Israel Medical Association Journal

Objectives: To compare the seasonality of children with T1DM in different populations around the world for which data were available.

Methods: We analyzed large cohorts of T1DM patients with a clinical disease onset before age 14 or 18 years.

Results: We found a seasonality pattern only in ethnically homogenous populations (such as Ashkenazi Jews, Israeli Arabs, individuals in Sardinia and Canterbury, New Zealand, and Afro-Americans) but not in heterogeneous populations (such as in Sydney, Pittsburgh and Denver).

Conclusions: Our findings attempt to explain the controversial data in the literature by showing that ethnically heterogeneous populations with a mixture of patients with various genetic backgrounds and environmental exposures mask the different seasonality pattern of month of birth that many children with diabetes present when compared to the general population.

Background: Venous thromboembolic diseases are treated initially with low molecular weight heparin followed by oral coumarins.

Objectives: To investigate an orally available direct thrombin inhibitor for the acute treatment of venous thromboembolism as well as for prophylaxis of recurrent events.

Methods: The direct thrombin inhibitor ximelagatran was compared with subcutaneous LMW[1] heparins followed by oral warfarin in a double-blind randomized prospective multicenter trial in patients with acute VTE[2]. A pharmacokinetic study was performed in the VTE patients. For assessing the prevention of recurrent VTE, double-blind prospective randomized studies were conducted as follows: a) ximelagatran compared to warfarin for 6 months, and b) prolonged anticoagulation of ximelagatran vs. placebo for 18 months after termination of 6 months coumarin therapy.

Results: Two dose-finding studies and the pharmacokinetic analysis of ximelagatran in acute VTE were completed. About 2,500 patients were randomized to investigate 2 x 36 mg ximelagatran versus 2 x 1 mg/kg body weight enoxaparin followed by warfarin. The study hypothesized that the efficacy was equal in both treatment regimens for recurrent VTE documented by objective methods. The second study, with 1,234 patients, aimed to demonstrate a reduced incidence of recurrent thromboembolic events documented by objective methods after 18 months of treatment with 2 x 24 mg ximelagatran daily compared to placebo.

Conclusion: These large-scale clinical trials will soon yield the results of the comparison between oral ximelagatran and subcutaneous LMW heparin for treatment of acute VTE, and of warfarin for prophylaxis of recurrent events for 6 months and for a prolonged prophylaxis for another 18 months.

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[1] LMW = low molecular weight

[2] VTE = venous thromboembolism