10 research outputs found
Nonautonomous dynamics: classification, invariants, and implementation
No full textThe work is a brief review of the results obtained in nonautonomous dynamics based on the concept of uniform equivalence of nonautonomous systems. This approach to the study of nonautonomous systems was proposed in [10] and further developed in the works of the second author, and recently - jointly by both authors. Such an approach seems to be fruitful and promising, since it allows one to develop a nonautonomous analogue of the theory of dynamical systems for the indicated classes of systems and give a classi cation of some natural classes of nonautonomous systems using combinatorial type invariants. We show this for classes of nonautonomous gradient-like vector elds on closed manifolds of dimensions one, two, and three. In the latter case, a new equivalence invariant appears, the wild embedding type for stable and unstable manifolds [14,17], as shown in a recent paper by the authors [5]
Paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction.
No full textBACKGROUND: There is no consensus regarding the safety and efficacy of drug-eluting stents, as compared with bare-metal stents, in patients with ST-segment elevation myocardial infarction who are undergoing primary percutaneous coronary intervention (PCI). METHODS: We randomly assigned, in a 3:1 ratio, 3006 patients presenting with ST-segment elevation myocardial infarction to receive paclitaxel-eluting stents (2257 patients) or otherwise identical bare-metal stents (749 patients). The two primary end points of the study were the 12-month rates of target-lesion revascularization for ischemia (analysis powered for superiority) and a composite safety outcome measure of death, reinfarction, stroke, or stent thrombosis (powered for noninferiority with a 3.0% margin). The major secondary end point was angiographic evidence of restenosis at 13 months. RESULTS: Patients who received paclitaxel-eluting stents, as compared with those who received bare-metal stents, had significantly lower 12-month rates of ischemia-driven target-lesion revascularization (4.5% vs. 7.5%; hazard ratio, 0.59; 95% confidence interval [CI], 0.43 to 0.83; P=0.002) and target-vessel revascularization (5.8% vs. 8.7%; hazard ratio, 0.65; 95% CI, 0.48 to 0.89; P=0.006), with noninferior rates of the composite safety end point (8.1% vs. 8.0%; hazard ratio, 1.02; 95% CI, 0.76 to 1.36; absolute difference, 0.1 percentage point; 95% CI, -2.1 to 2.4; P=0.01 for noninferiority; P=0.92 for superiority). Patients treated with paclitaxel-eluting stents and those treated with bare-metal stents had similar 12-month rates of death (3.5% and 3.5%, respectively; P=0.98) and stent thrombosis (3.2% and 3.4%, respectively; P=0.77). The 13-month rate of binary restenosis was significantly lower with paclitaxel-eluting stents than with bare-metal stents (10.0% vs. 22.9%; hazard ratio, 0.44; 95% CI, 0.33 to 0.57; P<0.001). CONCLUSIONS: In patients with ST-segment elevation myocardial infarction who were undergoing primary PCI, implantation of paclitaxel-eluting stents, as compared with bare-metal stents, significantly reduced angiographic evidence of restenosis and recurrent ischemia necessitating repeat revascularization procedures. No safety concerns were apparent at 1 year. (ClinicalTrials.gov number, NCT00433966.
Incidence, Predictors, and In-Hospital Outcomes of Transcatheter Aortic Valve Implantation After Nonelective Admission in Comparison With Elective Admission: From the Nationwide Inpatient Sample Database
No full textCandidates for transcatheter aortic valve implantation (TAVI) are generally older with multiple co-morbidities and are therefore susceptible to nonelective admissions before scheduled TAVI. Frequency, predictors, and outcomes of TAVI after nonelective admission are under-explored. We queried the Nationwide Inpatient Sample database, an administrative database, from January 2012 to September 2015 to identify hospitalization in those age \u3e/=50 who had transarterial TAVI. A propensity-matched cohort was created to compare the outcomes between nonelective and elective admission who had TAVI. The primary outcome was in-hospital mortality. A total of 9,521 TAVI admissions were identified during the study period. Of these admissions, 22.3% were nonelective admissions. Pulmonary circulation disorders (adjusted odds ratio [aOR] 1.38), anemia (aOR 1.54), congestive heart failure (aOR 1.37), chronic kidney disease (aOR 1.28; all p \u3c0.001), and atrial fibrillation (aOR 1.17, p=0.006) were independent risk factors for nonelective admission. In a propensity-matched cohort (1,683 admissions in each cohort), in-hospital mortality was similar (4.0% vs 2.8%, p=0.052). Nonelective admissions had higher rates of acute myocardial infarction (5.2% vs 0.7%), fatal arrhythmia (9.4% vs 6.0%), acute kidney injury (25.9% vs 17.1%), respiratory failure requiring intubation (0.26% vs 0.19%), cardiogenic shock (5.1% vs 2.1%; all p \u3c0.001), and bleeding requiring transfusion (13.1% vs 10.1%, p=0.006) during the index-hospitalization. Hospital length of stay (11.4 days vs 6.5 days, p \u3c0.001) and hospital cost (57,442, p \u3c0.001) were both increased in nonelective admissions. Nonelective admission accounted for approximately one-fifth of total TAVI with significantly different cohort profiles. Our results suggest that nonelective TAVI has higher adverse outcomes and increased health resource utilization. Expedition in TAVI process in high-risk cohorts may result in better outcomes
Meta-Analysis Comparing Patent Foramen Ovale Closure Versus Medical Therapy to Prevent Recurrent Cryptogenic Stroke
No full textAcute myocardial infarction: Clinical characteristics, management and outcome in a university medical centre in a developing Middle Eastern country
No full textBackground: The management and outcome of acute myocardial infarction (AMI) have not been Well studied in developing Countries, although demographic data from the World health Organization indicate that developing Countries Contribute a major share to the global burden of cardiovascular disease. Objectives: To analyze the clinical characteristics, management and outcome of patients hospitalize with AMI in a university medical centre in a developing Middle Eastern country. Methods: The study population comprised all patient hospitalized with AMI at the American University of Beirut between January 1, 1997, and December 30, 1998. The medical records of the patients were reviewed to deterimine their clinical characteristics, the diagnostic and invasive procedures used during the hospitalization, and any in-hospital complications, including death. Results: The population comprised 184 patients, with a mean age of 60±13 years. Fifty-two per cent of the infarcts were anterior and 76percent developed Q waves. Fifty-one per cent of the patients received thrombolitic therapy. At discharge, 80percent of the patients were given acetylsalicylic acid, 35percent were given beta-blockers, 34percent were given angiotensin-converting enzyme inhibitors and 30percent were given statins. Seventy-two per cent of the patients underwent coronary angiography, 23percent underwent percutaneous transluminal coronary angioplasty and 13percent had coronary artery bypass grafting. The in-hospital mortality was 13percent. The predictors of in-hospital mortality were advanced age (over 60 years), diabetes, prior AMI, Killip class greater than I and ejection fraction less that 40percent In contrast, the predictors of coronary angiography were younger age (less than 60 years), absence of diabetes or no history of AMI, Killip class I and ejection fraction greater than 40percent Conclusions: Coronary angiography after AMI was performed more frequently than expected in a university medical centre in a developing country, and it seemed to be selectively used in the low-risk patients rather than the high-risk ones. Furthermore, the under-use of medical therapy with beta-blockers and statins was evident. These findings Should prompt cardiac societies in these countries to initiate educational campaigns focusing on the cost-effectiveness of therapy in AMI to optimize the use of their limited resources. © 2004 Pulsus Group Inc. All rights reserved.BLUSTEIN J, 1993, JAMA-J AM MED ASSOC, V270, P344, DOI 10.1001-jama.270.3.344; EVERY NR, 1993, NEW ENGL J MED, V329, P546, DOI 10.1056-NEJM199308193290807; First International Study of Infarct Survival Collaborative Group, 1986, LANCET, V2, P57; Fox KAA, 2002, EUR HEART J, V23, P1177, DOI 10.1053-euhj.2001.3081; GRINES CL, 1993, NEW ENGL J MED, V328, P673, DOI 10.1056-NEJM199303113281001; HJALMARSON A, 1981, LANCET, V2, P823; Lopez Alan D., 1993, World Health Statistics Quarterly, V46, P91; Murray CJL, 1997, LANCET, V349, P1498, DOI 10.1016-S0140-6736(96)07492-2; PFEFFER MA, 1992, NEW ENGL J MED, V327, P669, DOI 10.1056-NEJM199209033271001; Pilote L, 1996, NEW ENGL J MED, V335, P1198, DOI 10.1056-NEJM199610173351606; Reddy KS, 1998, CIRCULATION, V97, P596; Rogers WJ, 2000, J AM COLL CARDIOL, V36, P2056, DOI 10.1016-S0735-1097(00)00996-7; PEDERSEN TR, 1994, LANCET, V344, P1383; Second International Study of Infarct Survival Collaborative Group (ISIS- 2), 1988, LANCET, V2, P349; TOPOL E, 1993, NEW ENGL J MED, V329, P67385
Acute myocardial infarction: Clinical characteristics, management and outcome in a university medical centre in a developing Middle Eastern country
No full textBackground: The management and outcome of acute myocardial infarction (AMI) have not been Well studied in developing Countries, although demographic data from the World health Organization indicate that developing Countries Contribute a major share to the global burden of cardiovascular disease. Objectives: To analyze the clinical characteristics, management and outcome of patients hospitalize with AMI in a university medical centre in a developing Middle Eastern country. Methods: The study population comprised all patient hospitalized with AMI at the American University of Beirut between January 1, 1997, and December 30, 1998. The medical records of the patients were reviewed to deterimine their clinical characteristics, the diagnostic and invasive procedures used during the hospitalization, and any in-hospital complications, including death. Results: The population comprised 184 patients, with a mean age of 60±13 years. Fifty-two per cent of the infarcts were anterior and 76percent developed Q waves. Fifty-one per cent of the patients received thrombolitic therapy. At discharge, 80percent of the patients were given acetylsalicylic acid, 35percent were given beta-blockers, 34percent were given angiotensin-converting enzyme inhibitors and 30percent were given statins. Seventy-two per cent of the patients underwent coronary angiography, 23percent underwent percutaneous transluminal coronary angioplasty and 13percent had coronary artery bypass grafting. The in-hospital mortality was 13percent. The predictors of in-hospital mortality were advanced age (over 60 years), diabetes, prior AMI, Killip class greater than I and ejection fraction less that 40percent In contrast, the predictors of coronary angiography were younger age (less than 60 years), absence of diabetes or no history of AMI, Killip class I and ejection fraction greater than 40percent Conclusions: Coronary angiography after AMI was performed more frequently than expected in a university medical centre in a developing country, and it seemed to be selectively used in the low-risk patients rather than the high-risk ones. Furthermore, the under-use of medical therapy with beta-blockers and statins was evident. These findings Should prompt cardiac societies in these countries to initiate educational campaigns focusing on the cost-effectiveness of therapy in AMI to optimize the use of their limited resources. © 2004 Pulsus Group Inc. All rights reserved.BLUSTEIN J, 1993, JAMA-J AM MED ASSOC, V270, P344, DOI 10.1001-jama.270.3.344; EVERY NR, 1993, NEW ENGL J MED, V329, P546, DOI 10.1056-NEJM199308193290807; First International Study of Infarct Survival Collaborative Group, 1986, LANCET, V2, P57; Fox KAA, 2002, EUR HEART J, V23, P1177, DOI 10.1053-euhj.2001.3081; GRINES CL, 1993, NEW ENGL J MED, V328, P673, DOI 10.1056-NEJM199303113281001; HJALMARSON A, 1981, LANCET, V2, P823; Lopez Alan D., 1993, World Health Statistics Quarterly, V46, P91; Murray CJL, 1997, LANCET, V349, P1498, DOI 10.1016-S0140-6736(96)07492-2; PFEFFER MA, 1992, NEW ENGL J MED, V327, P669, DOI 10.1056-NEJM199209033271001; Pilote L, 1996, NEW ENGL J MED, V335, P1198, DOI 10.1056-NEJM199610173351606; Reddy KS, 1998, CIRCULATION, V97, P596; Rogers WJ, 2000, J AM COLL CARDIOL, V36, P2056, DOI 10.1016-S0735-1097(00)00996-7; PEDERSEN TR, 1994, LANCET, V344, P1383; Second International Study of Infarct Survival Collaborative Group (ISIS- 2), 1988, LANCET, V2, P349; TOPOL E, 1993, NEW ENGL J MED, V329, P67385
Investigating the role of the JAK/STAT and MAPK pathways in ischaemia/reperfusion injury and inflammation
No full textThe signal transducer and activator of transcription (STAT) proteins are a family of transcription factors which transduce extracellular signals from cytokines, growth factors and G-proteins to the nucleus. STATs become activated by phosphorylation and translocate to the the nucleus where they bind to specific target promoters. STAT1 has previously been shown to have a role in inducing apoptosis in the myocardium following ischaemia/reperfusion injury (I/R), however the role of STAT3 in myocardial apoptosis is less clear. Here it is shown that STAT3 is phosphorylated in cardiac cells both in vito and in vivo in response to I/R injury and plays a protective role by reducing the levels of apoptosis. Several modulators of STAT3 activity were found to be upregulated following I/R, including JAK2, SOCS3 and GRIM-19. STAT3 was also found to be important in regulating DNA damage and repair through altered activity of DNA damage response proteins. Administration of the antioxidant tempol in vivo, reduced infarct size in a rat model of I/R injury and this was accompanied by a reduction in STAT1 and STAT3 phosphorylation. Increasing STAT1 phosphorylation with IFN-• treatment abolished the protective effect of tempol, suggesting that inhibition of STAT1 phosphorylation may be a key protective effect of tempol infusion. Affymetrix microarray analysis of hearts from the in vivo I/R model identified several novel gene expression changes and uncovered transcriptional reduction in large numbers of genes involved in mitochondrial respiration and transport. In addition, this approach identified several possible new regulators of cardiac protection mediated by tempol and the urocortin hormones.
The mitogen activated protein kinase (MAPK) family is involved in sensing cellular stress and play key roles in I/R injury and inflammation. MAPK activity is balanced by MAPK phosphatases (MKPs) such as MKP-1 and the role of MKP-1 in modulating the immune response was investigated. Mice deficient in MKP-1 were more susceptible to endotoxic shock and had elevated levels of serum cytokines. MKP-1 was found to be upregulated following toll-like recptor (TLR) stimulation and this was dependent on the signaling adaptors MyD88 and Trif. Macrophages deficient in MKP-1 had increased phosphorylation of p38 MAPK and JNK following TLR stimulation and secreted elevated amounts of the pro-inflammatory cytokines TNF-α, IL-12 and the anti-inflammatory cytokine IL-10. The temporal control and regulation of cytokine production in response to TLR stimulation was dissected using pharmacological inhibition of MAPKs. MKP-1 was not found to contribute to T cell differentiation but did have a role to play in the adaptive immune response as MKP-1- deficient mice failed to recover from an experimental model of multiple sclerosis
Investigations into the stability of growth factor induced-vasculature and the effects of synthetic biomaterials on heart remodelling after myocardial infarction
No full textThis work was based on the hypothesis that optimization of growth factor delivery rate and duration, combined with a biomaterial scaffold, could lead to an improved strategy for therapeutic neovascularization. To test this hypothesis, a novel in vivo model system that allows for characterization of stability and mural cell investment of newly created vessels was designed
Secondary prevention in heart failure: a special focus on aspirin, statins and exercise
No full textHeart failure (HF) is a leading killer in the Western world and is a serious financial burden on health care budgets. Moreover, the life quality of many HF patients decreases through multiple morbidities. In order to improve the prognosis of HF patients, evidence-based treatments are developing.
This thesis investigated areas of secondary prevention in HF without evidence. Subjects included those accessing cardiac rehabilitation (CR) referral, exercise-based CR and aspirin and statin prescription. Outcomes consisted of all-cause mortality, hospital admission and exercise capacities. HF was evaluated mainly as the reduced ejection fraction (HF-REF) subtype, while applied statistical models were parametric and non-parametric. Missing values were assessed through multiple imputations.
First, the CR referral effect on mortality after an acute myocardial infarction event was evaluated. The Evaluation of Methods and Management of Acute Coronary Events (EMMACE)-I and II observational studies demonstrated CR referral as an independent predictor of survival in 2003, but not in 1995. Similar results were shown in HF subgroups. Although decreasing between the studies, CR referral was associated with treatment inequalities, thus suggesting a risk-treatment paradox.
Second, the effect of enrolment in exercise-based CR in HF patients was assessed through a meta-analysis incorporating randomised controlled trials (RCTs). Over a minimum of six months, follow-up exercise capacities and hospital admissions significantly improved in the exercise intervention group as compared with the control group. In contrast, mortality was not significantly improved through exercise, although a trend suggested exercise to be superior to a sedentary lifestyle.
Confounders were patient selection in RCT recruitment and the unequal quality of care.
Third, the average treatment effects of aspirin and statins in HF patients (EMMACE studies) improved survival rates during 90 months follow-up.
In HF populations, CR attendance influenced key outcomes significantly, whereas aspirin and statins were beneficial to survival in observational studies
