A Case-Control Study Evaluating the Impact of Dedicated Palliative Care Training on Critical Care Interventions at the end of Life.

Many patients admitted to intensive care units (ICUs) are at high risk of dying. We hypothesize that focused training sessions for ICU providers by palliative care (PC) certified experts will decrease aggressive medical interventions at the end of life. We designed and implemented a 6-session PC training program in communication skills and goals of care (GOC) meetings for ICU teams, including house staff, critical care fellows, and attendings. We then reviewed charts of ICU patients treated before and after the intervention. Forty-nine of 177 (28%) and 63 of 173 (38%) patients were identified to be at high risk of death in the pre- and postintervention periods, respectively, and were included based on the study criteria. Inpatient mortality (45% vs 33%; P = .24) and need for mechanical ventilation (59% vs 44%, P = .13) were slightly higher in the preintervention population, but the difference was not statistically significant. The proportion of patients in whom the decision not to initiate renal replacement therapy was made because of poor prognosis was significantly higher in the postintervention population (14% vs 67%, P = .05). There was a nonstatistically significant trend toward earlier GOC discussions (median time from ICU admission to GOC 4 vs 3 days) and fewer critical care interventions such as tracheostomies (17% vs 4%, P = .19). Our study demonstrates that directed PC training of ICU teams has a potential to reduce end of life critical care interventions in patients with a poor prognosis.

Insulin-sensitizing effects of vitamin D repletion mediated by adipocyte vitamin D receptor: Studies in humans and mice.

OBJECTIVE: Adipose tissue inflammation and fibrosis appear to contribute to insulin resistance in obesity. Vitamin D receptor (Vdr) genes are expressed by adipocytes, macrophages, and fibroblasts, all of which could potentially play a role in adipose tissue inflammation and fibrosis. As vitamin D has been shown to have direct anti-inflammatory effects on adipocytes, we determined whether specific vitamin D receptor-mediated effects on adipocytes could impact adipose tissue inflammation and fibrosis and ultimately insulin resistance. METHODS: We examined the effects of repleting vitamin D in 25(OH)D-deficient, insulin resistant, overweight-to-obese human subjects (n = 19). A comprehensive assessment of whole-body insulin action was undertaken with stepped euglycemic (∼90 mg/dL) hyperinsulinemic clamp studies both before and after the administration of vitamin D or placebo. Adipose tissue fibrosis and inflammation were quantified by real-time rt-PCR and immunofluorescence in subcutaneous abdominal adipose tissue. To determine whether vitamin D's effects are mediated through adipocytes, we conducted hyperinsulinemic clamp studies (4 mU/kg/min) and adipose tissue analysis using an adipocyte-specific vitamin D receptor knockout (VDR-KO) mouse model (adiponectin-Cre + VDR+/fl) following high-fat diet feeding for 12 weeks. RESULTS: 25(OH)D repletion was associated with reductions in adipose tissue expression of pro-inflammatory and pro-fibrotic genes, decreased collagen immunofluorescence, and improved hepatic insulin sensitivity in humans. Worsening trends after six months on placebo suggest progressive metabolic effects of 25(OH)D deficiency. Ad-VDR-KO mice mirrored the vitamin D-deficient humans, displaying increased adipose tissue fibrosis and inflammation and hepatic insulin resistance. CONCLUSIONS: These complementary human and rodent studies support a beneficial role of vitamin D repletion for improving hepatic insulin resistance and reducing adipose tissue inflammation and fibrosis in targeted individuals, likely via direct effects on adipocytes. These studies have far-reaching implications for understanding the role of adipocytes in mediating adipose tissue inflammation and fibrosis and ultimately impacting insulin sensitivity.