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- Kristoffersson, Anders N., 1985-, et al.
(författare)
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Population pharmacokinetics of colistin and the relation to survival in critically ill patients infected with colistin susceptible and carbapenem-resistant bacteria
- 2020
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 26:12, s. 1644-1650
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death.METHODS: Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) < 50 mL/min. Individual colistin exposures were estimated from the developed population pharmacokinetic model and an optimized two-sample per patient sampling design. Time to death was evaluated in a parametric survival analysis.RESULTS: Out of 406 randomized patients, 349 contributed pharmacokinetic data. The median (90% range) colistin plasma concentration was 0.44 (0.14-1.59) mg/L at 15 minutes after the end of first infusion. In samples drawn 10 hr after a maintenance dose, concentrations were >2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and >120 mL/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03-1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19-1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen.DISCUSSION: The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations >2 mg/L at steady state, but only 66% at 4 hr after start of treatment. High colistin exposure was associated with poor kidney function, and was not related to a prolonged survival.
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- Feczkó, Tivadar, et al.
(författare)
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Stimulating brain recovery after stroke using theranostic albumin nanocarriers loaded with nerve growth factor in combination therapy
- 2019
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659. ; 293, s. 63-72
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Tidskriftsartikel (refereegranskat)abstract
- For many years, delivering drug molecules across the blood brain barrier has been a major challenge. The neuropeptide nerve growth factor is involved in the regulation of growth and differentiation of cholinergic neurons and holds great potential in the treatment of stroke. However, as with many other compounds, the biomolecule is not able to enter the central nervous system. In the present study, nerve growth factor and ultra-small particles of iron oxide were co-encapsulated into a chemically crosslinked albumin nanocarrier matrix which was modified on the surface with apolipoprotein E. These biodegradable nanoparticles with a size of 212 ± 1 nm exhibited monodisperse size distribution and low toxicity. They delivered NGF through an artificial blood brain barrier and were able to induce neurite outgrowth in PC12 cells in vitro. In an animal model of stroke, the infarct size was significantly reduced compared to the vehicle control. The combination therapy of NGF and the small-molecular MEK inhibitor U0126 showed a slight but not significant difference compared to U0126 alone. However, further in vivo evidence suggests that successful delivery of the neuropeptide is possible as well as the synergism between those two treatments.
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- Nault, Isabelle, et al.
(författare)
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Clinical value of fibrillatory wave amplitude on surface ECG in patients with persistent atrial fibrillation
- 2009
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Ingår i: Journal of Interventional Cardiac Electrophysiology. - : Springer Science and Business Media LLC. - 1572-8595 .- 1383-875X. ; 26:1, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- We postulated that amplitude of fibrillatory (F)-wave in patients with persistent AF would correlate with clinical characteristics and outcome in patients undergoing catheter ablation for AF. Maximal and mean amplitude of F-waves were measured in V1 and lead II in 90 patients prior to ablation for persistent AF. F-wave amplitudes were correlated to clinical, echocardiographic variables, and outcome. F-wave a parts per thousand yenaEuro parts per thousand 0.1 mV in lead II and V1was correlated with younger age and shorter AF history, and in lead II only was correlated with a smaller left atrium. Higher F-wave amplitude at baseline predicted AF termination during ablation. Maximal amplitude of a parts per thousand yenaEuro parts per thousand 0.07 mV predicted AF termination by ablation with 82%/79% sensitivity and 68%/73% specificity in V1/lead II respectively. An association between F-wave amplitude and AF recurrence was observed. Forty-three percent of patients with mean f wave amplitude < 0.05 in lead V1 had AF recurrence compared to 12% of those with F-wave a parts per thousand yenaEuro parts per thousand 0.05 (p = 0.004). Longer AF duration, older age and larger LA size are associated with fine AF amplitude. High F-wave amplitude predicts procedural termination of arrhyhmia in patients with persistent AF and freedom from AF upon follow-up.
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