Drug Des Dev Ther
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In a recent study utilizing a saline-lavaged adult rabbit model, we described a significant improvement in systemic oxygenation and pulmonary shunt after the instillation of a novel synthetic peptide-containing surfactant, Synsurf. Respiratory distress syndrome in the preterm lamb more closely resembles that of the human infant, as their blood gas, pH values, and lung mechanics deteriorate dramatically from birth despite ventilator support. Moreover, premature lambs have lungs which are mechanically unstable, with the advantage of being able to measure multiple variables over extended periods. Our objective in this study was to investigate if Synsurf leads to improved systemic oxygenation, lung mechanics, and histology in comparison to the commercially available porcine-derived lung surfactant Curosurf® when administered before first breath in a preterm lamb model. ⋯ Treatment with surfactants before first breath clearly resulted in improved systemic oxygenation within 30 minutes of instillation. Both Synsurf- and Curosurf®-treated animals experienced similar and more sustained improvement in oxygenation and decreased calculated shunt compared to saline-treated animals.
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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with no clear etiology and a paucity of therapeutic options. Nintedanib (previously known as BIBF 1120) is a tyrosine kinase receptor antagonist which inhibits a number of key receptors, including those for platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF). These growth factors are profibrotic and each has been investigated as a potential standalone therapeutic target in IPF. ⋯ The Phase IIb TOMORROW trial demonstrated that treatment with nintedanib may potentially slow decline in lung function, decrease the frequency of acute exacerbations, and improve quality of life in patients with IPF. While these observations are drawn from a single clinical trial, taken together with the preclinical data they suggest that nintedanib may yet become an important therapeutic option for individuals with IPF. The results of ongoing parallel, international, multicenter Phase III clinical trials are therefore eagerly awaited.
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Type 2 diabetes mellitus is a complex and progressive disease that is showing an apparently unstoppable increase worldwide. Although there is general agreement on the first-line use of metformin in most patients with type 2 diabetes, the ideal drug sequence after metformin failure is an area of increasing uncertainty. New treatment strategies target pancreatic islet dysfunction, in particular gut-derived incretin hormones. ⋯ In clinical studies, DPP-4 inhibitors were generally safe and well tolerated. However, there are limited data on their tolerability, due to their relatively recent marketing approval. Alogliptin will be used most when avoidance of hypoglycemic events is paramount, such as in patients with congestive heart failure, renal failure, and liver disease, and in the elderly.
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Review Comparative Study
Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections.
Tedizolid phosphate (TR-701), a prodrug of tedizolid (TR-700), is a next-generation oxazolidinone that has shown favorable results in the treatment of acute bacterial skin and skin-structure infections in its first Phase III clinical trial. Tedizolid has high bioavailability, penetration, and tissue distribution when administered orally or intravenously. The activity of tedizolid was greater than linezolid against strains of Staphylococcus spp., Streptococcus spp., and Enterococcus spp. in vitro studies, including strains resistant to linezolid and those not susceptible to vancomycin or daptomycin. ⋯ Given that the clinical and microbiological efficacy are similar for the 200, 300, and 400 mg doses, the lowest effective dose of 200 mg once daily for 6 days was selected for Phase III studies in acute bacterial skin and skin-structure infections, providing a safe dosing regimen with low potential for development of myelosuppression. Unlike linezolid, tedizolid does not inhibit monoamine oxidase in vivo, therefore interactions with adrenergic, dopaminergic, and serotonergic drugs are not to be expected. In conclusion, tedizolid is a novel antibiotic with potent activity against Gram-positive microorganisms responsible for skin and soft tissue infections, including strains resistant to vancomycin, linezolid, and daptomycin, thus answers a growing therapeutic need.
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Venous thromboembolism (VTE) is a frequent complication among acutely ill medical patients hospitalized for congestive heart failure, acute respiratory insufficiency, rheumatologic disorders, and acute infectious and/or inflammatory diseases. Based on robust data from randomized controlled studies and meta-analyses showing a reduced incidence of VTE by 40% to about 60% with pharmacologic thromboprophylaxis, prevention of VTE with low molecular weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux is currently recommended in all at-risk hospitalized acutely ill medical patients. In patients who are bleeding or are at high risk for major bleeding, mechanical prophylaxis with graduated compression stockings or intermittent pneumatic compression may be suggested. ⋯ The evidence on the use of prophylaxis for VTE in this latter group of patients, as well as in those at higher risk of bleeding complications, such as patients with thrombocytopenia, remains scarce. For critically ill patients hospitalized in intensive care units with no contraindications, LMWH or UFH are recommended, with frequent and careful assessment of the risk of bleeding. In this review, we discuss the evidence for use of thromboprophylaxis for VTE in acutely ill hospitalized medical patients, with a focus on (low-dose) fondaparinux.