Temporal trends in the use of antithrombotics at admission

Background and purpose — Currently, no clear evidence exists on the pattern of use of antithrombotics at admission in hip fracture patients and how this has changed over time. We investigated temporal trends in—and factors associated with—the use of antithrombotics in patients admitted with a fractured hip. Patients and methods — This was a population-based cohort study including all patients aged 18 years or above who were admitted with a hip fracture in Denmark from 1996 to 2012. The Danish national registries were used to collect information on medication use, vital status, and comorbidity. Results — From 1996 to 2012, the proportion of patients using antithrombotics in general increased by a factor of 2.3 from 19% to 43% (p < 0.001). More specifically, the use of anticoagulants increased by a factor of 6.8 and the use of antiplatelets increased by a factor of 2.1. When we adjusted for possible confounders, the use of antithrombotics still increased for every calendar year (relative risk (RR) = 1.03, CI: 1.03–1.04; p < 0.001). Age, sex, and Charlson comorbidity index were all associated with the use of antithrombotics (all p < 0.001). Interpretation — The proportion of hip fracture patients using antithrombotics at admission has increased substantially in Denmark over the last 2 decades. This highlights the need for evidence-based guidelines on how to handle patients using antithrombotics to ensure safe surgery and to avoid surgical delay

Biased signaling and allosteric modulation of G protein-coupled receptor 183 - a 7TM receptor also known as Epstein-Barr virus -induced gene 2

Abstract Background and Purpose The G protein-coupled receptor Epstein Barr virus-induced gene 2 (EBI2, also known as GPR183) is activated by oxysterols and plays a pivotal role for proper B cell migration during immune responses. While the molecular basis of agonist binding has been addressed in several studies, the concept of biased signaling of EBI2 has not been explored. Experimental Approach We investigated the effects of the EBI2 endogenous agonist 7α,25-OHC on G protein-dependent and -independent pathways as well as sodium ion allosterism using site-directed mutagenesis and functional studies. Moreover, we generated a homology model of EBI2 to investigate the structural basis of the allosteric modulation by sodium. Key Results We show that residue N114, located in the middle of TM-III at position III:11/3.35, functions as an efficacy switch. Thus, substituting N114 with an alanine (N114A) completely abolishes Gαi activation by 7α,25-OHC even though the specific binding of the [3H]-7,25-OHC radioligand increases. In contrast, the N114A mutant is still able to recruit β-arrestin and even with enhanced the potency (16-fold) compared to EBI2 wt. Underscoring the key role of N114, we also show that sodium has an negative allosteric effect on oxysterol binding and that this is mediated via N114. This is further supported by molecular modelling of the ion binding site based on a EBI2 homology model. Conclusions and Implications Collectively, our data points to N114 as a key residue for EBI2 signaling controlling the balance between G protein-dependent and -independent pathways and facilitating sodium binding

Orthogeriatric Service Reduces Mortality in Patients With Hip Fracture

Introduction: Orthogeriatric service has been shown to improve outcomes in patients with hip fracture. The purpose of this study is to evaluate the effect of orthogeriatrics at Bispebjerg University Hospital, Denmark. The primary outcome is mortality inhospital and after 1, 3, and 12 months for patients with hip fracture. The secondary outcome is mortality for home dwellers and nursing home inhabitants. Materials and Methods: This is a retrospective clinical cohort study with an historic control group including all patients with hip fracture admitted from 2007 to 2011. Patients with hip fracture are registered in a local database, and data are retrieved retrospectively using the Danish Civil Registration Number. Results: We included 993 patients in the intervention group and 989 patients in the control group. A univariate analysis showed only significantly decreased mortality inhospital 6.3% vs 3.1% ( P = .009) after orthogeriatrics. However, when adjusting for age, gender, and American Society of Anaesthesiologists (ASA) score in a multivariate analysis, including all patients with hip fracture, we find significantly reduced mortality inhospital (odds ratio [OR] 0.35), after 30 [OR 0.66] and 90 days [OR 0.72] and 1 year [OR 0.79]). When using a univariate analysis for home-dwelling patients, we found significantly reduced mortality inhospital (8.3-2.0%, P < .0001), after 30 days (12.2-6.8%, P = .004) and 90 days (20.5-13.0%, P = .002). One-year mortality was not significant. Patients from nursing homes had no significant decreasing mortality at any point of time in the univariate analysis. Conclusion: We have shown significant decreases for inhospital, 30 day, 90 day, and 1-year mortality after implementation of orthogeriatric service at Bispebjerg Hospital when adjusting for age, gender, and ASA score. Future trials should include frail patients with other fracture types who can benefit from orthogeriatrics