Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia

BACKGROUND Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizu- mab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials. METHODS In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approxi- mately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo. RESULTS Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, −1.0; 95% CI, −2.5 to 0; P=0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, –7.6 to 8.2; nominal P=0.94). CONCLUSIONS In this randomized trial involving hospitalized patients with severe Covid-19 pneu- monia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann–La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov num- ber, NCT04320615.

"If I am alive, I am happy": Defining quality of care from the perspectives of key maternal and newborn health stakeholders in Papua New Guinea.

Quality maternal and newborn healthcare is essential to improve experiences and health outcomes for mothers and babies. In many low to middle income countries, such as Papua New Guinea, there are initiatives to increase antenatal care attendance and facility births. To develop and implement initiatives that are appropriate, relevant, and contextualised to a community, it is important to understand how quality of care is perceived and defined by different maternal and newborn healthcare stakeholders. The aim of this study was to understand how women, their partners, healthcare professionals, healthcare managers, and provincial health administrators in East New Britain, Papua New Guinea define quality of pregnancy, childbirth, and immediate postnatal care. An exploratory qualitative study underpinned by a partnership-defined quality approach was undertaken. In total, 42 participants from five different healthcare facilities in East New Britain, Papua New Guinea, were interviewed. These included women, partners, healthcare professionals, healthcare managers, and provincial health administrators. Interviews were analysed using thematic analysis, assisted by NVivo computer software. Four themes were identified aligning with the journey a woman takes throughout the health system. These included (I) Ensuring Access: Arriving at the health centre, (II) Experiencing Positive Care: What the staff do, (III) Having the Bare Minimum: Resources available to the service, and (IV) Meeting Expectations: Outcomes of care. Stakeholder groups had significant overlap in how quality of care was defined, however women and partners focussed more on elements relating to experience of care, while clinical stakeholders focussed on elements relating to provision of care. There is a gap in how stakeholders define quality maternal and newborn healthcare, and the quality of the care which is administered and received

Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia

BACKGROUND Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials. METHODS In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo. RESULTS Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, −1.0; 95% CI, −2.5 to 0; P=0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points; 95% CI, –7.6 to 8.2; nominal P=0.94). CONCLUSIONS In this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann–La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov number, NCT04320615

Children as vulnerable consumers: a first conceptualisation

© 2015 Westburn Publishers Ltd. Understandings of consumer vulnerability remain contentious and despite recent developments, models remain unsuitable when applied to children. Taxonomic models, and those favouring a ‘state’- or ‘class’-based approach have been replaced by those attempting to tackle both individual and structural antecedents. However, these are still overly individualistic and fail to progress from an artificial view that these dimensions work separately and independently. In contrast, the new sociology of childhood conceptualises childhood as a hybridised, fluid combination of structure and agency. This paper introduces this approach, new to the consumer vulnerability field, and proposes that it has considerable implications for the way that children’s consumer vulnerability is theorised and researched, and for the formulation of policy

Opportunities and Constraints in Characterizing Landscape Distribution of an Invasive Grass from Very High Resolution Multi-Spectral Imagery

Understanding spatial distributions of invasive plant species at early infestation stages is critical for assessing the dynamics and underlying factors of invasions. Recent progress in very high resolution remote sensing is facilitating this task by providing high spatial detail over whole-site extents that are prohibitive to comprehensive ground surveys. This study assessed the opportunities and constraints to characterize landscape distribution of the invasive grass medusahead (Elymus caput-medusae) in a ∼36.8 ha grassland in California, United States from 0.15m-resolution visible/near-infrared aerial imagery at the stage of late spring phenological contrast with dominant grasses. We compared several object-based unsupervised, single-run supervised and hierarchical approaches to classify medusahead using spectral, textural, and contextual variables. Fuzzy accuracy assessment indicated that 44–100% of test medusahead samples were matched by its classified extents from different methods, while 63–83% of test samples classified as medusahead had this class as an acceptable candidate. Main sources of error included spectral similarity between medusahead and other green species and mixing of medusahead with other vegetation at variable densities. Adding texture attributes to spectral variables increased the accuracy of most classification methods, corroborating the informative value of local patterns under limited spectral data. The highest accuracy across different metrics was shown by the supervised single-run support vector machine with seven vegetation classes and Bayesian algorithms with three vegetation classes; however, their medusahead allocations showed some “spillover” effects due to misclassifications with other green vegetation. This issue was addressed by more complex hierarchical approaches, though their final accuracy did not exceed the best single-run methods. However, the comparison of classified medusahead extents with field segments of its patches overlapping with survey transects indicated that most methods tended to miss and/or over-estimate the length of the smallest patches and under-estimate the largest ones due to classification errors. Overall, the study outcomes support the potential of cost-effective, very high-resolution sensing for the site-scale detection of infestation hotspots that can be customized to plant phenological schedules. However, more accurate medusahead patch delineation in mixed-cover grasslands would benefit from testing hyperspectral data and using our study’s framework to inform and constrain the candidate vegetation classes in heterogeneous locations

Opportunities and Constraints in Characterizing Landscape Distribution of an Invasive Grass from Very High Resolution Multi-Spectral Imagery

Understanding spatial distributions of invasive plant species at early infestation stages is critical for assessing the dynamics and underlying factors of invasions. Recent progress in very high resolution remote sensing is facilitating this task by providing high spatial detail over whole-site extents that are prohibitive to comprehensive ground surveys. This study assessed the opportunities and constraints to characterize landscape distribution of the invasive grass medusahead (Elymus caput-medusae) in a ∼36.8 ha grassland in California, United States from 0.15m-resolution visible/near-infrared aerial imagery at the stage of late spring phenological contrast with dominant grasses. We compared several object-based unsupervised, single-run supervised and hierarchical approaches to classify medusahead using spectral, textural, and contextual variables. Fuzzy accuracy assessment indicated that 44–100% of test medusahead samples were matched by its classified extents from different methods, while 63–83% of test samples classified as medusahead had this class as an acceptable candidate. Main sources of error included spectral similarity between medusahead and other green species and mixing of medusahead with other vegetation at variable densities. Adding texture attributes to spectral variables increased the accuracy of most classification methods, corroborating the informative value of local patterns under limited spectral data. The highest accuracy across different metrics was shown by the supervised single-run support vector machine with seven vegetation classes and Bayesian algorithms with three vegetation classes; however, their medusahead allocations showed some “spillover” effects due to misclassifications with other green vegetation. This issue was addressed by more complex hierarchical approaches, though their final accuracy did not exceed the best single-run methods. However, the comparison of classified medusahead extents with field segments of its patches overlapping with survey transects indicated that most methods tended to miss and/or over-estimate the length of the smallest patches and under-estimate the largest ones due to classification errors. Overall, the study outcomes support the potential of cost-effective, very high-resolution sensing for the site-scale detection of infestation hotspots that can be customized to plant phenological schedules. However, more accurate medusahead patch delineation in mixed-cover grasslands would benefit from testing hyperspectral data and using our study’s framework to inform and constrain the candidate vegetation classes in heterogeneous locations

Positive litter feedbacks of an introduced species reduce native diversity and promote invasion in Californian grasslands

Questions: Californian grasslands have a long history of invasion, starting with the introduction of exotic forage species a century ago, and followed by newer waves of invaders. Both exotic and invasive species produce large amounts of litter, but the importance of litter accumulation on the growth and expansion of these species has not been rigorously assessed. We addressed the following questions: (1) do litter type (exotic or invasive species) and litter quantity affect exotic and invasive plant performance; (2) at which plant life stages does litter accumulation effects occur; and (3) is litter accumulation impacting native species recruitment and diversity? Location: Semi-natural grasslands, northern California. Methods: We created litter quantity gradients (0, 62.5, 125, 250 or 500 g.m(-2)) of three litter types (exotic or invasive species litter or a mixture of both). We evaluated litter effects on the germination, recruitment, production of flowers and biomass production of the exotic Avena fatua, the invasive Elymus caput-medusae and a mixture of native species. We used litter depth as a proxy for litter accumulation and measured litter impacts on light availability at ground level, soilmoisture, soil andmicrobial C and N. Results: We found a significant litter depth impact on all species, but no litter type effects. Litter accumulation principally reduced light availability at ground level and positively affected exotic and invasive species at different life-history stages. Above-ground biomass production of the exotic species Avena increased with increased litter depth, suggesting a litter accumulation feedback. The invasive species Elymus responded to increased litter with increased seed production, rather than biomass production. In contrast, litter negatively affected the recruitment and diversity of native species. Conclusion: Overall, our findings point to cascading effects in invasion with positive litter accumulation feedbacks of an exotic species simultaneously reducing native diversity and promoting seed production of a more recent invasive arrival. These results have strong consequences for invasion management and suggest that litter removal practices, such as burning and grazing, would better succeed at limiting the growth and spread of invasive species than herbicide application or seeding