PubMed Health⌕ Search

Biomedical subjects

S W Duffy

Publications and source records attributed to S W Duffy.

At least 73 records · Page 4Linked to original sources
PubMed1999

Update of the Swedish Two-County Trial of breast cancer screening: histologic grade-specific and age-specific results.

UNLABELLED: The benefit of mammographic screening in reducing mortality from breast cancer is well established. Questions remain with respect to the magnitude of the long-term benefit of modern mammography screening, age specific benefits and the timing of these, and histology specific effects. METHODS: The Swedish Two-County Trial was set up in 1977, with 77,080 women aged 40-74 randomised to invitation to mammographic screening for breast cancer (active study population, ASP) and 55,985 women randomised to no invitation (passive study population, PSP). There is now follow-up for mortality to 31 December 1996, approximately 18 years average follow-up. We investigated the effect of invitation of screening on breast cancer mortality and incidence of advanced tumours by age group (40-49 and 50-74) and histologic type. In addition we estimated progression rates by histologic grade using markov chain models. RESULTS: A significant 29% reduction in breast cancer mortality was observed in association with invitation to screening (relative risk = 0.71, 95% confidence interval 0.60-0.83), maintaining the effect observed at previous stages of follow-up. Age-specific analyses show a smaller and later mortality benefit in women aged 40-49. This is related to the fact that there is a considerable benefit from early detection in terms of mortality from aggressive, poorly differentiated cancers in women aged 50-74, whereas the major effect in women aged 40-49 is on the less aggressive tumours of good or intermediate differentiation. Among women aged 50-74, the incidence of grade III tumours in the ASP is significantly lower than in the PSP, but this is not the case for women aged 40-49. This is related to the greater prevalence and rapidity of progression with respect to histologic grade, as evidenced by the results of markov chain models and the proportions of grade III tumours by time since last screen. CONCLUSIONS: The substantial and significant mortality benefit of invitation to mammographic screening in women aged 40-74 is maintained at 18 years of follow-up. To achieve a substantial mortality benefit at an early stage in the screening program in women aged under 50 years, an interscreening interval of 12-18 months would be required.

Adult↗
PubMed1999

Evaluation of screening for nasopharyngeal carcinoma: trial design using Markov chain models.

In this paper, we develop a Markov chain model to estimate parameters pertaining to the natural history of nasopharyngeal carcinoma (NPC). The model is of progression from no disease to Epstein-Barr virus (EBV) infection, preclinical screen-detectable tumour and clinical tumour. We derive tentative estimates of the parameters of the model, based on limited published data, to assess the efficacy of serum screening in conjunction with clinical assessment (indirect mirror examination for NPC), for example the average duration of the preclinical screen-detectable phase is estimated as 3.1 years. We further apply these parameters to a hypothetical screening trial in the Hong Kong population to assess the efficacy of serum screening with clinical assessment by different combinations of screening regime. Results suggest: (1) there is no substantial difference between 3-yearly and 6-yearly serum screening; and (2) within the same serum screening regime annual and 3-yearly clinical assessment can prevent 33% and 28% of deaths from NPC respectively. Prediction of deaths and surrogate end points can be used to estimate the required sample size and duration for designing a randomized trial of screening for NPC. Based on these findings and power projections, we suggest a design for a randomized trial in a high incidence area such as Hong Kong.

Disease Progression↗
PubMed1999

Primary and adjuvant therapy, prognostic factors and survival in 1053 breast cancers diagnosed in a trial of mammography screening.

BACKGROUND: As mammographic screening becomes more widespread, larger numbers of tumours are diagnosed while small and node negative. METHODS: We examined detection mode, tumour size, node status, histological type, therapy and outcome in 1053 breast cancers diagnosed in one county of the Swedish Two-County Trial of mammographic screening for breast cancer. RESULTS: Of patients undergoing total mastectomy with axillary dissection, 65% were found to be node negative. For tumours of size 1-9 mm, 95% were node negative. The major effects on survival were tumour size, node status and histological type. Primary adjuvant therapy had no significant association with survival. CONCLUSIONS: The advent of mammography has substantially enhanced the possibilities for less radical treatment. There is an urgent need for therapeutic trials utilizing mammographic-pathological correlations to ascertain in advance which tumours can and which cannot benefit from more radical therapy.

Adult↗
PubMed1999

Use of person-years of CIN III exposure as a surrogate outcome measure in cervical cancer screening trials.

BACKGROUND: The reluctance to perform randomised trials on still unresolved issues of the cervical screening programme is largely due to the view that using invasive cancer as an end-point would require huge and lengthy studies. However, by assuming that the incidence of invasive cancer is related to the number of women with CIN III, an estimate of person-years of CIN III can act as a surrogate outcome. METHODS: By having a reliable model for the development of CIN III and the errors involved in taking the smears and biopsies, the person-years of CIN III can be estimated from a smear and biopsy history. Methods for comparing resulting distributions of person-years of CIN III are discussed. Sensitivity analyses on the error rates of smear and biopsy results, and on the incidence of onset and regression of CIN III are performed. RESULTS: Estimates of person-years of CIN III were calculated for women with mildly abnormal smears in two screening programmes. 11% of women in the Cambridge programme and 21% in the Aberdeen programme were estimated to have been exposed to CIN III for more than 12 months. The greater estimated person-years of CIN III in the Aberdeen study reflects the more conservative treatment policy which was operating there. DISCUSSION: The use of person-years of CIN III as a surrogate outcome can provide a practical and meaningful assessment of strategies for cervical cancer screening. Using CIN III, in place of invasive disease, considerably reduces the study duration and sample size required.

Biopsy↗
PubMed1999

Markov chain models and estimation of absolute progression rates: application to cataract progression in diabetic adults.

BACKGROUND: We present a case study in the use of Markov chain models of disease progression, with exponential regression to model the effects of covariates. METHODS: An exponential regression model was developed for a three-state Markov chain to model progression of cataracts in diabetic patients, with a view to estimation of absolute progression rates. Two methods of estimation were applied, a non-linear least squares approximation, and Markov Chain Monte Carlo (MCMC). RESULTS: Both methods gave estimated transition rates which can readily be transformed to absolute progression probabilities. Agreement was reasonable for most but not all of the parameters. CONCLUSIONS: The MCMC estimates had more conservative variance estimates.

Aged↗
PubMed1998

Efficacy of breast-cancer screening for female relatives of breast-cancer-index cases: Taiwan multicentre cancer screening (TAMCAS).

Although the efficacy of mass screening for breast cancer has been established in Western countries, this strategy may be too costly for other countries with low incidence rates of breast cancer. We propose an alternative approach to screen female relatives of breast-cancer-index cases from hospitals, as part of the Taiwan multicentre cancer screening (TAMCAS) project. In order to assess the efficacy of this programme, and to estimate how often this high-risk group should be screened, we firstly elucidated the disease natural history from the pre-clinical screen-detectable phase (PCDP) by estimating the relevant parameters based on Markov chain models. We further predicted the proportion of interval cancers, advanced breast tumours and deaths from breast cancers by different screening frequencies. Results showed that the estimate of mean sojourn time (MST) for this high-risk group (1.9 years; 95% CI.1.18-4.86) is shorter than that for females from the general population. Analysis of a surrogate endpoint based on regional lymph-node spread and tumour size shows that annual screening for this high-risk group is likely to confer a significant 33% reduction in breast-cancer mortality compared with a non-significant 25 and 20% reduction for 2 yearly and 3-yearly screening regimes respectively. The above results suggest that a 1-year interval might be appropriate for this high-risk group. A simple cost-effectiveness analysis indicates a cost per year of life saved for mass screening ($72,480) 15 times that for the high-risk group ($4,851 ).

Breast Neoplasms↗
PubMed1998

Estimating sensitivity and sojourn time in screening for colorectal cancer: a comparison of statistical approaches.

The effectiveness of cancer screening depends crucially on two elements: the sojourn time (that is, the duration of the preclinical screen-detectable period) and the sensitivity of the screening test. Previous literature on methods of estimating mean sojourn time and sensitivity has largely concentrated on breast cancer screening. Screening for colorectal cancer has been shown to be effective in randomized trials, but there is little literature on the estimation of sojourn time and sensitivity. It would be interesting to demonstrate whether methods commonly used in breast cancer screening could be used in colorectal cancer screening. In this paper, the authors consider various analytic strategies for fitting exponential models to data from a screening program for colorectal cancer conducted in Calvados, France, between 1991 and 1994. The models yielded estimates of mean sojourn time of approximately 2 years for 45- to 54-year-olds, 3 years for 55- to 64-year-olds, and 6 years for 65- to 74-year-olds. Estimates of sensitivity were approximately 75%, 50%, and 40% for persons aged 45-54, 55-64, and 65-74 years, respectively. There is room for improvement in all models in terms of goodness of fit, particularly for the first year after screening, but results from randomized trials indicate that the sensitivity estimates are roughly correct.

Aged↗
PubMed1998

Lung cancer among Chinese females in Singapore 1968-1992: time trends, dialect group differences and implications for aetiology.

BACKGROUND: Chinese females are distinguished internationally as having relatively high lung cancer incidence rates despite a low prevalence of cigarette smoking. In Singapore, this population comprises several dialect groups which have origins in different regions in China, each with its own traditional cultural practices. METHODS: An analysis of 4029 incident cases of the disease notified to the Singapore Cancer Registry for 1968-1992 was undertaken to provide some insight into important aetiologic factors among these women. RESULTS: The age-standardized incidence rate of lung cancer rose from 17.3 per 100,000 woman-years in 1968-1972 to 23.0 in 1978-1982 before falling off in more recent years. Age-period-cohort analysis indicated significant period and birth cohort effects, with the risk being highest for women born around 1908. Between the major dialect groups, Cantonese women had a significantly high rate compared with Hokkiens (relative risk [RR] = 2.6, 95% CI: 2.4-2.8). Histologically, there appears to be an increase in the proportion of adenocarcinomas diagnosed over this period (25.8% in 1968-1972 to 51.3% in 1988-1992). CONCLUSION: Our results suggest that traditional practices which have decreased over the years, and are more prominent among Southern Chinese, may play a part in the aetiology of lung cancer locally.

Adenocarcinoma↗
PubMed1998

Evaluation by Markov chain models of a non-randomised breast cancer screening programme in women aged under 50 years in Sweden.

STUDY OBJECTIVE: To apply Markov chain models that have previously been used on data in randomised trials of breast cancer screening to data from an uncontrolled service screening programme; to compare results with those from a randomised trial. DESIGN: A service screening programme in Uppsala county, Sweden, inviting 25,660 women aged 39-49 to mammographic screening every 20 months, and the Swedish Two-County Trial inviting 19,844 women aged 40-49 to two yearly screening, compared with 15,604 women of the same age in an unscreened control group. Data were analysed using Markov chain models and quasi-likelihood estimation procedures. MAIN RESULTS: The results with respect to parameters of disease progression were very similar between the two studies. Use of estimated progression rates to predict the effect on mortality ranged from a 10% to a 17% reduction in breast cancer mortality in the Two-County Study and predicted a 15% reduction in the Uppsala programme. These compare well with the observed mortality reduction of 13% in the Two-County Trial. CONCLUSIONS: The screening in the Uppsala programme is likely to have a similar effect to that observed in the Two-County Trial. It is feasible to evaluate non-randomised service screening programmes using Markov chain models.

Adult↗
PubMed1998

[Detection of cancer, sensitivity of the test and sensitivity of the screening program].

In assessment of screening for cancer, no distinction is usually made between the sensitivity of the screening test (St) and the sensitivity of the screening program (Sp). This paper was aimed to distinguish meaning, method for assessment and interest for each of them, and to determine their relationship. Sensitivity of the screening program can be directly assessed with data from on-going trials whilst assessment of sensitivity of screening test requires modelisation techniques, especially for assessing the mean duration of the preclinical phase of cancer. Assuming an exponential distribution of this duration, lambda as the time parameter, a mathematical relation between St and Sp is suggested as follows: [formula: see text] with r being the interval between two screening tests. The implementation of this equation with data from a mass-screening program for colorectal cancer in the department of Calvados allowed us to investigate the influence of the mean preclinical phase and the interval between two screening tests on the value of the sensitivity of the screening procedure. Such a modelisation could be useful in the development of a rational screening policy.

Colonic Neoplasms↗
PubMed1997

The Gothenburg breast screening trial: first results on mortality, incidence, and mode of detection for women ages 39-49 years at randomization.

BACKGROUND: The effect of mammography screening on breast carcinoma mortality in women ages < 50 years remains unclear. METHODS: A randomized trial of invitation to breast carcinoma screening with mammography was performed in the city of Gothenburg, Sweden. The purpose was to estimate the effect of mammographic screening on breast carcinoma mortality in women ages < 50 years. Randomization was initially by day-of-birth cluster (18% of subjects), and subsequently by individual (82% of subjects). Between September 1983 and April 1984, 11,724 women ages 39-49 years were randomized to the study group. This group was invited to mammographic screening every 18 months. Two-view mammography was used at each screen unless the density of the breast at the previous screen indicated that single view was adequate. Fourteen thousand two hundred and seventeen women in the same age range were randomized to a control group that was not invited to undergo screening until the fifth screen of the study group (between 6 and 7 years after randomization). Women with breast carcinoma diagnosed up to the time immediately after the first screen of the control group were followed for death from breast carcinoma until the end of December 1994. RESULTS: A 45% reduction in mortality from breast carcinoma was observed in the study group compared with the control group (relative risk [RR] = 0.55, P = 0.035, 95% confidence interval [CI], 0.31-0.96). A conservative estimate based on removal of the tumors detected at the first screen of the control group gave a mortality reduction of 44% (RR = 0.56, P = 0.046, 95% CI, 0.31-0.99). In both cases, the effect was statistically significant. CONCLUSIONS: Mammographic screening can reduce mortality from breast carcinoma in women ages < 50 years. The mortality reduction can be substantial if high quality mammography is used and an 18-month interscreening interval is strictly adhered to.

Adult↗
PubMed1997

Colorectal cancer mass-screening: estimation of faecal occult blood test sensitivity, taking into account cancer mean sojourn time.

Mass screening using the faecal occult blood test (FOBT) can reduce mortality from colorectal cancer. Reliable estimation of FOBT sensitivity is crucial in assessing the potential effectiveness of a mass-screening procedure. Available estimates could be inaccurate because they neglect the temporal aspect of screening. The aim of our study was to estimate the sensitivity of the FOBT in mass screening for colorectal cancer, taking into account the duration of the pre-clinical phase of the disease assessed by the mean sojourn time (MST), and to assess whether MST and FOBT sensitivity differ according to cancer subsite. We analysed data taken from the first round of the mass-screening programme of the department of Calvados (France), involving 164,364 subjects of whom 43.4% participated in FOB screening. MST and sensitivity were estimated using a simple empirical approach, a traditional maximum likelihood method and log-linear modelling using the Bayesian technique of Gibbs sampling. MST was estimated as between 4.5 and 5 years for all subsites combined. According to the Gibbs sampling method, MSTs were 3.5, 6.4 and 2.6 years for proximal colon, distal colon and rectal cancer, respectively. Our estimation methods give a low sensitivity for the FOBT (50%), results for different subsites being closer to each other, slightly higher for proximal cancer. Our results strongly suggest that tumour growth rates are very different according to subsite, slowest for distal cancer and speediest for rectal cancer. Consideration of FOBT sensitivity without MST appears unreliable. Our results by subsite suggest that combining FOBT and sigmoidoscopy could be a good strategy for colorectal cancer screening.

Aged↗
PubMed1997

The correction of risk estimates for measurement error.

PURPOSE: The methods available for the correction of risk estimates for measurement errors are reviewed. The assumptions and design implications of each of the following six methods are noted: linear imputation, absolute limits, maximum likelihood, latent class, discriminant analysis and Gibbs sampling. METHODS: All methods, with the exception of the absolute limits approach, require either repeated determinations on the same subjects with use of the methods that are prone to error or a validation study, in which the measurement is performed for a number of persons with use of both the error-prone method and a more accurate method regarded as a "gold standard". RESULTS: The maximum likelihood, latent class and absolute limits methods are most suitable for purely discrete risk factors. The linear imputation methods and the closely related discrimination analysis method are suitable for continuous risk factors which, together with the errors of measurement, are usually assumed to be normally distributed. CONCLUSIONS: The Gibbs sampling approach is, in principle, useful for both discrete and continuous risk factors and measurement errors, although its use does mandate that the user specify models and dependencies that may be very complex. Also, the Bayesian approach implicit in the use of Gibbs sampling is difficult to apply to the design of the case-control study.

Bayes Theorem↗
PubMed1997

Repeat measurement of case-control data: corrections for measurement error in a study of ischaemic stroke and haemostatic factors.

BACKGROUND: Haemostatic factors are suspected to be involved in the aetiology of cerebrovascular events. METHODS: In a case-control study of 105 cases of transient ischaemic attack and minor ischaemic stroke, and 241 controls, data were available on levels of the haemostatic factors-von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI), tissue plasminogen activator (TPA) and factor VII (FVII). These are subject to measurement error and within-person fluctuation of true levels, which may bias relative risk estimates. For all subjects, two determinations were performed on the same blood sample, which allowed estimation of pure measurement error. For estimation of within-person fluctuation, levels were measured from a repeat blood sample on 81 of the controls one year later. RESULTS: The pure measurement error accounted for a very small proportion of the total variation in all cases. Uncorrected for within-person fluctuation, the odds ratio estimates associated with exceeding the median of vWF, PAI, TPA and FVII respectively were 1.88, 0.87, 1.30 and 0.93. After correction for within-person fluctuation odds ratios were 3.56, 0.80, 1.41 and 0.91. Because the PAI determination was not robust to storage conditions, it was estimated that 75% of the variation in this factor was within-person rather than between-persons. Thus, estimates of relative risk relation to PAI cannot be regarded as reliable in this study. CONCLUSIONS: It is likely that elevated levels of vWF are associated with increased risk of ischaemic stroke, but interpretation must be tentative, due to relatively large within-person fluctuation of vWF levels.

Analysis of Variance↗
PubMed1997

Recent results from the Swedish Two-County Trial: the effects of age, histologic type, and mode of detection on the efficacy of breast cancer screening.

The effect of mammographic screening in reducing mortality from breast cancer is known to be smaller and more delayed in women aged 40-49 than in women over 50. In this study, we investigated how these phenomena relate to histology-specific breast cancer incidence and mortality. The data are from 2,468 women with breast cancer who participated in the Swedish Two-County Trial. The overall relative breast cancer mortality of invited to noninvited women aged 40-49 was 0.87, and the relative mortality from poorly differentiated (grade 3) ductal carcinoma was 0.95. These results were not statistically significant. The corresponding relative risks for invited women aged 50-74 were a statistically significant 0.65 and 0.61. We conclude that in this trial, with a two-year interscreening interval, the smaller and later effect of invitation to screening on breast cancer mortality in women 40-49 years old is due to the failure of screening to reduce mortality from grade 3 ductal carcinoma in this age group.

Adult↗
PubMed1997

The Gothenburg Breast Cancer Screening Trial: preliminary results on breast cancer mortality for women aged 39-49.

We carried out a randomized trial of invitation to screening mammography in the city of Gothenburg, Sweden, to estimate the effect of screening on breast cancer mortality in women under age 50 years. A total of 11,724 women aged 39-49 were randomized to the study group, which was invited to mammographic screening every 18 months; 14,217 women in the same age range were randomized to a control group, which was not invited to screening until the fifth screen of the study group. Breast cancers diagnosed in both groups between randomization and immediately after the first screen of the control group were followed up for death from breast cancer to the end of December 1994. There was a significant 44% reduction in mortality from breast cancer in the study group compared to the control group (relative risk [RR] = 0.56, P = 0.042, 95% confidence interval [CI]: 0.32-0.98). A conservative estimate based on removal of the cancers detected at the first screen of the control group gave an RR = 0.59 (P = 0.069, 95% CI: 0.33-1.05). The true answer is likely to lie between the two estimates. These data suggest that mammographic screening can reduce breast cancer mortality in women under age 50, particularly if high-quality mammography is used and a short interscreening interval is adhered to.

Adult↗