in multiple databases can save a great amount of work to people conducting systematic reviews and would improve the comprehensiveness and timeliness of evidence syntheses. This tool is particularly important for supporting living evidence synthesis processes.

COVID-19 transmission during swimming-related activities: a rapid systematic review.

BACKGROUND: There are uncertainties about mitigating strategies for swimming-related activities in the context of the COVID-19 pandemic. There is an opportunity to learn from the experience of previous re-openings to better plan the future one. Our objectives are to systematically review the evidence on (1) the association between engaging in swimming-related activities and COVID-19 transmission; and (2) the effects of strategies for preventing COVID-19 transmission during swimming-related activities. METHODS: We conducted a rapid systematic review. We searched in the L·OVE (Living OVerview of Evidence) platform for COVID-19. The searches covered the period from the inception date of each database until April 19, 2021. We included non-randomized studies for the review on association of COVID-19 transmission and swimming-related activities. We included guidance documents reporting on the strategies for prevention of COVID-19 transmission during swimming-related activities. We also included studies on the efficacy and safety of the strategies. Teams of two reviewers independently assessed article eligibility. For the guidance documents, a single reviewer assessed the eligibility and a second reviewer verified the judgement. Teams of two reviewers extracted data independently. We summarized the findings of included studies narratively. We synthesized information from guidance documents according to the identified topics and subtopics, and presented them in tabular and narrative formats. RESULTS: We identified three studies providing very low certainty evidence for the association between engaging in swimming-related activities and COVID-19 transmission. The analysis of 50 eligible guidance documents identified 11 topics: ensuring social distancing, ensuring personal hygiene, using personal protective equipment, eating and drinking, maintaining the pool, managing frequently touched surfaces, ventilation of indoor spaces, screening and management of sickness, delivering first aid, raising awareness, and vaccination. One study assessing the efficacy of strategies to prevent COVID-19 transmission did not find an association between compliance with precautionary restrictions and COVID-19 transmission. CONCLUSIONS: There are major gaps in the research evidence of relevance to swimming-related activities in the context of the COVID-19 pandemic. However, the synthesis of the identified strategies from guidance documents can inform public health management strategies for swimming-related activities, particularly in future re-opening plans.

Improving Social Justice in COVID-19 Health Research: Interim Guidelines for Reporting Health Equity in Observational Studies.

The COVID-19 pandemic has highlighted the global imperative to address health inequities. Observational studies are a valuable source of evidence for real-world effects and impacts of implementing COVID-19 policies on the redistribution of inequities. We assembled a diverse global multi-disciplinary team to develop interim guidance for improving transparency in reporting health equity in COVID-19 observational studies. We identified 14 areas in the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist that need additional detail to encourage transparent reporting of health equity. We searched for examples of COVID-19 observational studies that analysed and reported health equity analysis across one or more social determinants of health. We engaged with Indigenous stakeholders and others groups experiencing health inequities to co-produce this guidance and to bring an intersectional lens. Taking health equity and social determinants of health into account contributes to the clinical and epidemiological understanding of the disease, identifying specific needs and supporting decision-making processes. Stakeholders are encouraged to consider using this guidance on observational research to help provide evidence to close the inequitable gaps in health outcomes.

Pulmonary rehabilitation for COVID-19: A living systematic review protocol. / Rehabilitación pulmonar en COVID-19: protocolo de 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 pulmonary rehabilitation in the treatment of patients with COVID-19. DESIGN: This is the protocol of a living systematic review. DATA SOURCES: We will conduct searches in the L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that maps PICO questions to a repository maintained through regular searches in electronic databases, preprint servers, trial registries and other resources relevant to COVID-19. No date or language restrictions will be applied. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomized trials evaluating the effect of pulmonary rehabilitation as monotherapy or in combination with other interventions-versus sham or no treatment in patients with COVID-19. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will pool the results using meta-analysis and will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the certainty of the evidence for each outcome. ETHICS AND DISSEMINATION: No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.

OBJETIVO: Proporcionar un resumen oportuno, riguroso y continuamente actualizado de la evidencia disponible sobre el papel de la rehabilitación pulmonar en el tratamiento de los pacientes con COVID-19. DISEÑO: Es el protocolo de una revisión sistemática viva. FUENTE DE DATOS: Realizaremos búsquedas en la plataforma L·OVE (Living OVerview of Evidence) para COVID-19, un sistema que mapea los componentes de las preguntas de investigación (PICO) en un repositorio mantenido a través de búsquedas regulares en bases de datos electrónicas, servidores de pre-impresión, registros de ensayos y otros recursos relevantes para COVID-19. No se aplicarán restricciones de fecha ni de idioma. CRITERIOS DE ELEGIBILIDAD PARA LA SELECCIÓN DE ESTUDIOS Y MÉTODOS: Se adaptó un protocolo común ya publicado para revisiones sistemáticas paralelas múltiples a las especificidades de la pregunta. Se incluirán ensayos aleatorios que evalúen el efecto de la rehabilitación pulmonar como monoterapia o en combinación con otras intervenciones frente a un tratamiento simulado o ningún tratamiento en pacientes con COVID-19. Dos revisores examinarán de forma independiente cada estudio para determinar su elegibilidad, extraerán los datos y evaluarán el riesgo de sesgo. Se agruparán los resultados mediante un metaanálisis y se aplicará el sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE) para evaluar la certeza de las pruebas para cada resultado. ÉTICA Y DIFUSIÓN: No se considera necesaria la aprobación ética. Los resultados de esta revisión se difundirán ampliamente a través de publicaciones revisadas por pares, redes sociales y medios de comunicación tradicionales.

Perceived Stress in Dentists and Dental Students of Latin America and the Caribbean during the Mandatory Social Isolation Measures for the COVID-19 Pandemic: A Cross-Sectional Study.

This study aims to determine the impact of the COVID-19 pandemic, specifically considering the mandatory social isolation measures implemented, on the perceived stress of a sample of dentists and dental students from Latin America and the Caribbean, as well as the associated sociodemographic and pandemic-related variables. A cross-sectional survey was conducted with a sample of 2036 dentists and dental students (1433 women). For the main outcome, the 14-item Perceived Stress Scale (PSS-14) was used. The survey also questioned sociodemographic aspects, questions on the COVID-19 pandemic, health variables, and habits. Descriptive, bivariate, and multivariate analyses (linear regression) were applied to observe the factors associated with perceived stress. The PSS-14 mean score was 24.76 (±11.76). Hierarchical regression models showed significant variables associated with the PSS-14 scores: income level during mandatory social isolation, having older adults under care during mandatory social isolation, self-perceived level of concern regarding COVID-19, self-perceived health, Coffee consumption during mandatory social isolation. In general terms, the pandemic has influenced the personal, social, labor, and everyday life of dental staff and affected the mental health of this population specifically when perceived stress is considered. Public policies, strategies, and mental health surveillance systems are required for this population.

Remdesivir for the treatment of COVID-19: a living systematic review

OBJETIVO: Esta revisión sistemática viva tiene como objetivo entregar un resumen oportuno, riguroso y continuamente actualizado de la evidencia disponible sobre los efectos de remdesivir en pacientes con COVID-19. MÉTODOS: Se buscaron ensayos aleatorios que evaluaran el uso de remdesivir versus placebo o ningún tratamiento en pacientes con COVID-19. Se realizó una búsqueda en la plataforma L·OVE COVID-19 (Living OVerview of Evidence), un sistema que mantiene búsquedas regulares en bases de datos, registros de ensayos, servidores preprint y sitios web relevantes en COVID-19. Todas las búsquedas fueron realizadas hasta el 25 de agosto de 2020. No se aplicaron restricciones de fecha ni de idioma. Dos revisores evaluaron de forma independiente los artículos potencialmente elegibles, de acuerdo con criterios de selección predefinidos, y extrajeron los datos mediante un formulario estandarizado. Los resultados fueron combinados mediante un metanálisis utilizando modelos de efectos aleatorios y evaluamos la certeza de la evidencia utilizando el método GRADE. Una versión viva de esta revisión estará abiertamente disponible durante la pandemia de COVID-19. RESULTADOS: La búsqueda inicial arrojó 574 referencias. Finalmente, identificamos 3 ensayos aleatorios, que evaluaban el uso de remdesivir adicionado al tratamiento estándar versus tratamiento estándar. La evidencia es muy incierta acerca del efecto del remdesivir sobre la mortalidad (RR 0,7;IC del 95%: 0,46 a 1,05;certeza de la evidencia muy baja) y la necesidad de ventilación mecánica invasiva (RR 0,69;IC del 95%: 0,39 a 1,24;certeza de evidencia muy baja). Por otro lado, es probable que el uso de remdesivir produzca un aumento en la incidencia de efectos adversos en pacientes con COVID-19 (RR 1,29;IC del 95%: 0,58 a 2,84;evidencia de certeza moderada). CONCLUSIONES: La evidencia disponible sobre el papel del remdesivir en el tratamiento de pacientes con COVID-19 es insuficiente en relación a los desenlaces críticos para tomar decisiones, por lo que no es posible realizar un correcto balance entre los beneficios potenciales, los efectos adversos y los costos. OBJECTIVE: Provide a timely, rigorous and continuously updated summary of the evidence on the role of remdesivir in the treatment of patients with COVID-19. METHODS: Eligible studies were randomized trials evaluating the effect of remdesivir versus placebo or no treatment. We conducted searches in the special L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs regular searches in databases, trial registries, preprint servers and websites relevant to COVID-19. All the searches covered the period until 25 August 2020. No date or language restrictions were applied. Two reviewers independently evaluated potentially eligible studies according to predefined selection criteria, and extracted data on study characteristics, methods, outcomes, and risk of bias, using a predesigned, standardized form. We performed meta-analyses using random-effect models and assessed overall certainty in evidence using the GRADE approach. A living, web-based version of this review will be openly available during the COVID-19 pandemic. RESULTS: Our search strategy yielded 574 references. Finally, we included three randomized trials evaluating remdesivir in addition to standard care versus standard care alone. The evidence is very uncertain about the effect of remdesivir on mortality (RR 0.7, 95% CI 0.46 to 1.05;very low certainty evidence) and the need for invasive mechanical ventilation (RR 0.69, 95% CI 0.39 to 1.24;very low certainty evidence). On the other hand, remdesivir likely results in a large increase in the incidence of adverse effects in patients with COVID-19 (RR 1.29, 95% CI 0.58 to 2.84;moderate certainty evidence). CONCLUSIONS: The evidence is insufficient for the outcomes critical for making decisions on the role of remdesivir in the treatment of patients with COVID-19, so it is impossible to balance potential benefits, if there are any, with the adverse effects and costs.

Remdesivir for the treatment of COVID-19: a living systematic review.

OBJECTIVE: Provide a timely, rigorous and continuously updated summary of the evidence on the role of remdesivir in the treatment of patients with COVID-19. METHODS: Eligible studies were randomized trials evaluating the effect of remdesivir versus placebo or no treatment. We conducted searches in the special L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs regular searches in databases, trial registries, preprint servers and websites relevant to COVID-19. All the searches covered the period until 25 August 2020. No date or language restrictions were applied. Two reviewers independently evaluated potentially eligible studies according to predefined selection criteria, and extracted data on study characteristics, methods, outcomes, and risk of bias, using a predesigned, standardized form. We performed meta-analyses using random-effect models and assessed overall certainty in evidence using the GRADE approach. A living, web-based version of this review will be openly available during the COVID-19 pandemic. RESULTS: Our search strategy yielded 574 references. Finally, we included three randomized trials evaluating remdesivir in addition to standard care versus standard care alone. The evidence is very uncertain about the effect of remdesivir on mortality (RR 0.7, 95% CI 0.46 to 1.05; very low certainty evidence) and the need for invasive mechanical ventilation (RR 0.69, 95% CI 0.39 to 1.24; very low certainty evidence). On the other hand, remdesivir likely results in a large increase in the incidence of adverse effects in patients with COVID-19 (RR 1.29, 95% CI 0.58 to 2.84; moderate certainty evidence). CONCLUSIONS: The evidence is insufficient for the outcomes critical for making decisions on the role of remdesivir in the treatment of patients with COVID-19, so it is impossible to balance potential benefits, if there are any, with the adverse effects and costs. PROSPERO REGISTRATION NUMBER: CRD42020183384.

Recomendaciones odontológicas en la pandemia COVID-19: revisión narrativa

Introducción La enfermedad por coronavirus-19 (COVID-19) es un problema mundial de salud pública debido a su morbimortalidad, especialmente en grupos de riesgo. El entorno odontológico tiene un alto riesgo de transmisión viral, por ello el objetivo de este estudio fue identificar recomendaciones para la atención odontológica durante esta pandemia. Métodos Se realizó una búsqueda de evidencia científica publicada desde 2002 hasta el 23 de marzo de 2020 en bases de datos electrónicas (MEDLINE/PubMed, EMBASE, Cochrane y Epistemonikos) y en las páginas electrónicas de la Asociación Dental Americana, de Centers for Disease Control and Prevention Oral Health, del Ministerio de Salud de Chile y de sociedades científicas. Resultados Se incluyeron nueve artículos publicados, en los cuales se recomienda el uso irrestricto de elementos de protección personal, preferir técnicas radiográficas extraorales, uso de enjuagues bucales con peróxido de hidrógeno al 1% o povidona yodada al 0,2%, técnica a cuatro manos con aspiración constante y uso de suturas reabsorbibles. Además, existe consenso respecto a que durante los periodos de transmisión comunitaria se deben posponer los tratamientos odontológicos no urgentes. Conclusiones Debido al alto riesgo de infección cruzada que presentan los equipos odontológicos, deben implementarse recomendaciones basadas en la mejor evidencia disponible, con el fin de preservar la salud de los miembros del equipo y de la población a su cuidado. Introduction COVID-19 is a world public health problem due to its morbidity and mortality, especially in at-risk groups. The dental environment has a high risk of viral transmission;accordingly, this study aimed to identify recommendations based on the best available evidence for dental care during this pandemic. Methods We performed a search for scientific evidence published since 2002 to March 23th 2020 in electronic databases (MEDLINE/PubMed, EMBASE, Cochrane, and Epistemonikos) and the web pages of the American Dental Association, Centers for Disease Control and Prevention Oral Health, the Ministry of Health in Chile and scientific societies. Results We included nine published studies. The recommendations were the following: unrestricted use of personal protection elements, use of extraoral radiographic techniques, use of mouth rinses with 1% hydrogen peroxide or 0.2% iodine povidone, a four-hand technique with ongoing aspiration and the use of absorbable sutures. Furthermore, there is a consensus that non-urgent treatments should be postponed during periods of community transmission. Conclusions Dental practitioners are exposed to a high risk of cross-infection, meaning they must implement recommendations based on the best available evidence to preserve the health of team members and the population they are caring for.

[Dental recommendations in the COVID-19 pandemic: A narrative review]. / Recomendaciones odontológicas en la pandemia COVID-19: revisión narrativa.

INTRODUCTION: COVID-19 is a world public health problem due to its morbidity and mortality, especially in at-risk groups. The dental environment has a high risk of viral transmission; accordingly, this study aimed to identify recommendations based on the best available evidence for dental care during this pandemic. METHODS: We performed a search for scientific evidence published since 2002 to March 23th 2020 in electronic databases (MEDLINE/PubMed, EMBASE, Cochrane, and Epistemonikos) and the web pages of the American Dental Association, Centers for Disease Control and Prevention Oral Health, the Ministry of Health in Chile and scientific societies. RESULTS: We included nine published studies. The recommendations were the following: unrestricted use of personal protection elements, use of extraoral radiographic techniques, use of mouth rinses with 1% hydrogen peroxide or 0.2% iodine povidone, a four-hand technique with ongoing aspiration and the use of absorbable sutures. Furthermore, there is a consensus that non-urgent treatments should be postponed during periods of community transmission. CONCLUSIONS: Dental practitioners are exposed to a high risk of cross-infection, meaning they must implement recommendations based on the best available evidence to preserve the health of team members and the population they are caring for.

INTRODUCCIÓN: La enfermedad por coronavirus-19 (COVID-19) es un problema mundial de salud pública debido a su morbimortalidad, especialmente en grupos de riesgo. El entorno odontológico tiene un alto riesgo de transmisión viral, por ello el objetivo de este estudio fue identificar recomendaciones para la atención odontológica durante esta pandemia. MÉTODOS: Se realizó una búsqueda de evidencia científica publicada desde 2002 hasta el 23 de marzo de 2020 en bases de datos electrónicas (MEDLINE/PubMed, EMBASE, Cochrane y Epistemonikos) y en las páginas electrónicas de la Asociación Dental Americana, de Centers for Disease Control and Prevention Oral Health, del Ministerio de Salud de Chile y de sociedades científicas. RESULTADOS: Se incluyeron nueve artículos publicados, en los cuales se recomienda el uso irrestricto de elementos de protección personal, preferir técnicas radiográficas extraorales, uso de enjuagues bucales con peróxido de hidrógeno al 1% o povidona yodada al 0,2%, técnica a cuatro manos con aspiración constante y uso de suturas reabsorbibles. Además, existe consenso respecto a que durante los periodos de transmisión comunitaria se deben posponer los tratamientos odontológicos no urgentes. CONCLUSIONES: Debido al alto riesgo de infección cruzada que presentan los equipos odontológicos, deben implementarse recomendaciones basadas en la mejor evidencia disponible, con el fin de preservar la salud de los miembros del equipo y de la población a su cuidado.

Lopinavir-ritonavir for COVID-19: A living systematic review.

OBJECTIVE: Provide a timely, rigorous, and continuously updated summary of the evidence on the role of lopinavir/ritonavir in the treatment of patients with COVID-19. METHODS: We conducted searches in the special L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs regular searches in PubMed, Embase, CENTRAL, and other 33 sources. We searched for randomized trials and non-randomized studies evaluating the effect of lopinavir/ritonavir versus placebo or no treatment in patients with COVID-19. Two reviewers independently evaluated potentially eligible studies, according to predefined selection criteria, and extracted data using a predesigned standardized form. We performed meta-analyses using random-effect models and assessed overall certainty in evidence using the GRADE approach. A living, web-based version of this review will be openly available during the COVID-19 pandemic. RESULTS: Our search strategy yielded 862 references. Finally, we identified 12 studies, including two randomized trials, evaluating lopinavir/ritonavir, in addition to standard care versus standard care alone in 250 adult inpatients with COVID-19. The evidence from randomized trials shows lopinavir/ritonavir may reduce mortality (relative risk: 0.77; 95% confidence interval: 0.45 to 1.3; low certainty evidence), but the anticipated magnitude of the absolute reduction in mortality, varies across different risk groups. Lopinavir/ritonavir also had a slight reduction in the risk of requiring invasive mechanical ventilation, developing respiratory failure, or acute respiratory distress syndrome. However, it did not lead to any difference in the duration of hospitalization and may lead to an increase in the number of total adverse effects. The overall certainty of the evidence was low or very low. CONCLUSIONS: For severe and critical patients with COVID-19, lopinavir/ritonavir might play a role in improving outcomes, but the available evidence is still limited. A substantial number of ongoing studies should provide valuable evidence to inform researchers and decision-makers soon.

OBJETIVO: Esta revisión sistemática viva tiene como objetivo entregar un resumen oportuno, riguroso y constantemente actualizado de la evidencia disponible sobre los efectos de lopinavir/ritonavir en pacientes con COVID-19. MÉTODOS: Se realizó una búsqueda en la plataforma L·OVE COVID-19 (Living OVerview of Evidence), un sistema que mantiene búsquedas regulares en PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) y otras 33 fuentes. Se buscaron ensayos aleatorios y estudios no aleatorios que evaluaran el uso de lopinavir/ritonavir versus placebo o ningún tratamiento en pacientes con COVID-19. Dos revisores evaluaron de forma independiente los artículos potencialmente elegibles, de acuerdo con criterios de selección predefinidos, y extrajeron los datos mediante un formulario estandarizado. Los resultados fueron combinados mediante un metanálisis utilizando modelos de efectos aleatorios y evaluamos la certeza de la evidencia utilizando el método GRADE. Una versión viva de esta revisión estará disponible durante la pandemia de COVID-19. RESULTADOS: La búsqueda inicial arrojó 862 referencias. Finalmente, identificamos 12 estudios incluyendo 2 ensayos aleatorios, que evaluaban lopinavir/ritonavir adicionado al tratamiento estándar versus tratamiento estándar en 250 pacientes adultos hospitalizados con COVID-19. Los resultados provenientes de los ensayos aleatorios muestran que el uso de lopinavir/ritonavir puede reducir la mortalidad (riesgo relativo: 0,77; intervalo de confianza 95%: 0,45 a 1,3; certeza de evidencia baja), pero la magnitud de la reducción absoluta de la mortalidad varía según los diferentes grupos de riesgo. El uso de lopinavir/ritonavir mostró además una ligera reducción en el riesgo de requerir ventilación mecánica invasiva, desarrollar insuficiencia respiratoria o síndrome de dificultad respiratoria aguda. No se observó diferencias en la duración de la hospitalización y su uso puede producir un aumento en el número de efectos adversos totales. La certeza global de la evidencia fue baja o muy baja. CONCLUSIONES: Para pacientes graves y críticos con COVID-19, el uso de lopinavir/ritonavir podría desempeñar un papel en la mejora de los resultados, pero la evidencia disponible aún es limitada. La gran cantidad de estudios en curso deberían proporcionar evidencia valiosa para informar a los investigadores y los tomadores de decisiones en el futuro cercano.

Lopinavir-ritonavir para COVID-19: una revisión sistemática viva

Objective: Provide a timely, rigorous, and continuously updated summary of the evidence on the role of lopinavir/ritonavir in the treatment of patients with COVID-19. Methods: We conducted searches in the special L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs regular searches in PubMed, Embase, CENTRAL, and other 33 sources. We searched for randomized trials and non-randomized studies evaluating the effect of lopinavir/ritonavir versus placebo or no treatment in patients with COVID-19. Two reviewers independently evaluated potentially eligible studies, according to predefined selection criteria, and extracted data using a predesigned standardized form. We performed meta-analyses using random-effect models and assessed overall certainty in evidence using the GRADE approach. A living, web-based version of this review will be openly available during the COVID-19 pandemic. Results: Our search strategy yielded 862 references. Finally, we identified 12 studies, including two randomized trials, evaluating lopinavir/ritonavir, in addition to standard care versus standard care alone in 250 adult inpatients with COVID-19. The evidence from randomized trials shows lopinavir/ritonavir may reduce mortality (relative risk: 0.77;95% confidence interval: 0.45 to 1.3;low certainty evidence), but the anticipated magnitude of the absolute reduction in mortality, varies across different risk groups. Lopinavir/ritonavir also had a slight reduction in the risk of requiring invasive mechanical ventilation, developing respiratory failure, or acute respiratory distress syndrome. However, it did not lead to any difference in the duration of hospitalization and may lead to an increase in the number of total adverse effects. The overall certainty of the evidence was low or very low. Conclusions: For severe and critical patients with COVID-19, lopinavir/ritonavir might play a role in improving outcomes, but the available evidence is still limited. A substantial number of ongoing studies should provide valuable evidence to inform researchers and decision-makers soon.

Evidence synthesis relevant to COVID-19: a protocol for multiple systematic reviews and overviews of systematic reviews. / Síntesis de evidencia relevante para COVID-19: protocolo común para múltiples revisiones sistemáticas y revisiones panorámicas.

Introduction: The evidence on COVID-19 is being produced at high speed, so it is challenging for decision-makers to keep up. It seems appropriate, then, to put into practice a novel approach able to provide the scientific community and other interested parties with quality evidence that is actionable, and rapidly and efficiently produced. Methods and analysis: We designed a protocol for multiple parallel systematic reviews and overviews of systematic reviews in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will search for primary studies and systematic reviews that answer different questions related to COVID-19 using both a centralized repository (Epistemonikos database) and a manual search in MEDLINE/PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We will also search for literature in several other sources. At least two researchers will independently undertake the selection of studies, data extraction, and assessment of the quality of the included studies. We will synthesize data for each question using meta-analysis, when possible, and we will prepare Summary of Findings tables according to the GRADE approach. All the evidence will be organized in an open platform (L·OVE - Living OVerview of Evidence) that will be continuously updated using artificial intelligence and a broad network of experts. Ethics and dissemination: No ethics approval is considered necessary. The results of these articles will be widely disseminated via peer-reviewed publications, social networks, and traditional media, and will be sent to relevant international organizations discussing this topic.