Approximately 1-2% of colorectal cancers (CRC) arise because of germline mutations in DNA mismatch repair genes, referred to as Lynch syndrome. These tumours show microsatellite instability (MSI) and loss of expression of mismatch repair proteins. Presymptomatic identification of mutation carriers has been demonstrated to improve survival; however, there is concern that many are not being identified using current practices. We evaluated population-based MSI screening of CRC in young patients as a means of ascertaining mutation carriers. CRC diagnosed in patients aged <60 years were identified from pathology records. No prior information was available on family history of cancer. PCR techniques were used to determine MSI in the BAT-26 mononucleotide repeat and mutation in the BRAF oncogene. Loss of MLH1, MSH2, MSH6 and PMS2 protein expression was evaluated in MSI1 tumours by immunohistochemistry. MSI1 tumours were found in 105/1,344 (7.8%) patients, of which 7 were excluded as possible Lynch syndrome because of BRAF mutation. Of the 98 ''red flag'' cases that were followed up, 25 were already known as mutation carriers or members of mutation carrier families. Germline test results were obtained for 35 patients and revealed that 22 showed no apparent mutation, 11 showed likely pathogenic mutations and 2 had unclassified variants. The proportion of MSI1 cases in different age groups that were estimated to be mutation carriers was 89% (<30 years), 83% (30-39), 68% (40-49) and 17% (50-59). We recommend MSI as the initial test for population-based screening of Lynch syndrome in younger CRC patients, regardless of family history. ' 2008 Wiley-Liss, Inc.Key words: HNPCC; colorectal cancer; microsatellite instability; BRAF Hereditary non-polyposis colorectal cancer (HNPCC), or Lynch syndrome, is mainly caused by mutations in the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. 1,2 It accounts for approximately 1-2% of all colorectal cancers (CRC) and is also associated with an increased risk of endometrial and other extracolonic cancers. As a consequence of deficient MMR, almost all CRCs from patients with Lynch syndrome show microsatellite instability (MSI) in their tumour DNA. The MSI phenotype is characterized by ubiquitous changes in the length of nucleotide repeat sequences, with mononucleotide repeat tracts being particularly susceptible to deletions. 3 MSI is almost always accompanied by a loss of expression of MMR proteins. The most commonly observed combinations are loss of MLH1 with PMS2 and of MSH2 with MSH6, although other rarer patterns of loss have been reported. 4,5 Approximately 10% of sporadic CRCs also exhibit MSI and these tumours occur most frequently in the proximal colon of older women. 3 The large majority of sporadic MSI1 CRCs arise because of acquired, methylation-induced transcriptional silencing of MLH1 gene expression. 6 The MSI phenotype cannot therefore be used alone as a specific marker for Lynch syndrome. However, the presence of a hot-spot point mutation (V600E) in the BRAF onc...

The aim of this study was to determine the frequency of microsatellite instability (MSI ؉ )

Research has shown that the media over-estimates smoking rates and often associates smoking with favorable attributes or situations. Given that the media plays a large role in influencing youth culture, portrayal of smoking in the media is of concern. In order to explore young people's perceptions of smoking imagery in the media, 16 focus groups were conducted with 117 school students. Participants were asked to rate smoking images selected from audio-visual and print media, and to discuss their perceptions of these images. The results showed that young people perceived smoking in these media selections to be normal and acceptable. They identified with the stress-relieving and social aspects of smoking, despite being well aware of the harmful health effects. Its acceptability as part of a 'cool' image was also noted. Positive images of smoking in the media have the potential to down-play the serious health consequences of smoking by portraying it in a way that young people interpret as a normal part of everyday life. They may also encourage a more neutral or tolerant attitude towards smoking among young people and therefore act to counteract other health promotion efforts to reduce teenage smoking.

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Medical graduates require positive attitudes toward older people with cognitive impairment, in addition to knowledge and skills in the diagnosis and management of dementia. The Student Training Project in Dementia (STriDE) project was conducted to ensure that these needs are met through curricula in Western Australian medical schools. Two medical schools in Perth, Western Australia, participated. Mixed methods were utilized comprising a) focus groups and interviews and b) a survey of teachers and students. Participants recommended clearer structure and standardization in the curriculum to ensure that all students receive similar educational experiences regardless of hospital placement. Both teachers, and to a lesser extent students, held positive attitudes toward older people. Teachers tended to be more dissatisfied with current curricula than students. Teachers and learners endorsed a broad range of teaching and learning methods, assessments, and skills/competencies. The results of this study present major challenges for professional entry dementia education given the breadth, flexibility, and depth of dementia education recommended by teachers and learners.

People with diabetes face increased risk of serious COVID-19 complications, making self-care for optimal metabolic management crucial. However, the pandemic has reduced access to routine care among people with diabetes. The pandemic can also elicit distress, which can impact diabetes self-management and health. To understand the impact of COVID-19 on Western Australians with diabetes, we conducted an evaluation involving an online survey of consumers of diabetes health services and an analysis of routine program data (i.e. service utilisation/program attendance). Survey respondents were concerned about contracting COVID-19, many intended to change the way they utilised health services and many indicated they would continue to socially isolate. Utilisation of digital/telephone services peaked between April and June 2020. Despite the concerns indicated, a participation resurgence was observed upon resumption of face-to-face programs. Continued access to diabetes programs via multiple modes of delivery is critical to support optimal self-care and mitigate COVID-19 risks, distress and social isolation. This timely and pragmatic assessment of consumer beliefs synthesised with routinely collected evaluation data represents an agile approach to evaluation through an emerging public health crisis. The findings helped to ensure optimal service delivery to meet the needs of this priority population throughout the pandemic.

Objective To determine whether mammographic screening has affected the presentation of invasive breast cancer in Western Australia. Design Population‐based reviews of the presentation of all invasive breast cancers diagnosed in Western Australia in 1989 and 1994. Setting Western Australia (population 1.8 million). Active recruitment of women aged 50‐69 years for mammographie screening began in 1989. Main outcome measures Size and stage of invasive breast cancers at diagnosis. Results From 1989 to 1994, the age‐standardised incidence rose from 109 to 123 per 100000 woman‐years, based on 584 and 750 cases, respectively. The proportion of all invasive breast cancers detected as a result of a mammogram increased from 9.2% in 1989 to 34.5% in 1994. Among the cases where relevant information was recorded, the proportion of “impalpable” tumours increased from 7.7% in 1989 to 27.6% in 1994, and the average size of palpable tumours fell. There was an unexpected increase in the proportion of tumours that were negative on assays for oestrogen and progesterone receptors. Conclusions A relatively simple and inexpensive clinical review has boosted confidence that the outlay of public monies required to establish and conduct screening in Australia appears likely to yield the reductions in mortality from breast cancer that would be predicted on the basis of the earlier controlled trials of mammography.

There was consensus regarding the major curricular areas that online resources should encompass. The e-ageing modules developed in this project have been evaluated positively by users.