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PurposePrevious studies assessing impact of acute respiratory distress syndrome (ARDS) on mortality have shown conflicting results. We sought to assess the independent association of ARDS with in-hospital mortality among intensive care unit (ICU) patients with sepsis.MethodsWe studied two prospective sepsis cohorts drawn from the Early Assessment of Renal and Lung Injury (EARLI; n = 474) and Validating Acute Lung Injury markers for Diagnosis (VALID; n = 337) cohorts. ARDS was defined by Berlin criteria. We used logistic regression to compare in-hospital mortality in patients with and without ARDS, controlling for baseline severity of illness. We also estimated attributable mortality, adjusted for illness severity by stratification.ResultsARDS occurred in 195 EARLI patients (41%) and 99 VALID patients (29%). ARDS was independently associated with risk of hospital death in multivariate analysis, even after controlling for severity of illness, as measured by APACHE II (odds ratio [OR] 1.65 (95% confidence interval [CI] 1.02, 2.67), p = 0.04 in EARLI; OR 2.12 (CI 1.16, 3.92), p = 0.02 in VALID). Patients with severe ARDS (P/F < 100) primarily drove this relationship. The attributable mortality of ARDS was 27% (CI 14%, 37%) in EARLI and 37% (CI 10%, 51%) in VALID. ARDS was independently associated with ICU mortality, hospital length of stay (LOS), ICU LOS, and ventilator-free days.ConclusionsDevelopment of ARDS among ICU patients with sepsis confers increased risk of ICU and in-hospital mortality in addition to other important outcomes. Clinical trials targeting patients with severe ARDS will be best poised to detect measurable differences in these outcomes.

Angiopoietin-2 (Ang-2) is associated with vascular endothelial injury and permeability in the acute respiratory distress syndrome (ARDS) and sepsis. Elevated circulating Ang-2 levels may identify critically ill patients with distinct pathobiology amenable to targeted therapy. We hypothesized that plasma Ang-2 measured shortly after hospitalization among patients with sepsis would be associated with the development of ARDS and poor clinical outcomes. To test this hypothesis, we measured plasma Ang-2 in a cohort of 757 patients with sepsis, including 267 with ARDS, enrolled in the emergency department or early in their ICU course before the COVID-19 pandemic. Multivariable models were used to test the association of Ang-2 with the development of ARDS and 30-day morality. We found that early plasma Ang-2 in sepsis was associated with higher baseline severity of illness, the development of ARDS, and mortality risk. The association between Ang-2 and mortality was strongest among patients with ARDS and sepsis as compared to those with sepsis alone (OR 1.81 vs. 1.52 per log Ang-2 increase). These findings might inform models testing patient risk prediction and strengthen the evidence for Ang-2 as an appealing biomarker for patient selection for novel therapeutic agents to target vascular injury in sepsis and ARDS.

Background Studies quantifying SARS-CoV-2 have focused on upper respiratory tract or plasma viral RNA with inconsistent association with clinical outcomes. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 nucleocapsid antigen (N-antigen) concentration and both markers of host response and clinical outcomes. Methods SARS-CoV-2 N-antigen concentrations were measured in the first study plasma sample (D0), collected within 72 h of hospital admission, from 256 subjects admitted between March 2020 and August 2021 in a prospective observational cohort of hospitalized patients with COVID-19. The rank correlations between plasma N-antigen and plasma biomarkers of tissue damage, coagulation, and inflammation were assessed. Multiple ordinal regression was used to test the association between enrollment N-antigen plasma concentration and the primary outcome of clinical deterioration at one week as measured by a modified World Health Organization (WHO) ordinal scale. Multiple logistic regression was used to test the association between enrollment plasma N-antigen concentration and the secondary outcomes of ICU admission, mechanical ventilation at 28 days, and death at 28 days. The prognostic discrimination of an externally derived “high antigen” cutoff of N-antigen ≥ 1000 pg/mL was also tested. Results N-antigen on D0 was detectable in 84% of study participants. Plasma N-antigen levels significantly correlated with RAGE ( r  = 0.61), IL-10 ( r  = 0.59), and IP-10 ( r  = 0.59, adjusted p  = 0.01 for all correlations). For the primary outcome of clinical status at one week, each 500 pg/mL increase in plasma N-antigen level was associated with an adjusted OR of 1.05 (95% CI 1.03–1.08) for worse WHO ordinal status. D0 plasma N-antigen ≥ 1000 pg/mL was 77% sensitive and 59% specific (AUROC 0.68) with a positive predictive value of 23% and a negative predictive value of 93% for a worse WHO ordinal scale at day 7 compared to baseline. D0 N-antigen concentration was independently associated with ICU admission and 28-day mechanical ventilation, but not with death at 28 days. Conclusions Plasma N-antigen levels are readily measured and provide important insight into the pathogenesis and prognosis of COVID-19. The measurement of N-antigen levels early in-hospital course may improve risk stratification, especially for identifying patients who are unlikely to progress to severe disease.

IntroductionGlobal surveillance of physical activity (PA) of children and adolescents with questionnaires is limited by the use of instruments developed in high-income countries (HICs) lacking sociocultural adaptation, especially in low- and middle-income countries (LMICs); under-representation of some PA domains; and omission of active play, an important source of PA. Addressing these limitations would help improve international comparisons, and facilitate the cross-fertilisation of ideas to promote PA. We aim to develop and assess the reliability and validity of the app-based Global Adolescent and Child Physical Activity Questionnaire (GAC-PAQ) among 8–17 years old in 14 LMICs and HICs representing all continents; and generate the ‘first available data’ on active play in most participating countries.Methods and analysisOur study involves eight stages: (1) systematic review of psychometric properties of existing PA questionnaires for children and adolescents; (2) development of the GAC-PAQ (first version); (3) content validity assessment with global experts; (4) cognitive interviews with children/adolescents and parents in all 14 countries; (5) development of a revised GAC-PAQ; (6) development and adaptation of the questionnaire app (application); (7) pilot-test of the app-based GAC-PAQ; and, (8) main study with a stratified, sex-balanced and urban/rural-balanced sample of 500 children/adolescents and one of their parents/guardians per country. Participants will complete the GAC-PAQ twice to assess 1-week test–retest reliability and wear an ActiGraph wGT3X-BT accelerometer for 9 days to test concurrent validity. To assess convergent validity, subsamples (50 adolescents/country) will simultaneously complete the PA module from existing international surveys.Ethics and disseminationApprovals from research ethics boards and relevant organisations will be obtained in all participating countries. We anticipate that the GAC-PAQ will facilitate global surveillance of PA in children/adolescents. Our project includes a robust knowledge translation strategy sensitive to social determinants of health to inform inclusive surveillance and PA interventions globally.

Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration > 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration > 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level > 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. Conclusions Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.

The actions required to achieve higher-quality and harmonised global surveillance of child and adolescent movement behaviours (physical activity, sedentary behaviour including screen time, sleep) are unclear. To identify how to improve surveillance of movement behaviours, from the perspective of experts. This Delphi Study involved 62 experts from the SUNRISE International Study of Movement Behaviours in the Early Years and Active Healthy Kids Global Alliance (AHKGA). Two survey rounds were used, with items categorised under: (1) funding, (2) capacity building, (3) methods, and (4) other issues (e.g., policymaker awareness of relevant WHO Guidelines and Strategies). Expert participants ranked 40 items on a five-point Likert scale from 'extremely' to 'not at all' important. Consensus was defined as > 70% rating of 'extremely' or 'very' important. We received 62 responses to round 1 of the survey and 59 to round 2. There was consensus for most items. The two highest rated round 2 items in each category were the following; for funding (1) it was greater funding for surveillance and public funding of surveillance; for capacity building (2) it was increased human capacity for surveillance (e.g. knowledge, skills) and regional or global partnerships to support national surveillance; for methods (3) it was standard protocols for surveillance measures and improved measurement method for screen time; and for other issues (4) it was greater awareness of physical activity guidelines and strategies from WHO and greater awareness of the importance of surveillance for NCD prevention. We generally found no significant differences in priorities between low-middle-income (n = 29) and high-income countries (n = 30) or between SUNRISE (n = 20), AHKGA (n = 26) or both (n = 13) initiatives. There was a lack of agreement on using private funding for surveillance or surveillance research. This study provides a prioritised and international consensus list of actions required to improve surveillance of movement behaviours in children and adolescents globally.

Background Front-of-package labelling is a cost-effective strategy to help consumers make healthier choices and informed food purchases. The effect of labels is mediated by consumer understanding and acceptability of the label. We compared the acceptability and understanding of labels used in Latin-America among low- and middle-income Mexican adults. Methods Participants ( n  = 2105) were randomly assigned to one of three labels: Mexican Guideline Daily Allowances (GDA), Ecuador’s Multiple Traffic Lights (MTL), or Chile’s Warning Labels (WL) in red. Label acceptability was evaluated through items regarding likeability, attractiveness and perceived cognitive workload. Objective understanding was evaluated by asking participants to select the product with the lowest nutritional quality among three products. We measured the time participants took to choose the product. Differences in label acceptability, understanding and time required to choose a product across labels were tested. Results Compared to the GDA, a higher proportion of participants liked the MTL and WL, considered them attractive, and with a lower perceived cognitive workload ( p  < 0.05). Participants had 4.00 (2.86–5.59) times the odds of correctly identifying the product with the lowest nutritional quality when using the MTL label and 4.52 (3.24–6.29) times the odds when using the WL, in comparison to the GDA. Time required to choose the product was lower for the MTL (Median: 11.25 s; IQR = 8.00–16.09) and the WL (Median = 11.94 s, IQR = 8.56–16.52) compared to the GDA (Median: 15.31 s; IQR = 10.81–20.21; p  < 0.05). No differences were observed between the MTL and the WL. Conclusions GDA had the lowest acceptability and understanding among the labels tested. The MTL and the WL were more accepted and understood, and allowed low- and middle-income consumers to make nutrition-quality related decisions more quickly. WL or MTL may foster healthier food choices in the most vulnerable groups in Mexico compared to the current labelling format.

Front-of-pack labeling is a cost-effective strategy to decrease population consumption of sodium, sugar, saturated fat, total fat, and trans-fatty acids, considered critical nutrients for chronic disease. Our main objective was to explore the subjective understanding of labels that are currently used internationally among low- and middle-income Mexican consumers. We performed two phases of 10 focus groups with adolescents (13-15 y), young adults (21-23 y), mothers of children 3-12 y, fathers of children 3-12 y and older adults (55-70 y). Seven FOPL were evaluated: Guideline Daily Amounts, Multiple Traffic Light, Chilean Warning labels, Warning labels in Red, 5-Color Nutrition Label, Health Star Rating, and Healthy Choice label. Data was analyzed with a triangulation of researchers using a content analysis, based on three codes: 1) awareness and use of the Guideline Daily Amounts, 2) acceptability, and 3) subjective understanding of labels. Most participants were aware of the Guideline Daily Amounts, however they rarely used it because interpreting the information displayed on the label was too complicated. Health Star Rating, Warning labels, Multiple Traffic Light and the Healthy Choice logo labels were the most understandable, however the acceptability of the The Healthy Choice logo decreased as it did not provide information on specific ingredients. The Warning labels was the only label able to warn about critical nutrients that could represent a health risk. The Warning labels in red was more accepted compared to Warning labels in black. Results show that directive and semi-directive labels, such as Warning labels, Health Star Rating or Multiple Traffic Light, may be better at helping population of low- and middle income make healthier food choices, than non-directive FOPL such as the Guideline Daily Amounts implemented in México. The study results highlight the potential of Warning labels to support decreases in the consumption of critical ingredients in low- and middle-income Mexican consumers.

Physical inactivity and high sitting time are directly related to mortality and morbidity of non-communicable diseases (NCDs). Thus, improved understanding of the prevalence and trends of these behaviors could support the design of policies and interventions for NCDs prevention. To determine the current prevalence of physical inactivity and high sitting time, to analyze the trends, and to estimate the association of meeting/not meeting physical activity recommendations and low/high sitting time with sociodemographic characteristics and body mass index categories. Data from the 2018 National Health and Nutrition Survey were used. Moderate-to-vigorous physical activity (MVPA) and sitting minutes per week were calculated using the International Physical Activity Questionnaire short form (IPAQ). In total, 38,033 questionnaires of adults aged 20 to 69-year-old were analyzed. Adults were classified as physically inactive if they achieved less than 150 minutes per week of MVPA and as with high sitting time if they accumulated more than 420 minutes of sitting per day. Health and Nutrition National Surveys (ENSANUT) 2006, 2012 and 2018 were used to estimate the trends. In total, 16.5% were classified as physically inactive and 11.3% within the high sitting time category. Both prevalences increased more than 40% during the 12-y period (2006-2018). In 2018, men, younger adults, those living in urban areas, and people within the highest socioeconomical status and educational levels were more likely to not achieve physical activity recommendations and to be classified in the highest sitting time category. To stop current increased trends and achieve global targets, stronger and more concerted efforts to promote physical activity and reduce sitting time are required. Thus, continued surveillance of these behaviors is necessary.

Urban design, planning, and transport play an important role in the promotion of physical activity.1 Since 2010, active transportation systems and active urban design have been recognised as among the best investments for encouraging physical activity at scale.2 Designing and planning activity-promoting cities can help prevent premature mortality,3 reduce the high costs associated with physical inactivity,4,5 and help countries achieve some of the UN Sustainable Development Goals.6 During the COVID-19 pandemic, there have been declines in physical activity worldwide,7 highlighting the need for widespread, accessible, and safe public open spaces for active recreation and infrastructure for active transportation in cities. [...]as Adrian Bauman and colleagues show in their paper in this Lancet Series on physical activity, the Olympic Games alone do not improve population levels of physical activity.16 Transformational approaches that shift the focus away from individual responsibility and towards large-scale, systems-oriented strategies for physical activity promotion are crucial.1,6 These strategies are effective investments for physical activity promotion,2 and operate across multiple sectors and levels—eg, health care, education, urban planning and transport, environmental sustainability, communications, and public safety. somos_sonideas/Shutterstock.com Despite these known solutions for improving population levels of physical activity through urban initiatives, challenges for implementation remain.6 Securing funding for active recreation and active transport infrastructure can be difficult given competing interests—eg, some cities continue to prioritise maintaining and expanding infrastructure for cars. Too often there is a lack of alignment of local, regional, and national government priorities for the adoption of large-scale, systems-oriented strategies. [...]car-centric culture, policies, and design still predominate in many places.