Showing papers by "Clinical Trial Service Unit published in 2004"

Mortality in relation to smoking: 50 years' observations on male British doctors

Abstract: In 1951 the British Medical Association forwarded to all British doctors a questionnaire about their smoking habits, and 34440 men replied. With few exceptions, all men who replied in 1951 have been followed for 20 years. The certified causes of all 10 072 deaths and subsequent changes in smoking habits were recorded. The ratio of the death rate among cigarette smokers to that among lifelong non-smokers of comparable age was, for men under 70 years, about 2:1, while for men over 70 years it was about 1-5:1. These ratios suggest that between a half and a third of all cigarette smokers will die because of their smoking, if the excess death rates are actually caused by smoking. To investigate whether this is the case, the relation of many different causes of death to age and tobacco consumption were examined, as were the effects of giving up smoking. Smoking caused death chiefly by heart disease among middle-aged men (and, with a less extreme relative risk, among old men,) lung cancer, chronic obstructive lung disease, and various vascular diseases. The distinctive features of this study were the completeness of follow-up, the accuracy of death certification, and the fact that the study population as a whole reduced its cigarette consumption substantially during the period of observation. As a result lung cancer grew relatively less common as the study progressed, but other cancers did not, thus illustrating in an unusual way the causal nature of the association between smoking and lung cancer.

Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion

Abstract: Background: Measurement of plasma total homocysteine has become common as new methods have been introduced. A wide range of disorders are associated with increased concentrations of total homocysteine. The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total homocysteine measurements as diagnostic or screening tests in several target populations. Methods: Published data available on Medline were used as the basis for the recommendations. Drafts of the recommendations were critically discussed at meetings over a period of 3 years. Outcome: This review is divided into two sections: (a) determination of homocysteine (methods and their performance, sample collection and handling, biological determinants, reference intervals, within-person variability, and methionine loading test); and (b) risk assessment and disease diagnosis (homocystinuria, folate and cobalamin deficiencies, cardiovascular disease, renal failure, psychiatric disorders and cognitive impairment, pregnancy complications and birth defects, and screening of elderly and newborns). Each of these subsections concludes with a separate series of recommendations to assist the clinician and the research scientist in making informed decisions. The review concludes with a list of unresolved questions.

Vitamin B12 and folate deficiency in later life

Abstract: Objectives: to examine the prevalence of vitamin B12 deWciency and folate deWciency in later life in representative samples of the elderly population in the United Kingdom. Design: a population-based cross-sectional analysis of 3,511 people aged 65 years or older from three studies was used to estimate the age-speciWc prevalence of vitamin B12 deWciency and of folate deWciency. Vitamin B12 deWciency is

Mortality in relation to alcohol consumption: a prospective study among male British doctors

Abstract: Results In this elderly population, with mean alcohol consumption per drinker of 2 to 3 units per day, the causes of death that are already known to be augmentable by alcohol accounted for only 5% of the deaths (1% liver disease, 2% cancer of the mouth, pharynx, larynx, or oesophagus, and 2% external causes of death) and were significantly elevated only among men consuming � 2 units/day Vascular disease and respiratory disease accounted for more than half of all the deaths and were both significantly less common among current than among non-drinkers; hence, overall mortality was also significantly lower (relative risk, RR 081, CI 076‐087, P = 0001) The non-drinkers, however, include the ex-drinkers, some of whom may have stopped recently because of illness, and during the last decade of the study (1991‐2001) overall mortality was significantly higher in the few ex-drinkers who had been current drinkers in 1978 than in the neverdrinkers or current drinkers To avoid bias, these 239 ex-drinkers were considered together with the 6271 current drinkers and compared with the 750 men who had been non-drinkers in both questionnaires Even so, ischaemic heart disease (RR 072, CI 058‐088, P = 0002), respiratory disease (RR 069, CI 052‐092, P = 001), and all-cause (RR 088, CI 079‐098, P = 002) mortality were significantly lower than in the non-drinkers Conclusions Although some of the apparently protective effect of alcohol against disease is artefactual, some of it is real

Mortality in relation to smoking: 50 years’ observations on male British doctors

Abstract: Objective: To compare the hazards of cigarette smoking in men who formed their habits at different periods, and the extent of the reduction in risk when cigarette smoking is stopped at different ages. Design: Prospective study that has continued from 1951 to 2001. Setting: United Kingdom. Participants: 34 439 male British doctors. Information about their smoking habits was obtained in 1951, and periodically thereafter; cause specific mortality was monitored for 50 years. Main …

Verbal autopsy of 80,000 adult deaths in Tamilnadu, South India

Abstract: Registration of the fact of death is almost complete in the city of Chennai and not so in the rural Villupuram district in Tamilnadu, India. The cause of death is often inadequately recorded on the death certificate in developing countries like India. A special verbal autopsy (VA) study of 48 000 adult (aged ≥ 25 yrs) deaths in the city of Chennai (urban) during 1995–97 and 32 000 in rural Villupuram during 1997–98 was conducted to arrive at the probable underlying cause of death to estimate cause specific mortality. A ten day training on writing verbal autopsy (VA) report for adult deaths was given to non-medical graduates with at least 15 years of formal education. They interviewed surviving spouse/close associates of the deceased to write a verbal autopsy report in local language (Tamil) on the complaints, symptoms, signs, duration and treatment details of illness prior to death. Each report was reviewed centrally by two physicians independently. Random re-interviewing of 5% of the VA reports was done to check the reliability and reproducibility of the VA report. The validity of VA diagnosis was assessed only for cancer deaths. Verbal autopsy reduced the proportion of deaths attributed to unspecified and unknown causes from 54% to 23% (p < 0.0001) in urban and from 41% to 26% (p < 0.0001) in rural areas in Tamilnadu for adult deaths (≥ 25). The sensitivity of VA to identify cancer was 95% in the age group 25–69. A ten day training programme to write verbal autopsy report with adequate feed back sessions and random sampling of 5% of the verbal autopsy reports for re-interview worked very well in Tamilnadu, to arrive at the probable underlying cause of death reliably for deaths in early adult life or middle age (25–69 years) and less reliably for older ages (70+). Thus VA is practicable for deaths in early adult life or middle age and is of more limited value in old age.

Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome

Abstract: Additional chromosomal aberrations occur frequently in Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) of childhood. The treatment outcome of these patients is heterogeneous. This study assessed whether such clinical heterogeneity could be partially explained by the presence and characteristics of additional chromosomal abnormalities. Cytogenetic descriptions were available for 249 of 326 children with Ph+ ALL, diagnosed and treated by 10 different study groups/large single institutions from 1986 to 1996. Secondary aberrations were present in 61% of the cases. Chromosomes 9, 22, 7, 14, and 8 were most frequently abnormal. Most (93%) karyotypes were unbalanced. Three main cytogenetic subgroups were identified: no secondary aberrations, gain of a second Ph and/or >50 chromosomes, or loss of chromosome 7, 7p, and/or 9p, while other secondary aberrations were grouped as combinations of gain and loss or others. Of the three main cytogenetic subgroups, the loss group had the worst event-free survival (P=0.124) and disease-free survival (P=0.013). However, statistical significance was not maintained when adjusted for other prognostic factors and treatment. Karyotypic analysis is valuable in subsets of patients identified by molecular screening, to assess the role of additional chromosomal abnormalities and their correlation with clinical heterogeneity, with possible therapeutic implications.

Successful treatment without cranial radiotherapy of children receiving intensified chemotherapy for acute lymphoblastic leukaemia: results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI (ISRC TN 16757172).

Abstract: Concern about late adverse effects of cranial radiotherapy (XRT) has led to alternative approaches to eliminate leukaemia from the central nervous system (CNS) in childhood acute lymphoblastic leukaemia (ALL). The Medical Research Council UKALL XI trial recruited 2090 children with ALL between 1990 and 1997. Median follow-up is 7 years 9 months; event-free survival (EFS) and overall survival were 63.1% and 84.6%, respectively, at 5 years and 59.8% and 79.4% at 10 years. The isolated CNS relapse rate was 7.0% at 10 years. Patients were randomized for CNS-directed therapy within white blood cell (WBC) groups. For WBC /=50 x 10(9)/l, HDMTX with ITMTX was compared with XRT and a short course of ITMTX. CNS relapses were significantly fewer with XRT, but there was a non-significant increase in non-CNS relapses. EFS was not significantly different, being 55.2% (95% CI 47.8-62.6) at 10 years with XRT and 52.1% (95% CI 44.8-59.4) with HDMTX plus ITMTX.

Effect of temperature and light on the stability of fat-soluble vitamins in whole blood over several days: implications for epidemiological studies

Abstract: Results In whole blood stored under any of the four conditions for up to 7 days, concentrations of α -carotene, β-carotene, lutein, lycopene, retinol, and α -tocopherol changed by less than 8%, and cryptoxanthin and γ-tocopherol by less than 11%. Although significant temperature effects were observed for α -carotene, and α - and γ-tocopherol, and a significant effect of light was observed for α -carotene, cryptoxanthin, and lycopene, these analytes changed by less than 1% per day under all conditions. Conclusions Concentrations of these fat-soluble vitamins change by only a few per cent in whole blood during storage at room temperature for several days. Hence, delayed separation of blood samples (which may be required for practical reasons in large-scale epidemiological studies) does not preclude reliable measurement of fat-soluble vitamins.

Cardiovascular outcomes among participants with diabetes in the recent large statin trials.

Abstract: Purpose of reviewDespite their increased cardiovascular risk and its continuous relationship with cholesterol, until recently only diabetic patients with marked dyslipidaemia were routinely offered lipid-lowering therapy. The secondary prevention statin trials led to more widespread cholesterol lowe

Statin therapy in kidney disease populations: potential benefits beyond lipid lowering and the need for clinical trials.

Abstract: PURPOSE OF REVIEW This review outlines the limited information currently available on the effects of statins among patients with chronic kidney disease, and summarizes the ongoing randomized trials designed to address this question RECENT FINDINGS The effects of fluvastatin on major coronary events among renal transplant patients, and the effects of pravastatin and simvastatin in small subgroups of coronary patients with minor degrees of renal impairment, appear broadly compatible with those observed in trials conducted in non-renal populations In addition, recent evidence from trials among patients with vascular disease or diabetes suggests that statin therapy may delay progressive loss of renal function However, there remains substantial uncertainty regarding the effects of statin therapy among patients with established chronic kidney disease (pre-dialysis or dialysis patients) In particular, there does not appear to be a strongly positive relationship between blood cholesterol and cardiovascular events in such patients This may be because uraemic cardiomyopathy and arteriosclerosis, which cause the majority of these events in chronic kidney disease patients, do not depend strongly on blood cholesterol SUMMARY Statins appear effective for the prevention of vascular events in people with established vascular disease and mild renal impairment, and may delay renal disease progression in such individuals However, the effects of statins in patients with established chronic kidney disease are unknown, and we await the results of ongoing large-scale randomized trials of statin therapy among such patients

The usefulness of parody.

Abstract: A timely rescue from a ‘too clever’ idea.