Expert opinion on investigational drugs
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Subarachnoid hemorrhage (SAH) is associated with significant morbidity and mortality, even for patients who receive early neurointerventionist management. ⋯ Multiple mechanisms, including delayed vasospasm, may contribute to cerebral ischemia and poor outcome following SAH. Treatments that simultaneously target multiple secondary injury pathways show significant potential as therapeutic agents, particularly those that attenuate vasospasm in addition to having other neuroprotective properties.
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Regorafenib (BAY 73-4506) is a novel, orally active, diphenylurea multikinase inhibitor of VEGFR1-3, c-KIT, TIE-2, PDGFR-β, FGFR-1, RET, RAF-1, BRAF and p38 MAP kinase. ⋯ Regorafenib (BAY 73-4506) is a novel, orally active multikinase inhibitor that is well tolerated in preclinical mouse models as well as clinically according to Phase I - III trials performed. The toxicity profile is comparable with other oral multikinase inhibitors with similar molecular targets. Regorafenib has promising antineoplastic activity in various tumor types. Two large, randomized Phase III pivotal registration studies in patients with GIST and CRC, respectively, already completed enrolment, with final results being awaited. Further extensive clinical development as a single agent or in combination with standard chemotherapeutic agents in various malignant tumors is ongoing. Moreover, regorafenib has recently been granted Orphan Drug Status for GIST tumors and 'fast track' status for both GIST and CRC by the FDA.
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Expert Opin Investig Drugs · Jun 2012
ReviewAntibiotic prophylaxis in the era of multidrug-resistant bacteria.
The prophylactic use of antibiotics can only be justified when clinical benefits on relevant patient outcomes, such as morbidity or mortality, cost-effectiveness, and absence of immediate emergence of antibiotic resistance have been unequivocally demonstrated. In some intensive care unit (ICU) patients, antibiotic prophylaxis is used as part of selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD). Recent trials in ICUs with low levels of antibiotic resistance strongly suggest that both regimens reduce the incidence of ICU-acquired infections and improve patient survival. ⋯ Furthermore, the effects of both regimens on the non-culturable part of the intestinal flora remain unknown. Finally, cost-effectiveness has not been thoroughly investigated, and prices of the antimicrobial agents that have been used have increased dramatically in recent years. In this review, important knowledge gaps that so far prevent the widespread use of SDD and SOD will be addressed.