Population-based mammography screening and breast cancer incidence in New South Wales, Australia

To analyse breast cancer incidence trends in New South Wales (NSW), Australia, in relation to population-based mammography screening targeting women aged 50 to 69 years. Trends in age-specific incidence of invasive breast cancers in NSW women aged >= 40 years were examined in relation to mammography screening rates and screening cancer detection rates. Incidence of invasive breast cancer in NSW women increased in all age-groups over 1972 to 2002. The incidence trend for women aged 50 to 69 years showed that the steepest rise was associated with increased participation in population-based mammography screening, which was implemented from 1988 and achieved state-wide coverage in 1995. The elevated incidence of invasive cancer significantly exceeded pre-screening levels, and persisted after rates of initial screens declined. This elevated incidence was sustained by the contribution of cancers diagnosed through subsequent screening, and resulted from increased cancer detection rates in subsequent screens. The recent increase in invasive breast cancer incidence in NSW is associated with mammography screening, and occurred mostly in the target age-group women. Persistence of higher incidence after 1994 was not explicable by inflation of cancer incidence due to detection of prevalent screen cases, but was associated with a trend of increased cancer detection rates in subsequent screening rounds, probably consequent to quality improvements in mammography screening diagnosis.

Novel miniaturized systems in high-throughput screening

High-throughput screening (HTS) using high-density microplates is the primary method for the discovery of novel lead candidate molecules. However, new strategies that eschew 2D microplate technology, including technologies that enable mass screening of targets against large combinatorial libraries, have the potential to greatly increase throughput and decrease unit cost. This review presents an overview of state-of-the-art microplate-based HTS technology and includes a discussion of emerging miniaturized systems for HTS. We focus on new methods of encoding combinatorial libraries that promise throughputs of as many as 100 000 compounds per second.

Comparability of skin screening histories obtained by telephone interviews and mailed questionnaires: A randomized crossover study

The comparability of information collected through telephone interviews and information collected through mailed questionnaires has not been well studied. As part of the first phase of a randomized controlled trial of population screening for melanoma in Queensland, Australia, the authors compared histories of skin examination reported in telephone interviews and self-administered mailed questionnaires. A total of 1,270 subjects each completed a telephone interview and a mailed questionnaire 1 month apart in 1999; 564 subjects received the interview first, and 706 received the mailed questionnaire first. Agreement between the two methods was 91.2% and 88.6% for whole-body skin examination by a physician in the last 12 months and the last 3 years, respectively, and 81.9% for whole-body skin self-examination in the last 12 months. Agreement was lower for any skin self-examination. Agreement between the two methods was similar regardless of whether the interview or the questionnaire was administered first. Missing data were less frequent for interviews (0.5%) than for mailed questionnaires (3.8%). Costs were estimated at A$9.55 (US$6.21) per completed interview and A$3.01 (US$1.96) per questionnaire. The similarity of results obtained using telephone interviews and mailed questionnaires, coupled with the substantially higher cost of telephone interviews, suggests that self-administered mailed questionnaires are an appropriate method of assessing this health behavior.

Validity of self-reported skin screening histories

Screening by whole-body clinical skin examination may improve early diagnosis of melanoma and reduce mortality, but objective scientific evidence of this is lacking. As part of a randomized controlled trial of population screening for melanoma in Queensland, Australia, the authors assessed the validity of self-reported history of whole-body skin examination and factors associated with accuracy of recall among 2,704 participants in 2001. Approximately half of the participants were known to have undergone whole-body skin examination within the past 3 years at skin screening clinics conducted as part of the randomized trial. All positive and negative self-reports were compared with screening clinic records. Where possible, reports of skin examinations conducted outside the clinics were compared with private medical records. The validity of self-reports of whole-body skin examination in the past 3 years was high: Concordance between self-reports and medical records was 93.7%, sensitivity was 92.0%, and specificity was 96.3%. Concordance was lower (74.3%) for self-reports of examinations conducted in the past 12 months, and there was evidence of telescoping in recall for this more recent time frame. In multivariate analysis, women and younger participants more accurately recalled their history of skin examinations. Participants with a history of melanoma did not differ from other participants in their accuracy of recall.

Assessing the effectiveness of a mammography screening service

Background: Trials have shown that mammography screening reduces mortality and probably decreases morbidity related to breast cancer. Methods: We assessed whether the major mammography service in Western Australia (BreastScreen WA) is likely to reduce mortality by comparing prognostic variables between screen-detected and other cases of breast cancer diagnosed in 1999. We assessed likely reductions in morbidity by comparing treatments received by these two groups. To confirm mortality and morbidity reduction, we also compared prognostic variables and treatments with targets. Information on demographic variables, tumour characteristics at presentation and treatments were collected from medical records for all incident cases of breast cancer in Western Australia in 1999. We matched cases with the Western Australian Cancer Registry records to determine which cases had been detected by BreastScreen WA. Results: BreastScreen WA achieved the targets for mortality reduction. Tumours detected by BreastScreen WA were smaller in size, less likely to have vascular invasion, of lower histological grade and were more likely to be ductal carcinoma in situ alone without invasive carcinoma. Oestrogen receptor status was more likely to be positive, the difference in progesterone status was not significant, and lymph node involvement tended to be lower. BreastScreen WA patients were treated more often with local therapy and less often with systemic therapy, and the proportion of patients treated with breast-conserving surgery was close to the target for minimizing morbidity in breast cancer. Conclusion: Mammographic detection of breast cancer by BreastScreen WA is associated with reduced breast cancer morbidity and a more favourable prognosis.

Methods for prediction of peptide binding to MHC molecules: A comparative study

Background: A variety of methods for prediction of peptide binding to major histocompatibility complex (MHC) have been proposed. These methods are based on binding motifs, binding matrices, hidden Markov models (HMM), or artificial neural networks (ANN). There has been little prior work on the comparative analysis of these methods. Materials and Methods: We performed a comparison of the performance of six methods applied to the prediction of two human MHC class I molecules, including binding matrices and motifs, ANNs, and HMMs. Results: The selection of the optimal prediction method depends on the amount of available data (the number of peptides of known binding affinity to the MHC molecule of interest), the biases in the data set and the intended purpose of the prediction (screening of a single protein versus mass screening). When little or no peptide data are available, binding motifs are the most useful alternative to random guessing or use of a complete overlapping set of peptides for selection of candidate binders. As the number of known peptide binders increases, binding matrices and HMM become more useful predictors. ANN and HMM are the predictive methods of choice for MHC alleles with more than 100 known binding peptides. Conclusion: The ability of bioinformatic methods to reliably predict MHC binding peptides, and thereby potential T-cell epitopes, has major implications for clinical immunology, particularly in the area of vaccine design.

An educational workshop on the early detection of prostate cancer

The authors have developed an education program for GPs to facilitate informed choice about PSA testing.

Relationships between nutrition screening checklists and the health and well-being of older Australian women

Objectives: To examine associations between nutrition screening checklists and the health of older women. Design: Cross-sectional postal survey including measures of health and health service utilisation, as well as the Australian Nutrition Screening Initiative (ANSI), adapted from the Nutrition Screening Initiative (NSI). Setting: Australia, 1996. Subjects: In total, 12 939 women aged 70-75 years randomly selected as part of the Australian Longitudinal Study on Women's Health. Results: Responses to individual items in the ANSI checklist, and ANSI and NSI scores, were associated with measures of health and health service utilisation. Women with high ANSI and NSI scores had poorer physical and mental health, higher health care utilisation and were less likely to be in the acceptable weight range. The performance of an unweighted score (TSI) was also examined and showed similar results. Whereas ANSI classified 30% of the women as 'high-risk', only 13% and 12% were classified as 'high-risk' by the NSI and TSI, respectively. However, for identifying women with body mass index outside the acceptable range, sensitivity, specificity and positive predictive values for all of these checklists were less than 60%. Conclusions: Higher scores on both the ANSI and NSI are associated with poorer health. The simpler unweighted method of scoring the ANSI (TSI) showed better discrimination for the identification of 'at risk' women than the weighted ANSI method. The predictive value of individual items and the checklist scores need to be examined longitudinally.

Routine ultrasound screening in diabetic pregnancies

Objectives To assess the detection rate of congenital fetal malformations and specific problems related to routine ultrasound screening in women with pre-existing diabetes. Methods A retrospective study was carried out to assess the performance of routine ultrasound screening in women with pre-existing diabetes (Types 1 and 2) within a tertiary institution. The incidence, type and risk factors for congenital fetal malformations were determined. The detection rate of fetal anomalies for diabetic women was compared with that for the low-risk population. Factors affecting these detection rates were evaluated. Results During the study period, 12 169 low-risk pregnant women and 130 women with pre-existing diabetes had routine ultrasound screening performed within the institution. A total of 10 major anomalies (7.7%) and three minor anomalies (2.3%) were present in the fetuses of the diabetic women. Central nervous system and cardiovascular system anomalies accounted for 60% of the major anomalies. Peri-conceptional hemoglobin A 1 c of more than 9% was associated with a high prevalence of major anomalies (14311000). Women who had fetuses with major anomalies bad a significantly higher incidence of obesity (78% vs. 37%; P < 0.05). Ultrasound examination of these diabetic pregnancies showed high incidences of suboptimal image quality (37%), incomplete examinations, and repeat examinations (17%). Compared to the 'low-risk' non-diabetic population from the same institution, the relative risk for a major congenital anomaly among the diabetic women was 5.9-fold higher (95% confidence interval, 2.9-11.9). The detection rate for major fetal anomalies was significantly lower for diabetic women (30% vs. 73%; P < 0.01), and the mean body mass index for the diabetic group was significantly higher (29 vs. 23 kg/m(2); P < 0.001). Conclusion The incidence of congenital anomalies is higher in diabetic pregnancies. Unfortunately, the detection rate for fetal anomalies by antenatal ultrasound scan was significantly, worse than that for the low-risk population. This is likely to be related to the maternal body habitus and unsatisfactory examinations. Methods to overcome these difficulties are discussed.

High rate of detection of primary aldosteronism, including surgically treatable forms, after 'non-selective' screening of hypertensive patients

Background Wide testing of the aldosterone: renin ratio among hypertensive individuals has revealed primary aldosteronism to be common, with most patients normokalaemic. Some investigators, however, have reported aldosterone-producing adenoma to be rare among patients so detected. Objective To test the hypothesis that differences among reported studies in the rate of detection of aldosterone-producing adenoma (as opposed to bilateral adrenal hyperplasia) reflect differences in the procedures used for diagnosis of primary aldosteronism, and the methods used to identify aldosterone-producing adenomas. Methods In the newly established Princess Alexandra Hospital Hypertension Unit (PAHHU), we used procedures developed by Greenslopes Hospital Hypertension Unit (which reports that more than 30% of patients with primary aldosteronism have aldosterone-producing adenomas) to diagnose primary aldosteronism and determine the subtype. All patients with an increased aldosterone: renin ratio (measured after correction for hypokalaemia and while the patient was not receiving interfering medications) underwent fludrocortisone suppression testing to confirm or exclude primary aldosteronism; if they were positive, they underwent genetic testing to exclude glucocorticoid-remediable aldosteronism before adrenal venous sampling was used to differentiate lateralizing from bilateral primary aldosteronism. Results This approach allowed PAHHU to diagnose, within 2 years, 54 patients [only seven (13%) hypokalaemic] with primary aldosteronism. All tested negative for glucocorticoid-remediable aldosteronism. Aldosterone production was lateralized to one adrenal in 15 patients (31%; only six hypokalaemic) and was bilateral in 34 (69%; all normokalaemic) of 49 patients who underwent adrenal venous sampling. Among patients with lateralizing adrenal hyperplasia, computed tomography revealed an ipsilateral mass in only six and a contralateral lesion in one. Fourteen patients underwent unilateral adrenalectomy, which cured the hypertension in seven and improved it in the remainder. In patients with bilateral primary aldlosteronism, hypertension responded to spironolactone (112.5-50 mg/ day) or amiloride (2.5-10 mg/day). Conclusion When performed with careful regard to confounding factors, measurement of the aldosterone: renin ratio in all hypertensive individuals, followed by fludrocortisone suppression testing to confirm or exclude primary aldosteronism and adrenal venous sampling to determine the subtype, can result in the detection of significant numbers of patients with specifically treatable or potentially curable hypertension. (C) 2003 Lippincott Williams Wilkins.

Trusting technology: Women aged 40-49 years participating in screening for breast cancer - an exploratory study

Objective: This paper reports key findings from an exploratory study of factors associated with women's decision to participate in mass mammography screening in Tasmania. In particular, we explored factors that contribute to the choice to participate in screening by women who are outside the primary target group, and for whom the evidence of benefit remains contentious. Methods: Semi-structured interviews were conducted with a small sample of women aged between 40 and 49 years in rural Tasmania who had participated in mammography screening. Results: Key ideas that appeared to shape participation included the fear of breast cancer, trust in technology, and taking responsibility for health. Information provision is also an important factor in shaping participation patterns. Conclusions and implications: In order to facilitate informed consent, information provision in this area should take account of the dominant ideas that shape the decision to participate in breast cancer screening.

Rapid screening of 4000 individuals for germ-line variations in the BRAF gene

Background: The BRAF gene is frequently somatically altered in malignant melanoma. A majority of variations are at the valine 600 residue leading to a V600E substitution that constitutively activates the kinase. We screened 4000 patient and control DNAs for germ-line variations at the valine 600 residue. Methods: We developed a novel assay by adapting single-base variation assays and software for MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry to screen for all 5 reported variants at codon 600 of the BRAF gene. We screened a case-control collection comprising samples from 1082 melanoma patients and 154 of their unaffected relatives from 1278 families and from 2744 individuals from 659 unselected twin families with no history of melanoma. A panel of 66 melanoma cell lines was used for variation-positive controls. Results: All melanoma cell lines that we had found previously to carry a codon 600 variation were verified in this study. Three of the 4 possible variants (V600E n = 47, V600K n = 2, V600R n = 1) were detected, but no case of V600D was available. No germ-line variants were found in the samples from the 3980 melanoma patients or from the control individuals. Conclusions: This new assay is a high-throughput, automated alternative to standard sequencing and can be used as a rapid initial screen for somatic variants associated with melanoma. Germ-line variants at valine 600 are unlikely to exist and do not contribute to the reported role of the BRAF gene in melanoma predisposition. (c) 2006 American Association for Clinical Chemistry.

Distortion product otoacoustic emissions in children at school entry: A comparison with pure tone screening and tympanometry results

This study examined the test performance of distortion product otoacoustic emissions (DPOAEs) when used as a screening tool in the school setting. A total of 1003 children (mean age 6.2 years, SD = 0.4) were tested with pure-tone screening, tympanometry, and DPOAE assessment. Optimal DPOAE test performance was determined in comparison with pure-tone screening results using clinical decision analysis. The results showed hit rates of 0.86, 0.89, and 0.90, and false alarm rates of 0.52, 0.19, and 0.22 for criterion signal-to-noise ratio (SNR) values of 4, 5, and 11 dB at 1.1, 1.9, and 3.8 kHz respectively. DPOAE test performance was compromised at 1.1 kHz. In view of the different test performance characteristics across the frequencies, the use of a fixed SNR as a pass criterion for all frequencies in DPOAE assessments is not recommended. When compared to pure tone plus tympanometry results, the DPOAEs showed deterioration in test performance, suggesting that the use of DPOAEs alone might miss children with subtle middle ear dysfunction. However, when the results of a test protocol, which incorporates both DPOAEs and tympanometry, were used in comparison with the gold standard of pure-tone screening plus tympanometry, test performance was enhanced. In view of its high performance, the use of a protocol that includes both DPOAEs and tympanometry holds promise as a useful tool in the hearing screening of schoolchildren, including difficult-to-test children.