Methodology and experiences of rapid advice guideline development for children with COVID-19: responding to the COVID-19 outbreak quickly and efficiently.

BACKGROUND: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. RESULT: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. CONCLUSIONS: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.

Guidelines for the prevention and management of children and adolescents with COVID-19.

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. DATA SOURCES: The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric". RESULTS: Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. CONCLUSIONS: This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

Associations of personal exposure to domestic heating and cooking fuel emissions and epidemiological effects on rural residents in the Fenwei Plain, China.

Solid fuel combustion for domestic heating in northern China in the wintertime is of great environmental and health concern. This study assesses personal exposure to particulate matter with different aerodynamic diameters and multiple gaseous pollutants from 123 rural residents in Yuncheng, the Fenwei Plain. The subjects are divided into groups based on the unique energy source applied, including biomass, coal, and electricity/no heating activities. The health effects of the exposures are expressed with four urinary biomarkers. The personal exposure levels to three different aerodynamic particle sizes (i.e., PM10, PM2.5, and PM1) of the electricity/no heating group are 5.1 % -12 % lower than those of the coal group. In addition, the exposure levels are 25 %-40 % lower for carbon monoxide (CO) and 10.8 %-20.3 % lower for ozone (O3) in the electricity/no heating group than the other two fuel groups. C-reactive protein (CRP) in the urine of the participants in biomass and coal groups is significantly higher than that in the electricity/no heating group, consistent with the observations on other biomarkers. Increases in 8-hydroxy-2 deoxyguanosine (8-OHdG), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) are observed for the exposures to higher concentrations of air pollutants. For instance, PMs and nitrogen dioxide (NO2) show significant impacts on positive correlations with 8-OHdG and IL-8, while O3 positively correlates with CRP. PM1 exhibits higher effects on the biomarkers than the gaseous pollutants, especially on VEGF and IL-8. The study indicates that excessive use of traditional domestic solid fuels could pose severe health effects on rural residents. The promotion of using clean energy is urgently needed in the rural areas of northern China.

Inflammatory and oxidative stress responses of healthy elders to solar-assisted large-scale cleaning system (SALSCS) and changes in ambient air pollution: A quasi-interventional study in Xi'an, China.

An outdoor solar assisted large-scale cleaning system (SALSCS) was constructed to mitigate the levels of fine particulate matter (PM2.5) in urban areas of Xi'an China, providing a quasi-experimental opportunity to examine the biologic responses to the changes in pollution level. We conducted this outdoor SALSCS based real-world quasi-interventional study to examine the associations of the SALSCS intervention and changes in air pollution levels with the biomarkers of systemic inflammation and oxidative stress in healthy elders. We measured the levels of 8-hydrox-2-deoxyguanosine (8-OHdG), Interlukin-6 (IL-6), as well as tumor necrosis factor alpha (TNF-α) from urine samples, and IL-6 from saliva samples of 123 healthy retired participants from interventional/control residential areas in two sampling campaigns. We collected daily 24-h PM2.5 samples in two residential areas during the study periods using mini-volume samplers. Data on PM10, gaseous pollutants and weather factors were collected from the nearest national air quality monitoring stations. We used linear mixed-effect models to examine the percent change in each biomarker associated with the SALSCS intervention and air pollution levels, after adjusting for time trend, seasonality, weather factors and personal characteristics. Results showed that the SALSCS intervention was significantly associated with decreases in the geometric mean of biomarkers by 47.6% (95% confidence interval: 16.5-67.2%) for 8-OHdG, 66% (31.0-83.3%) for TNF-α, 41.7% (0.2-65.9%) and 43.4% (13.6-62.9%) for urinary and salivary IL-6, respectively. An inter-quartile range increase of ambient PM2.5 exposure averaged on the day of the collection of bio-samples and the day before (34.1 µg/m3) was associated, albeit non-significantly so, with 22.8%-37.9% increases in the geometric mean of these biomarkers. This study demonstrated that the SALSCS intervention and decreased ambient air pollution exposure results in lower burden of systemic inflammation and oxidative stress in older adults.

Urban VOC profiles, possible sources, and its role in ozone formation for a summer campaign over Xi'an, China.

To insight the urban volatile organic compound (VOC) profiles and its contribution to ozone, four-time per day (8:00-9:00, 15:00-16:00, 19:00-20:00, and 23:00-24:00) off-line VOC samples were collected from 16th July to 28th July 2018 for a summer investigation campaign over Xi'an, China. The diurnal variation was significant that the lowest TVOC concentrations were observed in the midnight period (28.4 ± 25.6 ppbv) while the highest was shown in the morning (49.6 ± 40.1 ppbv). The differences of total non-methane VOCs (TVOCs) between weekdays and weekend were also significant that the weekend showed significantly high VOC levels than weekdays (p < 0.05) but did not lead to significant ambient O3 increase (p > 0.05). Isopentane, a general marker for vehicle exhaust, showed descending concentrations from morning to midnight and good correlation with vehicle numbers on road, indicating a potential source to the VOCs at this site. The results from PMF proved that vehicular exhaust was the largest source to the VOCs in this study (64.4%). VOC categories showed a reverse sequence in abundance of concentrations and OFP contributions that alkenes showed the highest OFPs although with the lowest abundance in TOVCs due to their high reactivity in photochemical reactions. High OFPs from ethylene and isopentane indicated that vehicular emissions could be the largest potential OFP source in this site. OFPs from isoprene (from 1.85 to 13.4 ppbv) indicated that biogenic VOCs should not be negligible in urban Xi'an city when controlling O3 pollutants. Comparison of two OFP methods was conducted and MIR method was proved to be more reasonable and scientific in summer Xi'an. Therefore, vehicular emission, the largest contributor to ambient VOCs and also OFPs, as well as biological source should be priority controlled in guiding VOC emissions and reducing O3 control policies.