Prospective randomized controlled trial on the effect of fondaparinux sodium for prevention of venous thromboembolism after hip fracture surgery.

BACKGROUND: Hip fracture surgery (HFS) carries a high risk of venous thromboembolism (VTE) in the absence of thromboprophylactic treatment. Previous reports have suggested that fondaparinux sodium (FPX) administration decreases the incidence of VTE after HFS and total hip and knee arthroplasties. However, investigations of that effect in Japanese populations remain inadequate. We evaluated the efficacy of FPX after HFS in a prospective randomized controlled trial. METHODS: Subjects comprised 76 consecutive Japanese patients who underwent HFS and were randomly assigned to the FPX group, who received subcutaneous injections of FPX 2.5 mg/day for 14 days beginning the next after HFS, or the control group (non-FPX group). D-dimer values were measured on admission and 7 and 14 days after HFS. Subjects with D-dimer levels over the cutoff value (> 20 microg/ml on day 7) underwent enhanced computed tomography (CT) to evaluate the possibility of deep vein thrombosis (DVT) of the lower extremities. D-dimer values, the incidence of DVT, and side effects associated with a bleeding tendency (i.e., hematoma or massive bleeding) were compared between groups. RESULTS: The FPX group showed significantly lower D-dimer levels than the non-FPX group at 7 and 14 days after HFS (P < 0.05). Only one case in the FPX group exceeded the D-dimer cutoff compared to 12 cases in the non-FPX group (P = 0.001). DVTs were found with enhanced CT in one case in the FPX group and in five cases in the non-FPX group. In the FPX group, symptomatic hematoma at the surgical site and/or decreased hemoglobin > 2 g/dl was noted in four cases (10.5%). Postoperative drainage volumes did not differ significantly between groups. CONCLUSIONS: FPX administration demonstrated positive effects on the prevention of VTE after HFS. However, careful postoperative observation is warranted to prevent serious side effects after FPX administration.

The 3111T/C polymorphism of hClock is associated with evening preference and delayed sleep timing in a Japanese population sample.

Sleep timing is influenced by the circadian system. Morningness-eveningness (ME) preference in humans is affected by the free-running period, which is determined by circadian clock-relevant genes. In this study, we investigated association between the 3111T/C polymorphism in the 3'-flanking region of hClock (Homo sapiens Clock homolog) and ME preference in 421 Japanese subjects. The Horne-Ostberg ME questionnaire (MEQ) scores showed normal distribution, with mean score of 51.2 +/- 1.4 (range, 25-73), and scores were positively correlated with sleep onset time (r = 0.541, P < 0.001) and wake time (r = 0.513, P < 0.001). MEQ scores were significantly lower in subjects with 3111C/C (n = 12) than in subjects with 3111T/C (n = 106, P < 0.001) or 3111T/T (n = 303, P < 0.001), suggesting a stronger eveningness preference in 3111C/C homozygotes. This group also showed significantly delayed sleep onset (P < 0.001), shorter sleep time (P < 0.001), and greater daytime sleepiness (P < 0.001) in comparison to parameters in the subjects with the 3111T allele. There was no significant difference in any of these parameters between the 3111C/T and 3111T/T genotypes. The influence of the 3111T/C polymorphism on ME preferences in Caucasian populations remains controversial. The present findings in a Japanese population sample, which should have a relatively low risk of population stratification effects, suggest the significance of the association of the 3111C/C allele of hClock with evening preference.