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991.
992.
Richard P. Whitlock Jessica Vincent Mary Helen Blackall Jack Hirsh Stephen Fremes Richard Novick P.J. Devereaux Kevin Teoh Andre Lamy Stuart J. Connolly Salim Yusuf Michel Carrier Jeff S. Healey 《The Canadian journal of cardiology》2013
Background
Occlusion of the left atrial appendage (LAA) is a potential alternative to anticoagulation for patients with atrial fibrillation (AF); however, evidence of its safety and efficacy is lacking. The Left Atrial Appendage Occlusion Study II (LAAOS II) explored the feasibility of a definitive trial of LAA occlusion for stroke prevention in AF.Methods
A cross-sectional study of 1889 consecutive patients undergoing cardiac surgery was performed to determine the prevalence of AF and risk factors for stroke. We also randomized 51 patients with AF and increased stroke risk to LAA occlusion (n = 26) or no occlusion and oral anticoagulation (n = 25) to assess the rate of recruitment and the safety of LAA amputation.Results
In the cross-sectional study, 204 patients (10.8%) had AF and 98 (5.2%) met trial eligibility. Fifty-one patients were recruited into the trial at a rate of 1.6 patients per centre per month. No patient with occlusion had significant bleeding at the LAA site. At 1 year, 4 patients (15.4%) in the occlusion arm and 5 patients (20.0%) in the no-occlusion arm experienced death, myocardial infarction (MI), stroke, noncerebral systemic emboli, or major bleeding (relative risk [RR], 0.71; 95% confidence interval [CI], 0.19-2.66; P = 0.61). The predominant component of the composite was stroke, with 1 in the occlusion arm and 3 in the no-occlusion arm.Conclusions
LAA occlusion can be safely performed at the time of cardiac surgery. A large trial to evaluate the clinical efficacy of LAA occlusion in patients undergoing cardiac surgery is possible in motivated centres with some modifications to the design of LAAOS II. 相似文献993.
994.
Nathalie Rioux Edith Bellavance Serge Bourg Michel Garneau Maria D. Ribadeneira Jianmin Duan 《Biopharmaceutics & drug disposition》2013,34(7):396-401
The present study aims to determine if an in vivo rat model of drug–drug interaction (DDI) could be useful to discriminate a sensitive (buspirone) from a ‘non‐sensitive’ (verapamil) CYP3A substrate, using ketoconazole and ritonavir as perpetrator drugs. Prior to in vivo studies, ketoconazole and ritonavir were shown to inhibit midazolam hydroxylation with IC50 values of 350 ± 60 nm and 11 ± 3 nm , respectively, in rat liver microsomes (RLM). Buspirone and verapamil were also shown to be substrates of recombinant rat CYP3A1/3A2. In the rat model, the mean plasma AUC0‐inf of buspirone (10 mg/kg, p.o.) was increased by 7.4‐fold and 12.8‐fold after co‐administration with ketoconazole and ritonavir (20 mg/kg, p.o.), respectively. The mean plasma AUC0‐inf of verapamil (10 mg/kg, p.o.) was increased by 3.0‐fold and 4.8‐fold after co‐administration with ketoconazole and ritonavir (20 mg/kg, p.o.), respectively. Thus, the rat DDI model correctly identified buspirone as a sensitive CYP3A substrate (>5‐fold AUC change) in contrast to verapamil. In addition, for both victim drugs, the extent of DDI when co‐administered was greater with ritonavir compared with ketoconazole, in line with their in vitro CYP3A inhibition potency in RLM. In conclusion, our study extended the rat DDI model applicability to two additional victim/perpetrator pairs. In addition, we suggest that use of this model would increase our confidence in estimation of the DDI potential for victim drugs in early discovery. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
995.
Michael A. Letavic Brian Lord Francois Bischoff NatalieA. Hawryluk Serge Pieters Jason C. Rech Zachary Sales Adriana I. Velter Hong Ao Pascal Bonaventure Victor Contreras Xiaohui Jiang Kirsten L. Morton Brian Scott Qi Wang Alan D. Wickenden Nicholas I. Carruthers Anindya Bhattacharya 《ACS medicinal chemistry letters》2013,4(4):419-422
996.
997.
Coudeyre E Poiraudeau S Revel M Kahan A Drapé JL Ravaud P 《Joint, bone, spine : revue du rhumatisme》2002,69(6):597-603
How beneficial is the provision of information leaflets to low back pain patients before steroid injection under fluoroscopy? OBJECTIVES: To compare the value of information leaflets with verbal information on steroid injection under fluoroscopy. METHODS: Alternate month design. One hundred and twenty-three low back pain patients hospitalized for steroid injection under fluoroscopy were enrolled in the trial. Fifty-two patients received both written standardized information and non-standardized verbal information (intervention group), seventy one patients received only non-standardized verbal information (control group). Anxiety assessed at baseline evaluation and just before the injection; satisfaction related to the information received assessed on discharge day; knowledge about steroid injection assessed 4 hours and 1 month after the injection. RESULTS: Patients had a high anxiety level at baseline evaluation. Written standardized information did not decrease significantly anxiety (P = 0.068) before the injection, had no effect on pain during the injection, but increased patients' knowledge about the adverse effects on the day of injection and 1 month later (P = 0.040 and P = 0.084 respectively), and improve satisfaction with information received about potential complications of the steroid injections (P = 0.018). CONCLUSIONS: Providing an information leaflet to low back pain patents undergoing steroid injection under fluoroscopy tends to reduce state anxiety, and increases patients' knowledge and satisfaction with information about the risks of the injection. 相似文献
998.
Villoslada P Moreno B Melero I Pablos JL Martino G Uccelli A Montalban X Avila J Rivest S Acarin L Appel S Khoury SJ McGeer P Ferrer I Delgado M Obeso J Schwartz M 《Clinical immunology (Orlando, Fla.)》2008,128(3):294-305
The burden of neurological diseases in western societies has accentuated the need to develop effective therapies to stop the progression of chronic neurological diseases. Recent discoveries regarding the role of the immune system in brain damage coupled with the development of new technologies to manipulate the immune response make immunotherapies an attractive possibility to treat neurological diseases. The wide repertoire of immune responses and the possibility to engineer such responses, as well as their capacity to promote tissue repair, indicates that immunotherapy might offer benefits in the treatment of neurological diseases, similar to the benefits that are being associated with the treatment of cancer and autoimmune diseases. However, before applying such strategies to patients it is necessary to better understand the pathologies to be targeted, as well as how individual subjects may respond to immunotherapies, either in isolation or in combination. Due to the powerful effects of the immune system, one priority is to avoid tissue damage due to the activity of the immune system, particularly considering that the nervous system does not tolerate even the smallest amount of tissue damage. 相似文献
999.
Chronic Psychophysiological Insomnia: Hyperarousal and/or Inhibition Deficits? An ERPs Investigation 总被引:1,自引:0,他引:1
STUDY OBJECTIVES: Chronic primary insomnia has been hypothesized to result from conditioned arousal or the inability to initiate normal sleep processes. The event-related potentials (ERPs) N1, P2, and N350 are useful indexes of arousal. The objective is to compare these ERPs in primary chronic psychophysiological insomniacs (INS) and good sleepers (GS) during multiple recordings. PARTICIPANTS: Participants were 15 INS (mean age = 46 years, SD = 7.5) and 16 GS (mean age = 37 years, SD = 10.1). METHODS AND PROCEDURE: Following a multistep clinical evaluation, INS and GS participants underwent 4 consecutive nights of PSG recordings (N1 to N4). ERPs were recorded on the 3rd and 4th nights in the sleep laboratory (N3 and N4). ERPs recordings were made during wake on both nights (in the evening and upon awakening), with the addition of sleep-onset recordings on N4. Auditory stimuli consisted of "standard" and "deviant" tones. STATISTICAL ANALYSIS: Repeated measures ANOVAs were computed for each ERP for each recording for each type of stimulus. RESULTS: The amplitude of P2 and N350 was greater for the deviant than for the standard stimulus in both groups. The amplitude of N1 was larger in INS than GS in the morning and the evening. While the amplitude of N350 was larger in GS than in INS at sleep onset, the amplitude of P2 was greater in INS than in GS at that time. CONCLUSION: Signs of greater cortical arousal in psychophysiological insomnia individuals are observed, especially upon awakening in the morning. However, at sleep onset, difficulties from disengaging from wake processes and some inability at initiating normal sleep processes appear also present in individuals with insomnia compared to good sleepers. 相似文献