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PubMed1997

Predictors of long-term event-free survival after percutaneous balloon mitral valvuloplasty.

Previous studies have shown that long-term event-free survival after percutaneous balloon mitral valvuloplasty (PBMV) could be predicted by several baseline characteristics. However, the extent of the predictive variables has not been defined accurately yet. In this study, 40 baseline demographic, clinical, echocardiographic, and hemodynamic variables of 128 consecutive patients with mitral stenosis who underwent PBMV in a single institution, were analyzed in order to predict long-term event-free survival, defined as absence of death, mitral valve replacement, or repeat PBMV. Univariate survival analysis showed that age (p = 0.03), history of commissurotomy or mitral valvuloplasty (p = 0.05), calcium grade (p = 0.008), echo score (p = 0.0001), preprocedure cardiac output (p = 0.03), preprocedure valve area (p = 0.0007), postprocedure mean left atrial pressure (p = 0.0001), postprocedure valve area (p = 0.0001), postprocedure valve gradient (p = 0.013), and postprocedural mitral regurgitation (p = 0.01) were statistically significant predictors of event-free survival. Additionally, the absolute and/or relative procedural change of the following variables were found to be statistically significant predictors of event-free survival: left atrial pressure (p = 0.01), valve area (p = 0.0001), and valve gradient (p = 0.02). Multivariate Cox proportional hazard analysis indicated that when only variables available before the procedure were considered, echo score (p = 0.002) and preprocedure valve area (p = 0.0002) were found to be independent predictors of event-free survival. When both pre- and postprocedure variables were considered, echo score (p = 0.002) and postprocedure valve area (p = 0.0001) were found to be independent predictors of event-free survival. In conclusion, mitral valve morphology reflected by echo score, and baseline and postprocedure mitral valve area were found to be the strongest independent predictors of event-free survival after PBMV.

Aged↗
PubMed2006

What does transient global amnesia really mean? Review of the literature and thorough study of 142 cases.

Since the first reports of transient global amnesia (TGA) were published in 1956, several neuropsychological and functional imaging studies have shed light on different aspects of this neurological syndrome. By establishing diagnostic criteria, Hodges and Warlow (1990b) have made it far easier to identify clinical TGA-related features. However, no comprehensive survey has been yet carried out in order to validate their criteria/findings or provide information about previously unknown features. In the present paper, (i) we review the literature published since Hodges and Warlow's study and seek to characterize the demographic and clinical features of TGA more accurately, (ii) we report 142 personal TGA cases, with supplementary information regarding both episodes and patients, such as precipitating events, associated symptoms and personality, and (iii) we suggest the existence of different groups of TGA patients, on the basis of a hierarchical cluster analysis. This revealed that in women, episodes are mainly associated with an emotional precipitating event, a history of anxiety and a pathological personality. In men, they occur more frequently after a physical precipitating event. In younger patients, a history of headaches may constitute an important risk factor. No link was found with vascular risk factors. The relevance of each of the above-mentioned variables is discussed in the light of our classification. An extensive description of cases from both the literature and our patient population allows us to refine the characterization of clinical TGA features.

Adult↗
PubMed2006

Barriers to antiretroviral adherence: the importance of depression, abuse, and other traumatic events.

Among HIV-infected persons, high-level adherence to antiretroviral medications (>90%-95%) is associated with improved immunologic, virologic, and clinical outcomes, and is necessary to prevent the emergence of viral resistance. This study examines whether lifetime traumatic events including physical and sexual abuse, are associated with antiretroviral nonadherence. We present a cross-sectional analysis of the Coping with HIV/AIDS in the Southeast (CHASE) Study, analyzing data from the enrollment interview and medical records of study subjects. The CHASE Study is a prospective cohort study of consecutively sampled HIV-infected subjects from infectious diseases clinics in five southern states; Alabama, Georgia, Louisiana, North Carolina, and South Carolina. Four hundred seventy-four (78%) of the 611 CHASE study subjects reported being treated with antiretroviral medications at enrollment and are included in this analysis. Nonadherence was defined as the patient's self-report of missing any doses of their antiretroviral medications over the previous 7 days. Among study subjects, 54% reported a history of physical and/or sexual abuse, 91% reported at least one lifetime traumatic event, and 24% reported nonadherence with their antiretrovirals. In multivariable logistic regression analysis, the number of categories of lifetime traumatic events (p = 0.03), the Addiction Severity Index (ASI) alcohol score (p = 0.02), and being uninsured (p = 0.04) were associated with antiretroviral nonadherence. The finding that lifetime traumatic events are associated with antiretroviral nonadherence, particularly among those who have been traumatized in multiple ways, highlights the complex and often persisting manifestations of such trauma and calls for further investigation.

Adult↗
PubMed2006

The advanced glycation end product N(epsilon)-carboxymethyllysine is not a predictor of cardiovascular events and renal outcomes in patients with type 2 diabetic kidney disease and hypertension.

BACKGROUND: Advanced glycation end products (AGEs) are implicated in the pathogenesis of vascular damage, especially in patients with diabetes and renal insufficiency. The oxidatively formed AGE N(epsilon)-carboxymethyllysine (CML) is thought to be a marker of oxidative stress. METHODS: Four hundred fifty patients with type 2 diabetes and nephropathy from the Irbesartan in Diabetic Nephropathy Trial cohort (mean age, 58 +/- 8.2 years; 137 women, 313 men) with a mean glomerular filtration rate of 48.2 mL/min (0.80 mL/s; Modification of Diet in Renal Disease formula) were followed up for 2.6 years. Serum CML was measured by using an enzyme-linked immunosorbent assay. Relationships between CML levels, traditional risk factors, and cardiovascular and renal events were tested in Cox proportional hazards models. RESULTS: Mean serum CML level was 599.9 +/- 276.0 ng/mL, and mean hemoglobin A1c level was 7.5% +/- 1.6%. One hundred forty-three first cardiovascular events occurred during follow-up; 74 patients died, 44 of cardiovascular causes. Final multivariate analysis showed age (relative risk [RR], 1.87; confidence interval [CI], 1.13 to 3.11; P = 0.016 for the highest compared with lowest quartile), history of prior cardiovascular events (RR, 1.96; CI, 1.35 to 2.85; P < 0.0005), and 24-hour urinary albumin-creatinine ratio (RR, 1.29; CI, 1.11 to 1.50 per doubling; P < 0.0005) to be independent risk factors for a first cardiovascular event, but not CML level. CML level also did not correlate significantly with renal outcome. CONCLUSION: Serum CML level could not be identified as an independent risk factor for cardiovascular or renal outcomes in the examined population. This suggests that traditional risk factors might have a more important role for these end points or that other AGE compounds, as well as tissue AGE levels, might be of greater relevance compared with serum levels, which remains open to further study.

Aged↗
PubMed2001

Prognostic value of dipyridamole stress echocardiography in hypertensive patients with left ventricular hypertrophy, chest pain and resting electrocardiographic repolarization abnormalities.

BACKGROUND: Hypertension is a major cardiovascular risk factor in the development of coronary artery disease (CAD); therefore, evaluating the presence of CAD is a primary clinical goal. However, the noninvasive tests that are commonly used have poor diagnostic specificity, particularly in patients with left ventricular hypertrophy. OBJECTIVES: To assess the prognostic value of dipyridamole stress echocardiography (DET) for ischemic events in a subset of patients with hypertension with left ventricular hypertrophy, chest pain and resting electrocardiographic repolarization abnormalities. PATIENTS AND METHODS: Eighty-two patients (48 men and 34 women; average age 65+/-7.2 years with left ventricular hypertrophy documented echocardiographically (left ventricular mass index greater than 50 g/h(2.7)), and resting ST segment shift of 0.1 mV or more from baseline at 80 ms after J point in at least two contiguous leads, were submitted to DET according to high-dosage protocol and coadministered with atropine. RESULTS: The follow-up period was 25.11+/-8.3 months. The stress test produced positive results in 30 patients (36.5%); 16 (53%) and three (5%) cardiac events occurred in positive and negative stress test groups, respectively. At multivariate analysis, only positive DET response (P=0.000002), left ventricular mass index (P=0.028) and a family history of CAD (P=0.037) were independent predictors. The two-year event-free survival rates were 95% and 47% (log-rank 21.093, P=0.00001) for negative and positive stress test results, respectively. CONCLUSIONS: DET is a useful tool in the prognostic assessment of coronary events in this particular subgroup of patients with hypertension.

Aged↗
PubMed2003

Prior peripheral arterial disease and cerebrovascular disease are independent predictors of adverse outcome in patients with acute coronary syndromes: are we doing enough? Results from the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis In Myocardial Infarction (OPUS-TIMI) 16 study.

BACKGROUND: Cerebrovascular accidents (CVAs), transient ischemic attacks (TIAs), and peripheral arterial disease (PAD) frequently coexist with coronary artery disease (CAD) and were previously reported to adversely affect the prognosis of patients with chronic CAD. METHODS: We examined the effect of prior CVA/TIA or PAD (extra-cardiac vascular disease [EVD]) on the outcome of 10,281 patients with acute coronary syndromes enrolled in the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction (OPUS-TIMI) 16 trial of the oral glycoprotein IIb/IIIa antagonist orbofiban plus aspirin versus aspirin alone. We evaluated mortality, recurrent cardiac events, and stroke and used multivariate analysis to control for differences in baseline characteristics. RESULTS: Patients with EVD were older, had more coronary risk factors, had a history of CAD, and received more intensive medical treatment at baseline. The acute event in these patients was more often unstable angina pectoris and less commonly Q-wave myocardial infarction. With coronary angiography, patients with prior EVD more often had multivessel disease. During the 10 months of follow-up, the presence of EVD was predictive of an increased hazard of death, reinfarction, recurrent ischemia, stroke, and a composite of these events. Despite the increased severity of the CAD and increased risk of events, patients with EVD were treated less frequently with beta-blockers and more frequently with calcium blockers. Despite patients with EVD having a 45% higher incidence of hypercholesterolemia, lipid-lowering agents were prescribed in a similar percentage of patients as patients without EVD. CONCLUSION: In patients with acute coronary syndromes, the presence of prior CVA, TIA, or PAD is associated with more extensive CAD and worse outcome. These patients appear to receive less aggressive treatment, which may explain, at least in part, their worse outcome.

Aged↗
PubMed1997

Influence of menopause on blood cholesterol levels in women: the role of body composition, fat distribution and hormonal milieu. Virgilio Menopause Health Group.

OBJECTIVES: In this study we investigated the relationships between blood lipids and menopausal status. SETTING AND SUBJECTS: All data were obtained from the first cross-sectional examination of the Virgilio Menopause Health Project in a large cohort of middle-aged women in pre, peri-, and postmenopausal age. The data refer to 426 women without metabolic or endocrine diseases, relevant hepatic, renal and cardiovascular abnormalities, none were dieting or taking medications. MAIN OUTCOME MEASURES: A precoded questionnaire including full clinical history, socio-economic and personal information, habitual diet, physical activity, drug use and smoking habits, careful recording of gynaecological events and family history for disease was completed. Several anthropometric parameters and the bioelectrical impedance analysis was used to measure free fatty mass. Blood samples for hormones and biochemistry were also obtained. RESULTS: There were no significant differences on body mass index, fatty mass, free fatty mass and parameters of body fat distribution between the three groups. Again, there were no differences in smoking habits, dietary intake or indices of physical activity amongst the groups. There was a significant increase from pre to postmenopause of LH and FSH and a decrease of oestradiol and testosterone, whereas no difference was found in sex hormone-binding globulin. Age-adjusted values of glucose, triglycerides and high density lipoprotein (HDL-) cholesterol were similar in all groups, whereas postmenopausal women had significantly higher values of total and low density lipoprotein (LDL-) cholesterol. On the contrary, there was a significant fall in insulin levels passing from pre to postmenopause. In multiple regression models, total and LDL-cholesterol correlated positively with body mass index, waist-to-hip ratio and age, and negatively with free fatty mass and oestradiol blood levels. CONCLUSIONS: These results are consistent with the hypothesis that menopausal status may have a significant and independent effect in determining increased total and LDL-cholesterol concentrations in postmenopausal women.

Adipose Tissue↗
PubMed2001

Polysomnographic assessment of spells in sleep: nocturnal seizures versus parasomnias.

A dilemma can arise when attempting to distinguish a nocturnal seizure from a parasomnia because both phenomena can be characterized by a general increase in motor and autonomic activity with a transient reduction in the level of consciousness. An additional problem is that an accurate clinical diagnosis generally relies heavily on a detailed history. As sleep related disorders occur at a time when the patient is not fully cognizant, polysomnographic analysis can on occasion supplement for the intrinsic paucity of detailed history. Simultaneously, correlating the clinical and polysomnographic analysis immediately prior to, during, and following an event of interest, can be helpful in differentiating nocturnal seizures from parasomnias.

Adult↗
PubMed1995

Constraints on intron evolution in the gene encoding the myosin alkali light chain in Drosophila.

Interspecific comparisons of intron sequences reveal conserved blocks of invariant nucleotides and several other departures from the strictly neutral model of molecular evolution. To distinguish the past action of evolutionary forces in introns known to have regulatory information, we examined nucleotide sequence variation at 991 sites in a random sample of 16 Drosophila melanogaster alleles of the gene encoding the myosin alkali light chain (Mlc1). The Mlc1 gene of D. melanogaster encodes two MLC1 isoforms via developmentally regulated alternative pre-mRNA splicing. Analyses of these data reveal that introns 4 and 5, which flank the alternatively spliced exon 5, have reduced levels of both intraspecific polymorphism and interspecific divergence relative to intron 3. No polymorphism was observed in any of the exons examined in D. melanogaster. A genealogical analysis clearly demonstrates the occurrence of intragenic recombination in the ancestral history of Mlc1. Recombination events are estimated to be 13 times more likely than mutation events over the span of the sequenced region. Although there is little evidence for pairwise linkage disequilibrium in the Mlc1 region, higher order disequilibrium does seem to be present in the 5' half of the portion of the gene that was examined. Predictions of the folding free energy of the pre-mRNA reveal that sampled alleles have a significantly higher (less stable) free energy than do randomly permuted sequences. These results are consistent with the hypothesis that introns surrounding an alternatively spliced exon are subjected to additional constraints, perhaps due to specific aspects of secondary structure required for appropriate splicing of the pre-mRNA molecule.

Alternative Splicing↗
PubMed1989

Noninvasive predictors of cardiac events after myocardial infarction. Complementary value of exercise testing and signal-averaged electrocardiography.

Signal-averaged electrocardiography, resting radionuclide ventriculography and Holter monitoring were performed prior to hospital discharge, to assess their value in predicting recurrent cardiac events in 210 survivors of acute myocardial infarction. In addition, 153 of these patients also underwent exercise radionuclide ventriculographic assessment. During median follow-up of 14 months (6-24 months), there were 16 cardiac deaths, 15 patients had recurrent infarction and 7 patients represented with symptomatic ventricular tachycardia. Cox regression analysis identified independent predictors of 'ischemic events' (death or re-infarction) as a previous history of infarction (p = 0.01), Killip class III-IV (p = 0.03) and an abnormal exercise radionuclide study (p = 0.04); and predictors of 'arrhythmic events' (sustained ventricular tachycardia or sudden death) as an abnormal signal-averaged electrocardiograph (p = 0.01) and left ventricular ejection fraction less than 40% (p = 0.03). Patients with an abnormal signal-averaged electrocardiograph and reduced left ventricular ejection fraction had a 34% incidence of arrhythmic events during the first 6 months compared with a 4% incidence among patients without late potentials. In those patients who underwent exercise testing and signal averaging, 85% of total cardiac events and all cardiac deaths were predicted by an abnormality of either noninvasive test. In addition, exercise testing and signal-averaged ECG were independent predictors of outcome. Hence, using a combination of noninvasive tests, patients can be stratified according to the risk of recurrent life-threatening cardiac events after myocardial infarction; such patients may be suitable for intensive investigation and considered for trials involving active intervention.

Electrocardiography↗
PubMed1990

Bone marrow transplantation in patients with thalassemia.

We reviewed the results of transplantation of allogeneic marrow from HLA-identical donors in patients with beta-thalassemia who were less than 16 years old. Among the 222 consecutive patients who had received transplants since 1983, survival and event-free-survival curves leveled off about one year after transplantation, at 82 and 75 percent, respectively. Pretransplantation clinical characteristics were examined for their impact on survival, event-free survival, and the recurrence of thalassemia in the 116 consecutive patients who were treated with our current regimen, in use since June 1985. In a multivariate analysis, portal fibrosis and either the presence of hepatomegaly or a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly or portal fibrosis (class 1 had neither factor, class 2 had one, and class 3 had both). For class 1 patients the three-year probabilities of survival, event-free survival, and recurrence were 94, 94, and 0 percent, respectively. For class 2 patients the probabilities were 80, 77, and 9 percent, and for class 3 patients 61, 53, and 16 percent. We conclude that for patients under 16 years of age, transplantation of bone marrow from an HLA-identical donor offers a high probability of complication-free survival, particularly if they do not have hepatomegaly or portal fibrosis.

Adolescent↗
PubMed2003

Features of Posttraumatic Distress Among Adolescent Athletes.

OBJECTIVE: To examine features of posttraumatic distress related to sport injury among healthy and injured adolescent athletes. DESIGN AND SETTING: Healthy athletes with and without a prior injury history were screened before their competitive season, and injured and matched control athletes were surveyed at 1 week postinjury. SUBJECTS: We screened 283 athletes during the preseason and categorized them by injury history (n = 43) and no injury history (n = 240) groups. Twenty-four athletes (12 injured, 12 matched uninjured controls) were included in the postinjury analysis. MEASUREMENTS: The Impact of Events Scale, a 15-item self-report questionnaire, was used to measure athletes' frequency of experiencing intrusive thoughts and engaging in avoidance behavior regarding athletic injury. RESULTS: Athletes with a recent injury history exhibited a greater frequency of intrusive thoughts and avoidance behavior than did those without a recent injury history. Although postinjury findings did not reach statistical significance, injured athletes' scores increased by 35% to 49% from preinjury to postinjury, whereas only minimal changes (<1%) occurred in the control group. CONCLUSIONS: Younger athletes may be particularly sensitive to injury-related stimuli, which may result in heightened injury-related distress.

Journal Article↗
PubMed1991

Bone marrow transplantation in thalassemia.

Since 1983, 350 patients aged 1 to 19 years with beta-homozygous thalassemia were given infusions of HLA-identical marrow after high doses of busulphan and cyclophosphamide. Survival and event-free survival leveled off about 1 year after bone marrow transplantation at 82% and 75%, respectively. In 172 consecutive patients who were treated with our current regimen since June 1985, a multivariate analysis demonstrated that portal fibrosis, hepatomegaly, and a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly, portal fibrosis, and inadequate chelation therapy. Class 1 had none of the factors and class 3 had all three factors; class 2 had different associations of two out of the three factors. For class 1 patients, the 3-year probabilities of survival and event-free survival were 97% and 94%, respectively. For class 2 patients, the probabilities were 86% and 83%, and for class 3 patients, 58% and 52%. Bone marrow transplantation from HLA-identical donors is followed by a high probability of event-free survival in thalassemic patients, particularly if they belong to class 1.

Adolescent↗
PubMed2001

Phylogeography of the red-tailed chipmunk (Tamias ruficaudus), a northern Rocky Mountain endemic.

The northern Rocky Mountains have experienced a complex history of geological events and environmental fluctuation, including Pleistocene glaciation. To provide an initial assessment of the genetic impact of this history on the regional biota we estimated phylogenetic relationships within Tamias ruficaudus, a regional endemic, from cytochrome b sequence variation using parsimony, maximum likelihood, and nested clade analysis. Analyses of sequence variation in 187 individuals from 43 localities across the distribution of T. ruficaudus indicate a history of vicariance events and range fluctuation consistent with successive periods of extensive Pleistocene glaciation in the northern Rocky Mountains. Intraspecific divergence levels (c. 4.7% uncorrected) and phylogenetic structure are consistent with a genealogical vicariance initiated prior to the Late Pleistocene, whereas nested clade analyses indicate more recent population history structured by both fragmentation and range expansion. A comparison of sequence variation with bacular morphology indicates that the two genetically and morphologically differentiated entities exhibit a zone of differential character introgression. Sequence data support a multiple refugia hypothesis and provide a phylogeographical case study for the ongoing synthesis of regional biogeography for northern Rocky Mountain endemics.

Animals↗
PubMed2003

Preoperative risk stratification using stress myocardial perfusion scintigraphy with electrocardiographic gating.

UNLABELLED: This study was designed to assess the prognostic value of stress myocardial perfusion SPECT with electrocardiographic (ECG) gating in patients undergoing noncardiac surgical treatment. METHODS: The study included 481 consecutive patients who underwent noncardiac surgery and had been referred for preoperative myocardial perfusion scintigraphy. Myocardial scintigraphy used (99m)Tc-labeled perfusion agents and dipyridamole stress with ECG gating, permitting qualitative and quantitative analyses of both myocardial perfusion and cardiac function. Reconstructed perfusion images were analyzed qualitatively and semiquantitatively. The Quantitative Gated SPECT (QGS) program was used for gated SPECT analysis to calculate global left ventricular ejection fraction and estimate regional wall motion. We assessed the relationships between perioperative cardiac events and various predictors, including clinical risk factors, radionuclide perfusion, and functional variables. RESULTS: Univariate analysis indicated that age (P < 0.001), diabetes mellitus (P < 0.01), history of heart failure (P < 0.05) or perfusion imaging (P < 0.0001), and QGS analysis (P < 0.0001) yielded significant risk stratification. According to multivariate analysis, age, diabetes mellitus, perfusion imaging, and QGS analysis were independent predictors of perioperative cardiac events. The event rate was correlated with quantitative scintigraphic indices of perfusion images (rest perfusion and ischemic scores) and QGS analysis (global ejection fraction and the number of hypokinetic segments). Although QGS functional data offered no significant incremental prognostic value in patients with abnormal perfusion, it classified patients with normal perfusion into 2 risk groups (P < 0.0001). A combination of clinical risk factors, scintigraphic perfusion results, and functional data allowed further detailed risk stratification. CONCLUSION: Stress myocardial perfusion SPECT with ECG gating has an incremental prognostic value over conventional nongated stress perfusion imaging in predicting perioperative cardiac events.

Aged↗
PubMed1995

Lipoprotein (a) and apolipoprotein A-1 and B in schoolchildren whose grandparents had coronary and cerebrovascular events: a preliminary study of 12-13 year old Japanese children.

The aim of this study was to evaluate the relationship between the serum levels of lipoprotein (a) [Lp (a)] and apolipoproteins (apo A-1 and apo B) in schoolchildren with a history of coronary and cerebrovascular events in their grandparents. We measured serum concentrations of Lp (a) and apoliproteins immunochemically in 289 schoolchildren aged 12-13 years and questioned parents about coronary and cerebrovascular events in the children's grandparents. In boys and girls, mean +/- s.d. levels of apo A-1, apo B and Lp (a) were 134 +/- 20.3 and 136 +/- 17.4 mg/dL, 61 +/- 16 and 66 +/- 15 mg/dL and 12.5 +/- 15.3 and 12.5 +/- 15.1 mg/dL, respectively. There were no significant sex differences in the levels of apo A-1, apo B, and Lp (a). The Lp (a) levels (mean +/- s.d., 12.5 +/- 15.2 mg/dL; median 7.5 mg/dL, n = 289) were not affected by other variables. The Lp (a) distribution was strongly positively skewed and 75% of schoolchildren had very low levels. In the total 289 schoolchildren, thirty-two grandparents who had had coronary vascular events (21 myocardial infarction, 11 angina pectoris) and twenty-three grandparents who had had cerebrovascular events were recorded. By the boxplot statistical analysis, no difference was found in Lp (a) levels in children whose grandparents had myocardial infarction compared with those whose grandparents had no such history, or compared with those whose grandparents had suffered cerebrovascular events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2001

Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery.

BACKGROUND: After coronary artery bypass surgery, patients have a high cumulative rate of graft closure and recurrent ischemic events. We sought to determine whether antiplatelet therapy with clopidogrel would be more effective than aspirin, the accepted standard, in these patients. METHODS AND RESULTS: The event rates for all-cause mortality, vascular death, myocardial infarction, stroke, and rehospitalization were determined for the 1480 patients with a history of cardiac surgery randomized to either clopidogrel or aspirin in a trial of 19 185 patients. The event rate per year of vascular death, myocardial infarction, stroke, or rehospitalization was 22.3% in the 705 patients randomized to aspirin and 15.9% in the 775 patients randomized to clopidogrel (P:=0.001). A risk reduction was also seen in each of the individual end points examined, including a 42.8% relative risk reduction in vascular death in patients on clopidogrel versus aspirin (P:=0.030). In a multivariate model incorporating baseline clinical characteristics, clopidogrel therapy was independently associated with a decrease in vascular death, myocardial infarction, stroke, or rehospitalization in patients with a history of cardiac surgery, with a 31.2% relative risk reduction (95% CI, 15.8 to 43.8; P:=0.0003). Although clopidogrel therapy was efficacious in the entire Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) population, multivariate analysis demonstrated that patients with previous cardiac surgery derived particular benefit (P:=0.015). CONCLUSION: Compared with aspirin, clopidogrel therapy results in a striking reduction in the elevated risk for recurrent ischemic events seen in patients with a history of prior cardiac surgery, along with a decreased risk of bleeding.

Aspirin↗
PubMed2005

Joint modelling of repeated transitions in follow-up data--a case study on breast cancer data.

In longitudinal studies where time to a final event is the ultimate outcome often information is available about intermediate events the individuals may experience during the observation period. Even though many extensions of the Cox proportional hazards model have been proposed to model such multivariate time-to-event data these approaches are still very rarely applied to real datasets. The aim of this paper is to illustrate the application of extended Cox models for multiple time-to-event data and to show their implementation in popular statistical software packages. We demonstrate a systematic way of jointly modelling similar or repeated transitions in follow-up data by analysing an event-history dataset consisting of 270 breast cancer patients, that were followed-up for different clinical events during treatment in metastatic disease. First, we show how this methodology can also be applied to non Markovian stochastic processes by representing these processes as "conditional" Markov processes. Secondly, we compare the application of different Cox-related approaches to the breast cancer data by varying their key model components (i.e. analysis time scale, risk set and baseline hazard function). Our study showed that extended Cox models are a powerful tool for analysing complex event history datasets since the approach can address many dynamic data features such as multiple time scales, dynamic risk sets, time-varying covariates, transition by covariate interactions, autoregressive dependence or intra-subject correlation.

Algorithms↗