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1.
Medwave ; 21(2): e8105, 2021 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-33830976

RESUMEN

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.

2.
Cochrane Database Syst Rev ; 3: CD013881, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33734435

RESUMEN

BACKGROUND: Interleukin 6 (IL-6) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19). Their immunosuppressive effect might be valuable in patients with COVID-19 characterised by substantial immune system dysfunction by controlling inflammation and promoting disease tolerance. OBJECTIVES: To assess the effect of IL-6 blocking agents compared to standard care alone or with placebo on efficacy and safety outcomes in COVID-19. We will update this assessment regularly. SEARCH METHODS: We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (up to 11 February 2021) and the L-OVE platform, and Cochrane COVID-19 Study Register to identify trials up to 26 February 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating IL-6 blocking agents compared with standard care alone or with placebo for people with COVID-19, regardless of disease severity. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. The protocol was amended to reduce the number of outcomes considered. Two review authors independently collected data and assessed the risk of bias with the Cochrane Risk of Bias 2 tool. We rated the certainty of evidence with the GRADE approach for the critical outcomes such as clinical improvement (defined as hospital discharge or improvement on the scale used by trialists to evaluate clinical progression or recovery) (day (D) 28 / ≥ D60); WHO Clinical Progression Score of level 7 or above (i.e. the proportion of participants with mechanical ventilation +/- additional organ support OR death) (D28 / ≥ D60); all-cause mortality (D28 / ≥ D60); incidence of any adverse events; and incidence of serious adverse events. MAIN RESULTS: We identified 10 RCTs with available data including one platform trial comparing tocilizumab and sarilumab with standard of care. These trials evaluated tocilizumab (nine RCTs including two platform trials; seven were reported as peer-reviewed articles, two as preprints; 6428 randomised participants); and two sarilumab (one platform trial reported as peer reviewed article, one reported as preprint, 880 randomised participants). All trials included were multicentre trials. They were conducted in Brazil, China, France, Italy, UK, USA, and four were multi-country trials. The mean age range of participants ranged from 56 to 65 years; 4572 (66.3%) of trial participants were male. Disease severity ranged from mild to critical disease. The reported proportion of participants on oxygen at baseline but not intubated varied from 56% to 100% where reported. Five trials reported the inclusion of intubated patients at baseline. We identified a further 20 registered RCTs of tocilizumab compared to placebo/standard care (five completed without available results, five terminated without available results, eight ongoing, two not recruiting); 11 RCTs of sarilumab (two completed without results, three terminated without available results, six ongoing); six RCTs of clazakisumab (five ongoing, one not recruiting); two RCTs of olokizumab (one completed, one not recruiting); one of siltuximab (ongoing) and one RCT of levilimab (completed without available results). Of note, three were cancelled (2 tocilizumab, 1 clazakisumab). One multiple-arm RCT evaluated both tocilizumab and sarilumab compared to standard of care, one three-arm RCT evaluated tocilizumab and siltuximab compared to standard of care and consequently they appear in each respective comparison. Tocilizumab versus standard care alone or with placebo a. Effectiveness of tocilizumab for patients with COVID-19 Tocilizumab probably results in little or no increase in the outcome of clinical improvement at D28 (RR 1.06, 95% CI 1.00 to 1.13; I2 = 40.9%; 7 RCTs, 5585 participants; absolute effect: 31 more with clinical improvement per 1000 (from 0 fewer to 67 more); moderate-certainty evidence). However, we cannot exclude that some subgroups of patients could benefit from the treatment. We did not obtain data for longer-term follow-up (≥ D60). The effect of tocilizumab on the proportion of participants with a WHO Clinical Progression Score of level of 7 or above is uncertain at D28 (RR 0.99, 95% CI 0.56 to 1.74; I2 = 64.4%; 3 RCTs, 712 participants; low-certainty evidence). We did not obtain data for longer-term follow-up (≥ D60). Tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo (RR 0.89, 95% CI 0.82 to 0.97; I2 = 0.0%; 8 RCTs, 6363 participants; absolute effect: 32 fewer deaths per 1000 (from 52 fewer to 9 fewer); high-certainty evidence). The evidence suggests uncertainty around the effect on mortality at ≥ D60 (RR 0.86, 95% CI 0.53 to 1.40; I2 = 0.0%; 2 RCTs, 519 participants; low-certainty evidence). b. Safety of tocilizumab for patients with COVID-19 The evidence is very uncertain about the effect of tocilizumab on adverse events (RR 1.23, 95% CI 0.87 to 1.72; I2 = 86.4%; 7 RCTs, 1534 participants; very low-certainty evidence). Nevertheless, tocilizumab probably results in slightly fewer serious adverse events than standard care alone or placebo (RR 0.89, 95% CI 0.75 to 1.06; I2 = 0.0%; 8 RCTs, 2312 participants; moderate-certainty evidence). Sarilumab versus standard care alone or with placebo The evidence is uncertain about the effect of sarilumab on all-cause mortality at D28 (RR 0.77, 95% CI 0.43 to 1.36; 2 RCTs, 880 participants; low certainty), on all-cause mortality at ≥ D60 (RR 1.00, 95% CI 0.50 to 2.0; 1 RCT, 420 participants; low certainty), and serious adverse events (RR 1.17, 95% CI 0.77 to 1.77; 2 RCTs, 880 participants; low certainty). It is unlikely that sarilumab results in an important increase of adverse events (RR 1.05, 95% CI 0.88 to 1.25; 1 RCT, 420 participants; moderate certainty). However, an increase cannot be excluded No data were available for other critical outcomes. AUTHORS' CONCLUSIONS: On average, tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo and probably results in slightly fewer serious adverse events than standard care alone or placebo. Nevertheless, tocilizumab probably results in little or no increase in the outcome clinical improvement (defined as hospital discharge or improvement measured by trialist-defined scales) at D28. The impact of tocilizumab on other outcomes is uncertain or very uncertain. With the data available, we were not able to explore heterogeneity. Individual patient data meta-analyses are needed to be able to identify which patients are more likely to benefit from this treatment. Evidence for an effect of sarilumab is uncertain and evidence for other anti-IL6 agents is unavailable. Thirty-nine RCTs of IL-6 blocking agents with no results are currently registered, of which nine are completed and seven trials were terminated with no results available. The findings of this review will be updated as new data are made available on the COVID-NMA platform (covid-nma.com).


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Interleucina-6/antagonistas & inhibidores , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Sesgo , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto
4.
BMC Med Res Methodol ; 20(1): 286, 2020 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-33256642

RESUMEN

BACKGROUND: Systematic reviews allow health decisions to be informed by the best available research evidence. However, their number is proliferating quickly, and many skills are required to identify all the relevant reviews for a specific question. METHODS AND FINDINGS: We screen 10 bibliographic databases on a daily or weekly basis, to identify systematic reviews relevant for health decision-making. Using a machine-based approach developed for this project we select reviews, which are then validated by a network of more than 1000 collaborators. After screening over 1,400,000 records we have identified more than 300,000 systematic reviews, which are now stored in a single place and accessible through an easy-to-use search engine. This makes Epistemonikos the largest database of its kind. CONCLUSIONS: Using a systematic approach, recruiting a broad network of collaborators and implementing automated methods, we developed a one-stop shop for systematic reviews relevant for health decision making.

5.
Medwave ; 20(11): e8080, 2020 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-33361753

RESUMEN

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.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , /tratamiento farmacológico , Adenosina Monofosfato/efectos adversos , Adenosina Monofosfato/uso terapéutico , Alanina/efectos adversos , Alanina/uso terapéutico , Antivirales/efectos adversos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial/estadística & datos numéricos , Resultado del Tratamiento
6.
Medwave ; 20(10): e8062, 2020 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-33361754

RESUMEN

Objective: To provide a review of the literature on the presence of SARS-CoV-2 in the sexual fluids of patients with COVID-19 and to observe its possible sexual transmission in a timely, rigorous, and continuously updated manner. Data sources: We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature, and a centralized repository in 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. The search will cover the period until the day before submission to a journal. Eligibility criteria for selecting studies and methods: We adapted an already published standard protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomized trials evaluating the sexual transmission of the SARS-CoV-2 virus. Randomized trials evaluating the sexual transmission of other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomized studies in COVID-19 will be searched if no direct evidence from randomized trials is found or if the direct evidence provides a low to a very low level of certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE 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 the review if the conclusions change or if there are substantial updates. PROSPERO Registration: (CRD42020189368).


Asunto(s)
/transmisión , Enfermedades Virales de Transmisión Sexual/transmisión , /epidemiología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Revisiones Sistemáticas como Asunto
7.
Medwave ; 20(11): e8074, 2020 Dec 14.
Artículo en Español, Inglés | MEDLINE | ID: mdl-33361755

RESUMEN

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.


Asunto(s)
/tratamiento farmacológico , Macrólidos/uso terapéutico , /mortalidad , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial/estadística & datos numéricos , Resultado del Tratamiento
8.
Medwave ; 20(11): e8079, 2020 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-33382060

RESUMEN

Objective: This living, systematic review aims to provide a timely, rigorous, and continuously updated summary of the available evidence on the role of cell-based therapies 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). 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. All the searches covered the period until 23 April 2020 (one day before submission). Eligibility criteria for selecting studies and methods: We adapted an already published standard protocol for multiple parallel systematic reviews to the specificities of this question. We searched for randomized trials evaluating the effectiveness and safety of cell-based therapies versus placebo or no treatment in patients with COVID-19. Anticipating the lack of randomized trials directly addressing this question, we also searched for trials evaluating other coronavirus infections, such as MERS-CoV and SARS-CoV, and nonrandomized studies in COVID-19. Two reviewers independently screened each study for eligibility. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit this review to a peer-reviewed journal every time the conclusions change or whenever there are substantial updates. Results: We screened 1 043 records, but no study was considered eligible. We identified 61 ongoing studies, including 39 randomized trials evaluating different types of cell-based therapies in COVID-19. Conclusions: We did not find any studies that met our inclusion criteria, and hence there is no evidence to support or refute the use of cell-based therapies for treating patients with COVID-19. A substantial number of ongoing studies should provide valuable evidence to inform researchers and decision-makers in the near future. PROSPERO Registration number: CRD42020179711.


Asunto(s)
/terapia , Tratamiento Basado en Trasplante de Células y Tejidos , Humanos
9.
Medwave ; 20(11)31-12-2020.
Artículo en Inglés | LILACS | ID: biblio-1146051

RESUMEN

Objective This living, systematic review aims to provide a timely, rigorous, and continuously updated summary of the available evidence on the role of cell-based therapies 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). 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. All the searches covered the period until 23 April 2020 (one day before submission). Eligibility criteria for selecting studies and methods We adapted an already published standard protocol for multiple parallel systematic reviews to the specificities of this question. We searched for randomized trials evaluating the effectiveness and safety of cell-based therapies versus placebo or no treatment in patients with COVID-19. Anticipating the lack of randomized trials directly addressing this question, we also searched for trials evaluating other coronavirus infections, such as MERS-CoV and SARS-CoV, and nonrandomized studies in COVID-19. Two reviewers independently screened each study for eligibility. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit this review to a peer-reviewed journal every time the conclusions change or whenever there are substantial updates. Results We screened 1 043 records, but no study was considered eligible. We identified 61 ongoing studies, including 39 randomized trials evaluating different types of cell-based therapies in COVID-19. Conclusions We did not find any studies that met our inclusion criteria, and hence there is no evidence to support or refute the use of cell-based therapies for treating patients with COVID-19. A substantial number of ongoing studies should provide valuable evidence to inform researchers and decision-makers in the near future. PROSPERO Registration number CRD42020179711


Asunto(s)
Humanos , Neumonía Viral/terapia , Infecciones por Coronavirus/terapia , Tratamiento Basado en Trasplante de Células y Tejidos
10.
Medwave ; 20(11)31-12-2020.
Artículo en Inglés | LILACS | ID: biblio-1146034

RESUMEN

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.


Asunto(s)
Humanos , Neumonía Viral/tratamiento farmacológico , Infecciones por Coronavirus/tratamiento farmacológico , Macrólidos/uso terapéutico , Neumonía Viral/mortalidad , Respiración Artificial/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Infecciones por Coronavirus/mortalidad , Betacoronavirus/aislamiento & purificación
11.
Medwave ; 20(11)31-12-2020.
Artículo en Inglés | LILACS | ID: biblio-1146025

RESUMEN

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.


Asunto(s)
Humanos , Antivirales/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adenosina Monofosfato/análogos & derivados , Infecciones por Coronavirus/tratamiento farmacológico , Alanina/análogos & derivados , Antivirales/efectos adversos , Neumonía Viral/mortalidad , Respiración Artificial/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto , Adenosina Monofosfato/efectos adversos , Adenosina Monofosfato/uso terapéutico , Resultado del Tratamiento , Infecciones por Coronavirus/mortalidad , Alanina/efectos adversos , Alanina/uso terapéutico
12.
PLoS One ; 15(11): e0241955, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33201896

RESUMEN

BACKGROUND AND PURPOSE: The objective of our systematic review is to identify prognostic factors that may be used in decision-making related to the care of patients infected with COVID-19. DATA SOURCES: We conducted highly sensitive searches in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase. The searches covered the period from the inception date of each database until April 28, 2020. No study design, publication status or language restriction were applied. STUDY SELECTION AND DATA EXTRACTION: We included studies that assessed patients with confirmed or suspected SARS-CoV-2 infectious disease and examined one or more prognostic factors for mortality or disease severity. Reviewers working in pairs independently screened studies for eligibility, extracted data and assessed the risk of bias. We performed meta-analyses and used GRADE to assess the certainty of the evidence for each prognostic factor and outcome. RESULTS: We included 207 studies and found high or moderate certainty that the following 49 variables provide valuable prognostic information on mortality and/or severe disease in patients with COVID-19 infectious disease: Demographic factors (age, male sex, smoking), patient history factors (comorbidities, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, cardiovascular disease, cardiac arrhythmia, arterial hypertension, diabetes, dementia, cancer and dyslipidemia), physical examination factors (respiratory failure, low blood pressure, hypoxemia, tachycardia, dyspnea, anorexia, tachypnea, haemoptysis, abdominal pain, fatigue, fever and myalgia or arthralgia), laboratory factors (high blood procalcitonin, myocardial injury markers, high blood White Blood Cell count (WBC), high blood lactate, low blood platelet count, plasma creatinine increase, high blood D-dimer, high blood lactate dehydrogenase (LDH), high blood C-reactive protein (CRP), decrease in lymphocyte count, high blood aspartate aminotransferase (AST), decrease in blood albumin, high blood interleukin-6 (IL-6), high blood neutrophil count, high blood B-type natriuretic peptide (BNP), high blood urea nitrogen (BUN), high blood creatine kinase (CK), high blood bilirubin and high erythrocyte sedimentation rate (ESR)), radiological factors (consolidative infiltrate and pleural effusion) and high SOFA score (sequential organ failure assessment score). CONCLUSION: Identified prognostic factors can help clinicians and policy makers in tailoring management strategies for patients with COVID-19 infectious disease while researchers can utilise our findings to develop multivariable prognostic models that could eventually facilitate decision-making and improve patient important outcomes. SYSTEMATIC REVIEW REGISTRATION: Prospero registration number: CRD42020178802. Protocol available at: https://www.medrxiv.org/content/10.1101/2020.04.08.20056598v1.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/mortalidad , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , Anciano , Envejecimiento , Betacoronavirus , Comorbilidad , Manejo de Datos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Pronóstico , Factores de Riesgo , Factores Socioeconómicos
13.
Medwave ; 20(10)30-11-2020.
Artículo en Inglés, Español | LILACS | ID: biblio-1145808

RESUMEN

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


Asunto(s)
Humanos , Neumonía Viral/transmisión , Enfermedades Virales de Transmisión Sexual/transmisión , Infecciones por Coronavirus/transmisión , Betacoronavirus/aislamiento & purificación , Neumonía Viral/epidemiología , Proyectos de Investigación , Infecciones por Coronavirus/epidemiología , Ensayos Clínicos Controlados como Asunto , Revisiones Sistemáticas como Asunto
15.
Ocul Immunol Inflamm ; : 1-6, 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32886537

RESUMEN

PURPOSE: To evaluate the different definition of refractoriness in uveitis in the literature. METHODS: We systematically searched the literature in order to identify definitions of refractory noninfectious uveitis in adult patients. A search strategy in the databases of MEDLINE and Scopus was used to find articles published between January 2005 and October 2018. RESULTS: Definitions of corticosteroids-refractoriness were related to two main concepts: persistence of inflammation despite the use of corticosteroid and recurrences above a dosage threshold. In terms of immunomodulatory therapy and biologic agents, we observed a great variety of definitions: persistence of inflammation, number of attacks, side effects or complications, symptoms, and best-corrected visual acuity. CONCLUSIONS: The results of this systematic review demonstrate the current lack of consensus on the definition for refractory uveitis, regardless of the treatment being used and revealed a new terminology based on a comprehensive and operational definition for each specific category of refractoriness.

17.
Medwave ; 20(6): e7978, 2020 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-32759894

RESUMEN

Objective: This living systematic review aims to provide a timely, rigorous, and continuously updated summary of the available evidence on the role of vitamin C in treating 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). In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it comprises and has been customized to group all COVID-19 evidence in one place. All the searches covered the period until April 29, 2020 (one day before submission). Study selection and methods: We adapted an already published standard protocol for multiple parallel systematic reviews. We searched for randomized trials evaluating the effect, in patients with COVID-19, of vitamin C versus placebo or no treatment. Anticipating the lack of randomized trials directly addressing this question, we also searched for trials evaluating MERS-CoV and SARS-CoV, and non-randomized studies in COVID-19. Two reviewers independently screened each study for eligibility. A living, web-based version of this review will be openly available during the COVID-19 pandemic, and we will resubmit it to the journal whenever there are substantial updates. Results: We screened 95 records, but no study was considered eligible. We identified 20 ongoing studies, including 13 randomized trials evaluating vitamin C in COVID-19. Conclusions: We did not find any studies that met our inclusion criteria, and hence there is no evidence to support or refute the use of vitamin C in the treatment of patients with COVID-19. A substantial number of ongoing studies should provide valuable evidence to inform researchers and decision-makers soon. PROSPERO Registration number: CRD42020181216.


Asunto(s)
Ácido Ascórbico/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/terapia , Neumonía Viral/terapia , Vitaminas/uso terapéutico , Humanos , Pandemias , Síndrome Respiratorio Agudo Grave/terapia
18.
BMJ ; 370: m2980, 2020 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-32732190

RESUMEN

OBJECTIVE: To compare the effects of treatments for coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020. STUDY SELECTION: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. RESULTS: 23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference -4.5 days, low certainty), remdesivir (-2.6 days, moderate certainty), and lopinavir-ritonavir (-1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation. CONCLUSION: Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol is included as a supplement. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.


Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/terapia , Neumonía Viral/terapia , Respiración Artificial/estadística & datos numéricos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Betacoronavirus/patogenicidad , Centers for Disease Control and Prevention, U.S./estadística & datos numéricos , China/epidemiología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/virología , Bases de Datos Factuales/estadística & datos numéricos , Combinación de Medicamentos , Medicina Basada en la Evidencia/métodos , Medicina Basada en la Evidencia/estadística & datos numéricos , Glucocorticoides/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , Metaanálisis en Red , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/mortalidad , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/uso terapéutico , Índice de Severidad de la Enfermedad , Nivel de Atención , Resultado del Tratamiento , Estados Unidos/epidemiología
19.
J Clin Epidemiol ; 127: 177-183, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32853762

RESUMEN

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.

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