Depression may be a risk factor for coronary heart disease in midlife women <65 years: A 9-year prospective cohort study.

OBJECTIVE: Depression has been suggested as a risk factor for coronary heart disease (CHD). However, whether the risk may be affected by age is unknown. We seek to assess the difference in long-term CHD risk between younger (<65) and older (≥65) women with depressive symptoms. METHODS: Between June and August 2004, 1995 women presenting for routine mammography were enrolled to the primary study on breast arterial calcification. In 2005 (year 2), each woman completed a validated depression screening questionnaire. A similar questionnaire was mailed to each participant at year 4, 5, and 10 to obtain follow-up data (demographic and CHD risk factors) and record any change in CHD status. RESULTS: Of 1084 women who returned surveys at year 10, 998 had no history of CHD and answered depression screening questions at year 2 as well as questions about CHD events at year 10. Of 185 out of 998 (18.5%) who had positive depression screening at year 2, 24 (13.0%) developed ≥1 CHD events by year 10, which is significantly higher than the incidence of 6.5% (53/813) in control group (p < 0.001). With CHD risk factors including age adjusted in a logistic regression model, depression was the only significant predictive factor for CHD in women aged <65 (OR = 6.56, 95% CI 1.07-40.09, p = 0.042). However, in women aged ≥65, age was the only significant predictive factor for CHD. CONCLUSION: A history of depression may increase the risk of CHD over 9 years of follow-up, and more prominently in midlife women aged <65 years.

Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF.

BACKGROUND: It has been shown that severe insult to the immune system may trigger prolonged macrophage characteristics associated with excessive release of monocyte colony stimulating factor (M-CSF). However, it is unclear how persistent is the macrophage-like characteristics in circulating monocytes (MO). In this study, 20 patients who underwent non-emergent cardiopulmonary bypass had their monocytes characterized before surgery and 3 months after surgery. METHODS: We assessed the macrophage characteristics of MO using cytokine production, surface marker expression, an ability to stimulate T cells, and methylation of the promoter region of the gene encoding PU.1, a critical component to M-CSF production. MO function as well as activation and differentiation potential were longitudinally assessed. RESULTS: At 3 months after cardiopulmonary bypass, monocytes exhibited increased expression of MRP8, transforming growth factor-ß/latency-associated peptide, suppressor of cytokine signaling 3 while phagocytic properties were increased. Concomitantly, we observed a decreased expression of CD86, a decreased ability to form regulatory dendritic cells, and a diminished ability to stimulate T cells. These characteristics were accompanied by a persistent increase in the secretion of M-CSF, over-activation of PU.1, and decreased methylation of the PU.1 promoter region. Serum levels of C-reactive protein and anti-cytomegalovirus IgG antibody titers were also elevated in some patients at 3 months after surgery. CONCLUSIONS: We concluded that at 3 months after cardiopulmonary bypass, monocytes continued to express a new macrophage-like milieu that was associated with the persistent activation of the PU.1/M-CSF pathway.

Effects of prophylactic anticholinergic medications to decrease extrapyramidal side effects in patients taking acute antiemetic drugs: a systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness of prophylactic anticholinergic medications in reducing extrapyramidal symptoms in patients taking acute antiemetics with a dopamine D2 receptor antagonist effect. METHODS: Systematic searches of all published studies through March 2017 were identified from PubMed, Cochrane library, Embase, Web of Science and Scopus. Only randomised controlled trials of patients receiving dopamine D2 antagonist antiemetic therapy for acute migraine in which an anticholinergic or placebo was compared were included. Pooled ORs were calculated for incidence of extrapyramidal symptoms and sedation. RESULTS: Four placebo-controlled randomised controlled trials consisting of 737 patients met the inclusion criteria for our meta-analysis. The effect of diphenhydramine differed depending on the method of administration of the antiemetic. When the antiemetic was delivered as a 2 min antiemetic bolus, the odds of extrapyramidal symptoms were significantly reduced in the diphenhydramine group compared with placebo (OR 0.42; 95% CI 0.22 to 0.81; P=0.01). However, when the antiemetic was given as a 15 min infusion, there was no significant difference in extrapyramidal symptoms with or without diphenhydramine (OR 1.06; 95% CI 0.58 to 1.91; P=0.85). The lowest incidence of extrapyramidal symptoms was observed in patients receiving a 15 min antiemetic infusion without diphenhydramine prophylaxis (9.8%). In two trials including 351 patients that dichotomously reported sedation scales, diphenhydramine had significantly higher rates of sedation (31.6%vs19.2%, OR 2.01, 95% CI 1.21 to 3.33; P=0.007). CONCLUSION: Prophylactic diphenhydramine reduces extrapyramidal symptoms in patients receiving bolus antiemetic therapy with a dopamine D2 antagonist effect, but not when it is given as an infusion. Because of significantly greater sedation with diphenhydramine, the most effective strategy is to administer the D2 antagonist antiemetic as a 15 min infusion without prophylaxis.