190 research outputs found

    Pathways to a cancer-free future: A protocol for modelled evaluations to minimise the future burden of colorectal cancer in Australia

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    Introduction&nbsp;With almost 50% of cases preventable and the Australian National Bowel Cancer Screening Program in place, colorectal cancer (CRC) is a prime candidate for investment to reduce the cancer burden. The challenge is determining effective ways to reduce morbidity and mortality and their implementation through policy and practice. Pathways-Bowel is a multistage programme that aims to identify best-value investment in CRC control by integrating expert and end-user engagement; relevant evidence; modelled interventions to guide future investment; and policy-driven implementation of interventions using evidence-based methods.Methods and analysis&nbsp;Pathways-Bowel is an iterative work programme incorporating a calibrated and validated CRC natural history model for Australia (Policy1-Bowel) and assessing the health and cost outcomes and resource use of targeted interventions. Experts help identify and prioritise modelled evaluations of changing trends and interventions and critically assess results to advise on their real-world applicability. Where appropriate the results are used to support public policy change and make the case for optimal investment in specific CRC control interventions. Fourteen high-priority evaluations have been modelled or planned, including evaluations of CRC outcomes from the changing prevalence of modifiable exposures, including smoking and body fatness; potential benefits of daily aspirin intake as chemoprevention; increasing CRC incidence in people aged &lt;50 years; increasing screening participation in the general and Aboriginal and Torres Strait Islander populations; alternative screening technologies and modalities; and changes to follow-up surveillance protocols. Pathways-Bowel is a unique, comprehensive approach to evaluating CRC control; no prior body of work has assessed the relative benefits of a variety of interventions across CRC development and progression to produce a list of best-value investments.Ethics and dissemination&nbsp;Ethics approval was not required as human participants were not involved. Findings are reported in a series of papers in peer-reviewed journals and presented at fora to engage the community and policymakers.</div

    Stereotypes concerning students with special educational needs: teachersÂŽ beliefs, -expectations and -emotions

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    Dieses Kapitel geht der Frage nach, ob Lehrer*innenĂŒberzeugungen und -erwartungen je nach sonderpĂ€dagogischem Förderbedarf variieren. Außerdem wurde deren Einfluss sowohl auf die GefĂŒhle bei Auseinandersetzung mit der Inklusion von unterschiedlichen SchĂŒler*innen als auch auf die persönliche Bereitschaft, Inklusion umzusetzen, untersucht. Die Studien basieren einerseits auf dem Kontinuum-Modell der Eindrucksbildung und betrachten andererseits das Stereotype-Content-Modell, nach dem WĂ€rme und Kompetenz ĂŒber 80 % der Unterschiedlichkeit in der Personenwahrnehmung erklĂ€ren. Die Ergebnisse zeigten, dass Überzeugungen und Erwartungen von der Art des Förderbedarfs beeinflusst werden. Positivere Überzeugungen bezĂŒglich der SchĂŒler*innenmerkmale (WĂ€rme und Kompetenz) und höhere Leistungserwartungen waren hierbei mit positiveren GefĂŒhlen und einer stĂ€rker ausgeprĂ€gten persönlichen Bereitschaft, die SchĂŒler*innen mit sonderpĂ€dagogischem Förderbedarf zu inkludieren, verbunden. Abschließend werden die daraus resultierenden Konsequenzen fĂŒr die Lehreraus- und weiterbildung abgeleitet und diskutiert

    Pathways to a cancer-free future: a protocol for modelled evaluations to minimise the future burden of colorectal cancer in Australia.

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    INTRODUCTION:With almost 50% of cases preventable and the Australian National Bowel Cancer Screening Program in place, colorectal cancer (CRC) is a prime candidate for investment to reduce the cancer burden. The challenge is determining effective ways to reduce morbidity and mortality and their implementation through policy and practice. Pathways-Bowel is a multistage programme that aims to identify best-value investment in CRC control by integrating expert and end-user engagement; relevant evidence; modelled interventions to guide future investment; and policy-driven implementation of interventions using evidence-based methods. METHODS AND ANALYSIS: Pathways-Bowel is an iterative work programme incorporating a calibrated and validated CRC natural history model for Australia (Policy1-Bowel) and assessing the health and cost outcomes and resource use of targeted interventions. Experts help identify and prioritise modelled evaluations of changing trends and interventions and critically assess results to advise on their real-world applicability. Where appropriate the results are used to support public policy change and make the case for optimal investment in specific CRC control interventions. Fourteen high-priority evaluations have been modelled or planned, including evaluations of CRC outcomes from the changing prevalence of modifiable exposures, including smoking and body fatness; potential benefits of daily aspirin intake as chemoprevention; increasing CRC incidence in people aged <50 years; increasing screening participation in the general and Aboriginal and Torres Strait Islander populations; alternative screening technologies and modalities; and changes to follow-up surveillance protocols. Pathways-Bowel is a unique, comprehensive approach to evaluating CRC control; no prior body of work has assessed the relative benefits of a variety of interventions across CRC development and progression to produce a list of best-value investments. ETHICS AND DISSEMINATION:Ethics approval was not required as human participants were not involved. Findings are reported in a series of papers in peer-reviewed journals and presented at fora to engage the community and policymakers

    Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database

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    PURPOSE: Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer. METHODS: We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years. RESULTS: There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer. CONCLUSION: Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers

    Chronic pain after groin hernia repair: pain characteristics and impact on quality of life

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    Background: Chronic postsurgical pain (CPSP) after hernia repair research has mainly relied on unconfirmed self-reporting. We aimed to describe confirmed CPSP incidence, management, and quality of life (QoL) in a 2-year prospective study. Methods: Multicenter study (GENDOLCAT) of 3890 patients undergoing 4 common surgical procedures in 23 hospitals to develop a risk model for CPSP; 2352 men underwent open hernia repair. Patients with pain were identified by telephone at 1 and 3 months and referred to the hospital 4 months after surgery for a physical examination to confirm CPSP. Three validated tools were used: the Brief Pain Inventory (BPI) for severity, analgesic use, and interference with activities; the SF-12 questionnaire for QoL (validated Spanish version), and the Douleur Neuropathique 4 (DN4). Patients with CPSP were called again at 1 and 2 years. Results: In 1761 patients who underwent hernia repair and were eligible for physical examination for CPSP, the incidence of confirmed pain at 4 months was 13.6% (patient-reported pain, 6.2% at 1 year and 4.0% at 2 years). Neuropathic pain was diagnosed in 38.5% of the CPSP patients at 4 months. The incidences of neuropathic CPSP in patients with mesh or non-mesh repairs were similar (38.6 and 33.3%, respectively). SF-12 physical component scores changed little in all patients, whether or not they developed CPSP. The SF-12 mental component decreased significantly in all patients, but the decrease was clinically significant only in CPSP patients. CPSP interfered with activities (18%), work (15.6%), walking (15%) and mood (10.2%). At 2 years 52.1% of CPSP patients had moderate/intense pain and 28.2% took analgesics. Conclusion: CPSP affects QoL-related activities, and although it diminishes over the course of 2 years after surgery, many patients continue to have moderate/intense pain and take analgesics. CPSP and neuropathic pain rates seem to be similar after mesh and non-mesh repair. BPI and SF-12 mental component scores detect effects on QoL

    Pan-cancer analysis of whole genomes

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    Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
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