Social determinants of self-reported health for Canada's indigenous peoples: a public health approach.

OBJECTIVE: In Canada, indigenous peoples suffer from a multitude of health disparities. To better understand these disparities, this study aims to examine the social determinants of self-reported health for indigenous peoples in Canada. STUDY DESIGN: This study uses data from Statistics Canada's Aboriginal Peoples Survey 2012. METHODS: Multinomial logistic regression models were used to examine how selected social determinants of health are associated with self-reported health among off-reserve First Nations and Métis peoples in Canada. RESULTS: Our analysis shows that being older, female, and living in urban settings were significantly associated with negative ratings of self-reported health status among the indigenous respondents. Additionally, we found that higher income and levels of education were strongly and significantly associated with positive ratings of self-reported health status. Compared with indigenous peoples with an education level of grade 8 or lower, respondents with higher education were 10 times (5.35-22.48) more likely to report 'excellent' and 'very good' health. Respondents who earned more than $40,000 annually were three times (2.17-4.72) more likely to report 'excellent' and 'very good' health compared with those who earned less than $20,000 annually. When interacted with income, we also found that volunteering in the community is associated with better self-reported health. CONCLUSIONS: There are known protective determinants (income and education) and risk determinants (location of residence, gender, and age) which are associated with self-reported health status among off-reserve First Nations and Métis peoples. For indigenous-specific determinants, volunteering in the community appears to be associated with self-perceived health status. Thus, addressing these determinants will be necessary to achieve better health outcomes for indigenous peoples in Canada. Next steps include developing indigenous-specific social determinants of health indicators that adequately measure culture, connection, and community.

A Leishmania protein that modulates interleukin (IL)-12, IL-10 and tumor necrosis factor-alpha production and expression of B7-1 in human monocyte-derived antigen-presenting cells.

LeIF, a gene homologue of the eukaryotic initiation factor 4A was first described as a leishmanial antigen that induced a Th1-type T cell response in peripheral blood mononuclear cells (PBMC) from leishmaniasis patients. Moreover, the interferon (IFN)-gamma production by PBMC was found to be interleukin (IL)-12 dependent. Herein, we characterize the effects of LeIF on cytokine production and expression of surface molecules by normal human monocytes as well as by monocyte-derived macrophages and dendritic cells (MoDC). LeIF was a strong inducer of IL-12 and, to a lesser extent, of IL-10 and tumor necrosis factor (TNF)-alpha in macrophages and MoDC. IL-12 production did not require CD40 triggering, confirming that the ability of LeIF to induce IL-12 was not mediated through an effect on T cells. However, addition of soluble CD40 ligand (L) synergistically augmented IL-12 production in macrophages and MoDC. The cytokine-inducing activity of LeIF is located in the N-terminal portion of the molecule and was both proteinase K sensitive and polymyxin B resistant. LeIF, lipopolysaccharide and fixed Staphylococcus aureus all induced comparable amounts of IL-12, validating the potent cytokine-inducing effects of LeIF. Moreover, of these stimuli, LeIF had the highest IL-12/IL-10 and IL-12/TNF-alpha ratio demonstrating the preference of LeIF for IL-12 induction. Studies investigating the expression of surface molecules showed that LeIF up-regulated B7-1 and CD54 (ICAM-1) on macrophages and MoDC. To our knowledge this is the first report describing IL-12 production, up-regulation of co-stimulatory and intercellular adhesion molecules by monocytic antigen-presenting cells in response to a protein from a pathogenic microorganism. These immunomodulatory characteristics of LeIF might be excellent properties for a Th1-type adjuvant.

Reversible neurologic abnormalities associated with prolonged intravenous midazolam and fentanyl administration.

An encephalopathy developed in three infants in the intensive care unit after heavy sedation with midazolam and fentanyl for 4 to 11 days. The affected infants had poor social interaction, decreased visual attentiveness, dystonic postures, and choreoathetosis. Symptoms cleared completely in 5 days to 4 weeks. Retrospective review of records of all children treated in the intensive care unit with prolonged intravenous administration of midazolam revealed that 45 children could be assessed neurologically on withdrawal of sedation. Three children had definite and two had possible neurologic sequelae (5/45, 11.1%). All had received concomitant intravenous fentanyl therapy. Neurologic sequelae were significantly associated with young age, female gender, low serum albumin concentration, and concomitant administration of aminophylline. This encephalopathy may represent a benzodiazepine withdrawal syndrome, a prolonged agonist action on the benzodiazepine receptor, or the combined effects of multiple toxic, metabolic, and infectious insults to the central nervous system of infants in the intensive care unit. Prolonged use of intravenous midazolam sedation necessitates careful dosing, monitoring, and discontinuation, particularly in infants and young children.

In-vitro interaction of a novel immunosuppressant, FK 506, and antacids.

The effect of selected antacids on the amount of FK 506 in solution in simulated gastric juice has been studied. FK 506 (2.5 mg) was incubated in 100 mL simulated gastric fluid (SGF) with the equivalent of 500 mg of various antacids. The addition of Mylanta and Tums resulted in 14 and 30% loss of FK 506, respectively, in 24 h; 98% loss was observed in 12 h in the presence of Mag-Ox; 100% loss was observed in the presence of magnesium oxide powder in 2 h. The loss of FK 506 from these solutions appears to be due to a pH mediated degradation of FK 506. The addition of aluminium hydroxide gel USP (Roxane) to the FK 506 solution resulted in a 35% loss within 2 min but no further loss was noted for 24 h, indicative of adsorption of FK 506. These results suggest that until additional in-vivo studies are carried out, it is prudent not to dose FK 506 and antacids at the same time to avoid potential interactions.