Risk Prediction Models for Colorectal Cancer: A Systematic Review.

Colorectal cancer is the second leading cause of cancer-related death in Europe and the United States. Survival is strongly related to stage at diagnosis and population-based screening reduces colorectal cancer incidence and mortality. Stratifying the population by risk offers the potential to improve the efficiency of screening. In this systematic review we searched Medline, EMBASE, and the Cochrane Library for primary research studies reporting or validating models to predict future risk of primary colorectal cancer for asymptomatic individuals. A total of 12,808 papers were identified from the literature search and nine through citation searching. Fifty-two risk models were included. Where reported (n = 37), half the models had acceptable-to-good discrimination (the area under the receiver operating characteristic curve, AUROC >0.7) in the derivation sample. Calibration was less commonly assessed (n = 21), but overall acceptable. In external validation studies, 10 models showed acceptable discrimination (AUROC 0.71-0.78). These include two with only three variables (age, gender, and BMI; age, gender, and family history of colorectal cancer). A small number of prediction models developed from case-control studies of genetic biomarkers also show some promise but require further external validation using population-based samples. Further research should focus on the feasibility and impact of incorporating such models into stratified screening programmes.J Usher-Smith is funded by a National Institute of Health Research (NIHR) Clinical Lectureship and F Walter by an NIHR Clinician Scientist award. J Emery is funded by an Australian National Health and Medical Research Council (NHMRC) Practitioner Fellowship. A Wong has an NHMRC Early Career Fellowship. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.This is the author accepted manuscript. The final version is available from American Association for Cancer Research via http://dx.doi.org/10.1158/1940-6207.CAPR-15-027

Public attitudes towards screening for kidney cancer: an online survey

Funder: Kidney Cancer UKFunder: The Urology FoundationAbstract: Background: Kidney cancer is often asymptomatic, leading to proposals for a screening programme. The views of the public towards introducing a new screening programme for kidney cancer are unknown. The aim of this study was to explore attitudes towards kidney cancer screening and factors influencing intention to attend a future screening programme. Methods: We conducted an online population-based survey of 1021 adults aged 45–77 years. The main outcome measure was intention to attend four possible screening tests (urine, blood, ultrasound scan, low-dose CT) as well as extended low-dose CT scans within lung cancer screening programmes. We used multivariable regression to examine the association between intention and each screening test. Results: Most participants stated that they would be ‘very likely’ or ‘likely’ to undergo each of the screening tests [urine test: n = 961 (94.1%); blood test: n = 922 (90.3%); ultrasound: n = 914 (89.5%); low-dose CT: n = 804 (78.8%); lung CT: n = 962 (95.2%)]. Greater intention to attend was associated with higher general cancer worry and less perceived burden/inconvenience about the screening tests. Less worry about the screening test was also associated with higher intention to attend, but only in those with low general cancer worry (cancer worry scale ≤ 5). Compared with intention to take up screening with a urine test, participants were half as likely to report that they intended to undergo blood [OR 0.56 (0.43–0.73)] or ultrasound [OR 0.50 (0.38–0.67)] testing, and half as likely again to report that they intended to take part in a screening programme featuring a low dose CT scan for kidney cancer screening alone [OR 0.19 (0.14–0.27)]. Conclusion: Participants in this study expressed high levels of intention to accept an invitation to screening for kidney cancer, both within a kidney cancer specific screening programme and in conjunction with lung cancer screening. The choice of screening test is likely to influence uptake. Together these findings support on-going research into kidney cancer screening tests and the potential for combining kidney cancer screening with existing or new screening programmes

Influence of prior beliefs on perception in early psychosis: Effects of illness stage and hierarchical level of belief.

Alterations in the balance between prior expectations and sensory evidence may account for faulty perceptions and inferences leading to psychosis. However, uncertainties remain about the nature of altered prior expectations and the degree to which they vary with the emergence of psychosis. We explored how expectations arising at two different levels-cognitive and perceptual-influenced processing of sensory information and whether relative influences of higher- and lower-level priors differed across people with prodromal symptoms and those with psychotic illness. In two complementary auditory perception experiments, 91 participants (30 with first-episode psychosis, 29 at clinical risk for psychosis, and 32 controls) were required to decipher a phoneme within ambiguous auditory input. Expectations were generated in two ways: an accompanying visual input of lip movements observed during auditory presentation or through written presentation of a phoneme provided prior to auditory presentation. We determined how these different types of information shaped auditory perceptual experience, how this was altered across the prodromal and established phases of psychosis, and how this relates to cingulate glutamate levels assessed by magnetic resonance spectroscopy. The psychosis group relied more on high-level cognitive priors compared to both healthy controls and those at clinical risk for psychosis and relied more on low-level perceptual priors than the clinical risk group. The risk group was marginally less reliant on low-level perceptual priors than controls. The results are consistent with previous theory that influences of prior expectations in perceptions in psychosis differ according to level of prior and illness phase. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Wellcome Trus

Risk Prediction Models for Colorectal Cancer Incorporating Common Genetic Variants: A Systematic Review.

Colorectal cancer screening reduces colorectal cancer incidence and mortality. Risk models based on phenotypic variables have relatively good discrimination in external validation and may improve efficiency of screening. Models incorporating genetic variables may perform better. In this review, we updated our previous review by searching Medline and EMBASE from the end date of that review (January 2014) to February 2019 to identify models incorporating at least one SNP and applicable to asymptomatic individuals in the general population. We identified 23 new models, giving a total of 29. Of those in which the SNP selection was on the basis of published genome-wide association studies, in external or split-sample validation the AUROC was 0.56 to 0.57 for models that included SNPs alone, 0.61 to 0.63 for SNPs in combination with other risk factors, and 0.56 to 0.70 when age was included. Calibration was only reported for four. The addition of SNPs to other risk factors increases discrimination by 0.01 to 0.06. Public health modeling studies suggest that, if determined by risk models, the range of starting ages for screening would be several years greater than using family history alone. Further validation and calibration studies are needed alongside modeling studies to assess the population-level impact of introducing genetic risk-based screening programs

Action selection in early stages of psychosis: an active inference approach

BACKGROUND: To interact successfully with their environment, humans need to build a model to make sense of noisy and ambiguous inputs. An inaccurate model, as suggested to be the case for people with psychosis, disturbs optimal action selection. Recent computational models, such as active inference, have emphasized the importance of action selection, treating it as a key part of the inferential process. Based on an active inference framework, we sought to evaluate previous knowledge and belief precision in an action-based task, given that alterations in these parameters have been linked to the development of psychotic symptoms. We further sought to determine whether task performance and modelling parameters would be suitable for classification of patients and controls. METHODS: Twenty-three individuals with an at-risk mental state, 26 patients with first-episode psychosis and 31 controls completed a probabilistic task in which action choice (go/no-go) was dissociated from outcome valence (gain or loss). We evaluated group differences in performance and active inference model parameters and performed receiver operating characteristic (ROC) analyses to assess group classification. RESULTS: We found reduced overall performance in patients with psychosis. Active inference modelling revealed that patients showed increased forgetting, reduced confidence in policy selection and less optimal general choice behaviour, with poorer action-state associations. Importantly, ROC analysis showed fair-to-good classification performance for all groups, when combining modelling parameters and performance measures. LIMITATIONS: The sample size is moderate. CONCLUSION: Active inference modelling of this task provides further explanation for dysfunctional mechanisms underlying decision-making in psychosis and may be relevant for future research on the development of biomarkers for early identification of psychosis

External Validation of Risk Prediction Models Incorporating Common Genetic Variants for Incident Colorectal Cancer Using UK Biobank.

The aim of this study was to compare and externally validate risk scores developed to predict incident colorectal cancer that include common genetic variants (SNPs), with or without established lifestyle/environmental (questionnaire-based/classical/phenotypic) risk factors. We externally validated 23 risk models from a previous systematic review in 443,888 participants ages 37 to 73 from the UK Biobank cohort who had 6-year prospective follow-up, no prior history of colorectal cancer, and data for incidence of colorectal cancer through linkage to national cancer registries. There were 2,679 (0.6%) cases of incident colorectal cancer. We assessed model discrimination using the area under the operating characteristic curve (AUC) and relative risk calibration. The AUC of models including only SNPs increased with the number of included SNPs and was similar in men and women: the model by Huyghe with 120 SNPs had the highest AUC of 0.62 [95% confidence interval (CI), 0.59-0.64] in women and 0.64 (95% CI, 0.61-0.66) in men. Adding phenotypic risk factors without age improved discrimination in men but not in women. Adding phenotypic risk factors and age increased discrimination in all cases (P < 0.05), with the best performing models including SNPs, phenotypic risk factors, and age having AUCs between 0.64 and 0.67 in women and 0.67 and 0.71 in men. Relative risk calibration varied substantially across the models. Among middle-aged people in the UK, existing polygenic risk scores discriminate moderately well between those who do and do not develop colorectal cancer over 6 years. Consideration should be given to exploring the feasibility of incorporating genetic and lifestyle/environmental information in any future stratified colorectal cancer screening program

Validation and public health modelling of risk prediction models for kidney cancer using the UK Biobank

Funder: Kidney Cancer UKFunder: Yorkshire Cancer ResearchFunder: Mark Foundation For Cancer Research; Id: http://dx.doi.org/10.13039/100014599Funder: The Rosetrees TrustFunder: Urology Foundation; Id: http://dx.doi.org/10.13039/501100007568Objectives: To externally validate risk models for the detection of kidney cancer, as early detection of kidney cancer improves survival and stratifying the population using risk models could enable an individually tailored screening programme. Methods: We validated the performance of 30 existing phenotypic models predicting the risk of kidney cancer in the UK Biobank cohort (n = 450 687). We compared the discrimination and calibration of models for men, women, and a mixed‐sex cohort. Population level data were used to estimate model performance in a screening scenario for a range of risk thresholds (6‐year risk: 0.1–1.0%). Results: In all, 10 models had reasonable discrimination (area under the receiver‐operating characteristic curve >0.60), although some had poor calibration. Modelling demonstrated similar performance of the best models over a range of thresholds. The models showed an improvement in ability to identify cases compared to age‐ and sex‐based screening. All the models performed less well in women than men. Conclusions: The present study is the first comprehensive external validation of risk models for kidney cancer. The best‐performing models are better at identifying individuals at high risk of kidney cancer than age and sex alone; however, the benefits are relatively small. Feasibility studies are required to determine applicability to a screening programme

Acceptability and potential impact on uptake of using different risk stratification approaches to determine eligibility for screening: A population‐based survey

Funder: Kidney Cancer UKFunder: Renal Cancer Research FundAbstract: Background: Using risk stratification approaches to determine eligibility has the potential to improve efficiency of screening. Objectives: To compare the public acceptability and potential impact on uptake of using different approaches to determine eligibility for screening. Design: An online population‐based survey of 668 adults in the UK aged 45‐79 including a series of scenarios in the context of a potential kidney cancer screening programme in which eligibility was determined by age, sex, age and sex combined, a simple risk score (age, sex, body mass index, smoking status), a complex risk score additionally incorporating family history and lifestyle, or a genetic risk score. Outcome measures: We used multi‐level ordinal logistic regression to compare acceptability and potential uptake within individuals and multivariable ordinal logistic regression differences between individuals. Results: Using sex, age and sex, or the simple risk score were less acceptable than age (P < .0001). All approaches were less acceptable to women than men. Over 70% were comfortable waiting until they were older if the complex risk score or genetics indicated a low risk. If told they were high risk, 85% would be more likely to take up screening. Being told they were low risk had no overall influence on uptake. Conclusions: Varying the starting age of screening based on estimated risk from models incorporating phenotypic or genetic risk factors would be acceptable to most individuals and may increase uptake. Patient or Public Contribution: Two members of the public contributed to the development of the survey and have commented on this paper

Reasons for intending to accept or decline kidney cancer screening: thematic analysis of free text from an online survey

Objectives: Kidney cancer has been identified as a disease for which screening might provide significant benefit for patients. The aim of this study was to understand in detail the facilitators and barriers towards uptake of a future kidney cancer screening programme, and to compare these across four proposed screening modalities. Design: An online survey including free-text responses. Setting: UK Participants: 668 adults Primary and secondary outcome measures: The survey assessed participants’ self-reported intention to take-up kidney cancer screening with four different test methods (urine test, blood test, ultrasound scan and low-dose CT). We conducted thematic analysis of 2559 free-text comments made within the survey using an inductive approach. Results: We identified five overarching themes that influenced screening intention: ‘personal health beliefs’, ‘practicalities’, ‘opinions of the test’, ‘attitudes towards screening’ and ‘cancer apprehension’. Overall, participants considered the tests presented as simple to complete and the benefits of early detection to outweigh any drawbacks to screening. Dominant facilitators and barriers varied with patterns of intention to take up screening across the four tests. Most intended to take up screening by all four tests, and for these participants, screening was seen as a positive health behaviour. A significant minority were driven by practicalities and the risks of the tests offered. A smaller proportion intended to reject all forms of screening offered, often due to fear or worry about results and unnecessary medical intervention or a general negative view of screening. Conclusions: Most individuals would accept kidney cancer screening by any of the four test options presented because of strong positive attitudes towards screening in general and the perceived simplicity of the tests. Providing information about the rationale for screening in general and the potential benefits of early detection will be important to optimise uptake among uncertain individuals

Comment Re: Non-Compete Clause Rulemaking, Matter No. P201200

Within signed law professors and law students submitted this letter to the Federal Trade Commission, writing in their individual capacities, not as agents of their affiliated institutions, in support of the Federal Trade Commission’s proposed rule to ban most non-compete clauses (the “Proposal”) as an unfair method of competition. This letter offers comments in response to areas where the FTC has requested public comment. To make our views clear, this letter contains the following sections: I. Summary of the Proposal; II. The Commission Should Consider Expanding Its Definition of Non-Compete Clauses to Prevent Employers from Requiring Workers to Quit Before Seeking Alternative Employment; III. Non-Compete Clauses Are Unfair Methods of Competition; IV. Non-Compete Clauses Negatively Impact Workers and Their Families; V. The Proposed Rule Protects Small Businesses and Entrepreneurs; and VI. The Commission Should Consider a Factor Test for Its Unfairness Analysis for Senior Executive