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Biomedical subjects

S W Duffy

Publications and source records attributed to S W Duffy.

At least 55 records · Page 3Linked to original sources

Repeatability of sexual history in longitudinal studies on HPV infection and cervical neoplasia: determinants of reporting error at follow-up interviews.

BACKGROUND: Misclassification of sexual history due to faulty recall or reporting bias may be the reason for variability in the association between sexual history and human papillomavirus (HPV) infection seen in studies conducted in different geographical areas. This study aimed to assess the repeatability of questionnaire information on sexual-history variables and their correlates, using information from repeat interviews by six international prospective cohort studies. METHODS: The pooled dataset included over 14 775 women interviewed on two separate occasions, of whom 5690 returned for a third interview. At each return visit women were re-asked questions on age at first intercourse and number of sexual partners. The six cohorts originated from studies in Denmark, Costa Rica. San Francisco, Toronto, Montreal and São Paulo. RESULTS: Exact agreement between age at first intercourse recalled on separate occasions ranged from 60-85%, whereas exact recall rates for number of sexual partners were substantially lower and more study-dependent, varying between 20% and 77%. The intraclass correlation coefficients gauging the degree of repeatability in responses ranged from 0.68 to 0.97 for age at first intercourse and 0.08 to 0.94 for number of sexual partners. Age, ethnicity, education and cohort membership were the strongest predictors of reporting error for both sexual history markers, although study design characteristics also seemed to play a role. HPV infection status seemed to influence recall of number of partners, but not age at first intercourse. CONCLUSIONS: Information on sexual behaviours is not reliably collected in epidemiological studies of sexually transmitted diseases, which may influence the magnitude of relative risk estimates.

Adolescent↗

Development of a protocol for evaluation of mammographic surveillance services in women under 50 with a family history of breast cancer.

BACKGROUND: Preliminary retrospective data suggest it is possible to identify impalpable breast cancer in women presenting with a family history of breast cancer under the age of 50, by using regular mammography. In consequence, this service is offered in a number of centres in the UK. The effectiveness of such a service, however, has not been fully evaluated. METHODS: We propose to perform such an evaluation in a cohort of 20000 women under the age of 50 with a significant family history of breast cancer, given regular mammographic surveillance over 5 years. Comparison of surgical and pathological data with completed and ongoing population screening trials using analysis techniques of varying complexity will be performed to obtain an accurate prediction of future breast-cancer mortality reduction. The formal aims are: i) to estimate the difference in breast-cancer mortality in women under the age of 50 with a significant family history of breast cancer having regular mammography, compared with those not being screened; ii) to estimate the cost-effectiveness of regular mammography in this group of women, compared with no screening. The increase in health service resource use attributable to such a policy will be compared with no screening, and costed. Incremental cost-effectiveness ratios of implementing the standardised mammography strategy compared with no screening will be presented in terms of the additional cost per cancer detected, per life saved and per life-year saved.

Adult↗

A novel method for prediction of long-term outcome of women with T1a, T1b, and 10-14 mm invasive breast cancers: a prospective study.

BACKGROUND: Women with small mammographically detected breast cancers generally have good long-term outcomes, but a few with T1a (1-5 mm) and T1b (6-10 mm) tumours will eventually die from breast cancer. We investigated whether women at high risk of breast-cancer death could be identified with mammographic criteria and differentiated from women with small cancers of the breast and good outcomes. METHODS: We prospectively applied mammographic classifications of tumour type to a consecutive series of 343 mammograms of invasive breast cancers of size 1-14 mm. Classifications were: stellate (spiculated) mass with no calcifications; circular or oval lesions with no calcifications; spiculated or circular lesions with non-casting-type calcifications; and casting-type calcifications. FINDINGS: 20-year survival for women with 1-14 mm invasive tumours with casting-type calcifications was 55%. 14% of 138 women with 1-9 mm tumours had casting-type calcifications on mammography, which accounted for 73% of all breast-cancer deaths (p<0.001). T1a, T1b, and 10-14 mm tumours with casting-type calcifications behaved as if they were larger lesions, since the rate of death was similar to that for women with advanced high-grade tumours. Most women who died were node-negative. The long-term survival of women who had tumours of 1-9 mm with no casting-type calcifications was about 95%. INTERPRETATION: Mammographic classification seemed to reliably predict good and bad long-term outcomes for survival in tumours of 14 mm or smaller, and especially for those smaller than 10 mm. The implications for therapy are substantial.

Breast Neoplasms↗

The Swedish Two-County Trial twenty years later. Updated mortality results and new insights from long-term follow-up.

The benefit of invitation to mammographic screening observed in this trial is maintained as a highly significant 32% reduction in breast cancer mortality. Mammographic screening for breast cancer continues to save lives after up to 20 years. Screening derives this benefit by improving the distribution of tumors diagnosed with respect to prognostic categories based on node status, size, and histology of tumors. There is potential for modern screening programs with shorter interscreening intervals to achieve even greater improvements in prognostic category and greater reductions in breast cancer mortality. Mammography can discriminate a subpopulation of high-risk cases, those displaying casting-type calcifications on the mammogram, among very small tumors, with fundamental implications for diagnosis and treatment.

Adult↗

Quantifying the risks of hypertension, age, sex and smoking in patients with abdominal aortic aneurysm.

BACKGROUND: The prevalence of abdominal aortic aneurysm (AAA) in a community-based sample of men and women aged 65-79 years was correlated with known risk factors. In addition, the effect of high blood pressure and the use of antihypertensive medication on growth of AAAs were studied. METHODS: Aortic diameter was assessed by ultrasonography and data on risk factors were collected by self-administered questionnaire for 5356 men and women as part of a randomized controlled trial. RESULTS: Current hypertension increased the risk of having an aortic aneurysm by 30-40 per cent while use of antihypertensive medication increased the risk by 70-80 per cent, adjusting for current blood pressure. There was no clear relationship between hypertension and growth rates of existing aneurysms in this study, although these results were largely from data on small aneurysms. Men were nearly six times more likely to develop an AAA than women; the risk increased by 40 per cent every 5 years after the age of 65 years. Smoking was an independent risk factor for AAA, with level of exposure being more significant than duration. CONCLUSION: Male sex, smoking and hypertension are strong risk factors for the development of AAA. In this study hypertension did not significantly increase the growth rate of existing aneurysms. Smoking remains the most important avoidable risk factor for AAA. The analyses presented here suggest that selection for screening, other than by age and sex, is not worthwhile.

Age Factors↗

Mammographic parenchymal patterns and risk of breast cancer at and after a prevalence screen in Singaporean women.

BACKGROUND: The objective of this study was to assess the effect of mammographic parenchymal patterns on risk of breast cancer detected at first screen or in the period following a negative screen. METHODS: The study utilizes a nested case-control design with 132 breast cancer patients detected at first screen (from a total of 29 193 screened) and 42 breast cancer patients detected in the period following the first screen. These patients were matched to 348 screened-negative controls. The mammograms were classified according to Tabar's classification for parenchymal pattern and statistical analysis was done by conditional logistic regression. RESULTS: The risk of breast cancer for women with Tabar pattern IV was significantly high when compared to the remaining patterns (odds ratio 2.59). Risk factors for Tabar pattern IV coincided largely with established risk factors for breast cancer. CONCLUSION: The study confirms the increased risk of breast cancer associated with Tabar pattern IV (approximately Wolfe pattern P2), in an Asian population. This pattern is associated with nulliparity and high educational status and is strongly associated with grade 3 cancers.

Asian People↗

Variation in the interaction between familial and reproductive factors on the risk of breast cancer according to age, menopausal status, and degree of familiality.

BACKGROUND: Studies have found that reproductive factors might have a variable effect on the occurrence of breast cancer (BC) according to the existence or not of a family history of BC. The effect of a family history of BC on the risk of BC may also vary according to the age at diagnosis and the degree of kinship. This may confound the relation between familial risk and reproductive factors. A combined analysis was performed to study the interaction between familial risk and reproductive factors according to degree of familiality, age at interview and menopausal status. METHODS: The present analysis included 2948 cases and 4170 controls in seven case-control studies from four countries. The combined relative risks were estimated using a Bayesian random-effects logistic regression model. RESULTS: The main effects of reproductive life factors on the risk of BC are in agreement with previous studies. Two-way interactions between subject's age or menopausal status and a family history of BC were not significant. Although the three-way interaction between age, familial risk and parity was not significant, familial risk seemed to be increased slightly for women with high parity compared with women with low parity in the older age group, and seemed to be slightly decreased for women with high parity compared with women with low parity in younger women. The subject's age also appeared to have an effect on the interaction between familial risk and the age at first childbirth (P = 0.1). CONCLUSIONS: A possible influence of reproductive and menstrual factors on familial risk of BC has been suggested previously and was also evident in the present study. Three-way interactions between age, family history and parity or age at first childbirth might exist and they merit further investigation.

Adult↗

Estimation of sojourn time in chronic disease screening without data on interval cases.

Estimation of the sojourn time on the preclinical detectable period in disease screening or transition rates for the natural history of chronic disease usually rely on interval cases (diagnosed between screens). However, to ascertain such cases might be difficult in developing countries due to incomplete registration systems and difficulties in follow-up. To overcome this problem, we propose three Markov models to estimate parameters without using interval cases. A three-state Markov model, a five-state Markov model related to regional lymph node spread, and a five-state Markov model pertaining to tumor size are applied to data on breast cancer screening in female relatives of breast cancer cases in Taiwan. Results based on a three-state Markov model give mean sojourn time (MST) 1.90 (95% CI: 1.18-4.86) years for this high-risk group. Validation of these models on the basis of data on breast cancer screening in the age groups 50-59 and 60-69 years from the Swedish Two-County Trial shows the estimates from a three-state Markov model that does not use interval cases are very close to those from previous Markov models taking interval cancers into account. For the five-state Markov model, a reparameterized procedure using auxiliary information on clinically detected cancers is performed to estimate relevant parameters. A good fit of internal and external validation demonstrates the feasibility of using these models to estimate parameters that have previously required interval cancers. This method can be applied to other screening data in which there are no data on interval cases.

Aged↗

The effect of varying the screening interval on false positives and duration of undiagnosed disease in a screening programme for type 2 diabetes.

OBJECTIVES: The aims of this study were to quantify the proportion of people diagnosed as having type 2 diabetes by standard 75 g oral glucose tolerance test, in a hypothetical screening programme, who would actually be false positives (false positive percentage), and the effect on the false positive percentage of varying the time between repeat screens. We also calculated the duration in person years of exposure to undiagnosed disease in the population for each screening interval. SETTING: Ely, Cambridgeshire, UK. METHODS: We used the glucose tolerance data from 965 participants of the Ely Diabetes Project, who were tested 4.5 years apart, to calculate the population's between and within person variance for 2 hour plasma glucose, and constructed a probability matrix of observed v true glucose tolerance categories. The progression of the population between glucose tolerance categories was modelled assuming exponential times to progression. RESULTS: After one year, 47.5% of test positives were disease free: almost half of those labelled with diabetes would not have the disease. For a 5 year interval, the false positive percentage was 27.6%, but the population would have been exposed to undiagnosed diabetes for 144 person years. CONCLUSIONS: Screening can be associated with both benefit and harm; the balance is dependent on characteristics of the disease and the screening programme. This study has quantified the trade off between exposure to undiagnosed diabetes and false positive results to inform the debate about screening for type 2 diabetes.

Blood Glucose↗

A new era in the diagnosis of breast cancer.

The regular use of high-quality mammography on asymptomatic women enables most breast cancers to be detected in the preclinical phase. Earlier detection dramatically rearranges the spectrum of breast cancer outcomes, resulting in better control of breast cancer. The new era requires a shift in thinking and a re-evaluation of the traditional diagnostic and therapeutic approaches to breast diseases. Tumors are smaller, less often node-positive, and have a more favorable malignancy grade. The challenge for diagnosticians is to find as many breast cancers as possible in the preclinical phase. The challenge for therapists is to adapt the treatment guidelines accordingly, in order to avoid over-treatment.

Adult↗

Mammographic screening in women with a family history of breast cancer: some results from the Swedish two-county trial.

BACKGROUND: The objective of this study is to compare the effectiveness of mammographic screening in women with a family history of breast cancer to those without. In the invited arm of a randomised trial of breast cancer screening, data on family history of breast cancer were available on 29.179 women aged 40-74 attending for screening. Among those women, 358 were diagnosed with breast cancer during the trial. METHODS: Those with and without a family history were compared with respect to mammographic parenchymal pattern, interval cancer rates, mean sojourn time and sensitivity of screening. In the 358 cancers, the effect of family history was estimated on survival, incidence of advanced cancers and their relationship to screen detection. RESULTS: A significantly higher proportion of high risk mammographic patterns was observed in association with family history among women aged 40-49. Interval cancer rates were higher in women with a family history, and in older women at least, mean sojourn time was shortened in women with a family history (1.89 years compared to 2.70). Survival was better (although not significantly so) in cancers in women with a family history (relative hazard=0.52) independently of detection mode and was significantly poorer in interval cancers then screen detected cancers (relative hazard=2.72) independently of family history. Similarly, interval cancers tended to be larger, and worse malignancy grade in those with and without a family history of breast cancer. CONCLUSIONS: These results suggest that the policy often adopted of annual screening for woman aged 40-49, with a family history of breast cancer, is a reasonable one, and that it may also be necessary to shorten the inter-screening interval to one year in women aged over 50 but with a positive family history.

Adult↗

Some random-effects models for the analysis of matched-cluster randomised trials: application to the Swedish two-county trial of breast-cancer screening.

BACKGROUND: In the Swedish two-county trial women aged 40-74 years from two counties in Sweden were randomised to invitation to mammographic screening for breast cancer. METHODS: This paper uses random effects logistic regression models to analyse recent data from the trial. The analysis accounts for the structure of the trial, where small geographical units are randomised within larger geographical strata (blocks of two or three small units that are socio-economically similar). RESULTS: Fixed effects and a variety of random effects models show a strong degree of agreement and yield a significant 29% or 30% reduction in breast-cancer mortality. DISCUSSION: Fixed effects and random effects models agree for this example, because heterogeneity both between strata and within strata between clusters is small and because the effect of treatment does not vary much in different strata.

Adult↗

Measurement error in epidemiology: the design of validation studies I: univariate situation.

It is becoming standard practice in epidemiology to adjust relative risk estimates to remove the bias caused by non-differential errors in the exposure measurement. Estimation of the correction factor is often based on a validation study incorporating repeated measures of exposure, which are assumed to be independent. This assumption is difficult to verify and often likely to be false. We examine the effect of departures from this assumption on the correction factor estimate, and explore the design of validation studies using two or even three different types of measurement of exposure, where assumption of independence between the measures may be more realistic. The value of good biomarker measures of exposure is demonstrated even if they are feasible to use only in a validation study.

Bias↗

Evaluation of a selective screening for colorectal carcinoma: the Taiwan Multicenter Cancer Screening (TAMCAS) project.

BACKGROUND: Although the efficacy of mass screening for colorectal carcinoma (CRC) with a fecal occult blood test has been demonstrated in several randomized trials, a mass screening approach used in countries with intermediate or low incidence of CRC might be costly. Screening high risk people may be an alternative approach, to aid in the prevention of death from CRC. However, the efficacy of CRC screening for high risk people in such countries is uncertain. METHODS: For this study, a multicenter design was devised to identify high risk groups without clinical symptoms related to CRC; these subjects were identified through the study of index cases of CRC in Taiwan. Colonoscopy, in combination with a fecal occult blood test or double-contrast barium enema, was used to screen high risk groups. A total of 8909 subjects were invited to attend screening. Of 8909, 81 with asymptomatic CRC were detected in one-shot screening. Markov models, in conjunction with a simulated approach, were proposed to estimate relevant parameters in relation to disease progression and to assess the effect of the interval between screenings on the efficacy of CRC screening for these high risk groups. RESULTS: The estimated preclinical incidence rate was 0. 00396 (95% confidence interval [CI], 0.002944-0.004985), which was 21 times that reported from a cancer registry in 1994. The simultaneous estimations of mean sojourn time (the average duration between the preclinical screen-detectable phase and the clinical phase) and sensitivity were 2.8 years (95% CI, 2.15-4.30) and 95.0% (95% CI, 24.4-99.9%), respectively. Predictions of mortality reduction for people who received annual, biennial, and triennial screening regimes compared with controls were 26% (95% CI, 0-50%), 23% (95% CI, 0-48%), and 21% (95% CI, 0-47%), respectively. CONCLUSIONS: The efficacy of selective colorectal carcinoma screening has been demonstrated in this study. A high preclinical CRC incidence rate also suggests that such a screening strategy might be cost-effective for countries with intermediate or low incidence of CRC. Methods proposed in this study can be used to evaluate the efficacy of CRC screening in similar screening trials.

Colonoscopy↗

The natural history of breast carcinoma: what have we learned from screening?

BACKGROUND: The availability of breast carcinoma data from trials of mammographic screening provides an opportunity to study the natural history of breast carcinoma. METHODS: The Swedish Two-County study is a randomized, controlled trial of mammographic screening for breast carcinoma in which 77,080 women were randomized to receive an invitation to mammographic screening and 55,985 were randomized to receive no invitation. During the trial, a total of 2468 breast carcinoma cases were diagnosed. The authors examined the effect of screening on the pathologic attributes of the tumors diagnosed, mortality and survival from breast carcinoma, and the consequences of arresting tumor development by screening. RESULTS: Screening reduces mortality from breast carcinoma largely through its effect in detecting tumors at a smaller size, decreasing the probability of lymph node metastases, and reducing the opportunity for worsening of the grade of malignancy of the tumor. CONCLUSIONS: Breast carcinoma is not a systemic disease at its inception, but is a progressive disease and its development can be arrested by screening. The point at which the tumor's progression is arrested is crucial. Detection of small (<15 mm) and lymph node negative invasive tumors will save lives and confer an opportunity for less radical treatment. Tumor progression in the preclinical phase occurs more rapidly in women age <50 years, suggesting the need for a shorter screening interval for this group.

Adult↗

Randomised controlled trial of educational package on management of menorrhagia in primary care: the Anglia menorrhagia education study.

OBJECTIVE: To determine whether an educational package could influence the management of menorrhagia, increase the appropriateness of choice of non-hormonal treatment, and reduce referral rates from primary to secondary care. DESIGN: Randomised controlled trial. SETTING: General practices in East Anglia. SUBJECTS: 100 practices (348 doctors) in primary care were recruited and randomised to intervention (54) and control (46). INTERVENTIONS: An educational package based on principles of "academic detailing" with independent academics was given in small practice based interactive groups with a visual presentation, a printed evidence based summary, a graphic management flow chart, and a follow up meeting at 6 months. OUTCOME MEASURES: All practices recorded consultation details, treatments offered, and outcomes for women with regular heavy menstrual loss (menorrhagia) over 1 year. RESULTS: 1001 consultation data sheets for menorrhagia were returned. There were significantly fewer referrals (20% v 29%; odds ratio 0. 64; 95% confidence interval 0.41 to 0.99) and a significantly higher use of tranexamic acid (odds ratio 2.38; 1.61 to 3.49) in the intervention group but no overall difference in norethisterone treatment compared with controls. There were more referrals when tranexamic acid was given with norethisterone than when it was given alone. Those practices reporting fewer than 10 cases showed the highest increase in prescribing of tranexamic acid. CONCLUSIONS: The educational package positively influenced referral for menorrhagia and treatment with appropriate non-hormonal drugs.

Anti-Inflammatory Agents, Non-Steroidal↗