Post-covid-19 conditions in adults: systematic review and meta-analysis of health outcomes in controlled studies.

Objective: To assess the impact of post-covid-19 conditions among adults. Design: Systematic review and meta-analysis of health outcomes in controlled studies. Data sources: Two sources were searched from database inception to 20 October 2022: Cochrane covid-19 study register (comprising Cochrane Central Register of Controlled Trials, Medline, Embase, clinicalTrials.gov, World Health Organization's International Clinical Trials Registry Platform, medRxiv) and WHO's covid-19 research database. Eligibility criteria: Cohort studies recruiting more than 100 participants with a control group and a follow-up of at least 12 weeks were included. Adults who were documented to have SARS-CoV-2 infection based on clinical, imaging, or laboratory criteria were included. Data extraction and synthesis: Two independent reviewers extracted data. The main outcomes included quality of life, functionality in daily activities, use of resources, recovery rates (cluster of symptoms), and the incidence of new medical diagnoses. Data were pooled using a random effects model. The risk of bias was assessed with the Joanna Briggs Institute critical appraisal tool for cohort studies. Results: We included 63 controlled cohort studies, encompassing more than 96 million participants. Based on five studies, we found a reduction in overall quality of life between individuals with confirmed SARS-CoV-2 infection versus controls at six to 24 months follow-up, although heterogeneity was very high (mean difference in EQ-5D scale -5.28 (95% confidence interval -7.88 to 2.68; I2=93.81%). Evidence from ten studies, which could not be pooled in a meta-analysis, indicated that an increased rate of functional impairment associated with SARS-CoV-2 infection. Use of care increased compared with controls at six to 24 months follow-up at intensive care units (risk ratio 2.00 (95% confidence interval 0.69 to 5.80), five studies, I2=91.96%) and in outpatient care (1.12 (1.01 to 1.24), seven studies, I2=99.51%). Regarding persistent symptoms, individuals with documented SARS-CoV-2 infection had an increased risk of having two or more persistent symptoms at follow-up, especially those related to neurological clusters (ie, risk ratio 1.51 (95% confidence interval 1.17 to 1.93), I2=98.91%). Evidence also showed an increased incidence of a wide variety of metabolic, cardiovascular, neurological, respiratory, haematological and other incident diagnoses. Conclusion: Evidence suggests functional impairment after SARS-CoV-2 infection, in addition to a higher use of resources and a higher incidence of widely varying medical diagnoses. These results should be interpreted with caution, considering the high heterogeneity across studies and study limitations related to outcome measurement and attrition of participants. Systematic review registration: Open Science Framework, osf.io/drm39.

Short and Long-Term Wellbeing of Children following SARS-CoV-2 Infection: A Systematic Review.

Post-COVID conditions in children and adolescents were mostly investigated as the incidence of individual or clusters of symptoms. We aimed to describe the findings of studies assessing key outcomes related to global wellbeing and recovery in children and adolescents from a public health perspective. We searched the Cochrane COVID-19 Study Register and WHO COVID-19 Global literature on coronavirus disease database on 5 November 2021 and tracked ongoing studies published after this date. We included observational studies on children and adolescents with a follow-up greater than 12 weeks and focused on the outcomes of quality of life, recovery/duration of symptoms, school attendance and resource use/rehabilitation. We assessed their methodological quality, and we prepared a narrative synthesis of the results. We included 21 longitudinal and 4 cross-sectional studies (6 with a control group) with over 68 thousand unvaccinated children and adolescents with mostly asymptomatic or mild disease. Study limitations included convenience sampling, a poor description of their study population and heterogeneous definitions of outcomes. Quality of life was not largely affected in adolescents following COVID-19, but there might be greater impairment in young children and in those with more severe forms of the disease (4 studies). There might also be an impairment in daily activities and increased school absenteeism following COVID-19, but the findings were heterogeneous (5 studies). A total of 22 studies provided highly variable estimates based on heterogeneous definitions of overall persistence of symptoms (recovery), ranging from 0 to 67% at 8-12 weeks and 8 to 51% at 6-12 months. We found limited data on resource use and the need for rehabilitation. One controlled study indicated that the quality of life of infected children and adolescents might not substantially differ from controls. All controlled studies found a higher burden of persistent symptoms in COVID-19 cases compared with test-negative controls or cases of influenza. There is limited evidence on the short and long-term well-being of children following SARS-CoV-2 infection. High-quality longitudinal studies with control groups are needed to describe the outcomes in this population, especially in vaccinated children and those affected by new variants of the virus.

Long-Term Health Symptoms and Sequelae Following SARS-CoV-2 Infection: An Evidence Map.

Post-COVID-19 conditions, also known as 'Long-COVID-19', describe a longer and more complex course of illness than acute COVID-19 with no widely accepted uniform case definition. We aimed to map the available evidence on persistent symptoms and sequelae following SARS-CoV-2 in children and adults. We searched the Cochrane COVID-19 Study Register and the WHO COVID-19 Global literature on coronavirus disease database on 5 November 2021. We included longitudinal and cross-sectional studies and we extracted their characteristics, including the type of core outcomes for post-COVID-19 conditions. We included 565 studies (657 records). Most studies were uncontrolled cohort studies. The median follow-up time was 13 weeks (IQR 9 to 24). Only 72% of studies were conducted in high-income countries, 93% included unvaccinated adults with mild-to-critical disease, only 10% included children and adolescents, and less than 5% included children under the age of five. While most studies focused on health symptoms, including respiratory symptoms (71%), neurological symptoms (57%), fatigue (54%), pain (50%), mental functioning (43%), cardiovascular functioning (40%), and post-exertion symptoms (28%), cognitive function (26%), fewer studies assessed other symptoms such as overall recovery (24%), the need for rehabilitation (18%), health-related quality of life (16%), changes in work/occupation and study (10%), or survival related to long-COVID-19 (4%). There is a need for controlled cohort studies with long-term follow-up and a focus on overall recovery, health-related quality of life, and the ability to perform daily tasks. Studies need to be extended to later phases of the pandemic and countries with low resources.

Patients' participation in government-sponsored guidelines in Latin America: a cross-sectional study.

BACKGROUND: It is recommended that patients actively participate in clinical practice guideline (CPG) development, which allows consideration of their values and preferences and improves adherence to recommendations. The development of CPGs throughout Latin America is variable and diverse, and the inclusion of patients' participation is unknown. OBJECTIVES: To evaluate the methods of patients' participation in government-sponsored CPGs in Latin America, the type of CPG development and the use of Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methods. DESIGN: Cross-sectional study. We included CPGs developed over the last 10 years through a comprehensive hand search in official national government websites and biomedical databases. MAIN OUTCOME MEASURE: The type of patients' participation was coded according to five predefined categories. We also report the proportion of application of GRADE methods. RESULTS: We included 408 CPGs from 10 countries: 74% (n=303) were de novo development, 13%(n=55) used an adaptation method and 10%(n=41) used both adaptation and de novo methods. Only 45% (n=185) applied the GRADE approach, ranging from 14% (n=12) of CPGs in Brazil to 89% (n=56) of CPGs in Colombia. Only 23% (n=95) of CPGs included at least one method of patients' participation. Mexico was one of the largest CPG producers (100 CPGs), but none included methods of patients' participation; in turn, in countries with lower production of government-sponsored CPGs, patients' participation was found in almost 88%. Guidelines using the GRADE approach were more likely to use methods of patients' participation. These methods were highly variable: 46% (n=44) incorporated patients in the panel, 81% (n=77) searched for evidence about patients' values and preferences, 43% (n=39) used an external review of the draft recommendations by patients, 38% (n=36) used public comments, and 2% included other methods for stakeholders' participation. CONCLUSION: Only one quarter of government-sponsored CPGs in the Latin American region incorporated a method for patients' participation, which varied considerably across the selected countries. These findings highlight the need to improve CPG development methods to systematically incorporate patients' values and preferences when drafting recommendations.

Diaphragmatic dysfunction associated with invasive mechanical ventilation in critically ill adult patients / [Disfunción diafragmática asociada a la ventilación mecánica invasiva en pacientes adultos críticamente enfermos]

Invasive mechanical ventilation (VMI) is a life support therapy that is not free of complications, such as ventilator induced diaphragmatic dysfunction, which is characterized by atrophy and weakness of the muscle. Interest in this pathology seems to be based on the association found with negative clinical results. The prevalence ranges between 29 and 80%, probably due to the variability between the different diagnostic methods and the time of evaluation. The gold standard continues to be the transdiaphragmatic negative pressure generated by the bilateral stimulation of the phrenic nerves, although due to the lack of practicality, diaphragmatic ultrasound began to be used. Although it has several modalities, not all of them have correlation analysis with the gold standard. Another problem arises when analyzing the independent association between pathology and VMI, since confusing factors are not easy to isolate.

La ventilación mecánica invasiva (VMI) es una terapia de soporte vital que no está exenta de complicaciones, como la disfunción diafragmática inducida por la ventilación mecánica, que se caracteriza por atrofia y debilidad de dicho musculo. El interés en esta patología parece estar basado en la asociación encontrada con resultados clínicos negativos. La prevalencia oscila entre 29 y 80%, probablemente debido a la variabilidad entre los diferentes métodos diagnósticos y el momento de la evaluación. El patrón de oro continúa siendo la presión negativa transdiafragmática generada por la estimulación bilateral de los nervios frénicos, aunque por la falta de practicidad, se comenzó a utilizar la ecografía diafragmática. Si bien cuenta con varias modalidades, no todas tienen análisis de correlación con el patrón de oro. Otra problemática surge al momento de analizar la asociación independiente entre la patología y la VMI, ya que los factores confusores no son sencillos de aislar.

Rapid reviews: definitions and uses. / Revisiones rápidas: definiciones y usos.

This article is the first in a collaborative methodological series of narrative reviews on biostatistics and clinical epidemiology. This review aims to present rapid reviews, compare them with systematic reviews, and mention how they can be used. Rapid reviews use a methodology like systematic reviews, but through shortcuts applied, they can attain answers in less than six months and with fewer resources. Decision-makers use them in both America and Europe. There is no consensus on which shortcuts have the least impact on the reliability of conclusions, so rapid reviews are heterogeneous. Users of rapid reviews should identify these shortcuts in the methodology and be cautious when interpreting the conclusions, although they generally reach answers concordant with those obtained through a formal systematic review. The principal value of rapid reviews is to respond to health decision-makers needs when the context demands answers in limited time frames.

Este artículo es el primero de una serie metodológica colaborativa de revisiones narrativas sobre temáticas de bioestadística y epidemiología clínica. El objetivo de esta revisión es presentar las revisiones rápidas, compararlas con las revisiones sistemáticas y mencionar su uso actual. Las revisiones rápidas utilizan una metodología similar a las revisiones sistemáticas, pero mediante atajos utilizados en su desarrollo; permiten alcanzar respuestas en menos de seis meses y con menos recursos, por lo que son utilizadas por tomadores de decisiones tanto en América como Europa. No existe consenso sobre cuáles atajos tienen menor impacto en la confiabilidad de las conclusiones, por lo que las revisiones rápidas son heterogéneas entre sí. Los consumidores deben identificar estos atajos en la metodología y ser precavidos en la interpretación de las conclusiones, aunque generalmente alcanzan respuestas concordantes con las obtenidas mediante una revisión sistemática tradicional. Su principal atractivo es ajustarse a las necesidades de los tomadores de decisiones en salud, cuando el contexto exige respuestas en plazos de tiempo acotados.

Revisiones rápidas: definiciones y usos / Rapid reviews: definitions and uses

Este artículo es el primero de una serie metodológica colaborativa de revisiones narrativas sobre temáticas de bioestadística y epidemiología clínica. El objetivo de esta revisión es presentar las revisiones rápidas, compararlas con las revisiones sistemáticas y mencionar su uso actual. Las revisiones rápidas utilizan una metodología similar a las revisiones sistemáticas, pero mediante atajos utilizados en su desarrollo; permiten alcanzar respuestas en menos de seis meses y con menos recursos, por lo que son utilizadas por tomadores de decisiones tanto en América como Europa. No existe consenso sobre cuáles atajos tienen menor impacto en la confiabilidad de las conclusiones, por lo que las revisiones rápidas son heterogéneas entre sí. Los consumidores deben identificar estos atajos en la metodología y ser precavidos en la interpretación de las conclusiones, aunque generalmente alcanzan respuestas concordantes con las obtenidas mediante una revisión sistemática tradicional. Su principal atractivo es ajustarse a las necesidades de los tomadores de decisiones en salud, cuando el contexto exige respuestas en plazos de tiempo acotados.

This article is the first in a collaborative methodological series of narrative reviews on biostatistics and clinical epidemiology. This review aims to present rapid reviews, compare them with systematic reviews, and mention how they can be used. Rapid reviews use a methodology like systematic reviews, but through shortcuts applied, they can attain answers in less than six months and with fewer resources. Decision-makers use them in both America and Europe. There is no consensus on which shortcuts have the least impact on the reliability of conclusions, so rapid reviews are heterogeneous. Users of rapid reviews should identify these shortcuts in the methodology and be cautious when interpreting the conclusions, although they generally reach answers concordant with those obtained through a formal systematic review. The principal value of rapid reviews is to respond to health decision-makers' needs when the context demands answers in limited time frames.

Use of Cochrane reviews in nationally-developed clinical practice guidelines in Latin America. / Uso de revisiones Cochrane en guías de práctica clínica desarrolladas a nivel nacional en América Latina.

INTRODUCTION: Cochrane reviews, recognized as the benchmark for high-quality summaries, facilitates healthcare decision-making bringing together all the evidence on an intervention. To date, their inclusion in the Latin American guidelines remains unknown. OBJECTIVE: To evaluate the use of Cochrane reviews in nationally-developed clinical practice guidelines in Latin America. METHODS: We conducted a hand search in official government websites and biomedical databases between October 2019 and December 2019, including government-sponsored clinical practice guidelines with recommendations for both the management of health conditions or a healthy lifestyle of the last ten years. RESULTS: We included 408 clinical practice guidelines from ten countries. We found that 69.8% of them cited Cochrane reviews in their recommendations, and 76.1% of those also used them in their key recommendations. Clinical practice guidelines that did not use Cochrane reviews covered a wide range of topics for which several Cochrane reviews can be found. Countries using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for grading recommendations were more likely to use Cochrane reviews in a higher percentage of their guidelines (79.4% vs. 61.8%; odds ratio: 2.3; 95% confidence interval: 1.5 to 3.7, p = 0.0001). CONCLUSIONS: Over two-thirds of clinical practice guidelines in Latin America use Cochrane reviews to frame their recommendations. It is necessary to increase the uptake of Cochrane reviews in the region for the development of clinical practice guidelines.

INTRODUCCIÓN: Las revisiones Cochrane, reconocidas como el punto de referencia para resúmenes de alta calidad, facilitan la toma de decisiones en atención médica reuniendo toda la evidencia disponible sobre una intervención. Hasta la fecha, se desconoce su inclusión en las guías latinoamericanas. OBJETIVO: Evaluar el uso de revisiones Cochrane en guías de práctica clínica desarrolladas a nivel nacional en América Latina. MÉTODOS: Realizamos una búsqueda manual en sitios web oficiales del gobierno y bases de datos biomédicas entre octubre y diciembre de 2019, incluyendo guías de práctica clínica patrocinadas por los gobiernos nacionales con recomendaciones tanto para el manejo de condiciones de salud como para un estilo de vida saludable de los últimos diez años. RESULTADOS: Se incluyeron 408 guías de práctica clínica de diez países. Encontramos que 69,8% de ellas citó revisiones Cochrane en sus recomendaciones y 76,1% de ellas también las utilizó en sus recomendaciones clave. Las guías de práctica clínica que no utilizaron revisiones Cochrane cubrieron una amplia gama de temas, para los cuales se pueden encontrar varias revisiones Cochrane. Los países que utilizan el enfoque Grading of Recommendations, Assessment, Development and Evaluation (GRADE), tenían más probabilidades de utilizar las revisiones Cochrane en un porcentaje más alto de sus guías (79,4% frente a 61,8%; odds ratio: 2,3; intervalo de confianza del 95%: 1,5 a 3,7, p = 0,0001). CONCLUSIONES: Más de dos tercios de las guías de práctica clínica en América Latina utilizan revisiones Cochrane para enmarcar sus recomendaciones. Es necesario incrementar el uso de las revisiones Cochrane en la región para el desarrollo de guías de práctica clínica.

Clinical trials with sequential analysis that were early-stopped: How to interpret them? / Ensayos clínicos con análisis secuencial y su interrupción precoz ¿cómo interpretarlos?

Sequential analysis of clinical trials allows researchers a continuous monitoring of emerging data and greater security to avoid subjecting the trial participants to a less effective therapy before the inferiority is evident, while controlling the overall error rate. Although it has been widely used since its development, sequential analysis is not problem-free. Among them main issues to be mentioned are the balance between safety and efficacy, overestimation of the effect size of interventions and conditional bias. In this review, we develop different aspects of this methodology and the impact of including early-stopped clinical trials in systematic reviews with meta-analysis.

El análisis secuencial de ensayos clínicos permite el monitoreo continuo de los datos emergentes para el investigador, así como una mayor seguridad para evitar someter a los participantes a una terapia inferior o fútil en términos de eficacia o seguridad, antes que esta sea evidente, mientras se controla la tasa de error general. Si bien ha sido extensamente empleado desde su desarrollo, no está exento de problemas. Entre ellos se puede mencionar el balance entre seguridad y eficacia, el sesgo condicional y la sobrestimación del tamaño del efecto de las intervenciones. En esta revisión se desarrollan distintos aspectos de esta metodología y el impacto que tiene la inclusión de ensayos clínicos precozmente interrumpidos en las revisiones sistemáticas con metanálisis.

Ensayos clínicos con análisis secuencial y su interrupción precoz ¿cómo interpretarlos? / How to interpret clinical trials with sequential analysis that were stopped early

El análisis secuencial de ensayos clínicos permite el monitoreo continuo de los datos emergentes para el investigador, así como una mayor seguridad para evitar someter a los participantes a una terapia inferior o fútil en términos de eficacia o seguridad, antes que esta sea evidente, mientras se controla la tasa de error general. Si bien ha sido extensamente empleado desde su desarrollo, no está exento de problemas. Entre ellos se puede mencionar el balance entre seguridad y eficacia, el sesgo condicional y la sobrestimación del tamaño del efecto de las intervenciones. En esta revisión se desarrollan distintos aspectos de esta metodología y el impacto que tiene la inclusión de ensayos clínicos precozmente interrumpidos en las revisiones sistemáticas con metanálisis.

Sequential analysis of clinical trials allows researchers a continuous monitoring of emerging data and greater security to avoid subjecting the trial participants to a less effective therapy before the inferiority is evident, while controlling the overall error rate. Although it has been widely used since its development, sequential analysis is not problem-free. Among them main issues to be mentioned are the balance between safety and efficacy, overestimation of the effect size of interventions and conditional bias. In this review, we develop different aspects of this methodology and the impact of including early-stopped clinical trials in systematic reviews with meta-analysis.

Uso de revisiones Cochrane en guías de práctica clínica desarrolladas a nivel nacional en América Latina / Use of Cochrane reviews in nationally-developed clinical practice guidelines in Latin America

INTRODUCCIÓN: Las revisiones Cochrane, reconocidas como el punto de referencia para resúmenes de alta calidad, facilitan la toma de decisiones en atención médica reuniendo toda la evidencia disponible sobre una intervención. Hasta la fecha, se desconoce su inclusión en las guías latinoamericanas. OBJETTIVO: Evaluar el uso de revisiones Cochrane en guías de práctica clínica desarrolladas a nivel nacional en América Latina. Métodos: Realizamos una búsqueda manual en sitios web oficiales del gobierno y bases de datos biomédicas entre octubre y diciembre de 2019, incluyendo guías de práctica clínica patrocinadas por los gobiernos nacionales con recomendaciones tanto para el manejo de condiciones de salud como para un estilo de vida saludable de los últimos diez años. RESULTADOS: Se incluyeron 408 guías de práctica clínica de diez países. Encontramos que 69,8% de ellas citó revisiones Cochrane en sus recomendaciones y 76,1% de ellas también las utilizó en sus recomendaciones clave. Las guías de práctica clínica que no utilizaron revisiones Cochrane cubrieron una amplia gama de temas, para los cuales se pueden encontrar varias revisiones Cochrane. Los países que utilizan el enfoque Grading of Recommendations, Assessment, Development and Evaluation (GRADE), tenían más probabilidades de utilizar las revisiones Cochrane en un porcentaje más alto de sus guías (79,4% frente a 61,8%; odds ratio: 2,3; intervalo de confianza del 95%: 1,5 a 3,7, p = 0,0001). CONCLUSIONES: Más de dos tercios de las guías de práctica clínica en América Latina utilizan revisiones Cochrane para enmarcar sus recomendaciones. Es necesario incrementar el uso de las revisiones Cochrane en la región para el desarrollo de guías de práctica clínica.

INTRODUCTION: Cochrane reviews, recognized as the benchmark for high-quality summaries, facilitates healthcare decision-making bringing together all the evidence on an intervention. To date, their inclusion in the Latin American guidelines remains unknown. OBJECTIVE: To evaluate the use of Cochrane reviews in nationally-developed clinical practice guidelines in Latin America. METHODS: We conducted a hand search in official government websites and biomedical databases between October 2019 and December 2019, including government-sponsored clinical practice guidelines with recommendations for both the management of health conditions or a healthy lifestyle of the last ten years. RESULTS: We included 408 clinical practice guidelines from ten countries. We found that 69.8% of them cited Cochrane reviews in their recommendations, and 76.1% of those also used them in their key recommendations. Clinical practice guidelines that did not use Cochrane reviews covered a wide range of topics for which several Cochrane reviews can be found. Countries using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for grading recommendations were more likely to use Cochrane reviews in a higher percentage of their guidelines (79.4% vs. 61.8%; odds ratio: 2.3; 95% confidence interval: 1.5 to 3.7, p = 0.0001). CONCLUSIONS: Over two-thirds of clinical practice guidelines in Latin America use Cochrane reviews to frame their recommendations. It is necessary to increase the uptake of Cochrane reviews in the region for the development of clinical practice guidelines.

Movilización precoz en pacientes en ventilación mecánica: Una revisión narrativa / Early Mobilization In Mechanically Ventilated Patients. A Narrative Review

La aplicación de nuevas estrategias para el manejo del paciente crítico en ventilación mecánica ha llevado a un aumento de la supervivencia y, con ello, a un aumento de la incidencia de diversas complicaciones, entre ellas la debilidad muscular. Ésta se asocia a mayor duración de la ventilación mecánica y del proceso de destete, estadía más prolongada en la Unidad de Terapia Intensiva (UTI) y el hospital en general, y un pobre estado funcional al momento del alta hospitalaria. En vista de estos hallazgos, se ha propuesto la implementación de protocolos de movilización precoz con el fin de reducir el impacto negativo que la debilidad tiene en los pacientes que reciben ventilación mecánica.

New strategies for management of critically ill patients on mechanical ventilation have led to an increase in survival and the incidence of complications, including muscular weakness. The late is associated with longer duration of mechanical ventilation, longer duration of weaning process, longer intensive care unit and hospital stay and poor functional status at hospital discharge. In view of these findings, early mobilization protocols have been proposed in order to reduce the negative impact that muscular weakness has on patients receiving mechanical ventilation.