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S Duffy

Publications and source records attributed to S Duffy.

At least 19 recordsLinked to original sources

Predicted long-term mortality reduction associated with the second round of breast screening in East Anglia.

Randomized trials have demonstrated that mammographic screening can reduce breast cancer mortality. Our aim was to estimate the reduction in mortality expected from the East Anglian Breast Screening Programme. Breast screening achieves benefit by improving cancer prognosis (reducing tumour size, nodal involvement and possibly grade) through earlier diagnosis. We compared cancer prognosis between women invited for screening and those not yet invited in East Anglia, UK, in order to predict the mortality reduction achievable by screening, independently of any reduction due to changes in treatment and underlying disease. Participants (both invited and not-yet invited) were women eligible for invitation to first and second screens and diagnosed with invasive breast cancer in 1989-96. Death rates were predicted based on the observed distribution of tumour grade, size and node status amongst 950 cancers diagnosed following first invitation, up to and including at second screen (excluding those detected at first screening), and 451 cancers presenting symptomatically in women awaiting first invitation during the staggered introduction of screening, after adjustment for lead time amongst screen detected cases. For all ages, the ratio of predicted breast cancer mortality in the invited compared with the uninvited group was 0.85 (95% CI 0.78, 0.93). It was 0.93 (0.80, 1.08) for women aged 50-54 at diagnosis and 0.81 (0.72, 0.91) for those aged 55-64. We conclude that, by 2004, the second round of screening in East Anglia should reduce mortality by around 7% in women below age 55 at diagnosis, and by around 19% in those aged 55-64.

Age Factors↗

Mammographic parenchymal patterns and breast cancer natural history--a case-control study.

The relationship between tumour size, malignancy grade and dense mammographic parenchymal patterns was evaluated by using a nested case-control design with 875 breast cancer cases and 2 601 matched controls. Wolfe's classification was used to assess mammographic parenchymal patterns. The dense P2/DY mammographic parenchymal patterns were significantly associated with invasive ductal grade 3 carcinoma (OR = 2.03; 95%, CI 1.13-3.62, p = 0.016). Stratified by tumour size, we found that the odds ratio for grade 3 invasive ductal NOS breast cancer measuring 15-19 mm associated with P2/DY mammographic parenchymal patterns was 3.46 (95% CI 1.12-10.68). For tumours larger than 30 mm, the odds ratio was 10.09 (95% CI 1.27-79.93). The highest risk of grade 3 cancers being in tumours measuring 30 mm + may be due to dedifferentiation of missed cancers, but there is some excess even in the < 20 mm tumours, suggesting an increased risk in association with dense mammographic patterns of some aggressive cancers which are grade 3 at inception. Our results are consistent with the model that breast cancer is a progressive disease, whose development can be arrested by screening, and that the point at which individual tumour progression is stopped is crucial for prognosis not simply in terms of stage of disease, but also of histological grade.

Breast↗

Estimation of disease progression parameters from case-control data: application to mammographic patterns and breast cancer natural history.

BACKGROUND: Estimations of mean sojourn time (MST) and sensitivity (S) in disease screening have been previously calculated from case-control data, using simple models which did not include covariates. Many studies have shown an effect of mammographic parenchymal pattern (MPP) on breast-cancer risk and tumour histology. We have expanded previous models on these to estimate MST and S with the effects of MPP as a covariate. METHODS: Data were from a nested case-control study within the East Anglian screening programme, with 875 cases and 2,601 controls. Estimates of disease progression and screening parameters were based on conditional likelihood calculation, using a Markov process model. Ninety-five per cent confidence intervals (CI) were calculated using the profile likelihood wherever possible and using a numerical estimate of the information matrix or the area under the likelihood curve where necessary. RESULTS: We obtained estimates of the incidence of preclinical disease, rate of transition from preclinical to clinical and screening sensitivity, and evaluated the association of these parameters with mammographic parenchymal pattern. A higher incidence of preclinical disease was found for high-risk MPP [relative incidence = 1.62 (95% CI: 0.89; 2.73)]. However, no difference in progression rate from preclinical to clinical disease between different MPP was found. Dense MPPs were associated with decreased sensitivity [relative sensitivity = 0.24 (95% CI: 0.06; 15)]. Wide CIs were found, probably being a consequence of the relative sparsity of interval cancer data. DISCUSSION: It is possible to estimate multiple parameters of disease progression and screening quality from case-control data. The reduction in sensitivity of the screening process associated with high-risk patterns presented here, could be of paramount interest for proposing new screening strategies, such as possible additional screening tools.

Breast Neoplasms↗

Differential activation of coronary and pulmonary endothelial cells by thermal injury.

Remote organ dysfunction during resuscitation of severe thermal injury is characterized by early, transient pulmonary insufficiency and cardiac contractile dysfunction. Thermal injury is typified by profound systemic alterations of endothelial immunological, vasoactive, and barrier functions. The unique location of this ubiquitous, fragile monolayer makes it vulnerable to circulating serum factors created at remote cutaneous wounds. We examined endothelial "activation" in 2 distinct cell types, human coronary and pulmonary endothelial cells (EC), after severe thermal injury. By using human serum isolated at specific times after thermal injury ("early" [2 h post-burn] or "late" [26 h post-burn]), the endothelial release of vasoactive mediators, ICAM-1 expression, and monolayer permeability were assessed in vitro. Early burn serum enhanced coronary EC vasoconstrictor (ET-1) release and ICAM expression, inhibited vasodilator (PGI2) release, but had no effect on permeability. Conversely, under similar conditions, pulmonary EC PGI2 release and permeability were enhanced, ET-1 release was diminished, but ICAM was unaffected. Late burn serum enhanced vasodilator (NO) release and permeability to albumin in both coronary and pulmonary EC, whereas ET-1 release was inhibited. Under these conditions, only pulmonary ICAM expression was significantly enhanced. These data suggest that human endothelium isolated from divergent vascular beds are activated by burn injury in a unique manner for time post-burn and vascular site of cell origin.

Adult↗

Modeling of combined processing steps for reducing Escherichia coli O157:H7 populations in apple cider.

Probabilistic models were used as a systematic approach to describe the response of Escherichia coli O157:H7 populations to combinations of commonly used preservation methods in unpasteurized apple cider. Using a complete factorial experimental design, the effect of pH (3. 1 to 4.3), storage temperature and time (5 to 35 degrees C for 0 to 6 h or 12 h), preservatives (0, 0.05, or 0.1% potassium sorbate or sodium benzoate), and freeze-thaw (F-T; -20 degrees C, 48 h and 4 degrees C, 4 h) treatment combinations (a total of 1,600 treatments) on the probability of achieving a 5-log(10)-unit reduction in a three-strain E. coli O157:H7 mixture in cider was determined. Using logistic regression techniques, pH, temperature, time, and concentration were modeled in separate segments of the data set, resulting in prediction equations for: (i) no preservatives, before F-T; (ii) no preservatives, after F-T; (iii) sorbate, before F-T; (iv) sorbate, after F-T; (v) benzoate, before F-T; and (vi) benzoate, after F-T. Statistical analysis revealed a highly significant (P < 0.0001) effect of all four variables, with cider pH being the most important, followed by temperature and time, and finally by preservative concentration. All models predicted 92 to 99% of the responses correctly. To ensure safety, use of the models is most appropriate at a 0.9 probability level, where the percentage of false positives, i.e., falsely predicting a 5-log(10)-unit reduction, is the lowest (0 to 4.4%). The present study demonstrates the applicability of logistic regression approaches to describing the effectiveness of multiple treatment combinations in pathogen control in cider making. The resulting models can serve as valuable tools in designing safe apple cider processes.

Beverages↗

The influence of partial and full-mouth recordings on estimates of prevalence and extent of lifetime cumulative attachment loss: a study in a population of young male military recruits.

BACKGROUND: Previous studies have shown that the use of index teeth may underestimate the prevalence of chronic periodontitis in adults. However, there is little information on the effect of using index teeth to estimate the prevalence of early periodontitis in younger adults and the effect this may have on planning treatment needs and health care resources. The aim of this study was to compare full mouth examination with partial examination using index teeth in a group of young British males. METHODS: One hundred subjects aged between 16 and 20 years (mean 17 years) on entry to the study were examined at baseline, 12 months later, and 30 months later. Lifetime cumulative attachment loss (LCAL) > or =1 mm was measured on the mesio-buccal, disto-buccal, mesio-lingual, and disto-lingual surfaces of all teeth, excluding third molars. All data were entered into a database. The indices used to express LCAL were prevalence, defined as the percentage of subjects with LCAL > or =1 mm, 2 mm, or 3 mm, and extent, defined as the percentage of sites with LCAL > or =1 mm, 2 mm, or 3 mm. Two sets of index teeth were chosen to compare with full mouth recordings, Ramfjord index teeth and the Periodontal Index for Treatment (PIT) teeth. RESULTS: The prevalence of LCAL > or =1 mm was similar (approaching 100%) for the full mouth and both partial mouth recordings. However, as LCAL increased from a minimum of 1 to 3 mm, partial mouth recording resulted in an underestimation of the prevalence of disease. LCAL > or =2 mm was underestimated by up to 22% and LCAL > or =3 mm by up to 36%. The extent of LCAL was less affected by partial mouth recording, in that the percentage of sites with no sign of early attachment loss was underestimated by up to 11%. However, the percentage of sites with LCAL > or =1 mm and 2 mm were overestimated by 11% and, 7% respectively. CONCLUSIONS: These data indicate that the use of index teeth in epidemiological studies which include young adults may result in an underestimation of the prevalence of early periodontitis and an overestimation of the extent.

Adolescent↗

Modeling the survival of Escherichia coli O157:H7 in apple cider using probability distribution functions for quantitative risk assessment.

Outbreaks of foodborne illness from apple cider have prompted research on the survival of Escherichia coli O157:H7 in this food. Published results vary widely, potentially due to differences in E. coli O157:H7 strains, enumeration media, and other experimental considerations. We developed probability distribution functions for the change in concentration of E. coli O157:H7 (log CFU/day) in cider using data from scientific publications for use in a quantitative risk assessment. Six storage conditions (refrigeration [4 to 5 degrees C]; temperature abuse [6 to 10 degrees C]; room temperature [20 to 25 degrees C]; refrigerated with 0.1% sodium benzoate, 0.1% potassium sorbate, or both) were modeled. E. coli survival rate data for all three unpreserved cider storage conditions were highly peaked, and these data were fit to logistic distributions: ideal refrigeration, logistic (-0.061, 0.13); temperature abuse, logistic (-0.0982, 0.23); room temperature, logistic (-0.1, 0.29) and uniform (-4.3, -1.8), to model the very small chance of extremely high log CFU reductions. There were fewer published studies on refrigerated, preserved cider, and these smaller data sets were modeled with beta (4.27, 2.37) x 2.2 - 1.6, normal (-0.2, 0.13), and gamma (1.45, 0.6) distributions, respectively. Simulations were run to show the effect of storage on E. coli O157:H7 during the shelf life of apple cider. Under every storage condition, with and without preservatives, there was an overall decline in E. coli O157:H7 populations in cider, although a small fraction of the time a slight increase was seen.

Beverages↗

Chronic pelvic pain: defining the scope of the problem.

OBJECTIVE: To define the scope of the problems associated with chronic pelvic pain (CPP) and optimize management. METHOD: Clinical trial results and healthcare utilization data from the literature were reviewed. RESULTS: Recent evidence suggests that a large percentage of women experience CPP. While no etiology tends to be found in the majority of these women, the annual cost for diagnosing and treating CPP seems considerable. The management of patients with negative laparoscopies constitutes a clinical challenge. While surgical and medical therapy have a role in CPP, there appears to be no 100% effective cure. CONCLUSIONS: There is no consensus on management of patients with no visible pathology and chronic pelvic pain. Physicians should select a treatment for CPP that will be the least complicated and least risky and will deliver speedy symptomatic relief.

Chronic Disease↗

Patient satisfaction with outpatient hysteroscopy versus day case hysteroscopy: randomised controlled trial.

OBJECTIVE: To compare outpatient hysteroscopy with day case hysteroscopy in terms of patient satisfaction and acceptability. SETTING: Gynaecology clinic of a teaching hospital. PARTICIPANTS: 100 women. DESIGN AND INTERVENTIONS: Patients were randomly allocated to outpatient hysteroscopy or day case hysteroscopy provided they had no preference for either procedure. MAIN OUTCOME MEASURES: Satisfaction rate, requirements for postoperative analgesia, speed of recovery, time away from home, and time off work. RESULTS: The outpatient group recovered preoperative fitness more quickly than the day case group (2 days (range 1-2.7) versus 3 days (2-4), P<0.05). After the procedure, the outpatient group were also fully mobile more quickly than the day case group (0 minutes (0-5) versus 105 minutes (80-120), P<0.001). Requirements for postoperative analgesia were similar in both groups. Overall, 78% of patients considered that the pain from outpatient hysteroscopy was less than that usually experienced during menstruation. Patient satisfaction was similar in both groups (83.6% in the outpatient group versus 77.0% in the day case group). CONCLUSIONS: Outpatient hysteroscopy and day case hysteroscopy were equally acceptable to patients. Patients recovered significantly more quickly from outpatient hysteroscopy than from day case hysteroscopy.

Adult↗

Interval cancers as an indicator of performance in breast screening.

BACKGROUND: The literature shows that breast screening performance varies between centers. Those who monitor the performance of screening programs must use appropriate methods to demonstrate quality. Analysis of interval cancer rates provides one such measure. This study analyses interval cancers over a ten-year period in a single center of the UK National Breast Screening Program, offering screening to a population of 45,000 women. METHODS: 108,948 screening examinations were undertaken between 1987 and 1996. Sequential interval cancer rates were studied and compared with the results of the Swedish Two-County trial. More detailed analysis of the first prevalence round was undertaken. RESULTS: Improvement in rates occurred after three years. Two-year time bands show some fluctuation in rates, indicating variation in performance. For one time period, rates equivalent to the Two County Trial were achieved, but this was not consistently maintained. Overall rates equate to performance reported elsewhere in the UK (25% in the first year after screening, 48% in the second year after screening and 48% in the third year after screening, equivalent Two County rates are 17%, 32% and 57%). The prevalence round analysis shows that undiagnosed cancers arose after the film reading stage in 88% of interval cases. The team was able to distinguish minor signs from significant lesions effectively. Assessment procedures were effective once the patient had been recalled. CONCLUSION: Interval cancer rates fell initially but reached a plateau. Recall procedures were effective in making the diagnosis, and cases were missed at the film reading stage. Consistency of performance may be important in achieving low rates.

Breast Neoplasms↗

Size, node status and grade of breast tumours: association with mammographic parenchymal patterns.

A case-control study was designed to assess the association of mammographic parenchymal patterns with the risk of in-situ and invasive breast cancer. In addition, the relationship between tumour characteristics and mammographic patterns were also investigated. A total of 875 patients with breast cancer were selected and matched with 2601 controls. Mammographic parenchymal patterns of breast tissue were assessed according to Wolfe's classification, and statistical analysis was by conditional logistic regression. Relative to the N1 pattern, the odds ratios of having an invasive breast cancer associated with the P2 and DY patterns were 1.8 and 1. 4, respectively. In addition, the odd ratios of having an invasive grade 3 breast cancer associated with the P2 and DY patterns were 2. 8 and 3.9, respectively. Relative to the combined N1/P1 pattern, the odd ratios of having a breast cancer smaller than 14 mm, 15-29 mm, or larger than 30 mm associated with the combined high-risk P2/DY pattern (P2 + DY) were 1.2, 1.6, and 2.0, respectively. Finally, women with the P2/DY pattern were twice as likely to have a breast cancer which had already spread to the axillary nodes, compared to women with women with the N1/P1 pattern (odds ratios of 2.1 and 1.4, respectively). Our results confirm previous findings suggesting that mammographic parenchymal patterns may serve as indicators of risk for breast cancer. Our results also suggest that mammographic parenchymal patterns are associated with the stage at which breast cancer is detected.

Breast Neoplasms↗

High risk mammographic parenchymal patterns and diet: a case-control study.

Mammographic parenchymal patterns are related to breast cancer risk and are also thought to be affected by diet. We designed a case-control study comprising 200 cases with high-risk (P2 and DY) mammographic parenchymal pattern and 200 controls with low-risk (N1 and P1) patterns in order to investigate the effect of food and nutrient intake on mammographic patterns. Mammograms were evaluated according to the Wolfe classification system. Dietary data were obtained from 7-day food diaries. Mean daily intake of nutrients was computed from standard UK food tables. The adjusted odds ratio (OR) of having a high-risk pattern in women in the highest tertile of total protein and carbohydrate intake was twice that of women in the lowest tertile (OR = 2.00; 95% confidence interval (CI) 1.06-3.77; P = 0.04 and OR = 1.93; 95% CI 1.03-3.59; P = 0.04 respectively). There was no excess risk for fat intake. In addition, there was no association between intake of vitamins and mammographic parenchymal patterns. Total meat intake was strongly and positively associated with high-risk patterns among post-menopausal women (OR = 2.50, 95% CI 1.09-5.69, P = 0.03). Our study suggests that certain macronutrients and foods such as protein, carbohydrate and meat intake influence the risk of breast cancer through their effects on breast tissue morphology, whereas fat and vitamins do not affect mammographic density. It seems that parenchymal pattern acts as an informative biomarker of the effect of some macronutrient and foodstuffs intake on breast cancer risk.

Adipose Tissue↗

In vitro studies of cryoablation of the endometrium.

OBJECTIVE: The aims of this study were to quantify the tissue damage in vitro of a series of freezing protocols with the Endocryo (Spembley Medical Ltd, Andover, United Kingdom) cryoprobe for ablation of the endometrium and to determine the relative importance of the freezing parameters contributing to the cryolesion. STUDY DESIGN: The efficacy and safety of the Endocryo cryoprobe were assessed in vitro with 84 different experiments on freshly excised uterine specimens. Tissue necrosis was quantified by means of a histochemical technique after incubation of the uterine specimens under nearly physiologic conditions. RESULTS: A typical lesion was made up of a superficial area of tissue necrosis and a deeper area of sublethal damage. Tissue necrosis was >3 mm when the probe was in direct contact with the endometrium. Consistent tissue necrosis was only observed with tissue temperatures below -30 degrees C. Safe tissue damage was only consistently seen after < or =2 minutes of freezing. When the gap between the probe and the endometrium was filled with distention medium and was >2 mm, tissue damage was insufficient for clinical purposes irrespective of the medium used. CONCLUSION: The Endocryo cryoprobe provided a successful means of achieving endometrial ablation in vitro. The use of a uterine distention medium appeared to be of little value in improving the efficacy of the probe in vitro.

Cell Death↗

High-risk mammographic parenchymal patterns, hormone replacement therapy and other risk factors: a case-control study.

BACKGROUND: Mammographic parenchymal patterns are of particular interest because the denser patterns reduce screening sensitivity as well as increasing breast cancer risk, and because they have been shown to be affected by exogenous oestrogens. METHODS: We designed a case-control study comprising 200 cases with high-risk (P2 and DY) pattern and 200 controls with low-risk (N1 and P1) pattern. Mammograms were evaluated according to the Wolfe classification. RESULTS: Parity, body mass index (BMI) and current smoking were inversely and independently associated, whereas late age of menarche and history of benign breast disease were positively associated with high-risk mammographic patterns. Current-users of hormone replacement therapy (HRT) were more than twice as likely to have a high-risk pattern than never-users (OR = 2.48, 95% CI : 1.32-4.61). Women who used HRT for more than 5 years were almost three times more likely to have a high-risk pattern than never-users (OR = 2.77, 95% CI : 1.11-6.91). Relative to never-users, women who started HRT before the menopause were more than twice as likely to have a high-risk pattern (OR = 2.53, 95% CI : 1.31-4.87). CONCLUSIONS: Careful clinical and mammographical follow-up might be appropriate in women undergoing HRT. The HRT-induced mammographic pattern might be regarded as a new baseline and changes with respect to this new pattern could then be monitored over time.

Aged↗