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P Boyle

Publications and source records attributed to P Boyle.

At least 127 records · Page 7Linked to original sources
PubMed1998

Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study.

BACKGROUND: Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive. METHODS: In October, 1992, we started a double-blind placebo-controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy. Women were randomised to receive tamoxifen 20 mg per day or placebo, both orally for 5 years. The original plan was to follow the intervention phase by 5 years' follow-up. In June, 1997, the trialists and the data-monitoring committee decided to end recruitment primarily because of the number of women dropping out of the study. Recruitment ended on July 11, 1997, and the study will continue as planned. The primary endpoints are the occurrence of and deaths from breast cancer. This preliminary interim analysis is based on intention-to-treat. FINDINGS: 5408 women were randomised; participating women have a median follow-up of 46 months for major endpoints. 41 cases of breast cancer occurred so far; there have been no deaths from breast cancer. There is no difference in breast-cancer frequency between the placebo (22 cases) and tamoxifen (19) arms. There is a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone-replacement therapy during the trial: among 390 women on such therapy and allocated to placebo, we found eight cases of breast cancer compared with one case among 362 women allocated to tamoxifen. Compared with the placebo group, there was a significantly increased risk of vascular events and hypertriglyceridaemia among women on tamoxifen. INTERPRETATION: Although this preliminary analysis has low power, in this cohort of women at low-to-normal risk of breast cancer, the postulated protective effects of tamoxifen are not yet apparent. Women using hormone-replacement therapy appear to have benefited from use of tamoxifen. There were no deaths from breast cancer recorded in women in the study. It is essential to continue follow-up to quantify the long-term risks and benefits of tamoxifen therapy.

Adult↗
PubMed1998

Rearrangement reactions in the biosynthesis of molybdopterin--an NMR study with multiply 13C/15N labelled precursors.

The genes moaABC of Escherichia coli were ligated into the expression vector pNCO113. The resulting plasmid was transformed into a moeA mutant of E. coli. From cultures of the recombinant strain, a pteridine designated compound Z could be isolated at 5 mg/liter. Compound Z is a product of precursor Z, a biosynthetic precursor of molybdopterin. Cultures of the recombinant E. coli strain were supplied with [U-(13)C6]glucose, [U-(13)C5]ribulose 5-phosphate, or [7-(15)N,8-(13)C]guanine. The culture medium also contained a large excess of unlabeled glucose. Compound Z as well as nucleosides obtained by hydrolysis of RNA were isolated from the bacterial cultures, and their heavy isotope distribution was investigated by one-dimensional and two-dimensional NMR spectroscopy. The labelling patterns of compound Z show that the carbon atoms of a pentose or pentulose are diverted to the ring atoms C6 and C7 and to the side chain atoms C2', C3' and C4' of compound Z. Carbon atom C1' of compound Z is derived from carbon atom C8 of a guanine derivative. The remodeling of the carbon skeleton of the pentose and purine moieties proceed via intramolecular rearrangement reactions.

Carbon Isotopes↗
PubMed1998

Age-period-cohort analysis of chronic disease rates. I: Modelling approach.

Age-Period-cohort models are widely used by epidemiologists to analyse trends in disease incidence and mortality. The interpretation of such models is fraught with difficulty in view of the exact linear dependency between the three variables. It is the purpose of this paper to review, compare and contrast some of the more common approaches to this problem based on Poisson regression and a linear model for the log rates. Also the results of using the different approaches on a single series of data on breast cancer incidence among females in Scotland from 1960-1989 are presented for comparison. Recommendations as to the merits and drawbacks of the approaches are also given in the conclusions. Models which are based upon the estimable contrasts such as local curvatures and deviations from linearity are most suitable.

Adolescent↗
PubMed1998

Age-period-cohort models of chronic disease rates. II: Graphical approaches.

In a companion article we have reviewed a number of available modelling approaches employed in estimating the influence of age, period and cohort effects on chronic disease rates. Here we review some of the graphical methods for displaying disease rates with a view to extracting information about the separate and joint effects of age, period and cohort. The more traditional displays such as line charts are compared to approaches based on smoothing and two- and three-dimensional plots which have recently been proposed. Other graphical techniques which are principally concerned with displaying interactions, such as biplots and correspondence analysis, are also considered. These techniques are illustrated with examples to compare the techniques revealing their strengths and weaknesses. It is clear that graphical approaches can be useful tools in understanding the behaviour of chronic disease time trends.

Adult↗
PubMed1998

Mortality after the treatment of hyperthyroidism with radioactive iodine.

BACKGROUND: Hyperthyroidism affects many organ systems, but the effects are usually considered reversible. The long-term effects of hyperthyroidism on mortality are not known. METHODS: We conducted a population-based study of mortality in a cohort of 7209 subjects with hyperthyroidism who were treated with radioactive iodine in Birmingham, United Kingdom, between 1950 and 1989. The vital status of the subjects was determined on March 1, 1996, and causes of death were ascertained for those who had died. The data on the causes of death were compared with data on age-specific mortality in England and Wales. The standardized mortality ratio was used as a measure of relative risk, and the effect of covariates on mortality was assessed by regression analysis. RESULTS: During 105,028 person-years of follow-up, 3611 subjects died; the expected number of deaths was 3186 (standardized mortality ratio, 1.1; 95 percent confidence interval, 1.1 to 1.2; P<0.001). The risk was increased for deaths due to thyroid disease (106 excess deaths; standardized mortality ratio, 24.8; 95 percent confidence interval, 20.4 to 29.9), cardiovascular disease (240 excess deaths; standardized mortality ratio, 1.2; 95 percent confidence interval, 1.2 to 1.3), and cerebrovascular disease (159 excess deaths; standardized mortality ratio, 1.4; 95 percent confidence interval, 1.2 to 1.5), as well as fracture of the femur (26 excess deaths; standardized mortality ratio, 2.9; 95 percent confidence interval, 2.0 to 3.9). The excess mortality was most evident in the first year after radioiodine therapy and declined thereafter. CONCLUSIONS: Among patients with hyperthyroidism treated with radioiodine, mortality from all causes and mortality due to cardiovascular and cerebrovascular disease and fracture are increased.

Cardiovascular Diseases↗
PubMed1998

Population attributable risk for breast cancer: diet, nutrition, and physical exercise.

BACKGROUND: The percentages of breast cancer cases in a given population attributable to specific risk factors (i.e., the population-attributable risks) can be calculated; determination of such risks associated with potentially modifiable risks factors, such as diet (e.g., levels of consumption of fruits, vegetables, vitamins, etc.), alcohol consumption, exercise, and body weight, are necessary to focus prevention strategies. METHODS: With the use of data from a case-control study conducted in Italy from June 1991 through April 1994 on 2569 breast cancer case subjects and 2588 control subjects, we calculated multivariate odds ratios and population-attributable risks for breast cancer in relation to dietary beta-carotene and vitamin E intake, alcohol consumption, physical activity, and, for postmenopausal women, body mass index. RESULTS: Among all subjects, the following attributable risks for the indicated risk factors were observed: 10.7% (95% confidence interval [CI] = 4.4%-17.0%) for high alcohol intake (i.e., >20 g/day), 15.0% (95% CI = 7.4%-22.9%) for low beta-carotene intake (i.e., <3366 microg/day), 8.6% (95% CI = -0.4%-17.5%) for low vitamin E intake (i.e., <8.5 mg/day), and 11.6% (95% CI = -0.1%-23.3%) for low levels of physical activity. The risks associated with alcohol and beta-carotene intake were larger among premenopausal women, and the risk associated with physical activity was larger among postmenopausal women. Being overweight accounted for 10.2 % (95% CI = 0.2%-20.2%) of breast cancer cases in postmenopausal women. Beta-carotene plus alcohol accounted for 28.1% (95% CI = 16.8-39.4) of the cases. Beta-carotene and physical activity accounted for 32% (95% CI = 14.3-49.8), and these three factors together accounted for 33% (95% CI = 19.9-46.1) of the breast cancer cases in the overall dataset. CONCLUSION: Exposure to a few selected and potentially modifiable risk indicators explained about one third of the cases of breast cancer in this Italian population, indicating the theoretical scope for prevention of the disease.

Adult↗
PubMed1998

Age at any birth and breast cancer risk.

This paper reviews previously published models of the effect of parity and age at any birth on breast cancer risk. It is shown that these models are conceptually similar and can be written within a general model. Various restrictions on the parameters of the general model yield the specific models. The models are applicable in case control studies and are illustrated using data from a case control study of breast cancer in Italy.

Age Factors↗
PubMed1998

Health-related quality of life associated with lower urinary tract symptoms in four countries.

OBJECTIVES: To describe health-related quality of life (HRQL) associated with lower urinary tract symptoms (LUTS) assessed by validated questionnaires in four countries. METHODS: More than 6000 men, recruited by using community- or population-based sampling in four countries, completed questionnaires soliciting information about urinary symptom frequency, bother, degree of interference with daily activities, and other measures of HRQL. RESULTS: In all countries, disease-specific HRQL worsened with increasing age. Adjusting for age, most disease-specific HRQL measures were significantly worse with increasing symptom severity. The correlation between symptoms and HRQL was strongest in countries with higher prevalence of symptoms, such as Japan or the United States, and less pronounced in countries with lower prevalence (France, Scotland), possibly reflecting the lower variability in scores. CONCLUSIONS: HRQL measures are worse in older men, and increased urinary symptom severity is associated with worse disease-specific HRQL in all countries, despite potential cross-cultural differences in disease prevalence, medication use, perceptions, or willingness to report symptoms or worse HRQL. This cross-cultural consistency suggests that an assessment of symptom bother or interference with daily activities may be useful in patient evaluation.

Adult↗
PubMed1998

Cancer mortality in Europe: effects of age, cohort of birth and period of death.

Death certification data for 19 cancers or groups of cancers, plus total cancer mortality, in 16 major European countries were analysed using a log-linear Poisson model with arbitrary constraints on the parameters to disentangle the effects of age, birth cohort and period of death. Three major patterns emerged including: first, the prominent role of cohort of birth in defining trends in mortality from most cancer sites (except testis or Hodgkin's disease, where newer treatments had a major period of death effect); and second, the major role of lung and other tobacco-related neoplasm epidemics in determining the diverging pattern of cancer mortality, for each sex and in various European countries and geographic areas. In most countries, the peak male cohort values were reached for generations born between 1900 and 1930. This was observed in women only for Denmark and the U.K., i.e. the two countries where lung and other tobacco-related neoplasm epidemics had already reached appreciable levels. This confirms the importance of cigarette smoking in subsequent generations as a major cause of cancer deaths in Europe. Further, there is a persistent rise in several cancer rates, again chiefly on a cohort basis, in Eastern Europe, which calls for urgent intervention to control the cancer burden in these countries.

Adult↗
PubMed1998

Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin. EUROCLUS project.

The EUROCLUS project included information on residence at diagnosis for 13351 cases of childhood leukaemia diagnosed in the period 1980-89 in defined geographical regions in 17 countries. A formal algorithm permits identification of small census areas as containing case excesses. The present analysis examines spatial-temporal patterns of the cases (n = 970) within these clustered areas. The objectives were, first, to compare these results with those from an analysis conducted for UK data for the period 1966-83, and, second, to extend them to consider infant leukaemias. A modification of the Knox test investigates, within the small areas, temporal overlap between cases in a subgroup of interest at a putative critical time and all other cases at any time between birth and diagnosis. Critical times were specified in advance as follows: for cases of acute lymphoblastic leukaemia aged 2-4 years, the 18-month period preceding diagnosis; for cases of total leukaemia aged 5-14 years, 1 year before to 1 year after birth; and for infant cases (diagnosed < 1 year), 1 year before to 6 months after birth. Each of the analyses found evidence of excess space-time overlap compared with that expected; these were 10% (P = 0.005), 15% (P= 0.0002) and 26% (P= 0.03) respectively. The results are interpreted in terms of an infectious origin of childhood leukaemia.

Adolescent↗
PubMed1998

Spatial clustering of childhood leukaemia: summary results from the EUROCLUS project.

The interpretation of reports of clusters of childhood leukaemia is difficult, first because little is known about the causes of the disease, and second because there is insufficient information on whether cases show a generalized tendency to cluster geographically. The EUROCLUS project is a European collaborative study whose primary objective is to determine whether the residence locations of cases at diagnosis show a general tendency towards spatial clustering. The second objective is to interpret any patterns observed and, in particular, to see if clustering can be explained in terms of either infectious agents or environmental hazards as aetiological agents. The spatial distribution of 13351 cases of childhood leukaemia diagnosed in 17 countries between 1980 and 1989 has been analysed using the Potthoff-Whittinghill method. The overall results show statistically significant evidence of clustering of total childhood leukaemia within small census areas (P=0.03) but the magnitude of the clustering is small (extra-Poisson component of variance (%) = 1.7 with 90% confidence interval 0.2-3.1). The clustering is most marked in areas that have intermediate population density (150-499 persons km[-2]). It cannot be attributed to any specific age group at diagnosis or cell type and involves spatial aggregation of cases of different ages and cell types. The results indicate that intense clusters are a rare phenomenon that merit careful investigation, although aetiological insights are more likely to come from investigation of large numbers of cases. We present a method for detecting clustering that is simple and readily available to cancer registries and similar groups.

Adolescent↗
PubMed1998

Effect of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial. Italian Chemoprevention Group.

The combination of tamoxifen and transdermal hormone replacement therapy (HRT) may potentially reduce risks and side-effects of either agent, but an adverse interaction could attenuate their beneficial effects. We assessed the effects of their combination on cardiovascular risk factors within a prevention trial of tamoxifen. Baseline and 12-month measurements of total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, platelets and white blood cells were obtained in the following four groups: tamoxifen (n = 1117), placebo (n = 1112), tamoxifen and HRT (n = 68), placebo and HRT (n = 87). The analysis was further extended to women who were on HRT at randomization but discontinued it during the 12-month intervention period (n = 33 on tamoxifen and n = 35 on placebo) and to women who were not on HRT but started it during intervention (n = 36 in both arms of the study). Compared with small changes in the placebo group, tamoxifen was associated with changes in total, LDL- and HDL-cholesterol of approximately -9%, -19% and +0.2% in continuous HRT users compared with -9%, -14% and -0.8% in never HRT users. Similarly, there was no interaction on platelet count. In contrast, the decrease in total and LDL-cholesterol levels induced by tamoxifen was blunted by two-thirds in women who started HRT while on tamoxifen (P = 0.051 for the interaction term). We conclude that the beneficial effects of tamoxifen on cardiovascular risk factors are unchanged in current HRT users, whereas they may be attenuated in women who start transdermal HRT while on tamoxifen. Whereas a trial of tamoxifen in women already on transdermal HRT is warranted, prescription of HRT during tamoxifen may attenuate its activity.

Breast Neoplasms↗