Dscam is a transmembrane protein of the Ig superfamily that has been shown to play critical roles in the developing nervous system. Its known functions include isoneuronal dendritic and axonal self-avoidance, heteroneuronal avoidance in a process called "tiling", heteroneuronal synapse formation, and axon guidance. The importance of Dscam is further demonstrated by its high degree of sequence, structural and functional conservation in organisms across several phyla, including chordates, mollusks, platyhelminthes and arthropods. In arthropods, the Dscam gene is alternatively spliced and can create tens of thousands of isoforms, which are used for neuronal identity and may also serve a novel form of adaptive immune function. This ability to create multiple isoforms is not seen in chordates and mollusks. Here, we report on two Dscam orthologues that we have found in the medicinal leech (Hirudo medicinalis), which belongs to the annelid phylum. Both Dscam's are expressed in nervous tissue, indicating a conservation of neural function, but they do not appear to be alternatively spliced, thus placing the annelids with the chordates and mollusks in terms of Dscam structure

Background

Trial data for the benefits and risks of dabigatran versus warfarin in the treatment of nonvalvular atrial fibrillation are lacking. We sought to review real-world observational evidence for the comparative effectiveness and safety of these agents.

Methods and results

A systematic search of multiple databases was conducted from first available date to March 10, 2015 for longitudinal, observational studies comparing dabigatran with warfarin. Two reviewers evaluated studies for eligibility and extracted hazard ratios for ischemic stroke and gastrointestinal and intracranial bleeding. hazard ratios were pooled using random-effects meta-analysis. Metaregression was performed to assess treatment-effect heterogeneity. We identified 232 unique citations. Seven retrospective cohort studies met study eligibility criteria, with 348 750 patients and a mean follow-up of 2.2 years. In pooled analyses, dabigatran-150 mg was not superior to warfarin in preventing stroke (hazard ratio, 0.92; 95% confidence interval, 0.84-1.01; P=0.066), but had a significantly lower hazard of intracranial bleeding (0.44; 0.34-0.59; P<0.001). Dabigatran-150 mg had a significantly greater hazard of gastrointestinal bleeding than warfarin (1.23; 1.01-1.50; P=0.041), which was potentiated in studies of older (elderly) versus younger populations (median/mean age, ≥75 versus <75 years; β=1.53; 95% confidence interval, 1.10-2.14; P=0.020).

Conclusions

In real-world clinical practice, dabigatran is comparable with warfarin in preventing ischemic stroke among patients with nonvalvular atrial fibrillation. However, dabigatran is associated with a lower risk for intracranial bleeding relative to warfarin, but-particularly among the elderly-a greater risk for gastrointestinal bleeding. Bleeding outcomes from observational studies are consistent with those from the pivotal Randomized Evaluation of Long-Term Anticoagulation Therapy trial.