Prediction models for endometrial cancer for the general population or symptomatic women: a systematic review

OBJECTIVE: To provide an overview of prediction models for the risk of developing endometrial cancer in women of the general population or for the presence of endometrial cancer in symptomatic women. METHODS: We systematically searched the Embase and Pubmed database until September 2017 for relevant publications. We included studies describing the development, the external validation, or the updating of a multivariable model for predicting endometrial cancer in the general population or symptomatic women. RESULTS: Out of 2756 references screened, 14 studies were included. We found two prediction models for developing endometrial cancer in the general population (risk models) and one extension. Eight studies described the development of models for symptomatic women (diagnostic models), one comparison of the performance of two diagnostic models and two external validation. Sample size varied from 60 (10 with cancer) to 201,811 (855 with cancer) women. The age of the women was included as a predictor in almost all models. The risk models included epidemiological variables related to the reproductive history of women, hormone use, BMI, and smoking history. The diagnostic models also included clinical predictors, such as endometrial thickness and recurrent bleeding. The concordance statistic (c), assessing the discriminative ability, varied from 0.68 to 0.77 in the risk models and from 0.73 to 0.957 in the diagnostic models. Methodological information was often limited, especially on the handling of missing data, and the selection of predictors. One risk model and four diagnostic models were externally validated. CONCLUSIONS: Only a few models have been developed to predict endometrial cancer in asymptomatic or symptomatic women. The usefulness of most models is unclear considering methodological shortcomings and lack of external validation. Future research should focus on external validation and extension with new predictors or biomarkers, such as genetic and epigenetic markers

Women's perception, attitudes, and intended behavior towards predictive epigenetic risk testing for female cancers in 5 European countries: A cross-sectional online survey

BACKGROUND: Epigenetic markers might be used for risk-stratifying cancer screening and prevention programs in the future. Although the clinical utility of consequent epigenetic tests for risk stratification is yet to be proven, successful adoption into clinical practice also requires the public's acceptance of such tests. This cross-sectional online survey study sought to learn for the first time about European women's perceptions, attitudes, and intended behavior regarding a predictive epigenetic test for female cancer (breast, ovarian, cervical, and endometrial) risks. METHODS: 1675 women (40-75 years) from five European countries (Czech Republic, Germany, United Kingdom, Italy, Sweden), drawn from online panels by the survey sampling company Harris Interactive (Germany), participated in an online survey where they first received online leaflet information on a predictive epigenetic test for female cancer risks and were subsequently queried by an online questionnaire on their desire to know their female cancer risks, their perception of the benefit-to-harm ratio of an epigenetic test predicting female cancer risks, reasons in favor and disfavor of taking such a test, and their intention to take a predictive epigenetic test for female cancer risks. RESULTS: Most women desired information on each of their female cancer risks, 56.6% (95% CI: 54.2-59.0) thought the potential benefits outweighed potential harms, and 75% (72.0-77.8) intended to take a predictive epigenetic test for female cancer risks if freely available. Results varied considerably by country with women from Germany and the Czech Republic being more reserved about this new form of testing than women from the other three European countries. The main reason cited in favor of a predictive epigenetic test for female cancer risks was its potential to guide healthcare strategies and lifestyle changes in the future, and in its disfavor was that it may increase cancer worry and coerce unintended lifestyle changes and healthcare interventions. CONCLUSIONS: A successful introduction of predictive epigenetic tests for cancer risks will require a balanced and transparent communication of the benefit-to-harm ratio of healthcare pathways resulting from such tests in order to curb unjustified expectations and at the same time to prevent unjustified concerns

When evidence says no: gynaecologists' reasons for (not) recommending ineffective ovarian cancer screening

Introduction Most patients likely assume that physicians offer medical procedures backed by solid, scientific evidence that demonstrates their superiority—or at least non-inferiority—to alternative approaches.1 Doing otherwise would waste healthcare resources urgently needed elsewhere in the system and also would jeopardise patient health and safety as well as undermine patients’ trust in medicine2 and care. In some instances, however, physicians’ healthcare practices appear to act against scientific evidence.3–5 For example, evidence from two large randomised controlled trials6 7 on ovarian cancer screening’s effectiveness showed that the screening has no mortality benefits—neither cancer-specific nor overall—in average-risk women but considerable harms, including false-positive surgeries in women without ovarian cancer. Consequently, the US Preventive Services Task Force and medical associations worldwide recommend against ovarian cancer screening.8 Nevertheless, a considerable number of US gynaecologists persist in recommending the screening to average-risk women.9 To understand why physicians continue using a practice called into question by scientific evidence, we investigated gynaecologists’ reasons for or against recommending ovarian cancer screening, their assumptions about why other gynaecologists recommend it, and the association between their knowledge of basic concepts of cancer screening statistics10 and recommendation behaviour

Informal knowledge transfer in the period before formal health education programmes: case studies of mass media coverage of HIV and SIDS in England and Wales

Background: How advances in knowledge lead via behaviour change to better health is not well understood. Here we report two case studies: a rapid reduction in HIV transmission in homosexual men and a decline in Sudden Infant Death Syndrome ( SIDS) that took place in the period before the relevant national education programmes commenced, respectively, in 1986 and 1991. The role of newspapers in transferring knowledge relevant to reducing the risk of AIDS and SIDS is assessed. Methods: HIV. Searches were made of The Times (1981-1985), Gay News (1981-1984) and, for the key period of April to June 1983, of eight newspapers with the highest readership. Information on transmission route and educational messages were abstracted and analysed.SIDS Searches were made of The Times and the Guardian (1985-1991), The Sun ( selected periods only, 1988-1991) and selected nursing journals published in England and Wales. Information on sleeping position and educational messages were abstracted and analysed.Results: HIV Forty-five out of 50 articles identified in newspapers described homosexuals as an at risk group. Sexual transmission of AIDS was, however, covered poorly, with only 7 (14%) articles referring explicitly to sexual transmission. Only seven articles (14%) associated risk with promiscuity. None of the articles were specific about changes in behaviour that could be expected to reduce risk. Gay periodicals did not include specific advice on reducing the number of partners until early 1984.SIDS Out of 165 relevant articles in The Times and 84 in the Guardian, 7 were published before 1991 and associated risk with sleeping position. The reviewed nursing journals reflected a pervasive sense of uncertainty about the link between SIDS and sleeping position. Conclusion: Presumptively receptive audiences responded rapidly to new knowledge on how changes in personal behaviour might reduce risk, even though the 'signals' were not strong and were transmitted, at least partly, through informal and 'horizontal' channels. Advances in knowledge with the potential to prevent disease by behaviour change may thus yield substantial health benefits even without the mediation of formal education campaigns ('interventions'). Formal campaigns, when they came, did make important additional contributions, especially in the case of SIDS

Integration of genetic and epigenetic markers for risk stratification: opportunities and challenges

Common genetic susceptibility variants could be used for risk stratification in risk-tailored cancer screening and prevention programmes. Combining genetic variants with environmental risk factors would improve risk stratification. Epigenetic changes are surrogate markers of environmental exposures during individual's lifetime. Integrating epigenetic markers, in lieu of environmental exposure data, with genetic markers would potentially improve risk stratification. Epigenetic changes are reversible and acquired gradually, providing potentials for prevention and early detection strategies. The epigenetic changes are tissue-specific and stage-of-development-specific, raising challenges in choice of sample and timing for evaluation of cancer-associated changes. The Horizon 2020 funded research programme, FORECEE, using empirical data, will investigate the value of integration of epigenomics with genomics for risk prediction and prevention of women-specific cancers

Implementing a novel programme for nurses and allied health professionals to develop capacity for evidence-informed clinical practice

BACKGROUND: Nurses and allied health professionals (AHPs) require skills and support to access, appraise, interpret and use research evidence in clinical practice. We describe the process of designing and implementing the Evidence in Practice (EiP) programme at a UK hospital. METHODS: Key stakeholders were engaged to identify learning needs and priorities in appraising and implementing research evidence. To address these, we designed a multi-strategy bespoke programme of activities. RESULTS: The programme comprised the development of (a) a visual summary of a research paper, (b) five skills development masterclasses and (c) a six-month mentoring scheme to develop and implement plans for translating evidence into practice. DISCUSSION: The programme overcame many of the traditional barriers (lack of access, skills and time) to increase engagement of nurses and AHP staff in accessing, reviewing and using evidence in clinical practice. CONCLUSION: With clinical leadership support, it is feasible to use a multi-strategy approach to promote and enable nurses and AHPs to use evidence in clinical practice

SNP Interaction Pattern Identifier (SIPI): An Intensive Search for SNP-SNP Interaction Patterns

Motivation: SNP-SNP interactions may be the key for overcoming bottlenecks of genetic association studies. However, related statistical methods for testing SNP-SNP interactions are underdeveloped. / Results: We propose the SNP Interaction Pattern Identifier (SIPI), which tests 45 biologically mean-ingful interaction patterns for a binary outcome. SIPI takes various inheritance modes and model structures (including non-hierarchical models) into consideration. The simulation results show that SIPI has higher power than MDR-LR (Multifactor Dimensionality Reduction-Logistic Regression), AA_Full, and SNPassoc in general. Applying SIPI to the prostate cancer PRACTICAL consortium data with approximately 21,000 patients, the two SNP pairs in EGFR-MMP16 and EGFR-EGFR were found to be associated with prostate cancer aggressiveness with the exact pattern in the discovery and validation sets. We demonstrated that SIPI not only searches for more meaningful interaction patterns but can also overcome the unstable nature of interaction patterns

Adjusting the frequency of mammography screening on the basis of genetic risk: Attitudes among women in the UK.

Purpose To explore public attitudes towards modifying frequency of mammography screening based on genetic risk. Methods Home-based interviews were carried out with a population-based sample of 942 women aged 18–74 years in the UK. Demographic characteristics and perceived breast cancer (BC) risk were examined as predictors of support for risk-stratified BC screening and of the acceptability of raised or lowered screening frequency based on genetic risk, using multivariate logistic regression. Results Over two-thirds of respondents (65.8%) supported the idea of varying screening frequency on the basis of genetic risk. The majority (85.4%) were willing to have more frequent breast screening if they were found to be at higher risk, but fewer (58.8%) were willing to have less frequent screening if at lower risk (t (956) = 15.6, p < 0.001). Ethnic minority status was associated with less acceptability of more frequent screening (OR = 0.40, 95% CI = 0.21–0.74), but there were no other significant demographic correlates. Higher perceived risk of BC was associated with greater acceptability of more frequent screening (OR = 1.71, 95%CI = 1.27–2.30). Conclusion Women were positive about adjusting the frequency of mammography screening in line with personal genetic risk, but it will be important to develop effective communication materials to minimise resistance to reducing screening frequency for those at lower genetic risk

Risk-stratified breast cancer screening incorporating a polygenic risk score: a survey of UK General Practitioners’ knowledge and attitudes

A polygenic risk score (PRS) quantifies the aggregated effects of common genetic variants in an individual. A ‘personalised breast cancer risk assessment’ combines PRS with other genetic and nongenetic risk factors to offer risk-stratified screening and interventions. Large-scale studies are evaluating the clinical utility and feasibility of implementing risk-stratified screening; however, General Practitioners’ (GPs) views remain largely unknown. This study aimed to explore GPs’: (i) knowledge of risk-stratified screening; (ii) attitudes towards risk-stratified screening; and (iii) preferences for continuing professional development. A cross-sectional online survey of UK GPs was conducted between July–August 2022. The survey was distributed by the Royal College of General Practitioners and via other mailing lists and social media. In total, 109 GPs completed the survey; 49% were not familiar with the concept of PRS. Regarding risk-stratified screening pathways, 75% agreed with earlier and more frequent screening for women at high risk, 43% neither agreed nor disagreed with later and less screening for women at lower-than-average risk, and 55% disagreed with completely removing screening for women at much lower risk. In total, 81% felt positive about the potential impact of risk-stratified screening towards patients and 62% felt positive about the potential impact on their practice. GPs selected training of healthcare professionals as the priority for future risk-stratified screening implementation, preferring online formats for learning. The results suggest limited knowledge of PRS and risk-stratified screening amongst GPs. Training—preferably using online learning formats—was identified as the top priority for future implementation. GPs felt positive about the potential impact of risk-stratified screening; however, there was hesitance and disagreement towards a low-risk screening pathway