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Background: For hospitalized children admitted outside of a critical care unit, the location, mode of death, "do-not-resuscitate" order (DNR) use, and involvement of palliative care teams have not been described across high-income countries. Objective: To describe location of death, patient and terminal care plan characteristics of pediatric inpatient deaths inside and outside the pediatric intensive care unit (PICU). Design: Secondary analysis of inpatient deaths in the Evaluating Processes of Care and Outcomes of Children in Hospital (EPOCH) randomized controlled trial. Setting/Subjects: Twenty-one centers from Canada, Belgium, the United Kingdom, Ireland, Italy, the Netherlands, and New Zealand. Measurement: Descriptive statistics were used to compare patient and terminal care plan characteristics. A multivariable generalized estimating equation examined if palliative care consult during hospital admission was associated with location of death. Results: A total of 365 of 144,539 patients enrolled in EPOCH died; 219 (60%) died in PICU and 143 (40%) died on another inpatient unit. Compared with other inpatient wards, patients who died in PICU were less likely to be expected to die, have a DNR or palliative care consult. Hospital palliative care consultation was more common in older children and independently associated with a lower adjusted odds (95% confidence interval) of dying in PICU [0.59 (0.52–0.68)]. Conclusion: Most pediatric inpatient deaths occur in PICU where patients were less likely to have a DNR or palliative care consult. Palliative care consultation could be better integrated into end-of-life care for younger children and those dying in PICU. [ABSTRACT FROM AUTHOR]

Systemic inflammation and immune activation may persist in HIV-infected persons on suppressive combination antiretroviral therapy (cART) and contribute to adverse health outcomes. We compared markers of immune activation, inflammation, and abnormal glucose and lipid metabolism in HIV-infected adults according to herpes simplex virus type 2 (HSV-2) serostatus in a 6-month observational cohort study in Toronto, Canada. HIV-infected adults on suppressive (viral load <50 copies/ml) cART were categorized as HSV-2 seropositive or seronegative using the HerpeSelect ELISA, and underwent study visits at baseline, 3 months, and 6 months. The primary outcome was the median percentage of activated (CD38+HLADR+) CD8 T cells. Secondary outcome measures included additional immune (activated CD4, regulatory T cells) and inflammatory (hsCRP, D-dimer, IL-1b, IL-6, MCP-1, TNF, sICAM-1, sVCAM-1, Ang1/Ang2 ratio) markers. Metabolic outcomes included the proportion with impaired fasting glucose/impaired glucose tolerance/diabetes, insulin sensitivity (calculated using the Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and fasting lipids. The impact of HSV-2 on each outcome was estimated using generalized estimating equation regression models. Of 84 participants, 38 (45%) were HSV-2 seropositive. HSV signs and symptoms were uncommon. Aside from D-dimer, which was more often detectable in HSV-2 seropositives (adjusted odds ratio=3.58, 95% CI=1.27, 10.07), HSV-2 serostatus was not associated with differences in any other immune, inflammatory cytokine, acute phase reactant, endothelial activation, or metabolic markers examined in univariable or multivariable models. During the study, CD8 and CD4 T cell activation declined by 0.16% and 0.08% per month, respectively, while regulatory T cells increased by 0.05% per month. HSV-2 serostatus was not consistently associated with immune activation, inflammatory, or lipid and glucose metabolic markers in this cohort of HIV-infected adults on suppressive cART. [ABSTRACT FROM AUTHOR]

Older HIV-positive patients may experience reduced benefit and increased toxicities from combination anti-retroviral therapies (cART) due to late diagnosis, weakened immune systems, and other age-related physiological changes. This study investigates the effect of age on time to virologic suppression and CD4 cell count response to cART. Data were collected from a tertiary care immunodeficiency clinic in Toronto. HIV-positive patients with cART initiation after 1/1/1998 were included. Log logistic accelerated failure time models were used to estimate the effect of age on time to virologic suppression. Mixed linear models were used to evaluate CD4 cell response to treatment. A total of 502 patients were studied; 445 were less than 50 years old and 57 were age 50 or over. Of these 73% were male. Thirty-one percent started treatment with boosted protease inhibitors and 43% with non-nucleoside reverse transcriptase inhibitors. In a log logistic model adjusting for gender, immigration status, AIDS-defining illness, years since HIV diagnosis, baseline CD4 count and viral load, cART type, calendar year of cART initiation, and hepatitis C diagnosis, older age was not associated with time to virologic suppression (n =418, time ratio = 0.94, p = 0.20). In a multivariable mixed linear regression model adjusting for the same covariates, age was not associated with CD4 cell count response (n = 418, ß = 0.34, p = 0.96). Time to virologic suppression and im-munologic response were not significantly different among older and younger patients. Further studies should investigate adherence, comorbidities, and regimen changes in addition to the current covariates. [ABSTRACT FROM AUTHOR]