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Biomedical subjects

F E Alexander

Publications and source records attributed to F E Alexander.

At least 55 records · Page 3Linked to original sources
PubMed1997

A comparison of three methods of analysis for age-period-cohort models with application to incidence data on non-Hodgkin's lymphoma.

BACKGROUND: Various methods of analysis have been used to study age-period-cohort models. The main aim of this paper is to illustrate and compare three such methods. Those of Clayton and Schifflers, Robertson and Boyle, and De Carli and La Vecchia. The main differences between these methods lie in their approach to distinguish between linear-period and linear-cohort effects. Clayton and Schifflers do not attempt to solve this identification problem, whereas Robertson and Boyle, and De Carli and La Vecchia attempt to tackle this question. METHODS: In order to study the assumptions and problems of these methods, we analysed data from 2678 subjects aged 30-84 in Yorkshire, UK, who were diagnosed with non-Hodgkin's lymphoma (NHL) during the period 1978-1991. Loglinear Poisson models were used to examine the effects of age, period and cohort. RESULTS: All three methods of analysis agree that, after stratification for sex and county, the age-standardized rate has been increasing at about 5% per year. The Robertson-Boyle method differed from the Clayton-Schifflers method in showing a significant non-linear cohort effect, and a significant county-cohort interaction. The method of De Carli-La Vecchia agreed more closely with Clayton-Schifflers than with Robertson-Boyle. CONCLUSIONS: The linear increase in incidence would lead to a doubling of the number of cases within 15 years. There is controversy over whether the identification problem can be solved and should be solved. Many authors would not rely on the results of the methods of Robertson and Boyle, or De Carli and La Vacchia.

Adult↗
PubMed1997

Small area variation in the incidence of childhood insulin-dependent diabetes mellitus in Yorkshire, UK: links with overcrowding and population density.

BACKGROUND: The incidence of insulin-dependent diabetes mellitus (IDDM) incidence varies between and within countries. The origins of this variation are disputed, but they involve both genetic and non-genetic influences. To explore the role of environmental factors in the aetiology of IDDM we have examined the incidence in small geographical areas and related it to variables derived from national censuses. METHODS: This is an ecological analysis of incidence data from a register of children with IDDM covering the counties of West Yorkshire, North Yorkshire and Humberside in the north of England. All children aged < or = 16, diagnosed with IDDM between 1978 and 1990 were eligible for inclusion. Spatial variation in incidence between electoral wards was investigated using Poisson regression, in relation to socioeconomic status, population density, urban-rural status and measures of geographical isolation. Ward child populations varied in size from 84 to 7197 (mean = 1545). RESULTS: Rates were significantly lower in wards of high population density and with many overcrowded houses. The rate ratio for areas in the upper half of the childhood density distribution was 0.88 (95% confidence interval (CI): 0.78-0.99) and for the two upper tertiles of household overcrowding the rate ratios were 0.84 (95% CI: 0.74-0.95) and 0.68 (95% CI: 0.58-0.79) respectively. CONCLUSIONS: The incidence of childhood IDDM was associated with environmental factors including population density and overcrowded homes. A possible inference from these data is that patterns of infection are involved in the occurrence of IDDM. Analytical epidemiological studies will be needed to investigate these ideas further.

Adolescent↗
PubMed1997

Study design of randomized controlled clinical trials of breast cancer screening.

Evaluation of population screening must be based on a randomized clinical trial (RCT) with the study population randomized into two arms: an intervention group invited to screening and a control group not invited to screening. Reduced mortality in the intervention group is evidence of a benefit from screening. Individual randomization is the ideal, but cluster randomization is often used for logistical and ethical reasons. The use of volunteer subjects is methodologically acceptable, but results cannot be generalized. Seven RCTs of breast cancer screening by mammography have been carried out in the United States, Canada, Sweden, and Scotland. All the studies, except the Canadian, were designed to assess the effect of screening across a wide range of ages at entry. The question of the efficacy of breast cancer screening at younger ages (< 50 years) arose early, after the first results were reported. To address this question, basic elements of the screening protocol must be considered when interpreting the results; these are screening modality (e.g., mammography with or without physical examinations), interscreening interval, and number of screening rounds. This article examines the possible influence of these factors and reviews the design choices and the characteristics of the seven RCTs.

Adult↗
PubMed1997

The Edinburgh Randomized Trial of Breast Cancer Screening.

This article presents additional follow-up analysis of women aged 45-49 from the Edinburgh Randomized Trial of Breast Cancer Screening. The screening protocol included four mammographic examinations at two-year intervals and seven annual clinical examinations. Altogether, 21,774 women aged 45-49 were recruited from 1978 to 1985 using cluster randomization. After 10-14 years of follow-up, breast cancer mortality has been reduced by 12% to 18% (rate ratios, with and without adjustment for socio-economic status, are 0.88 and 0.82 respectively, with 95% confidence intervals [CIs] of 0.55-1.41 and 0.51-1.32). These benefits are smaller than that reported previously with shorter follow-up. This article also presents data from an observational study that compared survival beyond baseline (50-52 years) of women first offered screening before and after age 50. Based on six-year data, the results suggest that earlier screening confers follow-up benefit (hazard ratio for later screening = 1.60; 95% CI: 0.96-2.67), but these findings are not statistically significant. The trial is too small to yield statistically significant results by itself, but can make useful contributions to overview and meta-analyses.

Adult↗
PubMed1997

Screening status in relation to biological and chronological characteristics of breast cancers: a cross sectional survey.

OBJECTIVE: To determine the pathological and biological characteristics of breast cancers diagnosed by screening and examined at the Edinburgh University pathology department. METHODS: These cancers were classified by screening status: never screened (n = 111), prevalence screen detected (n = 105), and previously screened (n = 74). The last category arose in women who had been regularly screened during the trial; the cancers were diagnosed as interval cases before the first invitation to service screening (n = 33) or were incidence screen detected at that time (n = 41). RESULTS: Association (for operable invasive cancers, n = 250) of cancer characteristics with screening status reflects influences of biology (aggressiveness) or chronology (time of diagnosis), or both. The prognostic indicators tumour grade, histological type, and oestrogen receptor status were found in a smaller percentage of the patients with poor prognosis among the prevalence screen detected cases (9%, 77%, 18%) than among those previously screened (29%, 84%, 35%). The chronological factors size and node status were found in a smaller percentage of patients with poor prognosis among women previously screened (31%, 24%) than among those never screened (62%, 39%). Apart from these two, no other factors improved the diagnosis in the previously screened group compared with the never screened group. CONCLUSIONS: These results suggest that favourable characteristics of screen detected cases are often due to the effects of length bias on "biological factors" and fail to show that current local screening practice has succeeded in advancing the diagnosis of breast cancers to a less aggressive phase.

Breast Neoplasms↗
PubMed1996

Space-time clustering of childhood leukaemia in Greece: evidence supporting a viral aetiology.

The method introduced by Knox for evaluation of space-time clustering has been applied to 872 cases of childhood (0-14 year old) leukaemia diagnosed in Greece over the 10 year period 1980-89. Greek towns are characterised by substantial population mixing due to internal migration, whereas there is relative isolation in mountainous rural areas. Predetermined space (5 km) and time (1 year) limits were used on the basis of previous reports in order to define the clustering cell. There is highly significant evidence for clustering of childhood leukaemia in Greece as a whole, the observed number of pairs that are close in both spaces and time exceeding the expected number by 5.2% (P = 0.004). The excess is particularly evident for leukaemia cases in 0 to 4-year-old children, among whom the observed number of pairs that are close in both space and time exceeded the expected number by 9.4% (P = 0.004). There is no evidence of space-time clustering for leukaemia cases older than 5 years. The overall pattern is descriptively similar in urban and semiurban areas and is especially marked for acute lymphoblastic leukaemia at the childhood peak ages (2-4 years) with an excess of 19% (P = 0.0006). In the rural population there is evidence for clustering of cases belonging to older and broader age groups, a phenomenon compatible with a delay in the development of herd immunity against putative infectious aetiological agents. The findings of the present study provide support for the hypothesis that a substantial proportion of cases of childhood leukaemia may arise as a rare sequel to exposure to an agent or agents, most probably viral in nature.

Adolescent↗
PubMed1996

Isolation, car ownership, and small area variation in incidence of acute lymphoblastic leukaemia in children.

To determine whether increased rates of childhood acute lymphoblastic leukaemia (ALL) which had been reported in isolated areas could be attributed to higher proportions of households owning cars, ecological analysis was performed with electoral wards as area units. Previous data were re-analysed using the proportion of households having no car, taken from the 1981 census of England and Wales, as an additional explanatory factor. A specialist registry of haematopoietic malignancies covering one-third of England and Wales (3270 electoral wards) recorded 438 cases of ALL in children diagnosed 1984-89, including 304 in the childhood peak (at ages 1-7 years). Relative risks were derived by Poisson regression of total childhood ALL and at ages 1-7 years for groups of electoral wards classified by isolation and car ownership. Multivariable analyses included adjustment for socio-economic status. No evidence of increased risk of childhood ALL in areas where more households own cars was found. ALL at ages 1-7 years was inversely associated with car ownership (risk in wards with least cars relative to those with most cars = 2.28, 95% CI: 1.12-4.64). The associations with geographic isolation persisted after allowing for car ownership (risks for ALL in young children in isolated relative to built-up areas = 2.19, 95% CI: 1.44-3.33). Levels of car ownership cannot explain the increased rates of childhood ALL which have been observed in isolated areas. No support has been found for a hypothesis relating these excesses to benzene exposure of children transported in cars. The previous explanation for the small area variation of childhood ALL in terms of geographical isolation and interpretation in terms of exposure to common infections continues to be justified.

Adolescent↗
PubMed1995

Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomised trial. The Scottish Cancer Trials Breast Group.

OBJECTIVE: To determine any cardiac or vascular morbidity associated with long term treatment with tamoxifen given after mastectomy for primary breast cancer. DESIGN: Cohort study using linkage between database of a randomised trial and statistics of Scottish hospital inpatients to identify episodes of cardiac and vascular morbidity. SETTING: NHS hospitals in Scotland. SUBJECTS: 1312 women who had undergone mastectomy for breast cancer and who were randomised either to a treatment group to receive adjuvant tamoxifen or to a control group to be given tamoxifen only on first relapse of disease. Maximum duration of tamoxifen treatment was 14 years. Total woman years of follow up were 9943. MAIN OUTCOME MEASURES: Randomised and observational comparisons of risk (expressed as hazard ratios) of myocardial infarction, other cardiac event, cerebrovascular disease, or thromboembolic event according to treatment allocated and between nonusers, former users, and current users of tamoxifen. RESULTS: Use of tamoxifen was associated with lower rates of myocardial infarction. Hazard ratio for women in control group was 1.92 (95% confidence interval 0.99 to 3.73) compared with women allocated to adjuvant treatment. The association was stronger for current use: hazard ratio for non-users was 3.49 (1.52 to 8.03) compared with current users. Current users of tamoxifen, however, had higher rates of thromboembolic events:hazard ratio for non-users was 0.40 (0.18 to 0.90) compared with current users. CONCLUSIONS: Our results provide further evidence that tamoxifen reduces the risk of myocardial infarction. Thromboembolic events should be carefully monitored in trials of tamoxifen, particularly those of prophylactic treatment, in which tamoxifen is given to healthy women.

Adult↗
PubMed1995

Case clustering, Epstein-Barr virus Reed-Sternberg cell status and herpes virus serology in Hodgkin's disease: results of a case-control study.

The Leukaemia Research Fund Data Collection Study (DCS) is a specialist registry of leukaemias and lymphomas. The present study involves 494 cases of Hodgkin's disease (HD) registered with the DCS between 1985 and 1989. This entire data set has been tested for localised spatial clustering using an established nearest neighbour method with 18% of all cases in young people classified as clustered (P < 0.05). No clustering was found in older cases. Subsamples were selected from the registered cases for a pilot study in which case clustering, herpes virus antibody titres and Epstein-Barr virus (EBV) presence within the Reed-Sternberg (RS) cells (EBV-RS status) were investigated together. Firstly, a case-control study of HD in young people or nodular sclerosing (NS) subtype (39 HD cases and 26 healthy controls) found significant elevation of antibody titres to EBV-viral capsid antigen (VCA), EBV-early antigen (EA) and human herpes virus 6 (HHV-6) in HD cases compared with controls. EBV viral genome was present in 5 cases and 4 of these were in clusters of HD in young people. Elevation of antibody titres to the EBV antigens was not associated with case clustering or EBV-RS status. Antibody titres to HHV-6 differed significantly between EBV-RS+ and EBV-RS- cases (P = 0.04). Geometric mean titres for HHV-6 for EBV-RS+ and EBV-RS- cases were 11.5 and 73.7, respectively, with the former lower than the control value of 20.5. Secondly, a cluster study included all other cases (n = 14) in clusters containing known EBV-RS+ cases. 3 further cases were EBV-RS+ positive but no cluster consisted entirely of positive cases. Overall, 5/16 clustered, 2/12 peripheral and 1/25 random cases in these studies were EBV-RS+ (P = 0.017). The interpretation of these results in terms of shared aetiological exposures of cases within clusters and the roles of EBV and HHV-6 is discussed, and hypotheses for testing in future studies proposed.

Adolescent↗
PubMed1995

European School of Oncology Advisory report to the European Commission for the "Europe Against Cancer Programme" European Code Against Cancer.

A European School of Oncology Advisory Group has reviewed the European Code Against Cancer after its initial use over a 6-year period. With minor modifications, the original ten recommendations were found to be adequate, although it was agreed that an Annex was necessary to explain the scientific evidence supporting each point, and is presented herewith. Tobacco smoking clearly remains the most important cause of cancer, and now it can be quantified better than ever before. It is also clear that it is never too late to stop smoking: stopping even in middle age, prior to the onset of serious illness has a beneficial effect on life expectancy. Alcohol drinking is an important cause of cancer, and yet modest consumption levels protect against cardiovascular disease mortality. The optimal strategy seems to be a consumption not exceeding 2-3 drinks per day, although this limit may be lower for women. Increased consumption of fruits and vegetables, reduction in consumption of fatty foods, reduction of obesity and increased physical activity can all be recommended to reduce cancer risk. Exposure to excessive sunlight remains a problem which should be limited. Control of occupational cancer is a three-way partnership: legislation identifies and limits exposure to known carcinogens, employers enact the legislation and workers should respect the measures introduced. There are a number of signs and symptoms which may lead to cancer being diagnosed earlier, and patients with these should be referred to a doctor. For women, participation in organised programmes of cervical cancer and breast cancer (after 50 years of age) should lead to a reduction in mortality from these forms of cancer. The key element is organised programmes, where quality control and quality assurance are in force. These revised recommendations are the result of an agreement following advice, review and dialogue with cancer experts throughout Europe. They were approved by the European Community Cancer Experts at their meeting in Bonn on 28-29 November 1994. Their implementation by the European population should greatly reduce cancer incidence and mortality.

Alcohol Drinking↗