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ABSTRACT Exercise increases blood and lymph flow in working muscles, potentially affecting the bioavailability and effect of subcutaneously administered drugs. The aim of this study was to assess the influence of a single exercise session on pharmacokinetics and pharmacodynamics of a single dose of subcutaneously administered unfractionated heparin. In a crossover design, 15 healthy males underwent four experimental days where 15,000 IU of unfractionated heparin was injected subcutaneously into the thigh of the non‐dominant leg. Following the injection, one of four interventions was performed in randomized order on four separate occasions, each lasting 1 h: (1) no exercise, (2) double‐legged exercise, (3) single‐legged exercise with the non‐dominant leg (where heparin was injected), and (4) single‐legged exercise with the dominant leg. Blood was sampled during and after the interventions and analyzed for activated partial thromboplastin time (aPTT) and plasma heparin via an anti‐factor Xa assay. The primary endpoint (maximum aPTT minus baseline aPTT) showed no statistically significant differences between interventions, nor did maximum minus baseline plasma heparin activities. However, after 1 h, change in aPTT was greater, following double‐legged exercise compared with no exercise (mean difference 3.5 s, 95% CI 0.8–6.2) and greater after single‐legged exercise with the non‐dominant leg compared with the dominant (9.7 s, 3.9–15.5). Similar results were observed for plasma heparin activities. In conclusion, exercise does not affect the overall pharmacokinetics and pharmacodynamics of unfractionated heparin but tends to accelerate absorption and hence effect. The study thus underscores that physical exercise affects temporal uptake of subcutaneously administered therapy.

Background Intravenous high‐dose glucagon is a recommended antidote against beta‐blocker poisonings, but clinical effects are unclear. We therefore investigated hemodynamic effects and safety of high‐dose glucagon with and without concomitant beta‐blockade. Methods and Results In a randomized crossover study, 10 healthy men received combinations of esmolol (1.25 mg/kg bolus+0.75 mg/kg/min infusion), glucagon (50 µg/kg), and identical volumes of saline placebo on 5 separate days in random order (saline+saline; esmolol+saline; esmolol+glucagon bolus; saline+glucagon infusion; saline+glucagon bolus). On individual days, esmolol/saline was infused from −15 to 30 minutes. Glucagon/saline was administered from 0 minutes as a 2‐minute intravenous bolus or as a 30‐minute infusion (same total glucagon dose). End points were hemodynamic and adverse effects of glucagon compared with saline. Compared with saline, glucagon bolus increased mean heart rate by 13.0 beats per minute (95% CI, 8.0–18.0; P

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.