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PubMed2005

Non-homogeneous Markov processes for biomedical data analysis.

Some time ago, the Markov processes were introduced in biomedical sciences in order to study disease history events. Homogeneous and Non-homogeneous Markov processes are an important field of research into stochastic processes, especially when exact transition times are unknown and interval-censored observations are present in the analysis. Non-homogeneous Markov process should be used when the homogeneous assumption is too strong. However these sorts of models increase the complexity of the analysis and standard software is limited. In this paper, some methods for fitting non-homogeneous Markov models are reviewed and an algorithm is proposed for biomedical data analysis. The method has been applied to analyse breast cancer data. Specific software for this purpose has been implemented.

Algorithms↗

PubMed1990

Additional prognostic value of exercise testing and thallium-201 scintigraphy in catheterized patients without previous myocardial infarction.

To determine whether exercise testing and thallium scintigraphy provide additional prognostic information in symptomatic patients undergoing catheterization, we studied 432 consecutive male patients without a previous myocardial infarction by means of an exercise test, thallium scintigraphy and catheterization. The follow-up period was 46 +/- 24 months (from 12 to 96). Events were defined as death (27 patients), nonfatal myocardial infarction (occurring in 27 patients) or late (greater than 60 days after test) surgery or dilatation (needed in 45 patients). The 5 year survival rate was 89% and the event-free rate was 72%. History, noninvasive and invasive variables were submitted to a stepwise Cox regression analysis. By multivariate analysis, the significant variables related to death were the number of diseased vessels and exercise workload; the selected variables for all cardiac events were the number of diseased vessels; the score at thallium exercise testing and exercise workload. Among the subgroups of 337 coronary patients, the predictive variables for death were exercise workload and the number of diseased vessels. For all cardiac events, the selected variables were the number of diseased vessels, the score of defects during thallium exercise and exercise workload. Thus, in patients without a previous myocardial infarction, noninvasive variables do provide prognostic information which is not available either from the history or from catheterization.

Cardiac Catheterization↗

PubMed2006

Impact of body mass index on outcomes of enhanced external counterpulsation therapy.

OBJECTIVES: We evaluated the association of baseline body mass index (BMI) on the outcomes of enhanced external counterpulsation (EECP) therapy for chronic stable angina. BACKGROUND: We are in the midst of a pandemic of obesity, which is complicating the care of patients with coronary artery disease (CAD). METHODS: We examined 2730 patients enrolled from 2002 to 2004 in the IEPR-2. Baseline and outcome variables were stratified by the entry BMI in kilograms per meter squared. RESULTS: Obesity (BMI > 30 kg/m2) was common (40.6%) among patients with severe CAD referred for EECP. Within the total cohort, 2.6% was underweight (BMI < or = 20 kg/m2) and 4.5% was morbidly obese (BMI > 40 kg/m2). Prevalence of diabetes, hypertension, dyslipidemia, and heart failure (HF) was higher in obese patients. However, the rates of baseline angina and prior revascularization were similar among the groups. The peak diastolic augmentation ratio was similar between groups during the first (0.7 +/- 0.4 for lowest and highest BMI) and last hours of treatment (0.9 +/- 0.5 and 0.8 +/- 0.5). The cumulative hours of treatment, the change in angina class, and the Duke Activity Status Index were similar for all BMI groups. There was a greater reduction in weekly anginal episodes from baseline across ascending levels of BMI (-6.3 +/- 13.6 to -9.7 +/- 15.8, P = .03). The rates of discontinuation for clinical events were highest (14.3%) with skin breakdown being the most frequent cause (10.1%) in the underweight. The rates of clinical events including myocardial infarction, HF, and death trended higher across ascending levels of BMI (P = .52). Multivariate analysis found that older age, history of stroke, history of HF, and diabetes, but not BMI, were predictors of clinical events. CONCLUSIONS: More than 40% of patients with severe CAD referred for EECP were obese. Underweight patients had higher rates of discontinuation of treatment mainly because of skin breakdown. Symptomatic benefit of EECP was similar among all BMI groups. However, despite symptomatic improvement, there was a nonsignificant trend for higher rates of myocardial infarction, HF, and death as BMI increased.

Aged↗

PubMed1990

Drug use and its social covariates from the period of adolescence to young adulthood. Some implications from longitudinal studies.

This chapter presents a review and discussion of the dynamic relationship between drug use, especially the use of illicit drugs, and its social covariates from the period of adolescence to young adulthood. The discussion is based primarily on longitudinal studies. In particular, I include a review and discussion of my collaborative studies with Kandel, in which we employ life-course perspectives for the analysis of natural drug and life histories of individuals based on event-history models. Specifically, I discuss five covariates: (1) age, (2) onset age of drug use, (3) historical period, (4) family and work roles, and (5) influence of significant others, with the dynamic interdependence between drug use and family and work roles as the major topic of discussion. The discussion also includes some insights into the issue of causation vs. selection effects regarding the influence of drug use on life-course pattern, and presents a novel aspect of indirect effects in the analysis of the determinants of drug use progression.

Adolescent↗

PubMed1992

Prediction of late cardiac events by dipyridamole thallium imaging in patients undergoing elective vascular surgery.

Dipyridamole thallium scintigraphy has previously been shown to have prognostic value in the preoperative assessment of patients scheduled to undergo vascular surgery, but its effect on the long-term outcome is less well-defined. In the largest series to date, dipyridamole thallium scanning was performed in 360 patients before elective vascular surgery and survivors were followed for a mean of 31 months. In the 327 patients who underwent vascular surgery, operative death and nonfatal myocardial infarction occurred in 4.9 and 6.7%, respectively. A cardiac event (nonfatal myocardial infarction or cardiac death) occurred in 14.4% of patients with a transient thallium defect, as opposed to 1% with a normal scan (p < 0.001). Logistic regression analysis revealed that the best predictor of a perioperative event was the presence of a reversible thallium defect, elevating the risk by 4.3-fold. Late cardiac events occurred in 53 (15.2%) surgical survivors or nonsurgically treated patients. Patients with a fixed perfusion abnormality had a 24% late event rate, compared with 4.9% in those with a normal dipyridamole thallium study (p < 0.01). Cox analysis demonstrated that a fixed thallium defect was the strongest factor for predicting a late event and increased the relative risk by almost fivefold. A history of congestive heart failure was the only significant variable that contributed additional value to that of a fixed defect alone. Life-table analysis confirmed the strong relation of a fixed defect to cardiac event free survival (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed2003

Increasing hematocrit reduces early posttransplant cardiovascular risk in diabetic transplant recipients.

BACKGROUND: Cardiovascular disease remains epidemic in transplant recipients, despite aggressive treatment of cardiovascular risk factors. Thus, novel risk factors could play a role in the genesis of cardiovascular events in this population. METHODS: We evaluated the impact of early posttransplant anemia on cardiovascular events. We examined rolling average hematocrit values at 30-day intervals and determined the effect of increasing hematocrit on the risk for cardiovascular (CV) events in a single-center population of 404 type 1 diabetic end-stage renal disease patients who underwent either cadaveric kidney transplantation alone or simultaneous pancreas-kidney transplantation. RESULTS: Greater than 60% of the individuals in the study cohort had hematocrit less than or equal to 30% at least once during the first 30 days posttransplant. Forty-two individuals (10.4% of the study population) had at least one 30-day rolling hematocrit less than or equal to 30% and a CV event (myocardial infarction, CV death, angina, congestive heart failure) during the first 26 weeks of the posttransplant course. Increasing hematocrit (>30%) led to a reduction in the risk ratio (RR) for a CV event compared with hematocrit less than or equal to 30% (RR, 0.237; P=0.015). The association between anemia and CV events remained statistically significant in a multivariate analysis (RR, 0.65; P=0.022) that also included age and a history of pretransplant ischemic heart disease. CONCLUSIONS: These data suggest that anemia is an important risk factor for early posttransplant CV events in a high-risk population. Prospective studies of anemia management therapy in this setting are warranted to determine whether this will reduce early posttransplant CV risk.

Adult↗

PubMed1976

Urinary amino acid excretion in acute leukemia.

Urinary amino acid excretion was determined in 31 leukemic patients and 29 normal individuals by rapid gas chromatographic analysis of 16 amino acids as their N-acetyl-n-propyl esters. The leukemic patients were concurrently undergoing, or had recently completed, chemotherapy. It was found that aspartic acid, threonine, and serine were of significance in distinguishing between patients "on" therapy and those "off" therapy. Patients with advanced disease have the greatest aminoaciduria, although both the normal and leukemic populations have wide individual ranges. Within both populations, men excrete a greater variety and quantity of amino acids than women. It is concluded that analysis of urinary amino acids represents a history of complex metabolic events, which is potentially useful for evaluating patient response to chemotherapy in leukemia.

Amino Acids↗

PubMedDate not supplied

Neurological outcome after coronary artery bypass surgery.

BACKGROUND: Neurological dysfunction is a common complication after cardiac surgery. Despite significant advances in cardiopulmonary bypass (CPB) technology, surgical techniques and anaesthetic management, central nervous system complications occur in a large number of patients undergoing surgery requiring CPB. The objective of this study was to determine neurocognitive status of the patients undergoing coronary artery bypass grafting (CABG) and to find any causative or associated factor. METHODS: We evaluated 1000 consecutive patients undergoing primary isolated coronary artery bypass grafting (CABG) at a tertiary care cardiac institute from July 2000 to December 2001 to determine the neurological outcome after CABG and risk factors involved. The demographic and perioperative data were analyzed by Chi2 analysis. RESULTS: A history of diabetes, hypertension, increased age, preoperative neurological event, aortic atheromatous / calcific disease, bilateral carotid artery disease, intermittent aortic cross clamping and evidence of mural thrombi are all co-related with increased risk of neurological damage after CABG. When analyzed in a stepwise logistic regression model, diabetes mellitus, aortic disease increased age and mural thrombi carried a higher probability that the patient would have a postoperative neurological deficit. CONCLUSIONS: We conclude that although these factors are individually involved in the adverse neurological outcome after CABG but the combination of these factors greatly increases the risk of postoperative neurological consequences and only few of them are avoidable.

Coronary Artery Bypass↗

PubMed2004

Phylogenetic relationships in class I of the superfamily of bacterial, fungal, and plant peroxidases.

Molecular phylogeny among catalase-peroxidases, cytochrome c peroxidases, and ascorbate peroxidases was analysed. Sixty representative sequences covering all known subgroups of class I of the superfamily of bacterial, fungal, and plant heme peroxidases were selected. Each sequence analysed contained the typical peroxidase motifs evolved to bind effectively the prosthetic heme group, enabling peroxidatic activity. The N-terminal and C-terminal domains of catalase-peroxidases matching the ancestral tandem gene duplication event were treated separately in the phylogenetic analysis to reveal their specific evolutionary history. The inferred unrooted phylogenetic tree obtained by three different methods revealed the existence of four clearly separated clades (C-terminal and N-terminal domains of catalase-peroxidases, ascorbate peroxidases, and cytochrome c peroxidases) which were segregated early in the evolution of this superfamily. From the results, it is obvious that the duplication event in the gene for catalase-peroxidase occurred in the later phase of evolution, in which the individual specificities of the peroxidase families distinguished were already formed. Evidence is presented that class I of the heme peroxidase superfamily is spread among prokaryotes and eukaryotes, obeying the birth-and-death process of multigene family evolution.

Amino Acid Sequence↗

PubMed2003

Total arch replacement using antegrade selective cerebral perfusion with right axillary artery perfusion.

OBJECTIVE: Right axillary artery (AxA) perfusion, which can prevent cerebral embolism caused by retrograde perfusion via the femoral artery (FA), was used for selective cerebral perfusion (SCP) as well as cardiopulmonary bypass (CPB) in aortic arch repair. We review the outcome of aortic arch surgery using SCP with right AxA perfusion to clarify its efficacy. METHOD: Between 1998 and 2002, 120 patients underwent aortic arch repair using SCP with right AxA perfusion. The mean age was 69+/-10 years. Aneurysms were atherosclerotic in 79, dissecting in 32, and others in nine patients. Twenty of them (16.7%) required emergency surgery. CPB was initiated with right AxA and FA perfusion, and following SCP was established using right AxA and left common carotid artery perfusion. RESULTS: With right AxA perfusion, hospital mortality was 5.8%. Multivariate analysis showed only ruptured aneurysm was an independent determinant for hospital mortality. Permanent neurological dysfunction developed in one patient (0.8%), while seven (5.8%) suffered from temporary one. In univariate analysis, SCP time, stenosis of the carotid arteries, past history of cerebrovascular events, and atherosclerotic aneurysm were not related to temporary neurological deficits CONCLUSION: Right AxA perfusion in conjunction with SCP is a safe and useful alternative for brain protection in total arch replacement.

Adolescent↗

PubMed2000

Adjusting survival analysis for the presence of unadjudicated study events.

In the Coumadin Aspirin Reinfarction Study (CARS), the primary (efficacy) endpoint was time to the first occurrence of reinfarction, ischemic stroke, or cardiovascular death. Study events likely to be a component of the primary endpoint were reviewed by a blinded Events Classification Committee (ECC). To accommodate the inherent delay imposed by the adjudication process, we used the results of prior adjudication to predict classifications for selected unadjudicated study events in order to conduct "up-to-date" interim analyses for the Data and Safety Monitoring Committee (DSMC). Rates at which previously adjudicated study events were confirmed as primary event components were used to adjust the Kaplan-Meier estimates of survival and the log-rank statistics. Multiple events for a given subject were weighted according to the probability that prior events would be confirmed. Once all study events were adjudicated, final analyses confirmed the results of the adjusted interim analysis. For monitoring clinical trials with adjudicated endpoint events, models based on prior adjudication histories can be reliably used to predict event classifications for unadjudicated events and support accurate, contemporary interim analyses.

Anticoagulants↗

PubMed2002

Retrospective analysis of percutaneous transluminal coronary angioplasty and coronary stenting.

OBJECTIVE: To examine long-term efficacy of percutaneous transluminal coronary angioplasty (PTCA), coronary stenting and to assess the factors affecting its efficacy. METHODS: A total of 790 patients who underwent successful PTCA and PTCA + stent in this hospital were followed by direct interview or letter. The rate of follow-up was 84.2% and the period of follow-up was 0.9 - 12.7 (3.5 +/- 2.4) years. RESULTS: During follow-up, 4 (0.5%) patients died, 22 (2.8%) had nonfatal acute myocardial infarction, 10 (1.3%) had coronary artery bypass surgery, and 98 (12.4%) had repeat PTCA. The rate of recurrent angina pectoris was 31.1%. The cardiac event-free survival rate calculated by the Kaplan-Meier method was 88.2% at 1 year and 80.6% at 12.7 years. Cox regression analysis showed that there was a positive correlation between AMI history, stent implantation and the risk of cardiac events, and there was a negative correlation between the number of diseased arteries and the risk of cardiac events. Compared to the PTCA group, patients with PTCA + stent had significantly lower rates of total cardiac events. CONCLUSION: The long-term efficacy of PTCA, especially PTCA + stent in Chinese patients was very satisfactory, suggesting that PTCA + stent therapy should be the major treatment for revascularization in patients with coronary heart disease.

Adult↗

PubMed1988

Increased exercise thallium-201 lung uptake: a noninvasive prognostic index in two-vessel coronary artery disease.

To determine the physiologic impact of two-vessel coronary artery disease and its effect on prognosis, a series of clinical, angiographic, exercise and quantitative thallium-201 (Tl-201) imaging parameters were analyzed in 85 consecutive two-vessel coronary artery disease patients followed for 52 +/- 27 months after coronary angiography and Tl-201 scintigraphy. End points were cardiac death (n = 3), myocardial infarction (n = 6) and coronary bypass graft surgery more than three months after testing (n = 16). Using Cox Hazards survival analysis, early cardiac events were not predicted by: myocardial infarction or anginal history; resting left ventricular function; exercise blood pressure response; angina or severity of ECG ST segment depression (mm); Tl-201 defect size; redistribution or clearance; angiographic patterns; or the presence of proximal left anterior descending disease. Significant predictors of adverse cardiac events were: increased exercise lung to heart Tl-201 ratio (0.59 +/- 0.12 versus 0.46 +/- 0.1; P less than 0.0001); ECG lead extent of ST segment depression (P less than 0.03); and exercise heart rate response (P less than 0.047). Event-free survival for patients with normal and abnormally increased lung to heart Tl-201 ratios at 48 months was 76% versus 63% (P less than 0.003). It was concluded that two-vessel coronary artery disease survival correlates with exercise Tl-201 uptake which reflects exercise induced left ventricular dysfunction.

Actuarial Analysis↗

PubMed1999

Diabetes and cardiovascular events in hypertensive patients.

To determine the relation of self-reported history of diabetes as well as baseline and in-treatment blood sugar to subsequent cardiovascular disease (CVD) in treated hypertensive patients, we assessed the experience of 6886 participants in a systematic treatment program. The presence or absence of a history of diabetes was known for all patients, who were then stratified into 3 groups according to blood sugar at baseline and in treatment (<6.11, 6.11 to 7.74, and >/=7.75 mmol/L). Some 7.4% of all patients reported history of diabetes, and the overall prevalence of blood sugar >/=7. 75 mmol/L was 7.7% and 10.4% at baseline and in treatment, respectively. Patients with a history of diabetes were 10 or 8 times as likely to have blood sugar >/=7.75 mmol/L at baseline (47.2% versus 4.5%) or in treatment (55.0% versus 6.8%), as were patients without history. During an average 6.3 years of follow-up, patients with history of diabetes had a cardiovascular event incidence 2-fold higher than those without history (20.8 versus 8.6/1000 person-years). Age-gender-adjusted CVD incidence rate but not non-CVD was twice as high in the highest compared with the lowest blood sugar stratum (baseline 16.6 versus 8.4/1000 person-years; in treatment 15.2 versus 8.2). Three separate models of Cox multivariate analysis revealed that history of diabetes (with no history as reference) had a greater association with CVD events (hazard ratio 2.37, 95% confidence interval 1.80 to 3.11) than did baseline (1.75, 1.31 to 2.33) or in-treatment blood sugar (1.55, 1. 19 to 2.02). Furthermore, in the presence of history of diabetes (2. 15, 1.58 to 2.92), neither baseline nor in-treatment blood sugar was independently associated with CVD risk. In the elevated (>/=7.75 mmol/L) in-treatment blood sugar group, the age-gender-adjusted rate of CVD events in frequent diuretic users (30.79/1000 person-years) was significantly higher than in moderate (13.34, P=0.004) and rare users (13.25, P=0.008). These data affirm that the coincidence of diabetes and hypertension is common, that evidence of diabetes substantially increases CVD risk, that self-reported history is a more powerful predictor of CVD events than any measure of blood sugar, and that CVD increases in hypertensive diuretic users who develop hyperglycemia even when blood pressure is well controlled.

Adult↗

PubMed2002

Genetic diversity of intimin genes of attaching and effacing Escherichia coli strains.

In this study, we determined the sequences of four intimin variant genes detected in attaching and effacing Escherichia coli isolates of human origin. Three of them were novel and were designated eae-eta (eta), eae-iota (iota), and eae-kappa (kappa). The fourth was identical to the recently described eae-zeta (zeta), isolated from a bovine E. coli O84:NM isolate. We compared these sequences with those of published intimin-alpha, intimin-beta, intimin-gamma1, intimin-gamma2, intimin- epsilon, and intimin-theta alleles. Sequence analysis of these 10 intimin alleles confirmed extensive genetic diversity within the intimin gene family in E. coli. The genetic diversity was more prominent in the 3' region (starting at bp 2,112), which encodes the binding domain of intimin. Phylogenetic analyses revealed four groups of closely related intimin genes: alpha and zeta; beta and kappa; gamma1 and gamma2/theta; and epsilon and eta. Calculation of homoplasy ratios of sequences of the 5' region of eae (positions 1 to 2,111) revealed evidence for intragenic recombination. Split decomposition analysis also indicates that recombination events have played a role in the evolutionary history of eae. In conclusion, we recommend an eae nomenclature system based on the Greek alphabet and provide an updated PCR scheme for amplification and typing of E. coli eae.

Adhesins, Bacterial↗

PubMed2005

Elevated serum neopterin predicts future adverse cardiac events in patients with chronic stable angina pectoris.

AIMS: Serum levels of neopterin, an immune modulator secreted by activated macrophages, are elevated in patients with acute coronary syndromes compared with stable angina patients and control subjects. In unstable angina, serum neopterin levels correlate with the presence of vulnerable coronary stenosis, multiple complex coronary lesions, and patient outcome. The present study assessed the prognostic significance of raised serum neopterin concentrations in patients with stable angina pectoris. METHODS AND RESULTS: We carried out a 1-year follow-up prospective study in 297 patients with chronic stable chest pain undergoing diagnostic coronary angiography. The primary study endpoint was the composite of non-fatal myocardial infarction, unstable angina, and cardiac death. Fifty-one patients (17.2%) had adverse coronary events during follow-up. Mean serum neopterin levels were significantly higher in patients with events compared with those without (P=0.02). On multiple regression analysis, neopterin levels (P=0.021), severity of coronary artery disease (P=0.009), and a history of previous myocardial infarction (P=0.001) were independent predictors of adverse events. CONCLUSIONS: Serum neopterin is an independent predictor of major adverse coronary events in patients with chronic stable angina pectoris. This marker of macrophage activation may be useful for risk stratification in patients with chronic stable angina.

Aged↗

PubMed1995

Sex differences in perioperative and long-term cardiac event-free survival in vascular surgery patients. An analysis of clinical and scintigraphic variables.

BACKGROUND: Little information is available regarding the occurrence of perioperative and late cardiac events in women with vascular disease. The current study was performed to examine whether sex-specific differences exist in these outcomes in a large population of vascular surgery patients and to determine the value of clinical and dipyridamole thallium variables in predicting myocardial infarction and cardiac death. METHODS AND RESULTS: Preoperative dipyridamole thallium imaging was performed in 567 vascular surgery patients, including 380 men and 187 women. The incidence of nonfatal myocardial infarction and cardiac death was noted during the perioperative period and during a follow-up period of 50 +/- 5 months. Fixed and reversible thallium perfusion abnormalities were more common in men than in women (P < .001 and P = .004, respectively). Perioperative cardiac event rates were similar in men and women, 8.4% and 7.5%, respectively (P = .07). A transient thallium defect was associated with an increased risk of cardiac events by 3.9-fold in men (CI, 1.5 to 10.2) and 5.5-fold in women (CI, 1.4 to 22). Various clinical factors also were predictive of events but demonstrated substantial sex differences. For example, dipyridamole-induced ST-segment depression was strongly associated with perioperative events in men but not in women. There were 22 nonfatal myocardial infarctions and 29 cardiac deaths in men during the follow-up period, with comparable event rates noted for women. Cardiac event-free survival rates also were similar for men and women (P = .40). Multivariate analysis demonstrated that a history of heart failure was an important prognostic variable for both sexes, as was a fixed thallium defect. Significant sex differences in the predictive value of other clinical factors for late cardiac events was apparent. CONCLUSIONS: The present study demonstrates that (1) thallium perfusion defects are more common in men; (2) transient thallium defects are associated with perioperative myocardial infarction and cardiac death in both sexes; (3) long-term survival rates after vascular surgery are similar between men and women; (4) a fixed perfusion defect is predictive of late cardiac events in women, with a trend noted in men; and (5) sex-specific differences were noted with regard to the prognostic value of various clinical risk factors. Therefore, dipyridamole thallium plays a significant role in the assessment of perioperative and long-term prognosis for both male and female vascular surgery patients. On the basis of these observations, modifications in risk stratification based on sex may be appropriate for men and women with vascular disease.

Aged↗

PubMed2003

Ancient DNA enables timing of the pleistocene origin and holocene expansion of two adélie penguin lineages in antarctica.

The timing of divergent events in history is one of the central goals of contemporary evolutionary biology. Such studies are however dependent on accurate evolutionary rates. Recent developments in ancient DNA analysis enable the estimation of more accurate evolutionary rates and therefore more accurate timing of divergence events. Consequently, this leads to a better understanding of changes in populations through time. We use an evolutionary rate calculated from ancient DNA of Adélie penguins (Pygoscelis adeliae) to time divergent events in their history. We report the presence of two distinct and highly variable mitochondrial DNA lineages and track changes in these lineages through space and time. When the ancient DNA and the phylogenetic rates are used to estimate the time of origin of the lineages, two very different estimates resulted. In addition, these same rates provide very different estimates of the time of expansion of these lineages. We suggest that the rate calculated from ancient DNA is more consistent with the glacial history of Antarctica and requires fewer assumptions than does a narrative based on the phylogenetic rate. Finally, we suggest that our study indicates an important new role for ancient DNA studies in the timing of divergent events in history.

Animals↗