Dexmedetomidine pharmacokineticpharmacodynamic modelling in healthy volunteers:1. Influence of arousal on bispectral index and sedation

Background. Dexmedetomidine, a selective alpha(2)-adrenoreceptor agonist, has unique characteristics, such as maintained respiratory drive and production of arousable sedation. We describe development of a pharmacokinetic-pharmacodynamic model of the sedative properties of dexmedetomidine, taking into account the effect of stimulation on its sedative properties. Methods. In a two-period, randomized study in 18 healthy volunteers, dexmedetomidine was delivered in a step-up fashion by means of target-controlled infusion using the Dyck model. Volunteers were randomized to a session without background noise and a session with pre-recorded looped operating room background noise. Exploratory pharmacokineticpharmacodynamic modelling and covariate analysis were conducted in NONMEM using bispectral index (BIS) monitoring of processed EEG. Results. We found that both stimulation at the time of Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale scoring and the presence or absence of ambient noise had an effect on the sedative properties of dexmedetomidine. The stimuli associated with MOAA/S scoring increased the BIS of sedated volunteers because of a transient 170% increase in the effect-site concentration necessary to reach half of the maximal effect. In contrast, volunteers deprived of ambient noise were more resistant to dexmedetomidine and required, on average, 32% higher effect-site concentrations for the same effect as subjects who were exposed to background operating room noise. Conclusions. The new pharmacokinetic-pharmacodynamic models might be used for effect-site rather than plasma concentration target-controlled infusion for dexmedetomidine in clinical practice, thereby allowing tighter control over the desired level of sedation

Anterior capsule phimosis and capsular block syndrome in a patient with Steinert myotonic dystrophy: a case report

A 55-year-old man with myotonic dystrophy underwent phacoemulsification with IOL implantation in the right eye

Regional Sanctions Against Burundi: A Powerful Campaign and Its Unintended Consequences

This paper examines the impact of regionally imposed sanctions on the trajectory of the Burundian regime and its involvement in the peace process following the 1996 coup in the country. Despite the country's socioeconomic and geopolitical vulnerability, the Buyoya government withstood the pressure from the sanctions. Through a vocal campaign against these sanctions, the new government mitigated the embargo's economic consequences and partially reestablished its international reputation. Paradoxically, this campaign planted the seed for comprehensive political concessions in the long term. While previous literature has attributed the sanctions' success in pressuring the government into negotiations to their economic impact, the government actually responded to the sanction senders' key demand to engage in unconditional, inclusive peace talks under the auspices of the regional mediator once the economy had already started to recover. The regime's anti-sanctions campaign, with its emphasis on the government's willingness to engage in peace talks, backfired, with Buyoya forced to negotiate after having become entrapped in his own rhetoric

Steroid treatment in primary intracerebral haemorrhage

The efficiency of two types of steroid treatment was assessed in primary intracerebral haemorrhages. No significant difference in clinical evolution was observed between 57 cases treated with dexamethasone, 28 cases with methylprednisolone and 44 cases without corticosteroids. In a subgroup of 46 patients with putamino-capsular bleedings the non-steroid-treated group did significantly better than the steroid-treated one. Adverse reactions occurred at the same rate in the three groups