This study found that 25% of patients with Type 2 diabetes had insulin initiation delayed for at least 1.8 years, and 50% of patients delayed starting insulin for almost 5 years after failure of glycaemic control with OGLA polytherapy, even in the presence of diabetes-related complications. Interventions that reduce this delay to insulin initiation are required to help achieve and maintain recommended glycaemic targets in patients with Type 2 diabetes.

Inter-areal synchronization of neuronal oscillations at frequencies below ~100 Hz is a pervasive feature of neuronal activity and is thought to regulate communication in neuronal circuits. In contrast, faster activities and oscillations have been considered to be largely local-circuit-level phenomena without large-scale synchronization between brain regions. We show, using human intracerebral recordings, that 100–400 Hz high-frequency oscillations (HFOs) may be synchronized between widely distributed brain regions. HFO synchronization expresses individual frequency peaks and exhibits reliable connectivity patterns that show stable community structuring. HFO synchronization is also characterized by a laminar profile opposite to that of lower frequencies. Importantly, HFO synchronization is both transiently enhanced and suppressed in separate frequency bands during a response-inhibition task. These findings show that HFO synchronization constitutes a functionally significant form of neuronal spike-timing relationships in brain activity and thus a mesoscopic indication of neuronal communication per se.

Objective To compare the risk of suicide in adults using the antidepressant venlafaxine compared with citalopram, fluoxetine, and dothiepin. Results Venlafaxine users had a higher burden of risk factors for suicide, including previous suicide attempts and proxies for severe depression or depression that was difficult to treat. In the analysis for completed suicides, unadjusted and adjusted hazard ratios for venlafaxine compared with citalopram were 2.44 (95% confidence interval 1.12 to 5.31) and 1.70 (0.76 to 3.80), for venlafaxine compared with fluoxetine were 2.85 (1.37 to 5.94) and 1.63 (0.74 to 3.59), and for venlafaxine compared with dothiepin were 2.54 (1.07 to 6.02) and 1.31 (0.53 to 3.25). Compared with other study drugs, venlafaxine was also associated with an increased risk of attempted suicide, but adjustment for measured confounders substantially reduced the hazard ratios. Conclusions Venlafaxine use was consistently associated with higher risk of suicide compared with citalopram, fluoxetine, and dothiepin. Venlafaxine users had a higher burden of suicide risk factors, however, and adjustment for measured confounders substantially reduced the excess risks. Since the secondary data used in this analysis allowed only indirect and partial measurements of potential confounders, it is possible that residual confounding explains much, if not all, of the observed excess risk.

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1 The direct vascular effects of adenosine and ATP were compared in the isolated and perfused mesenteric arterial bed of the rat. The actions of analogues of adenosine and ATP were also examined. 2 In preparations at basal tone, adenosine lacked vasoconstrictor actions, while ATP elicited dosedependent vasoconstrictor responses. When the tone of preparations was raised by adding methoxamine to the perfusate, adenosine and its stable analogue, 2-chloroadenosine (2-CADO) elicited dose-dependent vasodilatation. The A2 adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA) was active at lower doses than adenosine, while the A2u-selective agonist, CGS 21680 and the selective Al agonist, N6-cyclopentyladenosine (CPA) failed to induce vasodilatation. ATP and its analogue, 2-methylthio ATP, elicited dose-dependent vasodilatation at doses 400 fold lower than adenosine. 3 Vasodilator responses to adenosine and 2-CADO were sensitive to antagonism by 1 M 8-sulphophenyltheophylline (8-SPT) and were unaffected by inhibition of nitric oxide synthase by N0-nitro-L-arginine methyl ester (L-NAME). In contrast, vasodilator responses to ATP were not sensitive to antagonism by 8-SPT and were almost abolished by L-NAME treatment. 4 These results indicate that in the rat mesenteric arterial bed, while both adenosine and ATP participate in the purinergic control of vascular tone, adenosine appears to be a weaker vasodilator than ATP and lacks vasoconstrictor action. A2b adenosine receptors account for the adenosine-induced vasodilatation which is independent of the production of nitric oxide.