Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohorts

Medical inspection of State schoolchildren in Australia, c. 1905-14.

From about 1905 some medical practitioners pressed State governments to back official physical examinations of State school children. Their campaign embodied a broader project to identify and reduce incapacities undermining public hygiene and national efficiency. Some of the activists became inspectors in Tasmania, Victoria, South Australia and Queensland. Evidence about their relations with children, teachers, parents, communities and local GPs seems to be meagre but worth pursuing. The campaign's immediate and longterm effects on child health apparently disappointed its proponents 'hopes, but still might have helped many children and benefited national fitness. Later repercussions of boys being classed as 'fit' could prove deadly in the Great War.

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Criteria for previously undiagnosed diabetes and risk of mortality: 15-year follow-up of the Edinburgh Artery Study cohort.

AIMS: To compare risk of all-cause and cardiovascular mortality associated with different criteria for undiagnosed diabetes and glucose tolerance. METHODS: A population-based cohort of 758 men and 738 women of 55-74 years of age who had an oral glucose tolerance test or known diabetes at baseline were followed up until death or for 15 years. Mortality outcomes were compared by baseline diabetes status using people with normal glucose tolerance (i.e. those without diabetes, impaired fasting glucose or impaired glucose tolerance) as the reference group. RESULTS: Prevalence of undiagnosed diabetes using World Health Organization (WHO) criteria (fasting glucose of > or = 7.0 mmol/l and/or a 2-h post-challenge glucose of > or = 11.1 mmol/l) was 6.6%, of which 81% was associated with fasting glucose > or = 7.0 mmol/l and 19% was associated with isolated post-challenge hyperglycaemia. Hazard ratios (95% CI) for all-cause mortality adjusted for age and sex were 1.51 (1.09-2.08) for new diabetes by the American Diabetes Association (ADA) criterion (fasting glucose of > or = 7.0 mmol/l regardless of post-challenge glucose), 1.60 (1.20-2.13) for new diabetes by WHO criteria and 1.98 (1.14-3.44) for isolated post-challenge hyperglycaemia. Hazard ratios (95% CI) for cardiovascular mortality adjusted for age and sex were 1.89 (1.17-3.00), 1.73 (1.12-2.66) and 1.08 (0.34-3.40) for new diabetes by ADA and WHO criteria and for isolated post-challenge hyperglycaemia, respectively. CONCLUSIONS: Undiagnosed diabetes was associated with increased risk of all-cause mortality by any criteria but significantly increased cardiovascular disease mortality was only associated with diabetes diagnosed using the fasting glucose criterion. Mortality risks were similar in this population using either ADA or WHO criteria for diagnosis of diabetes.

Improved prediction of fatal myocardial infarction using the ankle brachial index in addition to conventional risk factors: the Edinburgh Artery Study.

BACKGROUND: Prediction of major cardiovascular and cerebrovascular events using conventional risk factor models is limited. Noninvasive measures of subclinical atherosclerosis such as the ankle brachial index (ABI) could improve risk prediction and provide more focused primary prevention strategies. We wished to determine the added value of a low ABI in the prediction of long-term risk of cardiovascular and cerebrovascular events and death. METHODS AND RESULTS: In 1988, 1592 men and women 55 to 74 years of age were randomly selected from the age-sex registers of 11 general practices in Edinburgh, Scotland, and followed up over a period of 12 years for incident events. After adjustment for age and sex, an ABI < or =0.9 was predictive of an increased risk of fatal myocardial infarction (MI), cardiovascular death, all-cause death, combined fatal and nonfatal MI, and total cardiovascular events. After further adjustment for prevalent cardiovascular disease, diabetes, and conventional risk factors, a low ABI was independently predictive of the risk of fatal MI. Addition of the ABI significantly (P< or =0.01) increased the predictive value of the model for fatal MI compared with a model containing risk factors alone. Comparison of areas under receiver operator characteristic curves confirmed that a model including the ABI discriminated marginally better than one without. CONCLUSIONS: Addition of the ABI significantly improved prediction of fatal MI over and above that of conventional risk factors. We recommend that the ABI be incorporated into routine cardiovascular screening and that the potential of its inclusion into cardiovascular scoring systems (with a view to improving their accuracy) now be examined.

Developing a behavior rating scale for comparing teachers' ratings of children with and without craniofacial anomalies.

OBJECTIVE: Published psychometric tools are often insensitive to the experience of children with craniofacial anomalies (CFAs). The purposes of this study were to develop a valid and reliable assessment of behavior among children with and without CFAs and to compare teacher ratings of these two groups of children. METHODS: Teachers were asked prospectively to assess social competence and peer acceptance among 99 consecutively evaluated school-aged patients with CFAs and 99 "controls" (classmates without CFA matched by race, gender, intellectual status, general socioeconomic status, and grade). Sixth grade was the median grade of the subjects. OUTCOME MEASURE: Child Behavior Rating Scale (CBRS). RESULTS: Using oblique promax rotation, four factors emerged from the CBRS with the CFA patient group and controls. The factors explained 67% of the total variance and 69% of the variance of the two groups, respectively. The four factors were: (1) self-maintenance, (2) social adjustment, (3) independence, and (4) teasing. Cronbach alpha results averaged 0.77 for the CFA group and 0.83 for the controls; test-retest reliability estimates were .93. Results demonstrate the consistency of the factors and high level of interrelationship among the items across subject groups. Expected differences (p <.05) were found among subject groups on the total score and factor 4. CONCLUSIONS: The CBRS demonstrates psychometric worthiness. The findings indicated that patients with CFA had lower total scores on the CBRS, and they were rated as experiencing more teasing than their matched peers.

Relationship of estrogen and progesterone receptor protein levels in carcinomatous and adjacent non-neoplastic epithelium of the breast: a histopathologic and image cytometric study.

BACKGROUND: Results of a previous study demonstrating a correlation between steroid hormone receptor concentrations in benign and tumor tissue in patients with breast carcinoma suggest that receptor levels in breast epithelium undergoing malignant transformation may play a role in determining the receptor levels in the resulting carcinoma. Data used in that study were derived from ligand binding assays and may reflect shortcomings inherent in this methodology, particularly the dilution of receptor proteins from benign and malignant epithelial cells by stromal components. METHODS: We performed a correlation study of steroid hormone receptor expression in benign and malignant breast epithelial cells using computerized image cytometry and histologic sections stained for estrogen (ER) and progesterone receptor (PR), avoiding the problems of contribution of stromal cells to the measurements and uncertainty about the histologic composition of the sample. Sections which contained both tumor and non-neoplastic breast elements were obtained from surgical specimens from 50 patients with breast carcinoma. RESULTS: Positive area (PA) scores for ER in benign and malignant epithelium showed direct correlation that was significant (r = 0.46, p < 0.001), whereas those for PR, although trended in the same direction, did not (r = 0.17, p > 0.2). PA levels for both receptor proteins were higher in benign breast epithelium with proliferative features, compared to non-proliferative benign epithelium, and in tumors when the associated benign tissue had proliferative changes, but neither of these differences were statistically significant, suggesting that the correlation of ER levels in benign and malignant epithelium was not simply a function of proliferative change. CONCLUSION: Our results provide support for the concept that ER expression in breast carcinoma depends partially on epithelial cell receptor levels in the breast in which it arises, but not for the analogous hypothesis for PR. When costs and benefits of tamoxifen chemoprevention are weighed for a patient at risk for breast carcinoma, and when cyto- or histopathologic breast tissue specimens are available, it may be reasonable to include breast epithelial ER levels among the factors considered in making the treatment decision.

Tissue plasminogen activator and leucocyte elastase as predictors of cardiovascular events in subjects with angina pectoris: Edinburgh Artery Study.

AIMS: To evaluate the relationship between haemostatic and rheological factors and cardiovascular outcome in subjects with angina pectoris in the general population. METHODS AND RESULTS: Two hundred and seven men and women aged 55-74 had evidence of angina at baseline. Sixty-seven (32.3%) had a fatal or non-fatal cardiovascular event during follow-up. Median levels of tissue plasminogen activator antigen and leucocyte elastase were higher in the event group compared with the no event group (10.0 ng. ml(-1)vs 7.2 ng. ml(-1);P

Intravenous naftidrofuryl for critical limb ischaemia.

BACKGROUND: Peripheral arterial disease affects 5% of men and women by late middle age. In approximately 25% of those affected the condition will progress to critical limb ischaemia (rest pain, ulceration and gangrene) within five years. The vasoactive drug naftidrofuryl is a serotononergic receptor antagonist which may be beneficial in the treatment of severe lower limb disease such as critical limb ischaemia. OBJECTIVES: To determine whether the vasoactive drug, naftidrofuryl, when administered intravenously is effective in alleviating symptoms and reducing progression of disease in patients with critical limb ischaemia. SEARCH STRATEGY: Randomised controlled trials were identified using the search strategy of the Peripheral Vascular Diseases Review group, including MEDLINE and EMBASE searches and reviewing reference lists in papers. In addition, publications were identified through pharmaceutical companies. SELECTION CRITERIA: All randomised controlled trials of critical limb ischaemia in which patients were randomly allocated to intravenous naftidrofuryl or control (either pharmacological, inert placebo or conservative therapy) were included. Patients with intermittent claudication were not eligible for inclusion. Trials were selected by one reviewer and checked independently. DATA COLLECTION AND ANALYSIS: Fifteen trials were identified, but eight were excluded because of poor methodology. The seven remaining trials involved a total of 229 participants from five different countries. The following outcomes were reported: pain reduction, rest pain/necrosis, progression of disease in terms of incidence of surgical reconstruction/amputation, mortality and side effects. On extraction of the data, odds ratios and weighted mean differences were estimated where appropriate. MAIN RESULTS: Treatment with naftidrofuryl tended to show reduction of pain evaluated by both analogue score and analgesic consumption, but the effect was statistically non-significant (weighted mean difference -0.42, 95% confidence interval -1.19 to 0.35). Similarly, improvement in rest pain or skin necrosis occurred, but these effects were also not significant. The effect on mean ankle systolic ankle pressure was inconclusive. REVIEWER'S CONCLUSIONS: Based on the results of these trials, it cannot be confirmed that intravenous naftidrofuryl is effective in the treatment of patients with critical limb ischaemia. However, these results were based on trials of generally low methodological quality which had only a small number of participants, the duration of treatment was extremely short and the methods varied between the trials. The wide range of endpoints effectively precluded any meaningful pooling of the results. Intravenous naftidrofuryl was withdrawn as a treatment for peripheral arterial disease in 1995 because of reported side effects.

Plasma fibrinogen, haemostatic factors and prediction of peripheral arterial disease in the Edinburgh Artery Study.

The role of fibrinogen and other haemostatic factors in prediction of peripheral arterial disease (PAD) has not been established. We examined the associations of plasma fibrinogen, von Willebrand Factor (vWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer, and factor VII with the development and clinical progression of PAD. In the Edinburgh Artery Study, 1592 men and women, aged between 55 and 74 years, were followed prospectively over 5 years to detect the onset of PAD, and the deterioration of established PAD. At baseline, 418 individuals had evidence of PAD and 60 (14.4%) subsequently deteriorated. 1080 subjects had no baseline disease, but 59 (5.5%) developed PAD during follow-up. Median levels of fibrinogen and vWF were higher in the group developing disease compared with the group which did not (2.78 g/l versus 2.57 g/l, P< or =0.01; 116 IU/dl versus 104 IU/dl, P< or =0.05; respectively). After adjusting for age and sex, fibrinogen (P< or =0.01) and vWF (P< or =0.05) were significantly associated with the risk of developing PAD. The association between fibrinogen and development of disease remained after adjusting for cardiovascular risk factors and baseline ischaemic heart disease (relative risk, 1.35, 95% confidence interval, 1.05, 1.73; P< or =0.05). None of the haemostatic factors were significantly associated with progression of PAD. In conclusion, plasma fibrinogen levels are related to the future onset of PAD, providing further evidence of a possible role of elevated fibrinogen in the development of atherosclerotic disease.

Factors associated with victimization of personnel in emergency departments.

OBJECTIVE: The purpose of this study was to identify the incidence of ED personnel victimization in Central Florida and examine its relationship to victims' reports of 3 factors: characteristics of the patient/perpetrator, characteristics of the personnel victimized, and characteristics of the ED environment. METHODS: Data were collected anonymously in a mail survey using 37 items from Mahoney's Emergency Department Victimization Questionnaire (EDVQ) and a demographic questionnaire. Chi square, Spearman's rank correlation coefficient, and Pearson's product moment correlation were used to describe frequencies, incidence, and their relationships to the variables studied. A sample of 226 of the 600 direct care personnel (37%) from 18 of the 19 hospital emergency departments in a tri-county area (95%) participated. RESULTS: The incidence of physical assault was reported to be 42% during the past year and 72% during the respondents' careers. Alcohol use was associated with incidence (1-tailed Pearson; P =.001). Verbal abuse was significantly higher on day shift (P =.043). The most desired environmental variable was 24-hour security attendants, available to 51.8% of the respondents. More than a fourth of the subjects reported that they had completed no coursework or had no continuing education in violence prevention. DISCUSSION: Respondents reported avoiding identification on duty, underreporting, postvictimization staff turnover, dissatisfaction with security, and the desire for every security provision listed. The goals of reducing the fears and victimization of ED personnel should become a priority within the health care system.

Microvascular cytomegalovirus endothelialitis of the lung: a possible cause of secondary pulmonary hypertension in a patient with AIDS.

Postmortem examination of the lungs of a patient with advanced AIDS who had developed pulmonary arterial hypertension late in the course of the illness demonstrated extensive cytomegalovirus (CMV) infection in endothelial cells of the lung microvasculature. Enlarged CMV-infected endothelial cells were present in virtually all histologic sections of the lungs, protruded into and compromised the lumens of the small vessels they lined, and were estimated by image cytometry of immunohistochemically stained sections to comprise 0.8% of the total lung tissue volume. Comparison with experimental microvascular embolization studies suggests that this amount of compromise of the microvascular luminal area of the lung is sufficient to elevate pulmonary arterial pressure significantly. Pathologic features in this case differed from both the plexogenic arteriopathy seen in previously reported cases of AIDS-associated primary pulmonary hypertension and the usual form of CMV pneumonitis in AIDS in which alveolar epithelial cells are the predominant site of infection.

Smoking, hemorheologic factors, and progression of peripheral arterial disease in patients with claudication.

PURPOSE: The purpose of the current study was to determine whether hemostatic and rheologic factors are associated with the deterioration of peripheral arterial disease in patients with intermittent claudication and the influence of smoking and severity of underlying disease on these relationships. METHODS: We conducted a prospective cohort study with a 6-year follow-up period of a consecutive series of 607 patients with uncomplicated intermittent claudication. The study setting was the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. The main outcome measures were peripheral vascular intervention or onset of severe chronic leg ischemia (rest pain, ulceration, gangrene). RESULTS: A total of 210 patients died during follow-up. Two hundred three patients did not have a vascular event or deterioration of limb ischemia, 45 patients underwent a peripheral vascular intervention, and 64 progressed to severe chronic leg ischemia. Median levels (interquartile ranges) of whole blood viscosity were significantly higher in the vascular intervention group (3.75 mPa/sec; range, 3.38 to 4.13 mPa/sec) than in those who did not deteriorate 3.48 mPa/sec; range, 3.06 to 3.83 mPa/sec) (p < or = 0.05), and plasma von Willebrand factor was higher in those with severe chronic leg ischemia (154.0 IU/dl; range, 122.0 to 187.0 IU/dl) than in those who did not deteriorate (131.0 IU/dl; range, 106.0 to 165.0 IU/dl) (p < or = 0.01). After adjustment for age, sex, cigarette smoking, and ankle brachial pressure index, the levels of plasma fibrinogen and blood and plasma viscosities were each associated with an increased risk of vascular intervention (all p < or = 0.05). There were no significant associations between any of the hemorheologic factors and the risk of severe chronic leg ischemia on multivariate analyses. CONCLUSION: Elevations in rheologic factors may have important effects on further reduction of blood flow in the legs of patients with claudication and promote worsening ischemia and clinical progression of symptoms.

Haemostatic factors and prediction of ischaemic heart disease and stroke in claudicants.

Thrombotic risk factors may be important in determining cardiovascular outcome in patients with symptomatic peripheral arterial disease. A cohort study with a 6-year follow-up period was established to determine the relationships between haemostatic and rheological factors and incident ischaemic heart disease (IHD) and stroke events in patients with peripheral arterial disease. A consecutive series of 607 patients with intermittent claudication was examined between 1989 and 1990 at the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. Main outcome measures were combined fatal and non-fatal stroke, non-fatal myocardial infarction (MI), coronary death and total coronary events. A total of 210 patients died during follow-up. 203 patients did not experience a vascular event or deterioration of limb ischaemia. Median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer and whole blood viscosity were significantly higher in those who experienced an event compared with those who did not. After adjusting for age and sex, fibrin D-dimer was significantly associated with risk of non-fatal myocardial infarction (RR 1.50, 95% CI 1.09-2.06, P < or = 0.01). Both fibrinogen and fibrin D-dimer were associated with risk of total coronary events (P < or = 0.05). The risk of stroke was related to baseline levels of t-PA antigen (RR 1.87, 95% CI 1.04-3.34, P < or = 0.05) and whole blood viscosity (RR 1.33, 95% CI 1.07-1.65, P < or = 0.01). All the relationships became weaker and statistically non-significant after further adjustment for cigarette smoking, systolic blood pressure, glucose and baseline IHD. The associations of these factors to IHD and stroke may therefore be partly related to cardiovascular risk factors, but are likely to be important in the pathogenesis of future atherothrombotic events in subjects with peripheral arterial disease.

Haemostatic and rheological factors as predictors of restenosis following percutaneous transluminal angioplasty.

OBJECTIVES: To determine whether pre-angioplasty levels of haemostatic and rheological factors predicted restenosis of the dilated arterial segment following percutaneous transluminal angioplasty. DESIGN AND SETTING: Prospective study, Two regional hospital centres for angioplasty in Edinburgh and Glasgow, Scotland, UK. METHOD: Haemostatic and rheological factors were measured in 102 subjects with atherosclerotic disease of the lower limbs, immediately prior to percutaneous transluminal angioplasty. Subjects were followed up after 2-3 years for restenosis of the original angioplasty site using duplex scanning. RESULTS: Baseline clinical characteristics were similar between subjects who restenosed (n = 27) and those with no restenosis (n = 39), except that occluded lesions were more likely to restenose than stenoses (p < or = 0.05). There was no significant difference in age- and sex-adjusted mean levels of whole blood viscosity, plasma viscosity, haematocrit, von Willebrand factor, fibrin D-dimer or plasminogen activator inhibitor-1 activity between the stenosed and no restenosis groups (p > 0.1), but mean plasma fibrinogen was lower in the restenosed group (3.31 g/l vs. 3.75 g/l; p < or = 0.05). These results persisted after multivariate adjustment for smoking habit and type of lesion dilated. CONCLUSIONS: This study provides no evidence that raised, pre-angioplasty levels of haemostatic and rheological factors predict restenosis following percutaneous transluminal angioplasty of the arteries of the lower limbs.

Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study.

Plasma fibrinogen is a consistent predictor of ischemic heart disease (IHD) in prospective studies, but there are fewer data relating other hemostatic variables to IHD and also to stroke. We therefore studied the relationships of plasma fibrinogen, von Willebrand factor antigen, tissue plasminogen activator (TPA) antigen, factor VII, and fibrin D-dimer to incidence of IHD and stroke and determined whether any associations could be explained by conventional risk factors and baseline heart disease. In the Edinburgh Artery study, 1592 men and women aged 55 to 74 years, randomly sampled from the general population, were followed prospectively over 5 years to detect fatal and nonfatal IHD and stroke events. During the 5 years, 268 new vascular events were identified. Baseline plasma fibrinogen was independently related to risk of stroke in multivariate analysis that adjusted for cigarette smoking, LDL-cholesterol, systolic blood pressure, and preexisting IHD (relative risk [RR] 1.52, 95% confidence interval [CI] 1.17, 1.98). TPA antigen, and fibrin D-dimer were also independently associated with risk of stroke (RR 1.69,95% CI 1.22,2.35 and RR 1.96, 95% CI 1.12,3.41, respectively). Significant relationships were found between TPA antigen and myocardial infarction (P < or = .05). In older men and women, increased coagulation activity and disturbed fibrinolysis are predictors of future vascular events (both IHD and stroke).

Variation in cardiovascular risk factors by angiographic site of lower limb atherosclerosis.

OBJECTIVE: To determine differences in the levels of the cardiovascular risk factors, cigarette smoking, serum lipids and blood pressure, between three groups of patients with different sites of lower limb atherosclerosis. DESIGN: Cross-sectional survey of a consecutive series of patients with symptoms of either intermittent claudication or rest pain. METHODS AND MATERIALS: One hundred and ninety-two men and women who had undergone angiography were classified using the Bollinger scoring system into groups with predominantly aortoiliac, femoropopliteal or dual-site disease. History of cigarette smoking, serum cotinine, serum thiocyanate, total cholesterol and HDL cholesterol were estimated. Systolic and diastolic pressures were measured and the ankle brachial pressure index (ABPI) was calculated. RESULTS: Eighty-five patients were classified as having femoropopliteal disease, 34 aortoiliac disease and 73 dual-site disease. After adjusting for age, sex and severity of disease, aortoiliac patients were significantly younger (p

Smoking, haemostatic factors and the severity of aorto-iliac and femoro-popliteal disease.

To determine relationships between haemostatic and rheological factors and severity of peripheral atherosclerosis and differences by site, an angiographic cross-sectional survey was carried out on 192 men and women with intermittent claudication or rest pain. 34 patients were classified as having aorto-iliac disease, 85 femoro-popliteal disease and 73 dual-site disease. Mean levels of haemostatic or rheological factors did not differ significantly between the three site groups. In all 192 patients, disease severity in the femoro-popliteal segments was correlated with plasma nephelometric fibrinogen (r = 0.20, p < or = 0.01), von Willebrand factor (r = 0.14, p < or = 0.05) and fibrin D-dimer (r = 0.22, p < or = 0.001). On multiple regression analyses, fibrinogen was independently associated with disease severity in the femoro-popliteal segments (p < or = 0.05), but not in the aorto-iliac segments. Adjustment for packyears or serum thiocyanate had little effect on the association of fibrinogen with severity of disease. An inverse relationship between plasminogen activator inhibitor and disease severity in the femoro-popliteal segments was found only in men (r = 0.24, p < or = 0.01). We conclude that elevated fibrinogen and disturbed fibrinolytic activity may be related to the extent of disease within the femoro-popliteal arteries, more so than in the aorto-iliac arteries.

EM mixed model analysis of data from informatively censored normal distributions.

Maximum likelihood techniques using the EM algorithm are applied to correlated normally distributed survival data from a placebo-controlled, double-blind, dose-ranging crossover study to assess the short-term efficacy of an antianginal drug in patients with chronic stable angina. Censoring was informative and nonterminal and was not due to death or withdrawal from the study. Unlike previous approaches these techniques are mathematically and computationally tractable, do not require computations of high-dimensional integrals, and do not require the inversion of large matrices.