Showing papers by "Clinical Trial Service Unit published in 2001"

Fibrin D-dimer and coronary heart disease : Prospective study and meta-analysis

Abstract: Background—It is unknown whether modest increases of fibrin D-dimer, a circulating marker of fibrin turnover, are relevant to coronary heart disease (CHD) in the general population. Methods and Results—We measured serum concentrations of D-dimer antigen in the stored baseline blood samples of 630 CHD cases and 1269 controls “nested” in a prospective cohort of 5661 men who were monitored for 16 years, and we conducted a meta-analysis of previous relevant studies to place our findings in context. In a comparison of men in the top third compared with those in the bottom third of baseline fibrin D-dimer values (tertile cutoffs, >94 versus <49 ng/mL), the odds ratio for CHD was 1.67 (95% CI, 1.31 to 2.13; P<0.0001) after adjustments for age and town. The odds ratio increased slightly after further adjustment for smoking, other classic risk factors, and indicators of socioeconomic status (1.79; 95% CI, 1.36 to 2.36). Strong correlations were observed of fibrin D-dimer values with circulating concentrations of C...

Underestimation of the importance of homocysteine as a risk factor for cardiovascular disease in epidemiological studies.

Abstract: BackgroundIn epidemiological studies, within-person variability in plasma total homocysteine (tHcy) measurements may dilute the association of ‘usual’ levels of tHcy with risk of cardiovascular disease, referred to as ‘regression dilution’. The aim of this report was to estimate the magnitude of reg

Diet, smoking and lung cancer: a case-control study of 1000 cases and 1500 controls in South-West England.

Abstract: We have examined the relationship between diet and lung cancer in a case–control study of 982 cases of lung cancer and 1486 population controls in south-west England in which subjects were interviewed personally about their smoking habits and their consumption of foods and supplements rich in retinol or carotene. Analyses were performed for 15 dietary variables, including intake of pre-formed retinol and carotene. There were significant associations (P< 0.01) with lung cancer risk for 13 of the variables, eight of which remained after adjustment for smoking. When the 15 variables were considered simultaneously, independent significant associations remained for 5: pre-formed retinol (increased risk), and fish liver oil, vitamin pills, carrots and tomato sauce (decreased risk). It is unlikely that all five associations represent biological effects, or that they can all be explained by residual confounding by smoking, or by biases. We conclude that there is at least one as yet unidentified factor that is causally related to lung cancer risk and of considerable importance in terms of attributable risk in this population. © 2001 Cancer Research Campaign http://www.bjcancer.com

Assessment of homocysteine as a cardiovascular risk factor in clinical practice.

Abstract: Elevated plasma total homocysteine concentrations are a marker of vitamin deficiency and a risk factor for cardiovascular disease. It is possible that vitamin supplementation with folic acid and other B vitamins, which lower plasma homocysteine concentrations, may reduce the risk of cardiovascular disease. Large-scale clinical trials are currently underway to assess the homocysteine hypothesis of cardiovascular disease. Pending the outcome of such trials, measurement of plasma homocysteine concentrations in people at high risk of cardiovascular disease may help to identify patients who could benefit from more intensive treatment of classical cardiovascular risk factors. The introduction of immunoassays for homocysteine determination has made assessment of homocysteine status accessible to most routine hospital laboratories, and this review summarizes the evidence on why and how to assess homocysteine as a risk factor for cardiovascular disease in clinical practice.

DICE 2: a further investigation of the effects of chance in life, death and subgroup analyses.

Abstract: In an investigation into how chance might influence the distribution of deaths in a randomised trial and the time of those deaths, and to highlight the possible dangers of subgroup analyses, 100 randomised controlled trials were simulated and 50 subgroup pairs were simulated for some of these trials. Each of 580 control patients from a colorectal cancer trial was randomly coded to simulate allocation to treatment or control, the main outcome measure being time to death. Not surprisingly, most of the 100 trials gave non-significant results. Four were conventionally significant with logrank 2p-values of less than 0.05. The most extreme result was associated with a logrank 2p-value of 0.003, showing an absolute reduction in four-year mortality of 40% (SD 15) for patients allocated to treatment. One of the simulated prognostic factors for this trial (subgroup 13) showed that mortality for one type of patient was non-significantly slightly increased by treatment, whereas treatment reduced four-year mortality by 64% (SD 16) among the other patients in the trial (2p = 0.00006). Similar, extreme results were found for a trial of borderline statistical significance overall. Chance can influence the overall results of any randomised controlled trial, regardless of how well it is conducted, and can play an even more powerful role in the results of subgroup analyses. This should be borne in mind both by trialists when reporting their results and by readers and reviewers of those reports.

Antibiotics in the prevention of coronary heart disease: review of the randomised trials

Abstract: Over the past few decades, several different persistent infectious agents (includingChlamydia pneumoniae Helicobacter pyloriand cytomegalovirus) have been investigated as possible causes of vascular disease [1], but so far randomized trials have reported only on anti-chlamydial treatments in relation to clinical events.Chlamydia pneumoniaeis an intracellular bacterium of the lung that was identified in 1986, and recognized as a treatable cause of acute respiratory diseases (such as pneumonia) [2]. The organism is probably spread by respiratory droplets, and about one-third to one-half of middle-aged Westerners have serological evidence of previous exposure [3]. The first reported association between seropositivity to C.pneumoniaeand coronary heart disease (CHD) appeared in 1988 [4]; and, a few years later, C.pneumoniaeelementary bodies were directly observed by electron micrography in coronary plaques [5]. Since then, dozens of seroepidemiological and pathology-based studies have reported on possible associations between C.pneumoniaeinfection and vascular disease [1,6, 7]. These observational studies have encouraged trials of antibiotics to determine whether C.pneumoniaemay be a treatable cause of CHD. This chapter provides a brief review of the major randomized studies that have reported or are known to be in progress.