Do intracerebral cytokine responses explain the harmful effects of dexamethasone in HIV-associated cryptococcal meningitis?

Background The CryptoDex trial showed dexamethasone was associated with poorer clinical outcomes and slower fungal clearance in HIV-associated cryptococcal meningitis. We analysed CSF cytokine concentrations from CrytpoDex participants over the first week of treatment to investigate potential mechanisms of harm and test two hypotheses: dexamethasone reduced pro-inflammatory cytokine concentrations leading to poorer outcomes; and leukotriene A4 hydrolase (LTA4H) genotype (previously associated with dexamethasone responsiveness in tuberculous meningitis) influenced dexamethasone’s clinical impact. Methods We included participants from Vietnam, Thailand, and Uganda. We measured CSF concentrations of IFN-γ, TNF-α, GM-CSF, IL-6, IL-12p70, IL-8, MCP-1, MIP-1α, IL-4, IL-10, and IL-17 from days 1 to 7 of treatment using the Luminex system. We determined LTA4H genotype using a TaqMan genotyping assay of the promoter region SNP rs17525495. We assessed the impact of dexamethasone on cytokine concentration dynamics and the association between cytokine concentration dynamics and fungal clearance with mixed effect models. We measure the influence of LTA4H genotype on outcomes with Cox regression models. Results Dexamethasone increased the rate of TNF-α concentration decline (-0.13 pg/ml/day (95%CI -0.22 to -0.06) p=0.03), which was associated with slower fungal clearance (correlation -0.62 (-0.83 to -0.26)). LTA4H genotype had no statistically significant impact on outcome or response to dexamethasone therapy. Better clinical outcomes were associated with higher baseline concentrations of IFN-γ. Conclusions Dexamethasone may slow fungal clearance and worsen outcomes by increasing the rate of decline of TNF-α concentration

Climate-related corporate reporting and cost of equity capital

Purpose: This study aims to examine the reaction of stakeholders (i.e. capital providers) to climate-related corporate reporting. Climate-related corporate reporting is captured by the level of voluntary carbon disclosure, while the recognition and appreciation of capital providers are captured through the cost of equity capital (COE). Design/methodology/approach: This study uses a sample including the 350 largest companies by market capitalization on the London Stock Exchange, UK (FTSE350) from 2015 to 2019. The authors use fixed-effects regression models to examine the effect of climate-related corporate reporting on the COE. Findings: This study finds that voluntary carbon disclosure proxied by carbon disclosure score is negatively associated with COE. This suggests that firms’ superior quality disclosure of carbon information could contribute to a lower COE. This implies that the market and stakeholders positively appreciate the involvement in climate-related reporting by businesses. Originality/value: The finding provides insights to regulators, investors and other stakeholders in terms of the positive economic implication of actively engaging in reducing climate change impact through voluntary carbon disclosure. These findings also motivate corporates to be proactively involved in climate-related reporting by extending the quality of carbon information disclosure

Media audit reveals inappropriate promotion of products under the scope of the International Code of Marketing of Breast-milk Substitutes in South-East Asia.

To review regulations and to perform a media audit of promotion of products under the scope of the International Code of Marketing of Breast-milk Substitutes (‘the Code’) in South-East Asia. We reviewed national regulations relating to the Code and 800 clips of editorial content, 387 advertisements and 217 Facebook posts from January 2015 to January 2016. We explored the ecological association between regulations and market size, and between the number of advertisements and market size and growth of milk formula. Cambodia, Indonesia, Myanmar, Thailand and Vietnam. Regulations on the child’s age for inappropriate marketing of products are all below the Code’s updated recommendation of 36 months (i.e. 12 months in Thailand and Indonesia; 24 months in the other three countries) and are voluntary in Thailand. Although the advertisements complied with the national regulations on the age limit, they had content (e.g. stages of milk formula; messages about the benefit; pictures of a child) that confused audiences. Market size and growth of milk formula were positively associated with the number of newborns and the number of advertisements, and were not affected by the current level of implementation of breast-milk substitute laws and regulations. The present media audit reveals inappropriate promotion and insufficient national regulation of products under the scope of the Code in South-East Asia. Strengthened implementation of regulations aligned with the Code’s updated recommendation should be part of comprehensive strategies to minimize the harmful effects of advertisements of breast-milk substitutes on maternal and child nutrition and health