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51.
Elin M. Svensson Francesca Aweeka Jeong-Gun Park Florence Marzan Kelly E. Dooley Mats O. Karlsson 《Antimicrobial agents and chemotherapy》2013,57(6):2780-2787
Safe, effective concomitant treatment regimens for tuberculosis (TB) and HIV infection are urgently needed. Bedaquiline (BDQ) is a promising new anti-TB drug, and efavirenz (EFV) is a commonly used antiretroviral. Due to EFV''s induction of cytochrome P450 3A4, the metabolic enzyme responsible for BDQ biotransformation, the drugs are expected to interact. Based on data from a phase I, single-dose pharmacokinetic study, a nonlinear mixed-effects model characterizing BDQ pharmacokinetics and interaction with multiple-dose EFV was developed. BDQ pharmacokinetics were best described by a 3-compartment disposition model with absorption through a dynamic transit compartment model. Metabolites M2 and M3 were described by 2-compartment models with clearance of BDQ and M2, respectively, as input. Impact of induction was described as an instantaneous change in clearance 1 week after initialization of EFV treatment and estimated for all compounds. The model predicts average steady-state concentrations of BDQ and M2 to be reduced by 52% (relative standard error [RSE], 3.7%) with chronic coadministration. A range of models with alternative structural assumptions regarding onset of induction effect and fraction metabolized resulted in similar estimates of the typical reduction and did not offer a markedly better fit to data. Simulations to investigate alternative regimens mitigating the estimated interaction effect were performed. The results suggest that simple adjustments of the standard regimen during EFV coadministration can prevent reduced exposure to BDQ without increasing exposures to M2. However, exposure to M3 would increase. Evaluation in clinical trials of adjusted regimens is necessary to ensure appropriate dosing for HIV-infected TB patients on an EFV-based regimen. 相似文献
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Magnus Hakeberg Leif Dernevik Pantalei Gatzinsky Christer Eklöf Charles Kennergren Mats Jontell 《Scandinavian cardiovascular journal : SCJ》2013,47(1):5-8
The objective of this study was to evaluate the significance of preoperative dental treatment for the development of complications in the form of infections during the first postoperative weeks after heart valve surgery. In one group of patients (n = 149), oral health was examined and dental treatment performed 3-6 months prior to heart valve surgery. In a second group (n = 104), oral health was examined postoperatively and these patients did not receive any dental treatment before surgery. Infections were recorded for all patients during the first three weeks after surgery and correlated to the dental status at the time of surgery. Sepsis or endocarditis occurred in 5.4% of the first group and in 1.9% of the second group. Freedom from all infections for the two groups was 55% and 56%, respectively. The results did not reveal any significant differences between the groups regarding patients' oral health at the primary oral examination. The frequencies of postoperative complications such as focal infections, fever and increased CRP were also found to be similar for both groups. The combined scores of complications were 2.1% and 1.8%, respectively. Data from the present study do not support the suggestion that dental intervention will decrease the rate of early complications following heart valve surgery. 相似文献
54.
Per Adolphson Hassan Abbaszadegan Henrik Bodén Mats Salemyr Tomas Henriques 《Acta orthopaedica》2013,84(2):195-200
In a randomized study of 32 postmenopausal women with a Colles' fracture, we studied whether 8 weeks of treatment with clodronate, a bisphosphonate, could prevent posttraumatic osteopenia. The patients were treated with a plaster splint for 4 weeks. The bone mineral density (BMD) of the forearm bones was measured at 2 levels with dual-energy x-ray absorptiometry (DEXA) 2, 6 and 12 months after the fracture. At 2 months, in the clodronate group, there was a median 53% higher BMD in the fracture region of the radius than in the uninjured radius. In the placebo group, we found a 33% higher BMD in the fractured radius at that level than in the uninjured radius. This increase in BMD of the fractured radius, caused by clodronate, was statistically significant. At 12 months, the BMD of the fracture side had been reduced by 17% and 12%, respectively, at that time it was still significantly increased in the clodronate group alone. In the ulna at the same level, we found no significant changes in BMD in either group on either side at any time. At 2 months, at the level between the distal and middle thirds, in the fractured radius, the median BMD was 7% lower in the clodronate group and 6% lower in the placebo group than in the uninjured radius. Although the reduction in BMD at that level was significant, there was no difference between the two treatment groups. At this level, the ulna on the fractured side showed a similar pattern, with a 5% lower BMD in the clodronate group and a 4% lower BMD in the placebo group. This osteopenia showed a small but significant progression on the fractured side after 6 and 12 months. 相似文献
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56.
Flemming Javier Olsen MD Mats Christian Højbjerg Lassen MB Philip Brainin MD PhD Jan Bech MD PhD Alia Saed Alhakak MD Sune Pedersen MD PhD Brian Claggett PhD Thomas Fritz-Hansen MD Fredrik Folke MD PhD Gunnar H. Gislason MD PhD Tor Biering-Sørensen MD PhD MPH 《Echocardiography (Mount Kisco, N.Y.)》2020,37(11):1741-1748
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Adaptation and evaluation of the Family Involvement and Alienation Questionnaire for use in the care of older people,psychiatric care,palliative care and diabetes care 下载免费PDF全文
59.
Morten Tulstrup Thomas L. Frandsen Jonas Abrahamsson Bendik Lund Kim Vettenranta Olafur Gisli Jonsson Hanne Vibeke Hansen Marquart Birgitte Klug Albertsen Mats Heyman Kjeld Schmiegelow On behalf of the Nordic Society of Paediatric Haematology Oncology 《European journal of haematology》2018,100(1):53-60